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Cited by 3,549Lipoproteins and Cardiovascular HealthDiabetes, Cardiovascular Risks, and LipoproteinsBlood Pressure and Hypertension Studies

ESC/EAS Guidelines for the management of dyslipidaemias

Open access
Reiner, Željko, Catapano, Alberico L., De Backer, Guy, Graham, Ian, Taskinen, Marja-Riitta, Wiklund, Olov, Agewall, Stefan, Alegria, Eduardo +68 more·2011·European Heart Journal
DOI 10.1093/eurheartj/ehr158
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Abstract

Cardiovascular disease (CVD) due to atherosclerosis of the arterial vessel wall and to thrombosis is the foremost cause of premature mortality and of disability-adjusted life years (DALYs) in Europe, and is also increasingly common in developing countries.1 In the European Union, the economic cost of CVD represents annually E192 billion1 in direct and indirect healthcare costs. The main clinical entities are coronary artery disease (CAD), ischaemic stroke, and peripheral arterial disease (PAD). The causes of these CVDs are multifactorial. Some of these factors relate to lifestyles, such as tobacco smoking, lack of physical activity, and dietary habits, and are thus modifiable. Other risk factors are also modifiable, such as elevated blood pressure, type 2 diabetes, and dyslipidaemias, or non-modifiable, such as age and male gender. These guidelines deal with the management of dyslipidaemias as an essential and integral part of CVD prevention. Prevention and treatment of dyslipidaemias should always be considered within the broader framework of CVD prevention, which is addressed in guidelines of the Joint European Societies’ Task forces on CVD prevention in clinical practice.2 – 5 The latest version of these guidelines was published in 20075; an update will become available in 2012. These Joint ESC/European Atherosclerosis Society (EAS) guidelines on the management of dyslipidaemias are complementary to the guidelines on CVD prevention in clinical practice and address not only physicians [e.g. general practitioners (GPs) and cardiologists] interested in CVD prevention, but also specialists from lipid clinics or metabolic units who are dealing with dyslipidaemias that are more difficult to classify and treat.

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Crossref · 10.1093/eurheartj/ehr158

Cites

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Claims the paper makes

0 of 254 cited sources checked · 0 supported · 0 flagged

  • Findingcitation

    A meta-analysis by the Emerging Risk Factor Collaboration found that apolipoprotein B gives no additional benefit beyond non-HDL-cholesterol or traditional lipid ratios.

    “Recent data from a meta-analysis by the Emerging Risk Factor Collaboration 42 indicate that apo B does not provide any benefit beyond non-HDL-C or traditional lipid ratios.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [42] The Emerging Risk Factors Collaboration. Major lipids, apolipoproteins, and risk of vascular disease, 2009, JAMA source

      Not checked in the free run.

  • Findingnone given

    In some age groups, most men have estimated CV death risk above 5-10% from age and gender alone, even when other risk factors are relatively low.

    “In some age categories the vast majority, especially of men, will have estimated CV death risks exceeding the 5-10% level, based on age (and gender) only, even when other CV risk factor levels are relatively low.”
    Quote in the paperSubstantial claim
  • Findingcitation

    In another meta-analysis of LDL-cholesterol, non-HDL-cholesterol, and apolipoprotein B, apolipoprotein B was superior as a marker of cardiovascular risk.

    “in another meta-analysis of LDL-C, non-HDL-C, and apo B, the latter was superior as a marker of CV risk.48”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [48] Sniderman, Meta-analysis of LDL-C, non-HDL-C and apo B as markers of cardiovascular risk, Circulation

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  • Findingcitation

    In people with diabetes in the FIELD study, apolipoprotein B gave no benefit beyond traditional lipid markers.

    “apo B provided no benefit beyond traditional lipid markers in people with diabetes in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.47”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [47] Taskinen, 2010, Ability of traditional lipid ratios and apolipoprotein ratios to predict cardiovascular risk in people with type 2 diabetes, Diabetologia source

      Not checked in the free run.

  • Findingcitation

    Each 1.0 mmol/L (40 mg/dL) reduction in LDL-cholesterol is associated with a 22% reduction in cardiovascular mortality and morbidity.

    “Every 1.0 mmol/L ( 40 mg/dL) reduction in LDL-C is associated with a corresponding 22% reduction in CVD mortality and morbidity.15”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [15] Cholesterol Treatment Trialists' (CTT) Collaboration, 2010, Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170000 participants in 26 randomised trials, Lancet source

      Not checked in the free run.

  • May combine two claims. 117
  • Classified as probably not a substantial claim. 33

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    Findingcitation

    SCORE data show total CVD event risk is about three times fatal CVD risk in men; the multiplier is slightly higher in women and lower in older people.

    “The SCORE data indicate that the total CVD event risk is about three times higher than the risk of fatal CVD for men, so that a SCORE risk of 5% translates into a CVD risk of 15% of total (fatal plus non-fatal) hard CVD endpoints; the multiplier is slightly higher in women and lower in older persons.”
    Quote in the paperNot a substantial claim

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    Findingnone given

    Diabetes appears to increase CV risk more than in Framingham-based systems, with relative risks of 5 in women and 3 in men.

    “The impact of diabetes on risk appears greater than in risk estimation systems based on the Framingham cohort, with relative risks of 5 in women and 3 in men.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    Information on episodes of increased liver enzymes was not examined in this meta-analysis.

    “Information on episodes of increased liver enzymes was not examined in this meta-analysis.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15] Cholesterol Treatment Trialists' (CTT) Collaboration, 2010, Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170000 participants in 26 randomised trials, Lancet source

      Not checked in the free run.

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    Findingcitation

    In the CTT meta-analysis of more than 170,000 participants in 26 randomized trials, a 10% proportional reduction in all-cause mortality and a 20% reduction in coronary artery disease death were reported per 1.0 mmol/L (40 mg/dL) LDL-cholesterol reduction.

    “In the CTT meta-analyses of individual participant data from .170000 participants in 26 randomized trials of statins, 15 a 10% proportional reduction in all-cause mortality and 20% proportional reduction in CAD death per 1.0 mmol/L ( 40 mg/dL) LDL-C reduction is reported.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [15] Cholesterol Treatment Trialists' (CTT) Collaboration, 2010, Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170000 participants in 26 randomised trials, Lancet source

      Not checked in the free run.

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    Findingcitation

    The benefits of statins were significant within the first year but were greater in subsequent years.

    “The benefits were significant within the first year, but were greater in subsequent years.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15] Cholesterol Treatment Trialists' (CTT) Collaboration, 2010, Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170000 participants in 26 randomised trials, Lancet source

      Not checked in the free run.

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    Findingcitation

    Daily consumption of 2 g of phytosterols can lower total cholesterol and LDL-cholesterol by 7-10%, with little or no effect on HDL-cholesterol and triglycerides when taken with the main meal.

    “The daily consumption of 2 g of phytosterols can effectively lower TC and LDL-C by 7-10% in humans, with little or no effect on HDL-C and TG levels when consumed with the main meal.67”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [67] Abumweis, 2008, Plant sterols/stanols as cholesterol lowering agents: a meta-analysis of randomized controlled trials, Food Nutr Res source

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    Findingcitation

    Red yeast rice contains monacolins that lower total cholesterol and LDL-cholesterol, but the long-term safety of regular consumption is not fully documented.

    “Different commercial preparations of RYR have different concentrations of monacolins, the bioactive ingredients, and lower TC and LDL-C, 71 but the long-term safety of the regular consumption of these products is not fully documented.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [71] Becker, 2009, Red yeast rice for dyslipidemia in statin-intolerant patients: a randomized trial, Ann Intern Med source

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    Findingcitation

    Replacing 1% of dietary energy from saturated fatty acids with monounsaturated fatty acids lowers LDL-cholesterol by 0.041 mmol/L, with n-6 polyunsaturated fatty acids by 0.051 mmol/L, and with carbohydrate by 0.032 mmol/L.

    “If 1% of the dietary energy derived from SFAs is replaced by monounsaturated fatty acids (MUFAs), LDL-C decreases by 0.041 mmol/L (1.6 mg/dL); if replaced by n-6 polyunsaturated fatty acids (PUFAs) the decrease would be 0.051 mmol/L (2.0 mg/dL); and if replaced by carbohydrate it would be 0.032 mmol/L (1.2 mg/dL).63”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [63] Mensink, 2003, Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials, Am J Clin Nutr source

      Not checked in the free run.

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    Findingcitation

    Weight reduction improves insulin sensitivity and lowers triglyceride levels, with reductions of 20-30% in many studies.

    “Weight reduction improves insulin sensitivity and decreases TG levels.In many studies the reduction of TG levels due to weight reduction is between 20 and 30%”
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    • cites [70] Shaw, 2006, Exercise for overweight or obesity, Cochrane Database Syst Rev

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    Findingcitation

    Alcohol intake has a major negative impact on triglyceride levels; in individuals with hypertriglyceridaemia even a small amount can raise triglycerides, while in the general population detrimental effects occur only above moderate consumption (10-30 g/day).

    “Alcohol intake has a major negative impact on TG levels.While in individuals with HTG even a small amount of alcohol can induce a further elevation of TG concentrations, in the general population alcohol exerts detrimental effects on TG levels only if the intake exceeds what is considered a moderate consumption (up to 1-2 drinks/day corresponding to 10-30 g/day).74”
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    • cites [74] Rimm, 1999, Moderate alcohol intake and lower risk of coronary heart disease: meta-analysis of effects on lipids and haemostatic factors, BMJ source

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    Findingcitation

    A high monounsaturated fat diet significantly improves insulin sensitivity compared with a high saturated fat diet, with a parallel reduction in triglyceride levels.

    “A high monounsaturated fat diet significantly improves insulin sensitivity compared with a high saturated fat diet.84 This goes in parallel with a reduction in TG levels”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [84] Mattar, 2009, Fish oil and the management of hypertriglyceridemia, Nutr Health source

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    Findingcitation

    The excess risk of rhabdomyolysis with statins was small and not significant.

    “The excess risk of rhabdomyolysis with statins was small and not significant.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15] Cholesterol Treatment Trialists' (CTT) Collaboration, 2010, Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170000 participants in 26 randomised trials, Lancet source

      Not checked in the free run.

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    Findingcitation

    Low-dose supplementation with n-3 polyunsaturated fatty acid margarine (400 mg/day) or alpha-linolenic acid (2 g/day) did not significantly reduce triglycerides or major cardiovascular events in a randomized trial of 4837 post-myocardial infarction patients.

    “a low dose supplementation of a margarine with n-3 PUFAs (400 mg/day) or a-linolenic acid (2 g/day) did not significantly reduce TG levels in an RCT involving 4837 post-MI patients; neither did this supplementation reduce the rate of major CV events.92”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [92] Kromhout, 2010, n-3 Fatty acids and cardiovascular events after myocardial infarction, N Engl J Med source

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    Findingnone given

    Increases in HDL-cholesterol predict atherosclerosis regression, and low HDL-cholesterol is associated with excess events and mortality in coronary artery disease patients even when LDL-cholesterol is below 1.8 mmol/L.

    “increases in HDL-C predict atherosclerosis regression and low HDL-C is associated with excess events and mortality in CAD patients, even when LDL-C is lower than 1.8 mmol/L or 70 mg/dL.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    In controlled trials, statins are generally well tolerated, and serious adverse events are uncommon.

    “Statins are generally well tolerated, and serious adverse events are rare.”
    • Also stated in: § Muscle · plain
      “Over 129 000 patients have been systematically studied in controlled trials with blinded randomized assignment to statin vs. placebo treatment groups.15”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15] Cholesterol Treatment Trialists' (CTT) Collaboration, 2010, Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170000 participants in 26 randomised trials, Lancet source

      Not checked in the free run.

