2016 ESC/EAS Guidelines for the Management of Dyslipidaemias

In the paper

“High TG levels are often associated with low HDL-C and high levels of small dense LDL particles.”

In the paper

“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 þ non-fatal) hard CVD endpoints; the multiplier is ~4 in women and lower in older persons.”

In the paper

“However, the direct methods have been found to be unreliable in patients with HTG and should be used with caution in these cases 72 ; also, they may underestimate very low values of LDL-C.”

What the sources say

• Not checked yetcites [72] Langlois, 2014, Clinical impact of direct HDLc and LDLc method bias in hypertriglyceridemia. A simulation study of the EAS-EFLM Collaborative Project Group, Atherosclerosis source

In the paper

“Low HDL-C has been shown to be a strong and independent risk factor in several studies and is included in most of the risk estimation tools available, including HeartScore.”

In the paper

“A rare error occurs in patients with hyperglycerolaemia, where falsely very high values for TGs are detected.”

In the paper

“Based on epidemiological data, levels of HDL-C associated with increased risk for men are <1.0 mmol/L (40 mg/dL) and for women are <1.2 mmol/L (48 mg/dL).”

In the paper

“Some interventions resulted in significant CVD prevention, whereas others did not.”

What the sources say

• Not checked yetcites [132] Dalen, 2014, Diets to prevent coronary heart disease 1957–2013: what have we learned?, Am J Med source

In the paper

“Lp(a) has been found in several studies to be an additional independent risk marker; indeed, genetic data show it to be causal in the pathophysiology of atherosclerotic vascular disease and aortic stenosis.109e111”

What the sources say

• Not checked yetcites 109e111

In the paper

“Furthermore, loss of function mutations are associated with low TGs as well as with reduced risk for CVD.106,107”

What the sources say

• Not checked yetcites [106] Crosby, 2014, Loss-of-function mutations in APOC3, triglycerides, and coronary disease, N Engl J Med source
• Not checked yetcites [107] Jorgensen, 2014, Loss-of-function mutations in APOC3 and risk of ischemic vascular disease, N Engl J Med source

In the paper

“Particular consideration was given to results from systematic reviews confirming the dose-dependent reduction in CVD with LDL-C lowering; the greater the LDL-C reduction, the greater the CV risk reduction.65,66”

What the sources say

• Not checked yetcites [65] Fulcher, 2015, Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials, Lancet source
• Not checked yetcites [66] Mihaylova, 2012, The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials, Lancet source

In the paper

“although increases in HDL-C predict atherosclerosis regression”

In the paper

“PUFAs of the n-3 series have no hypocholesterolaemic effect; conversely, when they are used at high dosages (>3 g/day), the effect on LDL-C levels is either neutral or a slight increase [particularly with docosahexaenoic acid (DHA)] with a concomitant decrease of TGs.165”

What the sources say

• Not checked yetcites [165] 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

In the paper

“Stearic acid, in contrast to other SFAs (lauric, myristic and palmitic), does not increase TC levels.”

In the paper

“Quantitatively, dietary trans fatty acids have a similar elevating effect on LDL-C to that of SFAs; however, while SFAs increase HDL-C levels, trans fats decrease them.137”

What the sources say

• Not checked yetcites [137] Estruch, 2013, Primary prevention of cardiovascular disease with a Mediterranean diet, N Engl J Med source

In the paper

“Moderate alcohol consumption is associated with increased HDL-C levels as compared with abstainers, with a dose-response relationship.”

In the paper

“MUFA consumption as a replacement for SFAs has almost no effect on HDL-C, while n-6 PUFAs induce a slight decrease.”

In the paper

“These effects are dose dependent; with a habitual fructose consumption between 15 and 20% of the total energy intake, plasma TG increases as much as 30e40%.”

In the paper

“both have been proven to be effective in reducing CV risk factors and, possibly, to contribute to CVD prevention.133”

What the sources say

• Not checked yetcites [133] Eckel, 2014, 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, Circulation source

In the paper

“If 1% of the dietary energy derived from SFAs is replaced by n-6 polyunsaturated fatty acids (PUFAs), LDL-C decreases by 0.051 mmol/L (2.0 mg/dL); if replaced by monounsaturated fatty acids (MUFAs), the decrease would be 0.041 mmol/L (1.6 mg/dL); and if replaced by carbohydrate, it would be 0.032 mmol/L (1.2 mg/dL).”

In the paper

“Weight reduction improves insulin sensitivity and decreases TG levels.”

In the paper

“In this respect, both the glycaemic index and the fibre content do not seem to play a relevant role.178,179”

What the sources say

• Not checked yetcites [178] Goff, 2013, Low glycaemic index diets and blood lipids: a systematic review and meta-analysis of randomised controlled trials, Nutr Metab Cardiovasc Dis source
• Not checked yetcites [179] Bazzano, 2011, Non-soy legume consumption lowers cholesterol levels: a meta-analysis of randomized controlled trials, Nutr Metab Cardiovasc Dis source

In the paper

“In particular, the detrimental effects of a high carbohydrate diet on TGs occur mainly when refined carbohydrate-rich foods are consumed, while they are much less prominent if the diet is based largely on fibre-rich, low glycaemic index foods.”

