The DOI matches its Crossref record; 82 of the 82 references it cites were found in a registry or an index; 7 of the 21 sources its claims cite were checked for support.
Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions: A Systematic Review and Meta-analysis
Open accessAbstract
IMPORTANCE: The comparative clinical benefit of nonstatin therapies that reduce low-density lipoprotein cholesterol (LDL-C) remains uncertain. OBJECTIVE: To evaluate the association between lowering LDL-C and relative cardiovascular risk reduction across different statin and nonstatin therapies. DATA SOURCES AND STUDY SELECTION: The MEDLINE and EMBASE databases were searched (1966-July 2016). The key inclusion criteria were that the study was a randomized clinical trial and the reported clinical outcomes included myocardial infarction (MI). Studies were excluded if the duration was less than 6 months or had fewer than 50 clinical events. Studies of 9 different types of LDL-C reduction approaches were included. DATA EXTRACTION AND SYNTHESIS: Two authors independently extracted and entered data into standardized data sheets and data were analyzed using meta-regression. MAIN OUTCOMES AND MEASURES: The relative risk (RR) of major vascular events (a composite of cardiovascular death, acute MI or other acute coronary syndrome, coronary revascularization, or stroke) associated with the absolute reduction in LDL-C level; 5-year rate of major coronary events (coronary death or MI) associated with achieved LDL-C level. RESULTS: A total of 312 175 participants (mean age, 62 years; 24% women; mean baseline LDL-C level of 3.16 mmol/L [122.3 mg/dL]) from 49 trials with 39 645 major vascular events were included. The RR for major vascular events per 1-mmol/L (38.7-mg/dL) reduction in LDL-C level was 0.77 (95% CI, 0.71-0.84; P < .001) for statins and 0.75 (95% CI, 0.66-0.86; P = .002) for established nonstatin interventions that work primarily via upregulation of LDL receptor expression (ie, diet, bile acid sequestrants, ileal bypass, and ezetimibe) (between-group difference, P = .72). For these 5 therapies combined, the RR was 0.77 (95% CI, 0.75-0.79, P < .001) for major vascular events per 1-mmol/L reduction in LDL-C level. For other interventions, the observed RRs vs the expected RRs based on the degree of LDL-C reduction in the trials were 0.94 (95% CI, 0.89-0.99) vs 0.91 (95% CI, 0.90-0.92) for niacin (P = .24); 0.88 (95% CI, 0.83-0.92) vs 0.94 (95% CI, 0.93-0.94) for fibrates (P = .02), which was lower than expected (ie, greater risk reduction); 1.01 (95% CI, 0.94-1.09) vs 0.90 (95% CI, 0.89-0.91) for cholesteryl ester transfer protein inhibitors (P = .002), which was higher than expected (ie, less risk reduction); and 0.49 (95% CI, 0.34-0.71) vs 0.61 (95% CI, 0.58-0.65) for proprotein convertase subtilisin/kexin type 9 inhibitors (P = .25). The achieved absolute LDL-C level was significantly associated with the absolute rate of major coronary events (11 301 events, including coronary death or MI) for primary prevention trials (1.5% lower event rate [95% CI, 0.5%-2.6%] per each 1-mmol/L lower LDL-C level; P = .008) and secondary prevention trials (4.6% lower event rate [95% CI, 2.9%-6.4%] per each 1-mmol/L lower LDL-C level; P < .001). CONCLUSIONS AND RELEVANCE: In this meta-regression analysis, the use of statin and nonstatin therapies that act via upregulation of LDL receptor expression to reduce LDL-C were associated with similar RRs of major vascular events per change in LDL-C. Lower achieved LDL-C levels were associated with lower rates of major coronary events.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
45 Own result · 16 Own method · 9 Own interpretation · 6 Sources not found · 5 Partly supported · 1 Supported · 1 Not checked yet · 1 No basis given · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“the clinical benefit of the previously recommended use of nonstatin therapies to lower LDL-C is less definitive.7”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > Abstract
What the sources say
- Supportedcites [7] 7. Hegele RA, Gidding SS, Ginsberg HN, et al. Nonstatin low-density lipoprotein-lowering therapy and cardiovascular risk reduction. Arterioscler Thromb Vasc Biol. 2015;35(11):2269-2280. source
The Conclusion says statins have the greatest body of randomized-trial evidence for cardiovascular risk reduction. The Abstract describes mixed results for nonstatin therapies and says larger, longer trials were needed for definitive proof of benefit from emerging PCSK9 inhibitors. This supports the comparative claim that the clinical benefit of nonstatin LDL-C-lowering therapies was less definitive, without implying that none had demonstrated benefit. (LLM, conf=0.86)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“These data suggest that drugs that ultimately reduce LDL-C level predominantly through upregulation of LDL receptor expression should, barring any off-target adverse effects, lead to clinical benefit in proportion to the degree of LDL-C reduction.64”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > 77 Full-text articles assessed for eligibility