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    Findingcitation

    The risk of major coronary events was reduced by 23% and the risk of stroke by 17% per mmol/L (40 mg/dL) LDL-cholesterol reduction.

    “The risk for major coronary events was reduced by 23% and the risk for stroke was reduced by 17% per mmol/L (40 mg/dL) LDL-C reduction.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [15] Cholesterol Treatment Trialists' (CTT) Collaboration, 2010, Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170000 participants in 26 randomised trials, Lancet source

      Not checked in the free run.

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    Findingcitation

    Dietary fructose contributes to triglyceride elevations in a dose-dependent manner, becoming clinically relevant when intake exceeds 10% of daily energy, with 15-20% energy intake increasing plasma triglycerides by as much as 30-40%.

    “dietary fructose contributes to TG elevations; these effects are dose dependent and become clinically relevant when the intake is .10%energy daily-with a habitual fructose consumption between 15 and 20% of the energy intake, plasma TG increases as much as 30 -40%.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [76] Stanhope, 2009, Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans, J Clin Invest source

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    Findingcitation

    In FIELD, fenofibrate versus placebo produced small but significant increases in pancreatitis (0.8% vs 0.5%) and pulmonary embolism (1.1% vs 0.7%), and a non-significant trend toward more deep vein thrombosis (1.4% vs 1.0%).

    “In the FIELD study, small but significant increases in the incidence of pancreatitis (0.8% vs. 0.5%) and of pulmonary embolism (1.1% vs. 0.7%), and a non-significant trend toward an increase in deep vein thrombosis (1.4% vs. 1.0%) were seen in those taking fenofibrate compared with placebo; this is in line with data from other fibrate studies.127”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [127] Keech, 2005, Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial, Lancet source

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    Findingcitation

    Colesevelam lowers LDL-C and improves glycated haemoglobin in patients with type 2 diabetes.

    “The drug reduces LDL-C and also improves glycated haemoglobin (Hb A1C ) in patients with type 2 diabetes.109,110”
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    • cites [109] Levy P, 2010, Review of studies on the effect of bile acid sequestrants in patients with type 2 diabetes mellitus, Metab Syndr Relat Disord source

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    • cites [110] Fonseca, 2010, Colesevelam lowers glucose and lipid levels in type 2 diabetes: the clinical evidence, Diabetes Obes Metab source

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    Findingcitation

    Recent data strongly support triglyceride-rich lipoproteins as a cardiovascular risk factor, although the role of triglycerides has been debated.

    “Although the role of TG as a risk factor for CVD has been strongly debated, recent data strongly favour the role of TG-rich lipoproteins as a risk factor for CVD.121”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [121] Sarwar, 2010, Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies, Lancet source

      Not checked in the free run.

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    Findingcitation

    At 2 g daily, nicotinic acid lowers triglycerides by 20-40% and LDL-C by 15-18%, and raises HDL-C by 15-35%.

    “At the daily dose of 2 g it reduces TG by 20-40% and LDL-C by 15-18%, and increases HDL-C by 15-35%.130”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [130] Kamanna, 2008, Mechanism of action of niacin, Am J Cardiol source

      Not checked in the free run.

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    Findingcitation

    Fibrates are generally well tolerated; gastrointestinal disturbance occurs in 5% of patients and skin rashes in 2%.

    “Fibrates are generally well tolerated with mild side effects, gastrointestinal disturbance being reported in 5% of the patients and skin rashes in 2%.128”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [128] Davidson, 2007, Safety considerations with fibrate therapy, Am J Cardiol source

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    Findingcitation

    In SEAS, ezetimibe plus simvastatin in asymptomatic aortic stenosis reduced ischaemic cardiovascular events-by up to 46% in less severe aortic stenosis-but not aortic valve stenosis events.

    “The results of the SEAS study in patients with asymptomatic aortic stenosis showed that ezetimibe and simvastatin applied concomitantly reduce the incidence of ischaemic CVD events (up to 46% in the patients with less severe aortic stenosis) but not events related to aortic valve stenosis.38”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [38] Rossebø, 2008, Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis, N Engl J Med source

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    Findingcitation

    Clinical trials with bile acid sequestrants helped demonstrate that lowering LDL-C reduces cardiovascular events in hypercholesterolaemic patients, with benefit proportional to LDL-C reduction.

    “In clinical trials, bile acid sequestrants have contributed greatly to the original demonstration of the efficacy of LDL-C lowering in reducing CV events in hypercholesterolaemic subjects, with a benefit proportional to the degree of LDL-C lowering.108”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [108] Tyroler, 1984, Cholesterol and cardiovascular disease. An overview of Lipid Research Clinics (LRC) epidemiologic studies as background for the LRC Coronary Primary Prevention Trial, Am J Cardiol source

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    Findingcitation

    Recent meta-analyses found that fibrate therapy reduced major cardiovascular events by 13% (95% CI 7-19), with the greatest benefit in patients with triglycerides above 2.3 mmol/L (200 mg/dL).

    “Recent meta-analyses reported that fibrate therapy reduced major CVD events by 13% [95% confidence interval (CI) 7-19], the benefits being most robust in patients with elevated TG levels (.2.3 mmol/L or more than 200 mg/dl).52”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [52] Jun, 2010, Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis, Lancet source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingcitation

    About one-third of adults have triglycerides above 1.7 mmol/L (150 mg/dL), highlighting the burden of hypertriglyceridaemia as a cardiovascular risk factor.

    “The burden of HTG as a CVD risk factor is highlighted by the fact that about one-third of adult individuals have TG .1.7 mmol/L (more than 150 mg/dL).122”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [122] Kotseva, 2009, EUROASPIRE III: a survey on the lifestyle, risk factors and use of cardioprotective drug therapies in coronary patients from 22 European countries, Eur J Cardiovasc Prev Rehabil source

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  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing), S4 (based). May combine two claims.

    Findingcitation

    CK elevations above 5 times ULN and ALT elevations above 3 times ULN were more frequent with fenofibrate than placebo, but remained below 1% in both groups.

    “Elevations of both CK (.5 times above the ULN) and ALT (.3 times above the ULN) were reported more frequently for patients on fenofibrate than on placebo, but the incidence of these abnormalities remained ,1% in both treatment groups.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [127] Keech, 2005, Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial, Lancet source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    At 2 g/day, nicotinic acid raises HDL-C by 25% in a dose-dependent way and lowers LDL-C by 15-18% and triglycerides by 20-40%.

    “Nicotinic acid has broad lipid-modulating action, raising HDL-C in a dose-dependent manner by 25%, and reducing both LDL-C by 15 -18% and TG by 20-40% at the 2 g/day dose.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [130] Kamanna, 2008, Mechanism of action of niacin, Am J Cardiol source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    These trials showed consistent reductions in non-fatal myocardial infarction, often in post-hoc analyses, with the strongest effect in patients with elevated triglycerides and low HDL-C.

    “The data from these trials have shown consistent decreases in the rates of non-fatal MI (although often as a result of post-hoc analyses), the effect being most robust in subjects with elevated TG/low HDL-C levels.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [124] Frick, 1987, Helsinki Heart Study: primary prevention trial with gemfibrozil in middle-aged men with dyslipidaemia, N Engl J Med source

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    • cites [125] Rubins, 1999, Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol, N Engl J Med source

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    • cites [126] The BIP Study Group, 2000, Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease. The Bezafibrate Infarction Prevention (BIP) Study, Circulation source

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    • cites [127] Keech, 2005, Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial, Lancet source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In patients on a stable statin dose, phytosterol-containing functional food or plant sterol tablets lower LDL-C by up to 5-10%, and the combination is well tolerated and safe.

    “Functional food containing phytosterols as well as plant sterolcontaining tablets additionally reduce LDL-C levels by up to 5-10% in patients taking a stable dose of a statin, and this combination is also well tolerated and safe 67”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [67] Abumweis, 2008, Plant sterols/stanols as cholesterol lowering agents: a meta-analysis of randomized controlled trials, Food Nutr Res source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In elderly people without previous CVD, hypolipidaemic treatment reduces CV morbidity (stroke, MI) but does not prolong life.

    “In fact, although there is no evidence that hypolipidaemic treatment in elderly people prolongs life in patients without previous CVD, treatment reduces CV morbidity (stroke, MI) in elderly people in primary prevention.16”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [16] Brugts, 2009, The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials, BMJ source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    A more recent meta-analysis including the JUPITER female subgroup reported a 12% relative risk reduction in total mortality with statin use in high-risk subjects without established CVD, with no heterogeneity between men and women.

    “A more recent meta-analysis that included the large female subgroup from the JUPITER trial reported a 12% relative risk reduction (RRR) of total mortality with statin use in high risk subjects without established CVD, with no heterogeneity in treatment effect between men and women.16”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [16] Brugts, 2009, The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials, BMJ source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    The CARE trial showed that pravastatin reduced major coronary events, coronary death, and stroke by 32%, 45%, and 40% respectively in elderly patients; the NNT over 5 years was 11 to prevent one major coronary event and 22 to prevent one coronary death.

    “The Cholesterol and Recurrent Events (CARE) trial evaluated the effect of pravastatin on coronary events after MI and showed major coronary events, coronary death, and stroke were reduced by, respectively, 32, 45, and 40% in elderly patients; the number needed to treat (NNT) of older patients for 5 years was 11 in order to prevent one major coronary event and 22 to prevent one coronary death.20”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [20] Lewis, 1998, Effect of pravastatin on cardiovascular events in older patients with myocardial infarction and cholesterol levels in the average range. Results of the Cholesterol and Recurrent Events (CARE) trial, Ann Intern Med source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    HATS showed small regression of angiographic coronary plaques with combined nicotinic acid and statin versus progression on placebo, and a 90% lower cardiovascular event risk, though in very few patients.

    “The HATS study showed not only a small regression of angiographically measured coronary plaques due to combined nicotinic acid and statin treatment as compared with progression observed on placebo, but also 90% lower risk of CV events, although in a very small number of patients.145”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [145] Brown, 2001, Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Combining 4 g/day n-3 fatty acids with simvastatin reduced triglycerides more and slightly but significantly raised HDL-C compared with statin alone.

    “Treatment with a combination of 4 g/day n-3 fatty acids and simvastatin caused a stronger reduction of TG concentrations and a small but significant increase in HDL-C when compared with statin alone.146”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [146] Davidson, 2007, Efficacy and tolerability of adding rescription omega-3 fatty acids 4 g/d to simvastatin 40 mg/d in hypertriglyceridemic patients: an 8-week, randomized, double-blind, placebo-controlled study, Clin Ther source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In women with previous CVD, lipid-lowering therapy substantially reduces CV events, but no reduction in total mortality has been demonstrated.

    “The results of these trials concordantly showed that lipid-lowering therapy substantially reduces CV events in these patients, although no reduction in total mortality risk could be demonstrated.164”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [164] Walsh, 2004, Drug treatment of hyperlipidaemia in women, JAMA source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    PROSPER could not reduce total mortality or improve cognitive dysfunction.

    “It could not reduce total mortality or improve cognitive dysfunction.26”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [26] Shepherd, 2002, PROspective Study of Pravastatin in the Elderly at Risk. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial, Lancet source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    The CTT meta-analysis and a recent meta-analysis of primary prevention trials showed no significant differences in relative risk reduction between younger and older people.

    “The CTT meta-analysis showed no significant differences in RRR between younger and older people, 15 and neither did a recent meta-analysis of primary prevention trials.16”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [15] Cholesterol Treatment Trialists' (CTT) Collaboration, 2010, Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170000 participants in 26 randomised trials, Lancet source

      Not checked in the free run.

    • cites [16] Brugts, 2009, The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials, BMJ source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    A Swedish MI registry study found that statin treatment is associated with lower CV mortality in very elderly post-MI patients without increasing cancer risk.