In the paper

“SFAs increase HDL-C levels in parallel with LDL-C; in contrast, trans fats decrease them.137”

What the sources say

• Not checked yetcites [137] Estruch, 2013, Primary prevention of cardiovascular disease with a Mediterranean diet, N Engl J Med source

In the paper

“Glucose and lipid metabolism are strongly related, and any perturbation of carbohydrate metabolism induced by a high carbohydrate diet will also lead to an increase in TG concentrations.148,165”

What the sources say

• Not checked yetcites [148] Nordmann, 2006, Effects of low-carbohydrate vs low-fat diets on weight loss and cardiovascular risk factors: a meta-analysis of randomized controlled trials, Arch Intern Med source
• Not checked yetcites [165] 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

In the paper

“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 is excessive.152,177”

What the sources say

• Not checked yetcites [152] Rimm, 1999, Moderate alcohol intake and lower risk of coronary heart disease: meta-analysis of effects on lipids and haemostatic factors, BMJ source
• Not checked yetcites [177] Brien, 2011, Effect of alcohol consumption on biological markers associated with risk of coronary heart disease: systematic review and meta-analysis of interventional studies, BMJ source

In the paper

“Body weight reduction also influences TC and LDL-C, but the magnitude of the effect is rather small; in grossly obese subjects, a decrease in LDL-C concentration of ~0.2 mmol/L (8 mg/dL) is observed for every 10 kg of weight loss; the reduction of LDL-C is greater if weight loss is achieved with a low fat diet.147,148”

What the sources say

• Not checked yetcites [147] Dattilo, 1992, Effects of weight reduction on blood lipids and lipoproteins: a meta-analysis, Am J Clin Nutr source
• Not checked yetcites [148] Nordmann, 2006, Effects of low-carbohydrate vs low-fat diets on weight loss and cardiovascular risk factors: a meta-analysis of randomized controlled trials, Arch Intern Med source

In the paper

“In many studies the reduction of TG levels due to weight reduction is between 20e30%; this effect is usually preserved as long as weight is not regained.”

In the paper

“However, fat intakes that >35% of calories are generally associated with increased intakes of both saturated fat and calories.”

In the paper

“Conversely, a low intake of fats and oils increases the risk of inadequate intakes of vitamin E and of essential fatty acids, and may contribute to unfavourable changes in HDL-C.165”

What the sources say

• Not checked yetcites [165] 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

In the paper

“Even in the most advanced stages of the disease (critical limb ischaemia), statin therapy improved rates of 1-year mortality and major adverse CV events and increased amputation-free survival.409”

What the sources say

• Not checked yetcites [409] Westin, 2014, Association between statin medications and mortality, major adverse cardiovascular event, and amputation-free survival in patients with critical limb ischemia, J Am Coll Cardiol source

In the paper

“Atherosclerotic changes of retinal arteries correlate with TC, LDL-C, TG and apoB levels and also with CAD.412”

What the sources say

• Not checked yetcites [412] Tedeschi-Reiner, 2005, Relation of atherosclerotic changes in retinal arteries to the extent of coronary artery disease, Am J Cardiol source

In the paper

“In patients with first-episode schizophrenia spectrum disorders, cardiometabolic risk factors were present early in the illness; this was related to the underlying disorder, unhealthy lifestyle and antipsychotic medications, which interact with each other.437”

What the sources say

• Not checked yetcites [437] Correll, 2014, Cardiometabolic risk in patients with first-episode schizophrenia spectrum disorders: baseline results from the RAISE-ETP study, JAMA Psychiatry source

In the paper

“All this explains the higher prevalence of obesity, MetS, diabetes and dyslipidaemia in patients with these psychiatric diseases.438”

What the sources say

• Not checked yetcites [438] Andrade, 2013, Primary prevention of cardiovascular events in patients with major mental illness: a possible role for statins, Bipolar Disord source

In the paper

“A recent meta-analysis of RCTs in subjects >65 years of age at high CV risk without established CV disease showed that statins significantly reduce the incidence of MI and stroke, but do not significantly prolong survival in the short-term.327”

What the sources say

• Not checked yetcites [327] Savarese, 2013, Benefits of statins in elderly subjects without established cardiovascular disease: a meta-analysis, J Am Coll Cardiol source

In the paper

“In patients with bipolar disorder there was a reduction in life expectancy of 12e14 years.440”

What the sources say

• Not checked yetcites [440] Laursen, 2011, Life expectancy among persons with schizophrenia or bipolar affective disorder, Schizophr Res source

In the paper

“In a Finnish cohort of patients with schizophrenia, life expectancy was about 2 decades less than in persons of similar age from the general population.439”

What the sources say

• Not checked yetcites [439] Tiihonen, 2009, 11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study), Lancet source

In the paper

“The addition of ezetimibe to simvastatin in post-ACS patients had an incremental beneficial effect for ischaemic stroke or all strokes (marginal statistical significance for the latter).63”

What the sources say

• Not checked yetcites [63] Cannon, 2015, Ezetimibe added to statin therapy after acute coronary syndromes, N Engl J Med source

In the paper

“Secondary prevention therapy with statins reduces the risk of recurrent stroke (by 12%), MI and vascular death.422,428”

What the sources say

• Not checked yetcites [422] Amarenco, 2009, Lipid management in the prevention of stroke: review and updated meta-analysis of statins for stroke prevention, Lancet Neurol source
• Not checked yetcites [428] Amarenco, 2006, High-dose atorvastatin after stroke or transient ischemic attack, N Engl J Med source

In the paper

“Among 654 patients with bipolar disorder in the Fondamental Advanced Centers of Expertise in Bipolar Disorders (FACE-BD) cohort, 18.5% met the criteria for MetS; only 11% and 28% of the patients with hypercholesterolaemia and high fasting glycaemia, respectively, were treated for these conditions.441”

What the sources say

• Not checked yetcites [441] Godin, 2014, Metabolic syndrome in a French cohort of patients with bipolar disorder: results from the FACE-BD cohort, J Clin Psychiatry source

In the paper

“HIV-infected patients typically have low TC and LDL-C, as well as low HDL-C and increased TGs.430,431”

What the sources say

• Not checked yetcites [430] Riddler, 2003, Impact of HIV infection and HAART on serum lipids in men, JAMA source
• Not checked yetcites [431] Hemkens, 2014, HIV infection and cardiovascular disease, Eur Heart J source

In the paper

“A systematic review found that the incidence of drug-induced hepatotoxicity in patients taking statins is unknown, with very few cases occurring in large-scale RCTs.212,214”