What the sources say
- Partly supportedcites [64] 64. Cohen JC, Boerwinkle E, Mosley TH Jr, et al. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med. 2006;354(12):1264-1272. sourceExperimental — accuracy not yet measured
The Discussion reports that coronary-event reductions in clinical trials were directly related to the magnitude of LDL-C reduction, and the passage on statin treatment (p. 1272) says statins increase LDL-receptor gene expression. The paper does not establish that this relationship applies to drugs generally when they predominantly act through LDL-receptor upregulation, or assess the off-target-effects condition. (LLM, conf=0.82)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“These results are also supported by genetic association and Mendelian randomization studies demonstrating similarly lower rates of cardiovascular outcomes per unit lower LDL-C in patients with loss-of-function variants in the Niemann-Pick C1-Like1 protein (the target of ezetimibe) and in HMG-CoA reductase (the target of statins).62,63”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > 77 Full-text articles assessed for eligibility
What the sources say
- Partly supportedcites [62] 62. Ference BA, Majeed F, Penumetcha R, et al. Effect of naturally random allocation to lower low-density lipoprotein cholesterol on the risk of coronary heart disease mediated by polymorphisms in NPC1L1, HMGCR, or both. J Am Coll Cardiol. 2015;65(15):1552-1561. sourceExperimental — accuracy not yet measured
The Results (External Validation Analyses; page not available) report similar reductions in coronary heart disease risk per 10 mg/dl lower LDL-C mediated by NPC1L1 and HMGCR polymorphisms. But the Methods describe genetic scores based on selected polymorphisms, not loss-of-function variants in both genes. The Discussion mentions rare NPC1L1 loss-of-function mutations as a separate validation finding; it does not establish the claimed comparison for loss-of-function variants in both genes. (LLM, conf=0.88)
- Not matchedcites [63] 63. Grundy SM. Dyslipidaemia in 2015. Nat Rev Cardiol. 2016;13(2):74-75.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Specifically, each 1-mmol/L reduction in LDL-C was associated with an RR of 0.75 (95% CI, 0.66-0.86;P = .002)in major vascular events”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > Results
What the sources say
- Not checked — no full text of the sourcecites [49] 49. Dayton S, Pearce ML, Hashimoto S, et al. A controlled clinical trial of a diet high in unsaturated fat in preventing complications of atherosclerosis. Circulation. 1969;39-40(supp 2):1- 63. source
- Not checked — no full text of the sourcecites [50] 50. Dorr AE, Gundersen K, Schneider JC Jr, et al. Colestipol hydrochloride in hypercholesterolemic patients. J Chronic Dis. 1978;31(1):5-14. source
- Partly supportedcites [51] 51. Buchwald H, Varco RL, Matts JP, et al. Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia. N Engl J Med. 1990;323 (14):946-955. sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Major vascular event components (cardiovascular death, acute MI or other acute coronary syndrome, coronary revascularization, and stroke) have been shown to be reduced by therapies that lower LDL-C.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“This concept is further supported by human genetic analyses of variants that have been associated with low LDL-C, increased LDL receptors, and decreased coronary heart disease.58,62,63,65”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > 77 Full-text articles assessed for eligibility
What the sources say
- Not matchedcites [58] 58. Landray MJ, Haynes R, Hopewell JC, et al. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014;371(3):203- 212.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Partly supportedcites [62] 62. Ference BA, Majeed F, Penumetcha R, et al. Effect of naturally random allocation to lower low-density lipoprotein cholesterol on the risk of coronary heart disease mediated by polymorphisms in NPC1L1, HMGCR, or both. J Am Coll Cardiol. 2015;65(15):1552-1561. sourceExperimental — accuracy not yet measured
The Results (External Validation Analyses; page not provided) associate LDL-C-lowering polymorphisms with lower coronary heart disease risk and describe the hepatic LDL-C receptor as a common final pathway. The paper discusses receptor up-regulation by ezetimibe and statins, but does not establish that the studied variants themselves are associated with increased LDL receptors. (LLM, conf=0.84)
- Not matchedcites [63] 63. Grundy SM. Dyslipidaemia in 2015. Nat Rev Cardiol. 2016;13(2):74-75.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Could not verifycites [65] 65. Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk. Circulation. 2014;129(25)(suppl 2):S49-S73. sourceExperimental — accuracy not yet measured