    “Results from an MI registry study in Sweden demonstrate that statin treatment is associated with lower CV mortality in very elderly post-MI patients without increasing the risk of the development of cancer.167”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [167] Gransbo, 2010, Cardiovascular and cancer mortality in very elderly post-myocardial infarction patients receiving statin treatment, J Am Coll Cardiol source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    The Walsh et al. meta-analysis of 8272 women with previous CVD mainly treated with statins reported a 26% reduction in CV mortality, a 29% reduction in MI, and a 20% reduction in total CAD events.

    “The meta-analysis of Walsh et al. 164 reported, in a cohort of 8272 females with previous CVD mainly treated with statins, a 26% reduction of CV mortality, a 29% reduction of MI, and a 20% reduction of total CAD events.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [164] Walsh, 2004, Drug treatment of hyperlipidaemia in women, JAMA source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In HeFH, increased carotid intima-media thickness compared with unaffected siblings can be detected from age 10, and its progression can be reduced with statin therapy and/or apheresis.

    “There is evidence from carotid ultrasound measurements that increased CIMT compared with siblings who have not inherited HeFH can be detected from the age of 10 years onwards, and that the progression of increasing CIMT can be ameliorated with statin therapy and/or apheresis.161”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [161] Mehta, 2009, Low-density lipoprotein apheresis as a treatment for hyperlipidaemia, Curr Treat Options Cardiovasc Med source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Among studies of lipid-lowering therapy for primary and secondary CAD prevention, only a few included women, usually in small numbers, and results were often not reported separately by gender.

    “Among several studies that have evaluated the impact of lipid-lowering therapy on primary and secondary prevention of CAD, only a few have included women, usually in small numbers, and the results have often not been separately reported by gender.162”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [162] Jonsdottir, 2002, Do lipids, blood pressure, diabetes, and smoking confer equal risk of myocardial infarction in women as in men? The Reykjavik Study, J Cardiovasc Risk source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    The average triglyceride reduction is 30%, and the benefit appears dose dependent, reaching 45% in subjects with baseline triglycerides above 5.6 mmol/L (496 mg/dL).

    “The average reduction of TG is 30% and the benefit seems to be dose dependent, being 45% in subjects with baseline TG values .5.6 mmol/L (496 mg/dL).135”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [135] Balk, 2006, Effects of omega-3 fatty acids on serum markers of cardiovascular disease risk: a systematic review, Atherosclerosis source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    People with MetS have a 2-fold increase in CV outcomes and a 1.5-fold increase in all-cause mortality.

    “Data from recent meta-analyses indicate that people with MetS have a 2-fold increase in CV outcomes and 1.5-fold increase in all-cause mortality.168”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [168] Mottillo, 2010, The metabolic syndrome and cardiovascular risk. A systematic review and meta-analysis, J Am Coll Cardiol source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In one study, EPA plus low-dose pravastatin or simvastatin reduced major coronary events compared with statin alone without changing sudden cardiac death rates.

    “In one study EPA combined with low dose pravastatin or simvastatin compared with statin therapy alone reduced major coronary events without altering rates of sudden cardiac death.136”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [136] Yokoyama, 2007, Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised openlabel, blinded endpoint analysis, Lancet source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Hypertension, dyslipidaemia, and abdominal obesity commonly co-exist with type 2 diabetes and further aggravate risk, which is highest in people with type 2 diabetes and features of MetS.

    “Hypertension, dyslipidaemia, and abdominal obesity commonly co-exist with type 2 diabetes and further aggravate the risk that is highest in people with type 2 diabetes and features of MetS.169”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [169] Liu, 2007, Ten-year risk of cardiovascular indidence related to diabetes, prediabetes, and the metabolic syndrome, Am Heart J source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    People with known CVD, type 2 diabetes, type 1 diabetes with microalbuminuria, very high levels of individual risk factors, or chronic kidney disease are at very high or high total cardiovascular risk.

    “(1) Those with † known CVD † type 2 diabetes or type 1 diabetes with microalbuminuria † very high levels of individual risk factors † chronic kidney disease (CKD) are automatically at VERY HIGH or HIGH TOTAL CARDIOVASCULAR RISK and need active management of all risk factors.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [5] Graham, 2007, European guidelines on cardiovascular disease prevention in clinical practice: Fourth Joint Task Force of the European Society of Cardiology and other societies, Eur J Cardiovasc Prev Rehabil source

      Not checked in the free run.

    • Rests on an assumption: Atherosclerotic cardiovascular disease results from multiple risk factors acting together.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationnone given

    The cut-offs defining high risk are partly arbitrary and based on risk levels where trials show benefit.

    “The cut-off points that are used to define high risk are in part arbitrary and based on the risk levels at which benefit is evident in clinical trials.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationnone given

    Risk is continuous, and no threshold automatically indicates drug treatment for continuous risk factors.

    “risk is a continuum and there is no threshold at which, for example, a drug is automatically indicated, and this is true for all continuous risk factors such as plasma cholesterol or systolic blood pressure.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Most risk estimation systems perform similarly in populations similar to their derivation population and can be recalibrated for other populations.

    “In practice, most risk estimation systems perform rather similarly when applied to populations recognizably similar to that from which the risk estimation system was derived, 6,7 and can be re-calibrated for use in different populations.6”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [6] Cooney, 2009, Value and limitations of existing scores for the assessment of cardiovascular risk. A review for clinicians, J Am Coll Cardiol source

      Not checked in the free run.

    • cites [7] Cooney, 2010, Cardiovascular risk estimation systems in primary prevention. Do they differ? Do they make a difference? Can we see the future?, Circulation source

      Not checked in the free run.

    • Rests on an assumption: Atherosclerotic cardiovascular disease results from multiple risk factors acting together.

  • May combine two claims.

    Interpretationcitation

    Available evidence indicates that apolipoprotein B is at least as good a risk factor as LDL-cholesterol and a better index of the adequacy of LDL-lowering therapy than LDL-cholesterol.

    “Based on the available evidence, apo B appears to be a risk factor at least as good as LDL-C and a better index of the adequacy of LDL-lowering therapy than LDL-C.46”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [46] Charlton-Menys, 2009, Targets of statin therapy: LDL cholesterol, non-HDL cholesterol, and apolipoprotein B in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS), Clin Chem source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Risk estimates are lower for women than men at any age, but this may mislead because risk is deferred and eventually at least as many women as men die of CVD.

    “At any given age, risk estimates are lower for women than for men.This may be misleading since, eventually, at least as many women as men die of CVD.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Lipoproteins are heterogeneous, and evidence suggests that different LDL and HDL subclasses may carry different risks for atherosclerosis.

    “Lipoproteins are heterogeneous classes of particles, and a lot of evidence suggests that the different subclasses of LDL and HDL may bear different risks for atherosclerosis.54”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [54] Packard, 2006, Small dense low-density lipoprotein and its role as an independent predictor of cardiovascular disease, Curr Opin Lipidol source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    Lowering total and LDL cholesterol cuts cardiovascular risk; trials show fewer cardiovascular deaths, at least in high-risk patients.

    “The evidence showing that reducing TC and LDL-C can prevent CVD is strong and compelling, based on results from multiple randomized controlled trials (RCTs).”
    • Also stated in: § Lipid and lipoprotein analyses · boosted
      “multiple clinical trials have established beyond all reasonable doubt that, at least in high risk subjects, reduction of TC or LDL-C is associated with a statistically and clinically significant reduction in cardiovascular mortality.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    Extrapolating from available data, reaching an LDL-cholesterol level below 1.8 mmol/L or achieving at least a 50% relative reduction provides the best cardiovascular benefit.

    “Extrapolating from the available data, an absolute reduction to an LDL-C level ,1.8 mmol/L (less than 70 mg/dL) or at least a 50% relative reduction in LDL-C provides the best benefit in terms of CVD reduction.15”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [15] Cholesterol Treatment Trialists' (CTT) Collaboration, 2010, Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170000 participants in 26 randomised trials, Lancet source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    The apolipoprotein B/apolipoprotein A1 ratio has been used in large prospective studies as an indicator of risk.

    “The ratio between apo B and apo A1 has been used in large prospective studies as an indicator of risk.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    Current evidence suggests that the clinical benefit of statins is largely independent of the type of statin and depends on the extent of LDL-cholesterol lowering.

    “Current available evidence suggests that the clinical benefit is largely independent of the type of statin but depends on the extent of LDL-C lowering”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [15] Cholesterol Treatment Trialists' (CTT) Collaboration, 2010, Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170000 participants in 26 randomised trials, Lancet source

      Not checked in the free run.

    • cites [100] Catapano, 2009, Perspectives on low-density-lipoprotein cholesterol goal achievement, Curr Med Res Opin source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationreasoning

    The non-HDL-cholesterol target should be 0.8 mmol/L (30 mg/dL) higher than the corresponding LDL-cholesterol target, corresponding to the cholesterol carried in 1.7 mmol/L (150 mg/dL) of triglycerides.

    “The specific target for non-HDL-C should be 0.8 mmol/L ( 30 mg/dL) higher than the corresponding LDL-C target; this corresponds to the LDL-C level augmented by the cholesterol fraction which is contained in 1.7 mmol/L ( 150 mg/dL) of TG”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisereasoning

    Statins lower cholesterol synthesis in the liver by competitively inhibiting HMG-CoA reductase; the resulting fall in intracellular cholesterol induces LDL receptor expression, increasing LDL-cholesterol extraction from blood.

    “Statins reduce synthesis of cholesterol in the liver by competitively inhibiting HMG-CoA reductase activity.The reduction in intracellular cholesterol concentration induces low-density lipoprotein receptor (LDLR) expression on the hepatocyte cell surface, which results in increased extraction of LDL-C from the blood”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    By binding bile acids, these drugs keep bile acid out of the blood and remove much of it from the enterohepatic circulation.

    “By binding the bile acids, the drugs prevent the entry of bile acid into the blood and thereby remove a large portion of the bile acids from the enterohepatic circulation.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Bile acid sequestrants are not absorbed systemically and are not altered by digestive enzymes.

  • May combine two claims.

    Interpretationcitation

    Fibrate-induced homocysteine elevation may blunt HDL-C and apo A1 increases, possibly contributing to fenofibrate's smaller-than-expected outcome benefits.

    “However, the fibrate-induced increase in homocysteine may blunt the increases in both HDL-C and apo A1, and this may contribute to the smaller than estimated benefits of fenofibrate in the outcome parameters.129”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [129] Taskinen, 2009, Relationships of HDL cholesterol, apoA-I, and ApoA-II with homocysteine and creatinine in patients with type 2 diabetes treated with fenofibrate, Arterioscler Thromb Vasc Biol source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Because fenofibrate does not share gemfibrozil's pharmacokinetic pathways, the myopathy risk is much lower with fenofibrate-statin combination therapy.

    “As fenofibrate does not share the same pharmacokinetic pathways as gemfibrozil, the risk of myopathy is much less with the combination therapy.128”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [128] Davidson, 2007, Safety considerations with fibrate therapy, Am J Cardiol source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    Ezetimibe inhibits cholesterol absorption at the intestinal brush border, probably by interacting with NPC1L1, and thereby reduces the amount of lipoprotein cholesterol delivered to the liver.

    “By inhibiting cholesterol absorption at the level of the brush border of the intestine (most probably by interacting with the NPC1L1 protein), ezetimibe reduces the amount of lipoprotein cholesterol circulated to the liver.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Ezetimibe is the first lipid-lowering drug that inhibits intestinal uptake of dietary and biliary cholesterol without affecting fat-soluble nutrient absorption.

  • May combine two claims.

    Premisecitation

    In a recent meta-analysis of intervention studies in dyslipidaemic patients, statin-induced HDL-C elevations varied by dose and were typically only 5-10%.