What the sources say

• Not checked yetcites [212] Law, 2006, Statin safety: a systematic review, Am J Cardiol source
• Not checked yetcites [214] Naci, 2013, Comparative tolerability and harms of individual statins: a study-level network meta-analysis of 246 955 participants from 135 randomized, controlled trials, Circ Cardiovasc Qual Outcomes source

In the paper

“Various empirical models of health behaviour and behaviour change theory have been shown to predict adherence, including the Theory of Planned Behaviour 466 and the Health Belief Model.467”

What the sources say

• Not checked yetcites [466] Ajzen, 1991, The Theory of Planned Behaviour, Organ Behav Hum Decis Process source
• Not checked yetcites [467] Becker, 1974, The Health Belief Model and personal health behaviour, Health Educ Monogr source

In the paper

“Predictors of non-adherence with statins have been identified 450,472e474 and include their use in individuals for primary prevention as compared with their use in patients with disease or with multiple risk factors, lower income, being elderly, complex polypharmacy, cost and forgetfulness due to a lack of symptoms and psychological co-morbidities.”

What the sources say

• Not checked yetcites [450] Benner, 2002, Long-term persistence in use of statin therapy in elderly patients, JAMA source
• Not checked yetcites 472e474

In the paper

“Adherence declines over the duration of treatment 450e454 ; however, this is truer in patients treated for primary compared with secondary prevention of CVD, with reported rates of up to 77% discontinuing their statins within 2 years.”

What the sources say

• Not checked yetcites 450e454

In the paper

“Not surprisingly, this non-adherence has an impact on healthcare costs, morbidity, hospital readmissions and mortality.457e461”

What the sources say

• Not checked yetcites 457e461

In the paper

“Despite a wealth of evidence on the efficacy and effectiveness of statins in both primary and secondary prevention, adherence remains a consistent barrier, with rates of <50% demonstrated in several studies.”

What the sources say

• Not checked yetcites 450e454

In the paper

“Studies that investigated adherence to medications in long-term conditions identified factors such as high susceptibility, severity of the condition, strong intentions and high self-efficacy as being associated with good adherence, while poor lifestyle habits and low perceived behavioural control were associated with poor adherence.468,469”

What the sources say

• Not checked yetcites [468] Rich, 2015, Theory of planned behavior and adherence in chronic illness: a meta-analysis, J Behav Med source
• Not checked yetcites [469] Kamran, 2014, Determinants of patient's adherence to hypertension medications: application of health belief model among rural patients, Ann Med Health Sci Res source

In the paper

“This overview also found that the use of self-management or self-monitoring programmes, as well as a regular pharmacy review of prescribed medications with a view to taking out unnecessary medications, was helpful.”

What the sources say

• Not checked yetcites [484] Ryan, 2014, Interventions to improve safe and effective medicines use by consumers: an overview of systematic reviews, Cochrane Database Syst Rev

In the paper

“At 15 months, statistically significant differences between intervention and usual care were seen in self-reported adherence and changes in systolic blood pressure and LDL-C.”

What the sources say

• Not checked yetcites [482] Thom, 2013, Effects of a fixed-dose combination strategy on adherence and risk factors in patients with or at high risk of CVD: the UMPIRE randomized clinical trial, JAMA source

In the paper

“In phase 1, factors associated with non-adherence were younger age, depression, complex regimen, poorer health insurance coverage and low social support.”

What the sources say

• Not checked yetcites [483] Castellano, 2014, A polypill strategy to improve adherence: results from the FOCUS project, J Am Coll Cardiol source

In the paper

“Importantly, a sizable portion of patients on hypolipidaemic or antihypertensive drug treatment fail to take their treatment adequately or to reach their therapeutic goals, 28,29 with clinical and economic consequences.30”

What the sources say

• Not checked yetcites [28] Banegas, 2011, Achievement of treatment goals for primary prevention of cardiovascular disease in clinical practice across Europe: the EURIKA study, Eur Heart J source
• Not checked yetcites [29] Kotseva, 2010, Management of cardiovascular risk factors in asymptomatic high-risk patients in general practice: cross-sectional survey in 12 European countries, Eur J Cardiovasc Prev Rehabil source
• Not checked yetcites [30] Cherry, 2009, The clinical and economic burden of nonadherence with antihypertensive and lipid-lowering therapy in hypertensive patients, Value Health source

In the paper

“Coronary artery disease (CAD) mortality rates could be halved by only modest risk factor reduction, 39”

What the sources say

• Not checked yetcites [39] Capewell, 2010, Cardiovascular risk factor trends and potential for reducing coronary heart disease mortality in the United States of America, Bull World Health Org source

In the paper

“Patients who have had a clinical event such as acute coronary syndrome (ACS) or a stroke are at very high risk of a further event and automatically qualify for risk factor evaluation and management (Table 6).”

What the sources say

• Not checked yetcites Table 6

In the paper

“All current guidelines on the prevention of CVD in clinical practice recommend the assessment of total CAD or CV risk, because atherosclerotic CVD is usually the product of a number of risk factors, and prevention of CVD in a given person should be adapted to his/her total CV risk: the higher the risk, the more intense the action should be.”