Section 6.2, Critical Question 2 (page not supplied), discusses cumulative exposure to cardiovascular risk factors, but not genetic variants associated with low LDL-C, increased LDL receptors, and reduced coronary heart disease. Searches for those terms in our copy found no passage addressing the claimed genetic analyses. (LLM, conf=0.76)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The observed RR of major vascular events for each of the 5 different established interventions that ultimately act predominantly through upregulation of LDL receptor expression (ie, statins, diet, bile acid sequestrants, ileal bypass, and ezetimibe) was within 0.02 (ie, 2%) of the predicted value from the regression line”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > Results
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Major vascular event components (cardiovascular death, acute MI or other acute coronary syndrome, coronary revascularization, and stroke) have been shown to be reduced by therapies that lower LDL-C.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Combining the data from all 33 of the aforementioned trials generated the meta-regression line (predicted RR of major vascular events for various levels of LDL-C reduction) in Figure 3, in which each 1-mmol/L reduction in LDL-C was associated with an RR of 0.77 (95% CI, 0.75-0.79) in major vascular events.”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > Results
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Major vascular event components (cardiovascular death, acute MI or other acute coronary syndrome, coronary revascularization, and stroke) have been shown to be reduced by therapies that lower LDL-C.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For the 25 statin trials, each 1-mmol/L (38.7-mg/dL) reduction in LDL-C level was associated with an RR of 0.77 (95% CI, 0.71-0.84;P < .001)for major vascular events (Figure 2A).”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > Results
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Major vascular event components (cardiovascular death, acute MI or other acute coronary syndrome, coronary revascularization, and stroke) have been shown to be reduced by therapies that lower LDL-C.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“(P = .72for between-group difference with statin therapy)”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Major vascular event components (cardiovascular death, acute MI or other acute coronary syndrome, coronary revascularization, and stroke) have been shown to be reduced by therapies that lower LDL-C.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There were 15 trials of interventions that do not reduce LDL-C levels primarily through upregulation of LDL receptor expression (9 trials with fibrates, 3 trials with niacin [1 of which was a multigroup trial that also studied fibrates], and 3 trials with CETP inhibitors).”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Probably not a substantial claim. 16
- It may state two separate claims as one. 16
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“a timeframe during which a clinical benefit of lipid-lowering therapy would not be expected to emerge 10”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > Methods
What the sources say
- Partly supportedcites [10] 10. Bulbulia R, Bowman L, Wallendszus K, et al. Effects on 11-year mortality and morbidity of lowering LDL cholesterol with simvastatin for about 5 years in 20,536 high-risk individuals. Lancet. 2011;378(9808):2013-2020. sourceExperimental — accuracy not yet measured
The Results report no statistically significant reduction in major vascular events during the first year of simvastatin treatment, with significant reductions in subsequent years. The Discussion nevertheless notes fewer events in the first year. Neither passage establishes that clinical benefit would not be expected within six months, so the specific timeframe is unsupported. (LLM, conf=0.79)
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In terms of the other interventions, the observed RR of 0.94 (95% CI, 0.89-0.99)for major vascular events for niacin was greater (ie, less risk reduction) than the expected RR from meta-regression of 0.91 (95% CI, 0.90-0.92;P = .24),but with 95% CIs that encompass the regression line and z score testing showing no significant difference (P = .24).”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The observed RR of 0.88 (95% CI, 0.83-0.92)for fibrates was lower (ie, greater risk reduction) than the expected RR of 0.94 (95% CI, 0.93-0.94)(P = .02).”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“resulting in approximately 1.3 million person-years of follow-up.”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The mean follow-up was 4.3 years”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, the observed RR reduction in major vascular events was 4% (95% CI, -3% to 10%) in HPS2-Thrive, 11% (95% CI, 1% to 20%) in FIELD, and 8% (95% CI, -8% to 21%) in ACCORD, which were similar to the RR reductions predicted from the meta-regression (7%, 9%, and 0%, respectively).”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > 77 Full-text articles assessed for eligibility