    “In the recent meta-analysis 146 of several intervention studies in dyslipidaemic patients, elevations in HDL-C varied with dose among the respective statins; such elevations were typically limited to the range of 5-10%.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [146] Davidson, 2007, Efficacy and tolerability of adding rescription omega-3 fatty acids 4 g/d to simvastatin 40 mg/d in hypertriglyceridemic patients: an 8-week, randomized, double-blind, placebo-controlled study, Clin Ther source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A recent RCT did not confirm that lipid lowering slows aortic stenosis progression, but CAD was significantly reduced.

    “This was not confirmed in a recent RCT, yet the CAD was significantly reduced.38”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [38] Rossebø, 2008, Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Because type 2 diabetes patients have higher absolute risk, their absolute benefit from cholesterol-lowering therapy is greater, giving a lower number needed to treat.

    “but being at higher absolute risk the absolute benefit will be greater resulting in a lower NNT.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    In type 1 diabetes, there are potentially atherogenic changes in the composition of both HDL and LDL particles.

    “However, there are potentially atherogenic changes in the composition of both HDL and LDL particles.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In a post-hoc analysis of FIELD, fenofibrate reduced CVD events by 27% in patients with elevated TG (at least 2.3 mmol/L or more than 204 mg/dL) and reduced HDL-C, with a number needed to treat of 23.

    “In a post-hoc analysis of the FIELD study, fenofibrate reduced CVD events by 27% in those with raised TG (.2.3 mmol/L or more than 204 mg/dL) and reduced HDL-C (NNT ¼ 23).172”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [172] Scott, 2009, Effects of fenofibrate treatment on cardiovascular disease risk in 9,795 individuals with type 2 diabetes and various components of the metabolic syndrome, Diabetes Care source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Non-controlled observational studies showed favourable effects among statin users in heart failure trials, but RCTs do not support this.

    “Although non-controlled observational studies have shown favourable effects among statin users in HF trials, RCT studies do not support this notion.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Onset of heart failure increases mortality and morbidity risk 3-4 times compared with patients without heart failure.

    “Onset of heart failure (HF) increases the risk of mortality and morbidity 3-4 times compared with patients without HF.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In type 2 diabetes patients in the FIELD study, traditional lipid ratios (non-HDL-C/HDL-C and TC/HDL-C) predicted CVD risk as strongly as the apo B/apo A1 ratio and captured the impact of both atherogenic and antiatherogenic particles.

    “Recent data from patients with type 2 diabetes in the FIELD study revealed that traditional lipid ratios (non-HDL-C/HDL-C, TC/ HDL-C) were as strong predictors for CVD risk as the apo B/apo A1 ratio, and captured the impact of both atherogenic and antiatherogenic particles on CVD risk.47”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [47] Taskinen, 2010, Ability of traditional lipid ratios and apolipoprotein ratios to predict cardiovascular risk in people with type 2 diabetes, Diabetologia source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    Patients who have recently presented with acute coronary syndrome are at high risk of further cardiovascular events.

    “Patients who have presented recently with an ACS are at high risk of experiencing further CV events.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    In heart failure patients, low total cholesterol predicts poor prognosis, unlike in patients without heart failure.

    “In contrast to patients without HF, a low TC portends a poor prognosis in HF.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In a post-hoc analysis of the 4S trial, patients with low HDL-C (less than 1 mmol/L) and elevated TG (more than 1.80 mmol/L) had a relative risk of 0.48 for major coronary events and 0.44 for overall mortality with simvastatin.

    “A post-hoc analysis of patients with low HDL-C ,1 mmol/L (less than 40 mg/dL) and elevated TG .1.80mmol/L (more than 160 mg/dL) in the 4S trial demonstrated a relative risk for major coronary events of 0.48 with simvastatin.The respective relative risk for overall mortality was 0.44.174”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [174] Ballantyne, 2001, Influence of low high-density lipoprotein cholesterol and elevated triglyceride on coronary heart disease events and response to simvastatin therapy in 4S, Circulation source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A meta-analysis of fibrates in 11,590 people with type 2 diabetes found that fibrates significantly reduced non-fatal MI by 21% but had no effect on overall mortality or coronary mortality.

    “a meta-analysis of fibrates in the prevention of CVD in 11 590 people with type 2 diabetes showed that fibrates reduced the risk of non-fatal MI significantly by 21%, but had no effect on the risk of overall mortality or coronary mortality.175”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [175] Saha, 2009, Fibrates in the prevention of cardiovascular disease in patients with type 2 diabetes mellitus—a pooled meta-analysis of randomized placebo-controlled clinical trials, Int J Cardiol source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    In type 1 diabetes with good glycaemic control, the lipid profile is 'supernormal' with subnormal TG and LDL-C, while HDL-C is usually in the upper normal range or slightly elevated.

    “The lipid profile in type 1 diabetic subjects with good glycaemic control is 'supernormal' and characterized by subnormal TG and LDL-C, whereas HDL-C is usually within the upper normal range or slightly elevated.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Consumption of n-3 PUFAs, as oily fish or purified n-3 acid ethyl ester, reduced mortality in MI survivors in one study but not in another.

    “The consumption of n-3 PUFAs, as either increased (oily) fish intake or a highly purified n-3 acid ethyl ester prescription medication, has in one study been shown to reduce mortality in survivors of MI, 178 but not in another.92”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [178] GISSI-Prevenzione Investigators, 1999, Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-prevenzione trial, Lancet source

      Not checked in the free run.

    • cites [92] Kromhout, 2010, n-3 Fatty acids and cardiovascular events after myocardial infarction, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Nicotinic acid impairs glycaemic control at high doses, but at modest doses glycaemic control can generally be maintained by adjusting diabetes therapy.

    “The impairment of glycaemic control by nicotinic acid is seen at high doses, but at modest doses glycaemic control can in general be maintained by adjustment of diabetes therapy.176”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [176] Canner, 2005, Benefits of niacin by glycemic status in patients with healed myocardial infarction (from the Coronary Drug Project), Am J Cardiol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Conclusive evidence supports that hyperglycaemia accelerates atherosclerosis.

    “Conclusive evidence supports the proposition that hyperglycaemia accelerates atherosclerosis.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    Aortic stenosis is associated with LDL-C and Lp(a), and with increased cardiovascular events and mortality.

    “There is an association between aortic stenosis, LDL-C, and Lp(a), and also between aortic stenosis and increased risk for CV events and mortality.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisereasoning

    Fibrates do not affect creatinine excretion into urine, so estimation of GFR is hampered by the rise in creatinine.

    “As fibrates have no effect on creatinine excretion into urine, the estimation of GFR is hampered by the rise of creatinine and is a problem in clinical practice.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In AURORA, rosuvastatin lowered LDL-C as expected but had no significant effect on the composite CVD endpoint in 2776 haemodialysis patients.

    “The results from AURORA (A study to evaluate the Use of Rosuvastatin in subjects On Regular haemodialysis: an Assessment of survival and cardiovascular events) involving 2776 patients on haemodialysis 40 show that rosuvastatin lowered LDL-C as expected but had no significant effect on the composite CVD endpoint.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [40] Fellström, 2009, Rosuvastatin and cardiovascular events in patients undergoing hemodialysis, N Engl J Med source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    Lipid abnormalities are common after solid organ transplantation and predispose to atherosclerotic disease and transplant arterial vasculopathy, causing major vascular events.

    “Lipid abnormalities are common in patients who have undergone solid organ transplantation, and predispose to the development of both atherosclerotic disease and transplant arterial vasculopathy, resulting in major vascular events.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    Tacrolimus is also metabolized by CYP3A4 but appears to have less potential for harmful interaction with statins than ciclosporin.

    “Tacrolimus is also metabolized by CYP3A4 but appears to have less potential for harmful interaction with statins than ciclosporin.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    After stroke or TIA, patients are at risk not only of recurrent cerebrovascular events but also of other major cardiovascular events including MI.

    “Following stroke or TIA, 34 patients are at risk not only of recurrent cerebrovascular events but also of other major CV events including MI.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [34] Amarenco, 2006, High-dose atorvastatin after stroke or transient ischemic attack, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A systematic review of 18 trials with more than 10,000 patients found that lipid-lowering therapy in lower-limb atherosclerosis was associated with a 20% reduction in total cardiovascular events and a non-significant 14% reduction in all-cause mortality.

    “As for cardiac events, a recent systematic review 202 of 18 trials including .10 000 patients, with cholesterol levels from normal to elevated, reported that lipid-lowering therapy in subjects affected by atherosclerosis of the lower limbs is associated with a 20% reduction in total CV events, together with a non-significant 14% reduction of all-cause mortality.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [202] Maxwell, 2007, Lipid lowering for peripheral arterial disease of the lower limb, Cochrane Database Syst Rev

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Several trials have shown beneficial effects of lipid-lowering therapy on progression of carotid intima-media thickness and prevention of cardiovascular events.

    “Several trials have shown the beneficial effects of lipid-lowering therapy on the progression of CIMT and on the prevention of CV events.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    Calcineurin inhibitors increase hepatic lipase activity, decrease LPL, and bind the LDL receptor, resulting in reduced clearance of atherogenic lipoproteins.

    “Calcineurin inhibitors increase the activity of hepatic lipase, decrease LPL, and bind the LDLR, resulting in reduced clearance of atherogenic lipoproteins.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In SHARP, among 9500 high-risk CKD subjects, ezetimibe plus simvastatin reduced major atherosclerotic events by 17% (P=0.0022) and major vascular events by 15.3% (P=0.0012) versus placebo.

    “SHARP reported results in 9500 high risk subjects with CKD.Major atherosclerotic events were reduced by 17% (P ¼ 0.0022) and major vascular events by 15.3% (P ¼ 0.0012) in patients on ezetimibe plus simvastatin as compared with placebo.111”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [111] SHARP Collaborative Group, 2010, Study of Heart and Renal Protection (SHARP): randomized trial to assess the effects of lowering low-density lipoprotein cholesterol among 9,438 patients with chronic kidney disease, Am Heart J source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a meta-analysis of RCTs with more than 90,000 patients, statin therapy reduced the incidence of all strokes by 21%, with a strong correlation between LDL-C reduction and CIMT, and a 0.73% per year reduction in CIMT for each 10% decrease in LDL-C.

    “In a meta-analysis of RCTs enrolling .90000 patients, Amarenco et al. reported that statin therapy determines a 21% reduction in the incidence of all strokes in different populations, with a strong correlation between LDL-C reduction and CIMT, pointing to a 0.73% per year reduction of CIMT for each 10% decrease of LDL-C.205”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [205] Amarenco, 2004, Statins in stroke prevention and carotid atherosclerosis: systematic review and up-to-date meta-analysis, Stroke source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    Atherosclerotic changes of retinal arteries correlate with total cholesterol, LDL-C, triglycerides, apo B levels, and CAD.

    “Atherosclerotic changes of retinal arteries correlate with TC, LDL-C, TG, and apo B levels and also with CAD.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    Autoimmune diseases are characterized by inflammatory vasculitis and endothelial dysfunction.

    “The diseases are characterized by inflammatory vasculitis and endothelial dysfunction.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In a recent European survey, the standardized cardiovascular mortality rate was 38 per 1000 person-years (95% CI 37.2-39.0) higher in patients starting dialysis than in the general population.

    “In a recent survey in Europe the standardized CV mortality rate was 38 per 1000 person years (95% CI 37.2-39.0)higher in patients starting dialysis than in the general population.190”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [190] de Jager, 2009, Cardiovascular and noncardiovascular mortality among patients starting dialysis, JAMA source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    In CKD stages 3-5, safety issues and dose adjustment become important because adverse events are commonly dose-related and due to increased blood concentration of the compound.