In the paper

“Targeting lower levels in the health impact pyramid will also address the socio-economic divide in CV health, which has not diminished despite major improvements in the treatment of CVD in recent decades.9,10”

What the sources say

• Not checked yetcites [9] Heidenreich, 2011, Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association, Circulation source
• Not checked yetcites [10] McConnachie, 2014, Long-term impact on healthcare resource utilization of statin treatment, and its cost effectiveness in the primary prevention of cardiovascular disease: a record linkage study, Eur Heart J source

In the paper

“the elimination of health risk behaviours would make it possible to prevent at least 80% of CVD and even 40% of cancers, thus providing added value for other chronic diseases.3,4”

What the sources say

• Not checked yetcites [3] Liu, 2012, Healthy lifestyle through young adulthood and the presence of low cardiovascular disease risk profile in middle age: the Coronary Artery Risk Development in (Young) Adults (CARDIA) study, Circulation source
• Not checked yetcites [4] Ezzati, 2004

In the paper

“A report from the National Institute for Health and Care Excellence (NICE) estimated that a UK national programme reducing population CV risk by 1% would prevent 25 000 CVD cases and generate savings of V40 million per year.38”

What the sources say

• Not checked yetcites [38] National Institute for Health and Care Excellence, 2010

In the paper

“Most studies assessing the cost-effectiveness of prevention of CVD combine evidence from clinical research with simulation approaches, while data from randomized controlled trials (RCTs) are relatively scarce.7,10,11”

What the sources say

• Not checked yetcites [7] Mistry, 2012, Cost-effectiveness of a European preventive cardiology programme in primary care: a Markov modelling approach, BMJ Open
• Not checked yetcites [10] McConnachie, 2014, Long-term impact on healthcare resource utilization of statin treatment, and its cost effectiveness in the primary prevention of cardiovascular disease: a record linkage study, Eur Heart J source
• Not checked yetcites [11] Ward, 2007, A systematic review and economic evaluation of statins for the prevention of coronary events, Health Technol Assess source

In the paper

“The European Guidelines on CVD prevention in clinical practice (version 2012) 6 recommend use of the SCORE system because it is based on large, representative European cohort datasets.”

What the sources say

• Not checked yetcites [6] Perk, 2012, Eur Heart J source

In the paper

“According to the WHO, policy and environmental changes could reduce CVD in all countries for <US$1 per person per year, while interventions at the individual level are considerably more expensive.37”

What the sources say

• Not checked yetcites [37] Brown, 2011, Medication adherence: WHO cares?, Mayo Clin Proc source

In the paper

“Cost-effectiveness results strongly depend on parameters such as the target population's age, the overall population risk of CVD and the cost of interventions.Hence, results obtained in one country might not be valid in another.”

In the paper

“Lowering blood cholesterol levels using statins 10,11,23e25 and improving blood pressure control are also cost effective.26,27”

What the sources say

• Not checked yetcites 10,11,23e25
• Not checked yetcites [26] Stevanovic, 2014, Economic evaluation of primary prevention of cardiovascular diseases in mild hypertension: a scenario analysis for the Netherlands, Clin Ther source
• Not checked yetcites [27] Wisloff, 2012, Choice of generic antihypertensive drugs for the primary prevention of cardiovascular disease—a cost-effectiveness analysis, BMC Cardiovasc Disord source

In the paper

“A particular problem relates to young people with high levels of risk factors; a low absolute risk may conceal a very high relative risk requiring intensive lifestyle advice.”

In the paper

“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.”

In the paper

“Non-HDL-C is used as an estimation of the total amount of atherogenic lipoproteins in plasma (VLDL, VLDL remnants, intermediate-density lipoprotein (IDL), LDL, Lp(a)) and relates well to apoB levels.”

In the paper

“Social deprivation and psychosocial stress set the scene for increased risk.57”

What the sources say

• Not checked yetcites [57] Mortensen, 2015, The high-density lipoprotein-adjusted SCORE model worsens SCORE-based risk classification in a contemporary population of 30,824 Europeans: the Copenhagen General Population Study, Eur Heart J source

In the paper

“For example, HDL-C modifies risk at all levels of risk as estimated from the SCORE cholesterol charts.55 Furthermore, this effect is seen in both genders and in all age groups, including older women.”

What the sources say

• Not checked yetcites [55] Cooney, 2009, HDL cholesterol protects against cardiovascular disease in both genders, at all ages and at all levels of risk, Atherosclerosis source

In the paper

“Most available assays are of high quality”

In the paper

“ApoB is the major apolipoprotein of the atherogenic lipoprotein families (VLDL, IDL and LDL).ApoB is a good estimate of the number of these particles in plasma.”

In the paper

“Non-HDL-C also includes the atherogenic TG-rich lipoproteins (VLDL, IDL and remnants)”

In the paper

“Of these, some are at very high risk, and the high-risk chart may underestimate risk in these countries.”

In the paper

“Risk age can be used in any population regardless of baseline risk or secular changes in mortality, and therefore avoids the need for recalibration.”

In the paper

“Persons with documented CVD type 1 or type 2 diabetes very high levels of individual risk factors chronic kidney disease (CKD) (refer to section 9.9) are automatically at very high or high total CV risk.No risk estimation models are needed for them; they all need active management of all risk factors.”

In the paper

“The Friedewald formula may be unreliable when blood is obtained under non-fasting conditions.”

In the paper

“Some recent guidelines recommend non-HDL-C as a better risk indicator than LDL-C.82”

What the sources say

• Not checked yetcites [82] National Institute for Health and Care Excellence, 2014

In the paper

“It should also be considered that HTG might interfere with the direct HDL-C assays.”

In the paper

“The analytical performance is good and the assays do not require fasting conditions and are not sensitive to markedly elevated TG levels.”

In the paper

“Overall, HDL-C has a modest but useful effect in refining risk estimation, 56 but this may not be universal, as its effect may not be seen in some low-risk populations, particularly with a relatively high mean HDL-C level.57”

What the sources say

• Not checked yetcites [56] Cooney, 2009, How much does HDL cholesterol add to risk estimation? A report from the SCORE Investigators, Eur J Cardiovasc Prev Rehabil source
• Not checked yetcites [57] Mortensen, 2015, The high-density lipoprotein-adjusted SCORE model worsens SCORE-based risk classification in a contemporary population of 30,824 Europeans: the Copenhagen General Population Study, Eur Heart J source

In the paper

“These trials are consistent in showing that the higher the initial LDL-C level, the greater the absolute reduction in risk, while the relative risk reduction remains constant at any given baseline LDL-C level.”

What the sources say

• Not checked yetcites 61e71

In the paper

“Good immunochemical methods are available and easily run in conventional autoanalysers.”

In the paper

“These patients are always at high risk and should receive special attention.”

In the paper

“Recent work has shown that b-coefficients are not constant with ageing and that SCORE overestimates risk in older people.54”

What the sources say

• Not checked yetcites [54] Cooney, 2016, Cardiovascular risk estimation in older persons: SCORE O.P, Eur J Prev Cardiol source

In the paper

“Several methods for determination of Lp(a) are available, but standardization between assays is needed.112”

What the sources say

• Not checked yetcites [112] Marcovina, 2003, Report of the National Heart, Lung, and Blood Institute Workshop on Lipoprotein(a) and Cardiovascular Disease: recent advances and future directions, Clin Chem source

In the paper

“Lp(a) has properties in common with LDL, but it contains a unique protein, apolipoprotein(a) [apo(a)], that is structurally homologous to plasminogen.”

In the paper

“However, each HDL particle may carry from one to five apoA1 molecules.”

In the paper

“ApoE is present in three isoforms (apoE2, apoE3 and apoE4).”

In the paper

“Secondary targets have also been defined by inference for non-HDL-C and for apoB; they receive a moderate grading, as they have not been extensively studied in RCTs.”

In the paper

“Plasma apoA1 levels <120 mg/dL for men and <140 mg/dL for women correspond approximately to what is considered as low for HDL-C.”

In the paper

“ApoA1 is the major protein of HDL-C and provides a satisfactory estimate of HDL-C concentration.”

In the paper

“ApoCIII is a key regulator of TG metabolism, and high apoCIII plasma levels are associated with high plasma VLDL and plasma TGs.”

In the paper

“In FH, a genetic diagnosis is important for family screening, to establish the diagnosis in patients with borderline LDL-C and to improve patient adherence to therapy.121”

What the sources say

• Not checked yetcites [121] Nordestgaard, 2013, Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society, Eur Heart J source

In the paper

“The risk is regarded as significant when Lp(a) is above the 80th percentile (50 mg/dL).109”

What the sources say

• Not checked yetcites [109] Nordestgaard, 2010, Lipoprotein(a) as a cardiovascular risk factor: current status, Eur Heart J source

In the paper

“ApoE genotyping is used primarily for the diagnosis of dysbetalipoproteinaemia (apoE2 homozygosity) and is indicated in cases with severe combined hyperlipidaemia.”

In the paper

“Determination of small dense LDL may be regarded as an emerging risk factor and may be used in the future, but it is not currently recommended for risk estimation.119”

What the sources say

• Not checked yetcites [119] Mora, 2007, LDL particle subclasses, LDL particle size, and carotid atherosclerosis in the Multi-Ethnic Study of Atherosclerosis (MESA), Atherosclerosis source

In the paper

“At present, the use of genotyping for risk estimation is not recommended since known risk loci account for only a small proportion of risk.120”

What the sources say

• Not checked yetcites [120] Whitfield, 2014, Genetic insights into cardiometabolic risk factors, Clin Biochem Rev

In the paper

“ApoCIII has been identified as a new potential therapeutic target that is currently being studied, but whether it has a role in clinical practice is unknown and its measurements on a routine basis are not encouraged.108”

What the sources say

• Not checked yetcites [108] Graham, 2013, Antisense oligonucleotide inhibition of apolipoprotein C-III reduces plasma triglycerides in rodents, nonhuman primates, and humans, Circ Res source

In the paper

“Several genes have been associated with CVD.”

In the paper

“Ratios between atherogenic lipoproteins and HDL-C or apoA1 (TC:HDL-C, non-HDL-C:HDL-C, apoB:apoA1) are useful for risk estimation, but not for diagnosis or as treatment targets.”

In the paper

“Large GWASs have been published for coronary heart disease (CHD), as well as for associated biomarkers and risk factors.”

In the paper

“A major disadvantage of apoB is that it is not included in algorithms for calculation of global risk, and it has not been a predefined treatment target in controlled trials.”

In the paper

“The measurement of Lp(a) is particularly stable over time.”

In the paper

“This is due not only to methodological problems, particularly inadequate sample size or the short duration of many trials included in the systematic revision, but also to the difficulty of evaluating the impact of a single dietary factor independently of any other changes in the diet.”

In the paper

“Previous RCTs where omega-3 supplementation was beneficial were not blinded or had low use of standard CV medications (such as statins).”

In the paper

“Overall, the available evidence on functional foods so far identified in this field is incomplete; the major gap is the absence of diet-based intervention trials of sufficient duration to be relevant for the natural history of dyslipidaemia and CVD.”

In the paper

“The daily consumption of 2 g of phytosterols can effectively lower TC and LDL-C by 7e10% in humans (with a certain degree of heterogeneity among individuals), while it has little or no effect on HDL-C and TG levels. 143”

What the sources say

• Not checked yetcites [143] Musa-Veloso, 2011, A comparison of the LDL-cholesterol lowering efficacy of plant stanols and plant sterols over a continuous dose range: results of a meta-analysis of randomized, placebo-controlled trials, Prostaglandins Leukot Essent Fatty Acids source

In the paper

“Different commercial preparations of RYR have different concentrations of monacolins, and lower TC and LDL-C to a variable extent, 145”

What the sources say

• Not checked yetcites [145] Gordon, 2010, Marked variability of monacolin levels in commercial red yeast rice products: buyer beware, Arch Intern Med source

In the paper

“The degree of LDL-C reduction is dose dependent and varies between the different statins (supplementary Figure A and supplementary Table A).191”

What the sources say

• Not checked yetcites [191] Weng, 2010, A systematic review and meta-analysis on the therapeutic equivalence of statins, J Clin Pharm Ther source

In the paper

“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 was reported.”