    “Safety issues and dose adjustment become important in more advanced stages of CKD (stages 3-5), as adverse events are commonly dose related and due to increased blood concentration of the compound.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    The relationship between dyslipidaemia and atherothrombotic events including ischaemic stroke and TIA is well recognized, while the association of dyslipidaemia with other stroke types is uncertain.

    “The relationship between dyslipidaemia and atherothrombotic events including ischaemic stroke and transient ischaemic attack (TIA) is well recognized, while the association of dyslipidaemia with other types of stroke is uncertain.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisereasoning

    Most patients with stage 3-5 CKD have mixed dyslipidaemia and a highly atherogenic lipid profile with adverse changes in all lipoproteins.

    “Altogether, most patients with stage 3-5 CKD have mixed dyslipidaemia and the lipid profile is highly atherogenic with adverse changes in all lipoproteins.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisereasoning

    In CKD, non-HDL-C and apo B levels are clearly increased.

    “Consequently non-HDL-C and apo B levels are clearly increased.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisereasoning

    Ciclosporin is metabolized through CYP3A4 and may increase systemic statin exposure and the risk of myopathy.

    “Several potential drug interactions must also be considered, especially with ciclosporin which is metabolized through CYP3A4 and may increase systemic statin exposure and the risk of myopathy.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    Although abdominal aortic aneurysm is a risk equivalent condition, no clinical trials on cardiovascular risk reduction in patients with this condition are available.

    “Although the presence of abdominal aortic aneurysm represents a risk equivalent condition, there are currently no available clinical trials on CV risk reduction in patients affected by this condition.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Common general causes of dyslipidaemia in transplant patients are diabetes, obesity, metabolic syndrome, and CKD.

    “Common general causes of dyslipidaemia in these patients are diabetes, obesity, MetS, and CKD.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Statins are generally well tolerated at moderate doses in subjects with CKD stages 1-2.

    “Statins are generally well tolerated at moderate doses in subjects with CKD stages 1-2.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    The prevalence of chronic kidney disease, especially mild to moderate CKD, is rapidly increasing worldwide.

    “The prevalence of CKD, in particular mild to moderate CKD, is rapidly increasing worldwide.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    The immune system is believed to be involved in the pathogenesis of atherosclerosis.

    “The immune system is believed to be involved in the pathogenesis of atherosclerosis.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Randomized trial data show that statins have the potential to improve outcomes in heart transplant and renal transplant patients, but the amount of outcome data is not extensive.

    “Although randomized trial data have shown that statins have the potential to improve outcomes in heart transplant patients 195 -197 and renal transplant patients, 198 the amounts of outcome data are not extensive.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [195] Kobashigawa, 1995, Effect of pravastatin on outcomes after cardiac transplantation, N Engl J Med source

      Not checked in the free run.

    • cites [196] Wenke, 1997, Simvastatin reduces graft vessel disease and mortality after heart transplantation: a four-year randomized trial, Circulation source

      Not checked in the free run.

    • cites [197] Page, 2005, Drug therapy in the heart transplant recipient part IV: drug–drug interactions, Circulation source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Patients with peripheral arterial disease are at elevated risk of coronary events, and peripheral vascular atherosclerosis is an independent risk factor for MI and cardiovascular death.

    “Patients with PAD are at elevated risk of coronary events, and the presence of peripheral vascular atherosclerosis represents an independent risk factor for MI and CV death.200,201”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [200] Mc Dermott, 2003, Knowledge and attitudes regarding cardiovascular disease risk and prevention in patients with coronary or peripheral arterial disease, Arch Intern Med source

      Not checked in the free run.

    • cites [201] Hertzer, 1987, Basic data concerning associated coronary disease in peripheral vascular patients, Ann Vasc Surg source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    In stage 1-2 CKD, dyslipidaemia typically involves elevated triglycerides and low HDL-C, with less marked changes in total cholesterol and LDL-C.

    “Dyslipidaemia comprises typically elevations of TG and lowering of HDL-C, whereas the changes of TC and LDL-C are less marked in stage 1 -2 CKD.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisereasoning

    Glucocorticoid therapy causes weight gain and worsens insulin resistance, leading to increases in total cholesterol, VLDL, triglycerides, and LDL particle size and density.

    “Glucocorticoid therapy causes weight gain and exacerbates insulin resistance, leading to increases in TC, VLDL, and TG, and in the size and density of LDL particles.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    The value of other lipid-lowering therapies in the primary prevention of stroke is uncertain.

    “The value of other lipid-lowering therapies in the primary prevention of stroke is uncertain.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Cholesterol-lowering therapy reduces the risk of ischaemic cardiovascular events and worsening of claudication, and improves walking performance.

    “Cholesterol-lowering therapy reduces the risk of ischaemic CV events and worsening of claudication, and improves walking performance.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Other important patient-related factors may include understanding and acceptance of the disease, perception of health risk, awareness of costs and benefits, and active participation in monitoring and decision-making.

    “Other important patient-related factors may include understanding and acceptance of the disease, perception of the health risk related to the disease, awareness of the costs and benefits of treatment, and active participation in monitoring and decision-making in relation to management of the disease.222”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [222] Reiner, 2010, Public perceptions of cardiovascular risk factors: the PERCRO survey, Prev Med source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    Routine repeat CK testing has no predictive value for rhabdomyolysis because CK can rise with muscle injury or excess muscular exercise.

    “There is no predictive value of routine repeat CK testing for rhabdomyolysis since the test can rise with muscle injury or excess muscular exercise.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Two of the most important factors contributing to poor adherence are the asymptomatic and lifelong nature of the disease.

    “Two of the most important factors contributing to poor adherence are undoubtedly the asymptomatic and lifelong nature of the disease.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    Response to statin therapy can be assessed at 6-8 weeks after initiation or dose increase, while response to fibrates and lifestyle may take longer.

    “Response to therapy can be assessed at 6-8 weeks from initiation or dose increases for statins, but response to fibrates and lifestyle may take longer.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    Other potential determinants of adherence include demographic factors, patient understanding and perception, healthcare provider's mode of treatment delivery, patient-provider relationships, health system influences, and complex chronic drug regimens.

    “Other potential determinants of adherence may be related to: † demographic factors such as age and education † the patient's understanding and perception of dyslipidaemia † the healthcare provider's mode of delivering treatment † the relationships between patients and healthcare professionals † influences from the health systems, and † complex chronic drug regimens.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Lipoprotein metabolism is influenced to a lesser extent by nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors.

    “Lipoprotein metabolism is influenced to a lesser extent by nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    Dietary changes, regular physical activity, and switching HAART may favourably affect dyslipidaemia, but most patients still need pharmacological therapy to reach lipid goals.

    “Dietary changes and regular physical activity as well as switching to another HAART regimen may act favourably on dyslipidaemia, but most patients still need pharmacological therapy to reach the lipid goals.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Because HAART also increases blood pressure and insulin resistance, this could contribute to the increased CAD risk.

    “Since HAART also increases blood pressure and insulin resistance, this could contribute to the increased CAD risk too.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Stroke aetiology may influence response to statins; patients with atherothrombosis underlying cerebrovascular events appear to benefit most, while those with haemorrhagic stroke may not benefit or may be harmed, particularly if they lack evidence of atherosclerotic disease.

    “However, the aetiology of stroke may influence the response to statins, and those patients with evidence of atherothrombosis underlying their cerebrovascular events appear to benefit most, while those with haemorrhagic stroke may not benefit or may even be harmed by statins, particularly if patients do not have evidence of atherosclerotic disease.210”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [210] Amarenco, 2009, Lipid management in the prevention of stroke: review and updated meta-analysis of statins for stroke prevention, Lancet Neurol source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    Secondary prevention therapy with statins reduces the risk of stroke, MI, and vascular death.

    “Secondary prevention therapy with statins reduces the risk of stroke, MI, and vascular death.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    A systematic review found that the incidence of drug-induced hepatotoxicity in patients taking lipid-lowering drugs is unknown, with few cases occurring in large-scale randomized trials.

    “A systematic review 218 found that the incidence of drug-induced hepatotoxicity in patients taking lipid-lowering drugs is unknown, with few cases occurring in large-scale randomized trials.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [218] Law, 2003, Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease and stroke: systematic review and meta-analysis, BMJ source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    HAART increases LDL-C and triglycerides and causes predominance of small dense LDL particles, doubling CAD risk compared with HIV-negative subjects.

    “Highly active antiretroviral treatment (HAART) causes an increase of LDL-C and TG, and predominance of small, dense LDL particles, thus doubling their CAD risk when compared with HIV-negative subjects.212”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [212] Glass, 2006, Prevalence of risk factors for cardiovascular disease in HIV-infected patients over time: the Swiss HIV Cohort Study, HIV Med source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    The combination of rosuvastatin with lopinavir/ritonavir should be used with caution.

    “the combination of rosuvastatin with lopinavir/ritonavir should also be used with caution.215”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [215] Van der Lee, 2007, Pharmacokinetics and pharmacodynamics of combined use of lopinavir/ritonavir and rosuvastatin in HIV-infected patients, Antivir Ther source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    Follow-up at 6 or 12 monthly intervals is advised to monitor potential toxic side effects, but these assessments have a limited scientific basis.

    “Follow-up is advised at 6 or 12 monthly intervals to monitor potential toxic side effects, but such assessments have a limited scientific basis.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    No smoking, healthy eating, and physical activity are the foundations of preventive cardiology.

    “No smoking, healthy eating, and being physically active are the foundations of preventive cardiology.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    In everyday care, statins are usually prescribed at the lowest dose and often not up-titrated to achieve goals.

    “However, in everyday care, statins are usually prescribed at the lowest dose and often not up-titrated to achieve goals.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    These lifestyles are most effectively achieved through formal preventive care programmes, which are also more appropriate for initiating and up-titrating drug therapies, achieving treatment goals, and long-term adherence, improving event-free survival.

    “These lifestyles are most effectively achieved through formal programmes of preventive care; such programmes are also more appropriate for initiating and up-titrating drug therapies, achieving the treatment goals, and adherence over the long-term which in turn improves eventfree survival.220”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [220] Rasmussen, 2007, Relationship between adherence to evidence-based pharmacotherapy and long-term mortality after acute myocardial infarction, JAMA source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    It is unclear whether monitoring alone or a combination of education, regular contact, and adherence assessment is critical for adherence.

    “It is unclear if only the process of monitoring is critical in achieving this, or a combination of education, regular contact, and adherence assessment.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductnone given

    Evidence for monitoring lipids and for toxicity tests such as ALT and CK in treated patients is limited, and recommendations are consensus-based rather than evidence-based.

    “Evidence for what tests should be carried out to monitor lipids in patients on treatment is limited.Similar limited evidence applies to tests of possible toxicity such as ALT and CK.Recommendations stem from consensus rather than evidence-based guidelines.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    There is limited evidence that some statins are more likely to be associated with muscle symptoms (but not CK change) or liver enzyme changes.

    “There is limited evidence to suggest that some statins have more likelihood of being associated with muscle symptoms (but not CK change), or liver enzyme changes.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    Standard follow-up monitoring is 6-12 months, but these intervals are arbitrary.

    “Standard practice for subsequent follow-up monitoring is 6-12 months, but such monitoring intervals are arbitrary.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    HIV-infected patients often have low total cholesterol and LDL-C as well as low HDL-C and increased triglycerides.

    “Human immunodeficiency virus (HIV)-infected patients often have low TC and LDL-C as well as low HDL-C and increased TG.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    Poor socioeconomic status, illiteracy, and unemployment are important risk factors for poor adherence.

    “Poor socioeconomic status, illiteracy, and unemployment are important risk factors for poor adherence.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Not up-titrating statin dose and poor adherence are the main reasons why over half of coronary patients and four out of five high-risk patients do not achieve lipid goals and maximum preventive benefits.