What the sources say

• Not checked yetcites [64] Baigent, 2010, Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials, Lancet source

In the paper

“six trials were available for this purpose: the berberine group contained 229 patients and the control group contained 222 patients.190”

What the sources say

• Not checked yetcites [190] Lan, 2015, Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension, J Ethnopharmacol source

In the paper

“Poor response to statin treatment in clinical studies is to some extent caused by poor compliance, but may also be explained by a genetic background involving variations in genes of both cholesterol metabolism and of statin uptake and metabolism in the liver.192,193”

What the sources say

• Not checked yetcites [192] Chasman, 2012, Genetic determinants of statin-induced low-density lipoprotein cholesterol reduction: the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial, Circ Cardiovasc Genet source
• Not checked yetcites [193] Reiner, 2014, Resistance and intolerance to statins, Nutr Metab Cardiovasc Dis source

In the paper

“The risk of major coronary events was reduced by 23% and the risk of stroke was reduced by 17% per 1 mmol/L (40 mg/dL) LDL-C reduction.”

What the sources say

• Not checked yetcites [64] Baigent, 2010, Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials, Lancet source

In the paper

“Foods enriched with these fibres are well tolerated, effective and recommended for LDL-C lowering at a daily dose of at least 3 g/day.186,187”

What the sources say

• Not checked yetcites [186] AbuMweis, 2010, β-glucan from barley and its lipid-lowering capacity: a meta-analysis of randomized, controlled trials, Eur J Clin Nutr source
• Not checked yetcites [187] Wolever, 2010, Physicochemical properties of oat beta-glucan influence its ability to reduce serum LDL cholesterol in humans: a randomized clinical trial, Am J Clin Nutr source

In the paper

“The studies, showing a statistically significant heterogeneity, were all performed in China in people of Asian ethnicity.”

What the sources say

• Not checked yetcites [190] Lan, 2015, Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension, J Ethnopharmacol source

In the paper

“This treatment seems to induce beneficial effects not only on the overall risk factor profile, but also on CV events.181”

What the sources say

• Not checked yetcites [181] Puzziferri, 2014, Long-term follow-up after bariatric surgery: a systematic review, JAMA source

In the paper

“For most individuals, a wide range of total fat intakes is acceptable and will depend upon individual preferences and characteristics.”

In the paper

“Smoking cessation has clear benefits on the overall CV risk, and specifically on HDL-C, but special attention should be paid in order to prevent weight gain in people who stop smoking.163”

What the sources say

• Not checked yetcites [163] Maeda, 2003, The effects of cessation from cigarette smoking on the lipid and lipoprotein profiles: a meta-analysis, Prev Med source

In the paper

“Observational evidence supports the recommendation that the intake of fish (at least twice a week) and long chain n-3 fatty acids supplements at low dosage may reduce the risk of CV death and stroke in primary prevention, but have no major effects on plasma lipoprotein metabolism.183”

What the sources say

• Not checked yetcites [183] Mozaffarian, 2013, Plasma phospholipid long-chain omega-3 fatty acids and total and cause-specific mortality in older adults: a cohort study, Ann Intern Med source

In the paper

“The increased risk for myopathy with nicotinic acid has been debated, but in recent reviews no increased risk of myopathy was found with this agent.236,237”

What the sources say

• Not checked yetcites [236] Guyton, 2007, Safety considerations with niacin therapy, Am J Cardiol source
• Not checked yetcites [237] Cziraky, 2006, Statin safety: an assessment using an administrative claims database, Am J Cardiol source

In the paper

“The frequency of rhabdomyolysis has been estimated to represent 1e3 cases/100√000 patient-years.212”

What the sources say

• Not checked yetcites [212] Law, 2006, Statin safety: a systematic review, Am J Cardiol source

In the paper

“The proteinuria induced by statins is of tubular origin and is supposed to be due to reduced tubular reabsorption and not to glomerular dysfunction.229”

What the sources say

• Not checked yetcites [229] Vidt, 2005, Statins and proteinuria, Curr Atheroscler Rep source

In the paper

“Patients with mild ALT elevation due to steatosis have been studied during statin treatment and there is no indication that statins cause any worsening of liver disease.222e224”

What the sources say

• Not checked yetcites [222] Chalasani, 2004, Patients with elevated liver enzymes are not at higher risk for statin hepatotoxicity, Gastroenterology source
• Not checked yetcites [223] Vuppalanchi, 2005, Patients with elevated baseline liver enzymes do not have higher frequency of hepatotoxicity from lovastatin than those with normal baseline liver enzymes, Am J Med Sci source
• Not checked yetcites [224] Dongiovanni, 2015, Statin use and non-alcoholic steatohepatitis in at risk individuals, J Hepatol source

In the paper

“Current available evidence from meta-analyses suggests that the clinical benefit is largely independent of the type of statin but depends on the extent of LDL-C lowering, therefore the type of statin used should reflect the LDL-C goal in a given patient.”

In the paper

“and the risk for diabetes is higher in the elderly and in the presence of other risk factors for diabetes such as overweight or insulin resistance.227”

What the sources say

• Not checked yetcites [227] Waters, 2013, Cardiovascular event reduction versus new-onset diabetes during atorvastatin therapy: effect of baseline risk factors for diabetes, J Am Coll Cardiol source

In the paper

“The benefits were significant within the first year, but were greater in subsequent years.”

What the sources say

• Not checked yetcites [64] Baigent, 2010, Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials, Lancet source

In the paper

“A recent Cochrane review found that colesevelam, when added to other antidiabetic agents, showed significant effects on glycaemic control; however, more research on the impact of CV risk is required.238”

What the sources say

• Not checked yetcites [238] Ooi, 2014, Colesevelam for type 2 diabetes mellitus: an abridged Cochrane review, Diabet Med source

In the paper

“In this analysis, all-cause mortality was reduced by 14%, CVD events by 27%, fatal and non-fatal coronary events by 27% and stroke by 22% per 1 mmol/L (40 mg/ dL) LDL-C reduction.”