    “Not up-titrating the dose of statin, and poor adherence to this therapy, are the main reasons why over half of all coronary patients, and four out of five of all high risk patients, are not achieving the lipid goals and, as a consequence, are not achieving the maximum benefits of these preventive strategies.221”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [221] Wood, 2008, Nurse-coordinated multidisciplinary, family-based cardiovascular disease prevention programme (EUROACTION) for patients with coronary heart disease and asymptomatic individuals at high risk of cardiovascular disease: a paired, cluster-randomised controlled trial, Lancet source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    Epidemiological studies show that non-HDL-C and apo B measurement may correlate modestly better with outcomes, but there are no data on their use in routine clinical settings.

    “Epidemiological studies show that non-HDL-C and apo B measurement may correlate modestly better with outcomes, but there are no data on the use in routine clinical settings.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Safety blood tests including ALT and CK at baseline are advised by regulators for statin users to identify patients where treatment is contraindicated.

    “Where statins are used, safety blood tests are advised by regulators, including ALT and CK at baseline to identify the limited number of patients where treatment is contraindicated.”
    Quote in the paperNot a substantial claim
135 of 135

  • The authors state this as an assumption.

    The Friedewald formula assumes a constant cholesterol-to-triglyceride ratio in VLDL.

    “A constant cholesterol/TG ratio in VLDL is assumed.”

  • The paper relies on this without support.

    Atherosclerotic cardiovascular disease results from multiple risk factors acting together.

    “in most people, atherosclerotic CVD is the product of a number of risk factors.”

  • The paper relies on this without support.

    Apolipoprotein B is the main apolipoprotein of VLDL, IDL, and LDL.

    “Apo B is the major apolipoprotein of the atherogenic lipoprotein families VLDL, IDL, and LDL.”

  • The paper relies on this without support.

    Apolipoprotein B concentration estimates the number of VLDL, IDL, and LDL particles in plasma.

    “The concentration of apo B is a good estimate of the number of these particles in plasma.”

  • The paper relies on this without support.

    Apolipoprotein A1 is the main protein of HDL and estimates HDL concentration.

    “Apo A1 is the major protein of HDL and provides a good estimate of HDL concentration.”

  • The paper relies on this without support.

    Plasma apolipoprotein A1 below 120 mg/dL in men and below 140 mg/dL in women corresponds to low HDL-cholesterol.

    “Plasma apo A1 of ,120 mg/dL for men and ,140 mg/dL for women approximately correspond to what is considered as low for HDL-C.”

  • The paper relies on this without support.

    Different lipid ratios give similar information.

    “The different ratios give similar information.”

  • The paper relies on this without support.

    Plasma lipoprotein(a) level is largely genetically determined.

    “The plasma level of Lp(a) is to a major extent genetically determined.”

  • The paper relies on this without support.

    Several genes are associated with cardiovascular disease.

    “Several genes have been associated with CVD.”

  • The paper relies on this without support.

    Apolipoprotein E exists in three isoforms: E2, E3, and E4.

    “Apo E is present in three isoforms (apo E2, apo E3, and apo E4).”

  • The paper relies on this without support.

    Treatment targets for dyslipidaemia are primarily based on clinical trial results.

    “Treatment targets of dyslipidaemia are primarily based on results from clinical trials.”

  • The paper relies on this without support.

    In nearly all lipid-lowering trials, LDL-cholesterol was used as the indicator of response to therapy.

    “In nearly all lipid-lowering trials the LDL-C level has been used as an indicator of response to therapy.”

  • The paper relies on this without support.

    In most patients, an LDL-cholesterol target below 1.8 mmol/L or a 50% reduction is achievable with statin monotherapy.

    “In the majority of patients, this is achievable with statin monotherapy.”

  • The paper relies on this without support.

    Apolipoprotein B determination has less laboratory error than LDL-cholesterol determination, particularly in patients with hypertriglyceridaemia.

    “there now appears to be less laboratory error in the determination of apo B than of LDL-C, particularly in patients with HTG.”

  • The paper relies on this without support.

    Apolipoprotein B is not presently measured in all clinical laboratories.

    “However, apo B is not presently being measured in all clinical laboratories.”

  • The paper relies on this without support.

    No specific targets for HDL-cholesterol or triglycerides have been determined in clinical trials.

    “To date, no specific targets for HDL-C or TG levels have been determined in clinical trials”

  • The paper relies on this without support.

    Clinical trial evidence is lacking on whether intervening on HDL-cholesterol or triglycerides reduces cardiovascular risk further.

    “clinical trial evidence is lacking on the effectiveness of intervening on these variables to reduce CV risk further”

  • The paper relies on this without support.

    Advanced age, small body size, female sex, renal or hepatic dysfunction, perioperative periods, hypothyroidism, multisystem disease, and alcohol abuse raise the chance of statin side effects.

    “Factors such as advanced age, small body size, female gender, renal and hepatic dysfunction, perioperative periods, hypothyroidism, multisystem disease, and alcohol abuse increase the likelihood of side effects with statins.”

  • The paper relies on this without support.

    The most serious adverse effect of statins is myopathy, which can progress to rhabdomyolysis and then to renal failure and death.

    “The most serious adverse effect associated with statin therapy is myopathy, which may progress to rhabdomyolysis, and that, in turn, can lead to renal failure and death.”

  • The paper relies on this without support.

    An increase in creatine phosphokinase is the best, though not definitive, indicator of statin-induced myopathy.

    “An elevation of CK is the best indicator, although not unequivocal, of statin-induced Table 13 Examples of causes of secondary hypercholesterolaemia myopathy.”

  • The paper relies on this without support.

    In clinical trials, myopathy occurs in fewer than 1 per 1000 treated patients, and the excess risk versus placebo is less than 1 per 10 000 treated patients.

    “The incidence of myopathy is low (,1/1000 patients treated) and the excess risk in comparison with placebotreated patients has been ,1/10 000 patients treated in clinical trials.”

  • The paper relies on this without support.

    Myopathy is most likely in people with complex medical problems, those taking multiple medications, and elderly individuals, especially women.

    “Myopathy is most likely to occur in persons with complex medical problems and/or who are taking multiple medications, or in elderly persons, especially women.”

  • The paper relies on this without support.

    Myalgia without creatine phosphokinase elevation occurs in 5–10% of patients in clinical practice.

    “Myalgia (without CK elevation) occurs in 5-10% of patients in clinical practice.”

  • The paper relies on this without support.

    Elevated hepatic transaminases occur in 0.5–2.0% of statin-treated patients and are dose dependent.

    “Elevated hepatic transaminases occur in 0.5 -2.0% of statin-treated patients and are dose dependent.”

  • The paper relies on this without support.

    Progression to liver failure is exceedingly rare.

    “Progression to liver failure is exceedingly rare.”

  • The paper relies on this without support.

    Transaminase elevation often reverses when the dose is reduced.

    “Reversal of transaminase elevation is frequently noted with reduction of dose;”

  • The paper relies on this without support.

    Several important drug interactions with statins can raise the risk of side effects.

    “A number of important drug interactions with statins have been described that may increase the risk of side effects.”

  • The paper relies on this without support.

    All currently available statins except pravastatin, rosuvastatin, and pitavastatin undergo major hepatic metabolism through cytochrome P450 enzymes.

    “All currently available statins, except pravastatin, rosuvastatin, and pitavastatin, undergo major hepatic metabolism via the CYPs.”

  • The paper relies on this without support.

    Bile acid sequestrants are not absorbed systemically and are not altered by digestive enzymes.

    “The bile acid sequestrants are not systemically absorbed or altered by digestive enzymes.”

  • The paper relies on this without support.

    Bile acid sequestrants also lower glucose levels in hyperglycaemic patients, though the mechanism is not fully clear.

    “These agents also reduce glucose levels in hyperglycaemic patients; however, the mechanism behind this reduction is not completely clear.”

  • The paper relies on this without support.

    At maximum doses—24 g cholestyramine, 20 g colestipol, or 4.5 g colestagel—LDL-C falls by 18–25%.

    “At the top dose of 24 g of cholestyramine, 20 g of colestipol, or 4.5 g of cholestagel, a reduction in LDL-C of 18-25% has been observed.”

  • The paper relies on this without support.

    Bile acid sequestrants have no major effect on HDL-C, but triglycerides may rise in some predisposed patients.

    “No major effect on HDL-C has been reported, while TG may increase in some predisposed patients.”

  • The paper relies on this without support.

    Gastrointestinal side effects—most often flatulence, constipation, dyspepsia, and nausea—are common with bile acid sequestrants even at low doses and limit their practical use.

    “Gastrointestinal adverse effects (most commonly flatulence, constipation, dyspepsia and nausea) are often present with these drugs even at low doses, which limit their practical use.”

  • The paper relies on this without support.

    Reduced absorption of fat-soluble vitamins has been reported with bile acid sequestrants.

    “Reduced absorption of fat-soluble vitamins has been reported.”

  • The paper relies on this without support.

    Bile acid sequestrants may raise triglycerides in some patients.

    “Furthermore, these drugs may increase TG in certain patients.”

  • The paper relies on this without support.

    Bile acid sequestrants have important interactions with many commonly prescribed drugs.

    “Bile acid sequestrants have important drug interactions with many commonly prescribed drugs and should therefore be administered either 4 h before or 1 h after other drugs.”

  • The paper relies on this without support.

    Colesevelam is a newer bile acid sequestrant that may be better tolerated than cholestyramine.

    “Colesevelam represents a newer formulation of the bile acid sequestrant, which may be better tolerated than cholestyramine.”

  • The paper relies on this without support.

    Colesevelam has fewer interactions with other drugs and can be taken with statins.

    “Colesevelam has fewer interactions with other drugs and can be taken together with statins.”

  • The paper relies on this without support.

    Ezetimibe is the first lipid-lowering drug that inhibits intestinal uptake of dietary and biliary cholesterol without affecting fat-soluble nutrient absorption.

    “Ezetimibe is the first lipid-lowering drug that inhibits intestinal uptake of dietary and biliary cholesterol without affecting the absorption of fat-soluble nutrients.”

  • The paper relies on this without support.

    In clinical studies, ezetimibe monotherapy lowers LDL-C by 15–22% in hypercholesterolaemic patients.

    “In clinical studies ezetimibe in monotherapy reduces LDL-C in hypercholesterolaemic patients by 15-22%.”

  • The paper relies on this without support.

    Adding ezetimibe to a statin gives an additional LDL-C reduction of 15–20%.

    “Combined therapy with ezetimibe and a statin provides an incremental reduction in LDL-C levels of 15 -20%.”

  • The paper relies on this without support.

    Ezetimibe is rapidly absorbed and extensively metabolized to the active ezetimibe glucuronide.

    “Ezetimibe is rapidly absorbed and extensively metabolized to the pharmacologically active ezetimibe glucuronide.”

  • The paper relies on this without support.

    Age, sex, and race have no clinically significant effect on ezetimibe pharmacokinetics, and no dose adjustment is needed for mild hepatic impairment or mild to severe renal insufficiency.

    “There are no clinically significant effects of age, sex, or race on ezetimibe pharmacokinetics, and no dosage adjustment is necessary in patients with mild hepatic impairment or mild to severe renal insufficiency.”

  • The paper relies on this without support.

    Ezetimibe can be co-administered with any dose of any statin.

    “Ezetimibe can be co-administered with any dose of any statin.”

  • The paper relies on this without support.

    No major side effects have been reported for ezetimibe; the most frequent are moderate liver enzyme elevations and muscle pain.

    “No major side effects have been reported; the most frequent side effects are moderate elevations of liver enzymes, and muscle pain.”

  • The paper relies on this without support.

    Adding a bile acid sequestrant to a statin lowers LDL-C by an additional 10–20% on average.

    “On average the addition of a bile acid sequestrant to a statin reduces LDL-C further by 10 -20%.”

  • The paper relies on this without support.

    Adding ezetimibe to a bile acid sequestrant (colesevelam, colestipol, or cholestyramine) further lowers LDL-C without extra adverse effects compared with the sequestrant alone.

    “Co-administration of ezetimibe and bile acid sequestrants (colesevelam, colestipol, or cholestyramine) resulted in an additional reduction of LDL-C levels without any additional adverse effects when compared with the stable bile acid sequestrant regimen alone.”

  • The paper relies on this without support.

    Adding ezetimibe to nicotinic acid further lowers LDL-C and does not affect the HDL-C increase caused by nicotinic acid.

    “Adding ezetimibe to nicotinic acid further reduces LDL-C and does not affect nicotinic acid-induced HDL-C increase.”

  • The paper relies on this without support.

    Triple therapy with a bile acid sequestrant, a statin, and either ezetimibe or nicotinic acid further lowers LDL-C.

    “Also triple therapy (bile acid sequestrant, statin, and ezetimibe or nicotinic acid) will further reduce LDL-C.”

  • The paper relies on this without support.

    Acute pancreatitis is one of the major clinical risks of markedly elevated triglycerides.

    “One of the major clinical risks of dramatically elevated TG is acute pancreatitis.”

  • The paper relies on this without support.

    The risk of pancreatitis becomes clinically significant when triglycerides exceed 10 mmol/L (880 mg/dL).

    “The risk of pancreatitis is clinically significant if TG exceed 10 mmol/L (more than 880 mg/dL) and actions to prevent acute pancreatitis are mandatory.”

  • The paper relies on this without support.

    Hypertriglyceridaemia causes 10% of all pancreatitis cases.

    “Notably HTG is the cause of 10% of all cases with pancreatitis,”

  • The paper relies on this without support.

    Pancreatitis can occur even when triglyceride levels are between 5 and 10 mmol/L (440–880 mg/dL).

    “and patients can develop pancreatitis even when their TG concentration is between 5 and 10 mmol/L ( 440 -880 mg/dL).”

  • The paper relies on this without support.

    In general, triglyceride levels fall sharply within 2–5 days.

    “In general a sharp decrease of TG values is seen within 2-5 days.”

  • The paper relies on this without support.

    The effect of lifestyle management on triglyceride levels is well documented.

    “The influence of lifestyle management on TG levels is well documented.”

  • The paper relies on this without support.

    Weight reduction plus regular moderate-intensity physical activity can lower triglycerides by 20–30%.

    “Weight reduction together with a regular physical activity programme of moderate intensity can reduce TG between 20 and 30%,”

  • The paper relies on this without support.

    Statins have significant effects on mortality and most cardiovascular outcome parameters.

    “As statins have significant effects on mortality as well as most CVD outcome parameters, these drugs are the first choice to reduce both total CVD risk and moderately elevated TG levels.”

  • The paper relies on this without support.

    More potent statins—atorvastatin, rosuvastatin, and pitavastatin—robustly lower triglycerides, especially at high doses and in patients with elevated triglycerides.

    “More potent statins (atorvastatin, rosuvastatin, and pitavastatin) demonstrate a robust lowering of TG levels, especially at high doses and in patients with elevated TG.”

  • The paper relies on this without support.

    Fibrates are PPAR-α agonists that act through transcription factors regulating lipid and lipoprotein metabolism.

    “Fibrates are agonists of peroxisome proliferator-activated receptor-a (PPAR-a), acting via transcription factors regulating various steps in lipid and lipoprotein metabolism.”

  • The paper relies on this without support.

    Myopathy risk is higher in patients with chronic kidney disease and varies with the fibrate and statin used in combination.

    “The risk of myopathy is greater in patients with CKD, and it varies with different fibrates and statins used in combination.”

  • The paper relies on this without support.

    Gemfibrozil inhibits statin metabolism through glucuronidation, greatly increasing statin plasma concentrations.

    “Gemfibrozil inhibits the metabolism of statins via the glucuronidation pathway that leads to highly increased plasma concentrations of statins.”

  • The paper relies on this without support.

    Fibrates as a class have been reported to raise serum creatinine and homocysteine in short- and long-term studies, but the effect appears fibrate-specific.

    “As a class, fibrates have been reported to raise both serum creatinine and homocysteine in both short-term and long-term studies, but the effect seems to be fibrate specific.”

  • The paper relies on this without support.

    The homocysteine increase caused by fibrates has been considered relatively innocent for cardiovascular risk.

    “The increase in homocysteine by fibrates has been considered to be relatively innocent with respect to CVD risk.”

  • The paper relies on this without support.

    Nicotinic acid has been reported to reduce fatty acid influx to the liver and hepatic VLDL secretion, partly through effects on hormone-sensitive lipase in adipose tissue.

    “Nicotinic acid has been reported to decrease fatty acid influx to the liver and the secretion of VLDL by the liver; this effect appears to be mediated in part by the effects on hormone-sensitive lipase in the adipose tissue.”

  • The paper relies on this without support.

    In clinical practice, flushing is the most frequent and troublesome side effect of nicotinic acid and its derivatives, often preventing dose titration to maximal efficacy even with aspirin.

    “In clinical practice, skin reactions (flushing) are the most frequent and troublesome side effect of nicotinic acid and its derivatives, often preventing titration of the dose to maximal efficacy, even using aspirin as a modulator of flushing.”

  • The paper relies on this without support.

    Other side effects of nicotinic acid include hyperuricaemia, liver toxicity, and acanthosis nigricans.

    “Other side effects of nicotinic acid include hyperuricaemia, liver toxicity, and acanthosis nigricans.”

  • The paper relies on this without support.

    The mediator is prostaglandin D2 released from arachidonic acid.

    “The mediator is prostaglandin D2 released from arachidonic acid.”

  • The paper relies on this without support.

    A recent survey found that fewer than 15% of new users of extended-release nicotinic acid were still taking it after 1 year.

    “A recent survey revealed that ,15% of new users of ER nicotinic acid were still using the drug after 1 year.”

  • The paper relies on this without support.

    Liver enzyme elevation with extended-release nicotinic acid is less common (<1%) than with older nicotinic acid compounds.

    “Elevation of liver enzymes in users of ER nicotinic acid is less common (,1%) than with previous nicotinic acid compounds.”

  • The paper relies on this without support.

    Nicotinic acid may interfere with glycaemic control by raising blood glucose, which is a concern in diabetes.

    “The issue that nicotinic acid may interfere with glycaemic control by increasing blood glucose levels is of concern in treating people with diabetes.”

  • The paper relies on this without support.

    At pharmacological doses above 2 g/day, n-3 fatty acids affect serum lipids and lipoproteins, especially VLDL concentration.

    “n-3 fatty acids at pharmacological doses (.2 g/day) affect serum lipids and lipoproteins, in particular VLDL concentration.”

  • The paper relies on this without support.

    Fish oil lowers triglycerides by 30%, but its effects on other lipoproteins are trivial.

    “Fish oil reduces TG by 30%, but the effects on other lipoproteins are trivial in their magnitude.”

  • The paper relies on this without support.

    n-3 fatty acid administration appears safe and free of clinically significant interactions.

    “The administration of n-3 fatty acids appears to be safe and devoid of clinically significant interactions.”

  • The paper relies on this without support.

    The antithrombotic effects of n-3 fatty acids may increase bleeding tendency, especially when added to aspirin or clopidogrel.

    “However, the antithrombotic effects may increase the propensity to bleed, especially when given in addition to aspirin/clopidogrel.”

  • The paper relies on this without support.

    Patients taking nicotinic acid with a statin—mostly simvastatin or atorvastatin—report similar all-cause adverse event rates, and flushing incidence is similar with and without statin treatment.

    “Patients taking concomitant statin therapy, mostly simvastatin or atorvastatin, with nicotinic acid report a similar incidence of all-cause adverse events, and the incidence of flushing is similar in patients with and without statin treatment.”

  • The paper relies on this without support.

    Adding n-3 fatty acids to pravastatin and fenofibrate further lowered triglycerides and homocysteine in patients with diabetic dyslipidaemia.

    “Adding n-3 fatty acids to pravastatin and fenofibrate in a triple combination further decreased TG concentrations and homocysteine as well in patients with diabetic dyslipidaemia.”

  • The paper relies on this without support.

    No significant interactions of any drug with n-3 fatty acids have been described.

    “No significant interactions of any drug with n-3 fatty acids have been described.”

  • The paper relies on this without support.

    Therapeutic lifestyle changes (weight reduction, exercise, smoking cessation, and moderate alcohol consumption) can increase HDL-C levels by up to 10%.

    “While HDL-C levels may be increased by up to 10% by implementing therapeutic lifestyle changes, including weight reduction, exercise, smoking cessation, and moderate alcohol consumption”

  • The paper relies on this without support.

    Fibrates lower TG levels by up to 50% and raise HDL-C by up to 10-15% in short-term studies.

    “As a class, fibrates differ in their potential to modulate the atherogenic lipid profile by concomitantly lowering TG levels (up to 50%) and by raising those of HDL-C (up to 10 -15% in short-term studies).”

  • The paper relies on this without support.

    CETP inhibition by small molecule inhibitors is the most efficacious pharmacological approach to elevating low HDL-C levels.

    “To date, the most efficacious pharmacological approach to elevation of low HDL-C levels has involved direct inhibition of cholesteryl ester transfer protein (CETP) by small molecule inhibitors”

  • The paper relies on this without support.

    The deleterious effects of torcetrapib arose primarily from off-target toxicity related to activation of the renin-angiotensin-aldosterone system (RAAS).

    “Retrospectively, it appears that the deleterious effects of torcetrapib arose primarily from off-target toxicity related to activation of the renin-angiotensin -aldosterone system (RAAS).”

  • The paper relies on this without support.

    HeFH affects 1 in 500 people of European descent.

    “Heterozygous familial hypercholesterolaemia (HeFH) affects 1 in 500 people of European descent.”

  • The paper relies on this without support.

    FCH is a common genetic dyslipidaemia (1:100) and a major cause of premature CAD.

    “FCH is a highly prevalent genetic dyslipidaemia (1:100) and an important cause of premature CAD.”

  • The paper relies on this without support.

    Elevated LDL-C is more dangerous when HTG coexists.

    “It emphasizes both the importance of considering family history in deciding how rigorously to treat dyslipidaemia, and that raised LDL-C levels are riskier when HTG is also present.”

  • The paper relies on this without support.

    Statins lower CV risk by the same relative amount in people with and without HTG.

    “Statin treatment has been shown to decrease CV risk by the same relative amount in people with HTG as in those without.”

  • The paper relies on this without support.

    Without treatment, most HeFH patients develop symptomatic coronary disease by age 60, and half of men and 15% of women die.

    “Untreated, the majority of affected men and women will have symptomatic coronary disease by 60 years and half of the men and 15% of the women will have died.”

  • The paper relies on this without support.

    Tendon xanthomata are virtually diagnostic of HeFH.

    “The presence of tendon xanthomata is, however, virtually diagnostic of HeFH.”

  • The paper relies on this without support.

    In HeFH, TC levels are elevated from birth.

    “High TC levels are present from birth in HeFH.”

  • The paper relies on this without support.

    HoFH is rare in Europeans (about 1 in 10^6 births) except with founder effects or consanguinity.

    “HoFH is rare in European populations ( 1 in 10 6 births) unless there is a founder gene effect or consanguinity”

  • The paper relies on this without support.

    Without treatment, HoFH usually causes death in adolescence or early adulthood from myocardial ischaemia or aortic stenosis.