What the sources say

• Not checked yetcites [200] Taylor, 2013, Statins for the primary prevention of cardiovascular disease, Cochrane Database Syst Rev

In the paper

“The analysis included 19 studies with different statins and with somewhat varying inclusion criteria.”

What the sources say

• Not checked yetcites [200] Taylor, 2013, Statins for the primary prevention of cardiovascular disease, Cochrane Database Syst Rev

In the paper

“A recent Cochrane analysis could not find support for beneficial effects on renal function based on studies where creatinine clearance was available, and no deleterious effects were observed.228”

What the sources say

• Not checked yetcites [228] Palmer, 2014, HMG CoA reductase inhibitors (statins) for kidney transplant recipients, Cochrane Database Syst Rev

In the paper

“In rhabdomyolysis, creatine kinase (CK) levels are elevated at least 10 times, often up to 40 times the upper limit of normal.211”

What the sources say

• Not checked yetcites [211] Stroes, 2015, Ginsberg HN;, European Atherosclerosis Society Consensus Panel. Statin-associated muscle symptoms: impact on statin therapy—European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management, Eur Heart J source

In the paper

“In clinical trials the frequency of proteinuria is in general low and in most cases is not higher than for placebo.231”

What the sources say

• Not checked yetcites [231] Davidson, 2004, Rosuvastatin safety: lessons from the FDA review and post-approval surveillance, Expert Opin Drug Saf source

In the paper

“The statin-induced reduced pinocytosis is directly related to the inhibition of cholesterol synthesis.230”

What the sources say

• Not checked yetcites [230] Sidaway, 2004, Inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase reduce receptor-mediated endocytosis in opossum kidney cells, J Am Soc Nephrol source

In the paper

“In the FIELD study, small but significant increases in the incidence of pancreatitis (0.8% vs. 0.5%) and pulmonary embolism (1.1% vs. 0.7%) and a nonsignificant 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.261”

What the sources say

• Not checked yetcites [261] Keech, 2005, d'Emden M, Whiting M, Ehnholm C, Laakso M. 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

In the paper

“A total of 18 144 patients were randomized and 5314 patients over 7 years experienced a CVD event; 170 fewer events (32.7 vs. 34.7%)were recorded in the group taking simvastatin plus ezetimibe (P ¼ 0.016).”

What the sources say

• Not checked yetcites [63] Cannon, 2015, Ezetimibe added to statin therapy after acute coronary syndromes, N Engl J Med source

In the paper

“After two large studies with nicotinic acid, one with extended-release niacin 251 and one with niacin plus laropiprant, 252 showed no beneficial effect, but rather an increased frequency of serious adverse effects, no medication containing nicotinic acid is currently approved in Europe.”

What the sources say

• Not checked yetcites [251] Boden, 2011, Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy, N Engl J Med source
• Not checked yetcites [252] GroupLandray, 2014, Effects of extended-release niacin with laropiprant in high-risk patients, N Engl J Med source

In the paper

“Two large randomized clinical trials [the Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes (AIM-HIGH) and the Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE)] using, respectively, extended release (ER) nicotinic acid vs. placebo in addition to simvastatin, and ER nicotinic acid/l”

What the sources say

• Not checked yetcites [251] Boden, 2011, Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy, N Engl J Med source
• Not checked yetcites [252] GroupLandray, 2014, Effects of extended-release niacin with laropiprant in high-risk patients, N Engl J Med source

In the paper

“Functional foods containing phytosterols as well as plant sterolecontaining tablets additionally reduce LDL-C levels by up to 5e10% in patients taking a stable dose of a statin, and this combination is also well tolerated and safe.142,255”

What the sources say

• Not checked yetcites [142] Gylling, 2014, Plant sterols and plant stanols in the management of dyslipidaemia and prevention of cardiovascular disease, Atherosclerosis source
• Not checked yetcites [255] Abumweis, 2008, Plant sterols/stanols as cholesterol lowering agents: a meta-analysis of randomized controlled trials, Food Nutr Res

In the paper

“As compared with the overwhelming evidence for the benefits of LDL-C reduction, the evidence on the benefits of lowering elevated TG levels is still modest, and is primarily derived from subgroup or post hoc analyses.”

In the paper

“However, the study supports the proposition that LDL-C lowering by means other than statins is beneficial and can be performed without adverse effects.”

What the sources say

• Not checked yetcites [63] Cannon, 2015, Ezetimibe added to statin therapy after acute coronary syndromes, N Engl J Med source

In the paper

“Naturally occurring mutations that inactivate the protein were found to be associated with reduced plasma LDL-C and reduced risk for CAD.245”

What the sources say

• Not checked yetcites [245] Won, 2014, Inactivating mutations in NPC1L1 and protection from coronary heart disease, N Engl J Med source

In the paper

“Therefore this pharmacological approach is effective in the vast majority of patients, including those with heterozygous FH (HeFH) and, albeit to a lower level, those with homozygous FH (HoFH) with residual LDLR expression.”

In the paper

“The average LDL-C during the study was 1.8 mmol/L in the simvastatin group and 1.4 mmol/ L in patients taking ezetimibe plus simvastatin.”