    “Regardless of this, HoFH is always an extremely serious disease, which untreated leads to death typically in adolescence or early adulthood due to myocardial ischaemia or aortic stenosis.”

  • The paper relies on this without support.

    Familial dysbetalipoproteinaemia is uncommon and usually follows autosomal recessive inheritance with variable penetrance.

    “Familial dysbetalipoproteinaemia (syn.type III hyperlipoproteinaemia; remnant removal disease) is rare and is generally inherited as an autosomal recessive disorder with variable penetrance.”

  • The paper relies on this without support.

    CAD risk is very high in familial dysbetalipoproteinaemia.

    “The risk of CAD is very high, and accelerated atherosclerosis of the femoral and tibial arteries is also prevalent.”

  • The paper relies on this without support.

    Familial LPL deficiency is an uncommon cause of severe HTG.

    “Familial LPL deficiency is a rare cause of severe HTG which may cause severe disorders of the pancreas.”

  • The paper relies on this without support.

    The most common genetic hypolipidaemia is hypobetalipoproteinaemia.

    “The most common genetic hypolipidaemia is hypobetalipoproteinaemia which is dominantly inherited and often due to truncation of apo B.”

  • The paper relies on this without support.

    Very high levels of HDL-C in CETP deficiency are not associated with disease.

    “This is not associated with disease.”

  • The paper relies on this without support.

    Low-dose third-generation oral contraceptives do not seem to raise adverse coronary event risk.

    “Currently used third-generation low oestrogen-progestin dose oral contraceptives do not appear to increase adverse coronary events”

  • The paper relies on this without support.

    Older adults are less likely to be prescribed lipid-lowering drugs or to adhere to statins.

    “Elderly individuals are less likely to receive lipid-lowering medications or adhere to statin therapy.”

  • The paper relies on this without support.

    Chronic kidney disease is a coronary artery disease risk equivalent.

    “CKD is acknowledged as a CAD risk equivalent.”

  • The authors state this as an assumption.

    Most problems related to adherence to lifestyle changes are similar to those related to compliance with lipid-lowering drug therapy.

    “Most of the problems related to adherence to lifestyles are currently assumed to be similar to those related to compliance with lipid-lowering drug therapy.”

  • The paper relies on this without support.

    Health system issues play an important role in promoting adherence.

    “Issues related to health systems also play an important role in the promotion of adherence.”

  • The paper relies on this without support.

    In most low-income countries, medication supplies are limited and often must be purchased out-of-pocket.

    “In most low income countries, supplies of medications are limited and they often have to be bought out-of-pocket.”

  • The paper relies on this without support.

    Strategies that improve access to drugs, such as sustainable financing, affordable prices, and reliable supply systems, have an important influence on patient adherence.

    “Strategies for improving access to drugs such as sustainable financing, affordable prices, and reliable supply systems have an important influence on patient adherence.”

  • The paper relies on this without support.

    Determinants of adherence to hypolipidaemic therapy include drug tolerability, regimen complexity, drug costs, and treatment duration.

    “Some of the better recognized determinants of adherence to hypolipidaemic therapy are related to aspects of the drug treatment itself, and include drug tolerability, regimen complexity, drug costs, and treatment duration.”

  • The paper relies on this without support.

    Regimen complexity is a treatment-related factor identified as a possible cause of poor adherence.

    “The complexity of the regimen is, for instance, a treatmentrelated factor that has been identified as a possible cause of poor adherence.”

  • The paper relies on this without support.

    Frequency of dosing, number of concurrent medications, and changes in medications contribute to regimen complexity.

    “Frequency of dosing, number of concurrent medications, and changes in medications are some of the factors that contribute to the complexity of a regimen, and these have been investigated in many observational studies.”

  • The paper relies on this without support.

    Fewer daily doses, monotherapies, and fewer changes in medications are associated with better adherence.

    “Fewer daily doses of drugs, monotherapies, and fewer changes in medications have all been associated with better adherence.”

  • The paper relies on this without support.

    The listed adherence interventions have tended to be used alone.

    “While many interventions (e.g.education in self-management; pharmacy management programmes; nurse, pharmacist, and other non-medical health professional intervention protocols; counselling; behavioural interventions; follow-up; and reminders) have been shown to be effective in significantly improving adherence rates, 224 they have tended to be used alone.”

  • The paper relies on this without support.

    Several programmes have demonstrated good results using multilevel team approaches.

    “Several programmes have demonstrated good results using multilevel team approaches.”

  • The paper relies on this without support.

    Patients with dyslipidaemia have low rates of adherence.

    “Healthcare providers need to be made aware of the low rates of adherence of patients with dyslipidaemia.”
109 of 109

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Lp(a) measurement has been shown to provide clinically significant improved risk reclassification under certain conditions.

    “Measurement of Lp(a) has been shown to provide clinically significant improved risk reclassification under certain conditions”

    From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [112]

  • Familial hypercholesterolaemia is a dominantly inherited condition affecting 1 in 500 people of European descent (heterozygous), most commonly caused by a mutation of the LDL receptor, and characterized by very high LDL cholesterol levels (usually 5-10 mmol/L).

    “Familial hypercholesterolaemia is a dominantly inherited condition affecting 1 in 500 people of European descent (heterozygous) most commonly caused by a mutation of the LDL receptor, and is characterized by very high levels of LDL cholesterol (usually 5-10 mmol/L or 200-400 mg/dL).42”

    From European Guidelines on cardiovascular disease prevention in clinical practice (version 2012) (2012) · cites this paper as [42]

  • Evidence that reducing plasma LDL cholesterol reduces CVD risk is unequivocal.

    “The evidence that reducing plasma LDL cholesterol reduces CVD risk is unequivocal”

    From European Guidelines on cardiovascular disease prevention in clinical practice (version 2012) (2012) · cites this paper as [42]

  • Chronic kidney disease stages 2-5 (GFR below 90 mL/min/1.73m2) is acknowledged as a coronary heart disease risk-equivalent.

    “CKD (stages 2 -5, i.e.GFR ,90 mL/min/1.73m 2 ) is acknowledged as a CHD risk-equivalent, and the LDL cholesterol target in these patients has been adapted to the degree of renal failure (see page 1653).42”

    From European Guidelines on cardiovascular disease prevention in clinical practice (version 2012) (2012) · cites this paper as [42]

  • The 2011 EAS/ESC and AHA/ACC guidelines strongly emphasize the importance of LDL-C lowering to prevent cardiovascular disease.

    “In both the 2011 EAS/ESC guidelines for the management of dyslipidaemias 125 and the American Heart Association/American College of Cardiology (AHA/ACC) guidelines on the treatment of blood cholesterol to reduce atherosclerotic CV risk in adults, 71 the importance of LDL-C lowering to prevent CVD is strongly emphasized.”

    From 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias (2016) · cites this paper as [125]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • A single trial is cited as a statin meta-analysis

    Minor

    The text describes reference 146 as a meta-analysis of several studies on statins and HDL-C. The reference list identifies it instead as one eight-week randomized trial of omega-3 fatty acids added to simvastatin.

  • A single imaging study is cited as a stroke-prevention meta-analysis

    Minor

    The stroke-prevention statement calls reference 133 a meta-analysis. The listed reference is a randomized imaging study, not a meta-analysis.

2 of 2

Cites

Flagged first, then by citations

Research works printed but not linked: 5

  1. Sniderman, Meta-analysis of LDL-C, non-HDL-C and apo B as markers of cardiovascular risk, Circulation
  2. The European Atherosclerosis Society Consensus Panel, 2011, Triglyceride-rich lipoprotein and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management, Eur Heart J
  3. Poulter, 1999, The impact of micronized fenofibrate on lipid subfractions and on reaching HDL-target levels in 7,098 patients with dyslipidaemia, Br J Cardiol, 6, 682
  4. DeMott, 2008, Clinical guidelines and evidence review for familial hypercholesterolaemia: the identification and management of adults and children with familial hypercholesterolaemia.
  5. World Health Organization, Human Genetics Programme, 1999, Familial hypercholesterolemia: Report of a second WHO consultation

Cited by

Sorted by citations

Related

Authors
Reiner, Ž., Catapano, A. L., De Backer, G., Graham, I., Taskinen, M.-R., Wiklund, O., Agewall, S., Alegria, E., Chapman, M. J., Durrington, P., Erdine, S., Halcox, J., Hobbs, R., Kjekshus, J., Filardi, P. P., Riccardi, G., Storey, R. F., Wood, D., Bax, J., Vahanian, A., Auricchio, A., Baumgartner, H., Ceconi, C., Dean, V., Deaton, C., Fagard, R., Filippatos, G., Funck-Brentano, C., Hasdai, D., Hobbs, R., Hoes, A., Kearney, P., Knuuti, J., Kolh, P., McDonagh, T., Moulin, C., Poldermans, D., Popescu, B. A., Reiner, Ž., Sechtem, U., Sirnes, P. A., Tendera, M., Torbicki, A., Vardas, P., Widimsky, P., Windecker, S., Reviewers:, D., Funck-Brentano, C., Poldermans, D., Berkenboom, G., De Graaf, J., Descamps, O., Gotcheva, N., Griffith, K., Guida, G. F., Gulec, S., Henkin, Y., Huber, K., Kesaniemi, Y. A., Lekakis, J., Manolis, A. J., Marques-Vidal, P., Masana, L., McMurray, J., Mendes, M., Pagava, Z., Pedersen, T., Prescott, E., Rato, Q., Rosano, G., Sans, S., Stalenhoef, A., Tokgozoglu, L., Viigimaa, M., Wittekoek, M. E., & Zamorano, J. L.
Affiliations
  • University of Milan (IT)
  • The disclosure forms of the authors and reviewers are available on the ESC website www.escardio.org/guidelines
ORCID
Venue
European Heart Journal
Publisher
Oxford University Press (OUP)
Published
2011-01-01
Volume
32
Issue
14
Pages
1769-1818
ISSN
  • 0195-668X (ISSN-L)
  • 1522-9645
DOI
10.1093/eurheartj/ehr158
OpenAlex
W1972661406
Cited by
3,549
References
236
Citations by year
2026: 31 · 2025: 69 · 2024: 71 · 2023: 88 · 2022: 108 · 2021: 128 · 2020: 167 · 2019: 165 · 2018: 212 · 2017: 312 · 2016: 490 · 2015: 504 · 2014: 492 · 2013: 383 · 2012: 271
FWCI
390.95
Type
journal article
Language
en
Open access
Locations
  • European Heart Journal (publishedVersion)
  • PubMed (publishedVersion)
  • Radboud Repository (Radboud University) (publishedVersion)
  • SERVAL (Université de Lausanne) (publishedVersion)
  • Bern Open Repository and Information System (University of Bern) (submittedVersion, other-oa)
  • Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
  • IRIS (submittedVersion)
  • Open Repository and Bibliography (University of Liège) (submittedVersion, other-oa)
  • Radboud Repository (Radboud University) (submittedVersion)
Funders
  • European Atherosclerosis Society
  • European Society of Cardiology
Topics
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
Keywords
dyslipidemia, dyslipidemia management, cardiovascular disease prevention, atherosclerosis, cardiovascular risk factors, lipid-lowering therapy, coronary artery disease, ischemic stroke, peripheral arterial disease, cardiovascular risk assessment
MeSH terms
Adult, Hypolipidemic Agents, Energy Intake, Cardiovascular Diseases, Child, Diet, Dietary Fats, Female, Humans, Kidney Failure, Chronic, Life Style, Male, Patient Compliance, Primary Prevention, Risk Factors, Specimen Handling, Transplantation, Weight Loss, Exercise, Risk Assessment, Dietary Supplements, Early Diagnosis, Dyslipidemias, Lipid Metabolism, Secondary Prevention

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-04.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-04.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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