What the sources say

• Not checked yetcites [63] Cannon, 2015, Ezetimibe added to statin therapy after acute coronary syndromes, N Engl J Med source

In the paper

“The efficacy at reducing LDL-C is in the range of 50e70%, independent of the presence of a background therapy (statins, ezetimibe, etc.); preliminary data from phase 3 trials suggest a reduction of CV events in line with the LDL-C reduction achieved.115,116”

What the sources say

• Not checked yetcites [115] Robinson, 2015, Efficacy and safety of alirocumab in reducing lipids and cardiovascular events, N Engl J Med source
• Not checked yetcites [116] Sabatine, 2015, Efficacy and safety of evolocumab in reducing lipids and cardiovascular events, N Engl J Med source

In the paper

“At a daily dose of 2 g it reduces TGs by 20e40% and LDL-C by 15e18% and increases HDL-C by 15e35%.257,277,278”

What the sources say

• Not checked yetcites [257] Canner, 1986, Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin, J Am Coll Cardiol source
• Not checked yetcites [277] Kamanna, 2008, Mechanism of action of niacin, Am J Cardiol source
• Not checked yetcites [278] Bruckert, 2010, Meta-analysis of the effect of nicotinic acid alone or in combination on cardiovascular events and atherosclerosis, Atherosclerosis source

In the paper

“Results from other meta-analyses suggest reduced major CVD events in patients with high TGs and low HDL-C in fibrate-treated patients, but no decrease in CVD or total mortality.270e272”

What the sources say

• Not checked yetcites 270e272

In the paper

“In some studies an increase of patient-reported neurocognitive effects was described.This finding requires further scrutiny.250”

What the sources say

• Not checked yetcites [250] Zhang, 2016, Comparative efficacy and safety of everolimus-eluting bioresorbable scaffold versus everolimus-eluting metallic stents: a systematic review and meta-analysis, Ann Intern Med source

In the paper

“Fibrates are generally well tolerated with mild adverse effects, gastrointestinal disturbances being reported in <5% of patients and skin rashes in 2%.273”

What the sources say

• Not checked yetcites [273] Davidson, 2007, Safety considerations with fibrate therapy, Am J Cardiol source

In the paper

“although a relative risk reduction is seen in the oldest subjects, the increased frequency of CAD means that the absolute number of cases associated with cholesterol is highest in this group.”

In the paper

“In the Heart Protection Study (HPS), 20 536 individuals were allocated to simvastatin or placebo.After 5 years the relative risk reduction was 18% for coronary death and 25% for coronary events.The reduction was similar in age groups <65, 65e70 and >70 years.333”

What the sources say

• Not checked yetcites [333] 2002, MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial, Lancet source

In the paper

“The Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) study included patients 70e82 years of age with CVD or at high risk for CVD.330 Patients were treated with pravastatin 40 mg daily or placebo.The relative risk reduction for a combined CAD endpoint was reduced by 15%, whereas no reduction was shown for stroke.”

What the sources say

• Not checked yetcites [330] Shepherd, 2002, Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial, Lancet source

In the paper

“Oestrogen replacement therapy, despite some favourable effects on the lipid profile, has not been demonstrated to reduce CV risk and cannot be recommended for CVD prevention in women.318”

What the sources say

• Not checked yetcites [318] Manson, 2003, Estrogen plus progestin and the risk of coronary heart disease, N Engl J Med source

In the paper

“Results from a meta-analysis on blood cholesterol and vascular mortality indicates that high TC is a significant risk factor for CAD mortality at all ages, but this association is attenuated in older adults”

What the sources say

• Not checked yetcites [321] Lewington, 2007, Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths, Lancet source
• Not checked yetcites [322] Prevention of coronary heart disease in clinical practice, 1998, Recommendations of the Second Joint Task Force of European and other societies on coronary prevention, Eur Heart J source

In the paper

“Diabetes itself is an independent risk factor for CVD and is associated with a higher risk of CVD, even more so in women.”

In the paper

“Data from recent meta-analyses indicate that people with MetS have a two-fold increase in CV outcomes and a 1.5fold increase in all-cause mortality.348”

What the sources say

• Not checked yetcites [348] Mottillo, 2010, The metabolic syndrome and cardiovascular risk a systematic review and meta-analysis, J Am Coll Cardiol source

In the paper

“Ezetimibe further reduced LDL-C and offered additional benefit (6.4% relative risk reduction in composite clinical endpoint) in association with simvastatin in post-ACS patients. 63”

What the sources say

• Not checked yetcites [63] Cannon, 2015, Ezetimibe added to statin therapy after acute coronary syndromes, N Engl J Med source

In the paper

“In the Studies Assessing Goals in the Elderly (SAGE) trial, 893 patients 65e83 years of age with stable CAD were recruited to treatment with atorvastatin 80 mg or pravastatin 40 mg.331 The atorvastatin group had a lower all-cause mortality (HR 0.33) and a non-significant trend towards reduction in major CAD events.”

What the sources say

• Not checked yetcites [331] Deedwania, 2007, Effects of intensive versus moderate lipid-lowering therapy on myocardial ischemia in older patients with coronary heart disease: results of the Study Assessing Goals in the Elderly (SAGE), Circulation source

In the paper

“The meta-analysis of Walsh and Pignone 314 reported a 26% reduction of CV mortality, a 29% reduction of MI and a 20% reduction of total CAD events in a cohort of 8272 females with previous CVD mainly treated with statins.”

What the sources say

• Not checked yetcites [314] Walsh, 2004, Drug treatment of hyperlipidemia in women, JAMA source

In the paper

“The rate of the composite endpoint of death from CV causes, MI or stroke was significantly lower, by 1.8 percentage points, in the combination group and the benefit of simvastatineezetimibe was consistent for women.63”

What the sources say

• Not checked yetcites [63] Cannon, 2015, Ezetimibe added to statin therapy after acute coronary syndromes, N Engl J Med source

In the paper

“a metaanalysis of fibrates in the prevention of CVD in 11 590 people with T2DM showed that fibrates significantly reduced the risk of non-fatal MI by 21%, but had no effect on the risk of overall mortality or coronary mortality.353”

What the sources say

• Not checked yetcites [353] Saha, 2010, 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

In the paper

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

In the paper

“Recent data indicate that diabetes per se increases CVD risk about two-fold on average, but the risk is subject to wide variation depending on the population.342”

What the sources say

• Not checked yetcites [342] Sattar, 2013, Revisiting the links between glycaemia, diabetes and cardiovascular disease, Diabetologia source

In the paper

“Type 1 diabetes is associated with high CVD risk, in particular in patients with microalbuminuria and renal disease.355”

What the sources say

• Not checked yetcites [355] Laing, 2003, Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes, Diabetologia source