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“0.88 (95% CI, 0.83-0.92)vs 0.94 (95% CI, 0.93-0.94)for fibrates (P = .02),which was lower than expected (ie, greater risk reduction)”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There were 2 trials with PCSK9 inhibitors.”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The absolute reduction in LDL-C accounted for 98% of the between-study variability (R 2 value) in the reduction of major vascular events, whereas the percentage reduction in LDL-C only accounted for 79%.”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > Results
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A total of 240 citations were identified and reviewed for eligibility (Figure 1)”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When recalculating the regression slope using non-HDL-C, the RR per 1-mmol/L reduction in non-HDL-C was 0.80 (95% CI, 0.77-0.82),which was similar to the RR with LDL-C reduction.”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In this systematic review and meta-regression analysis of 49 trials involving 9 different interventions to lower LDL-C that included more than 300 000 patients and approximately 40 000 major vascular events, there was a similar association”
- Also stated in: § 77 Full-text articles assessed for eligibility · plain
“between absolute reductions in LDL-C and lower RRs for major vascular events across therapies that ultimately work predominantly through upregulation of LDL receptor expression, such that each 1-mmol/L (38.7-mg/dL) reduction in LDL-C was associated with an RR of 0.77 (ie, 23% relative reduction) in the risk of major vascular events.”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > Discussion
plaincorrelationaln = 300,000- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The therapies classified as acting predominantly via upregulation of LDL receptor expression indeed act predominantly through that mechanism.
- Also stated in: § 77 Full-text articles assessed for eligibility · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There were 25 statin trials.”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The observed RR of 1.01 (95% CI, 0.94-1.09)associated with CETP inhibitors was significantly greater than the expected RR of 0.90 (95% CI, 0.89-0.91;P = .002)(ie, less risk reduction) with no appreciable clinical benefit in a meta-analysis of the compounds studied to date.”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“49 trials, spanning 9 different treatment modalities were included in the meta-regression analysis”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the RR reduction for major vascular events was 6.4% (95% CI, 1%-11%), with an absolute risk reduction of 2% over 7 years.”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > 77 Full-text articles assessed for eligibility
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The estimated RR of 0.49 (95% CI, 0.34-0.71)associated with PCSK9 inhibitors was numerically lower, but not significantly different, than the expected RR of 0.61 (95% CI, 0.58-0.65),with wide 95% CIs that included the regression line (P = .25).”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > Results
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“1.01 (95% CI, 0.94-1.09)vs 0.90 (95% CI, 0.89-0.91)for cholesteryl ester transfer protein inhibitors (P = .002),which was higher than expected (ie, less risk reduction)”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, the data in the present meta-regression analysis raise the possibility that other interventions, especially those that ultimately act predominantly through upregulation of LDL receptor expression, may provide additional options and may potentially be associated with the same relative clinical benefit per each 1-mmol/L reduction in LDL-C.”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > 77 Full-text articles assessed for eligibility
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The therapies classified as acting predominantly via upregulation of LDL receptor expression indeed act predominantly through that mechanism.
In the paper
“A systematic review and trial-level meta-regression analysis of randomized clinical trials that evaluated the effect of therapy to lower LDL-C on cardiovascular outcomes was performed and the results are reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines.9”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > Methods
What the sources say
- Not matchedcites [9] 9. Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses. Ann Intern Med. 2009;151(4):264-269, W64.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All disagreements were discussed and resolved by consensus.”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > Methods
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In the earlier trials that did not report LDL-C levels, LDL-C values at baseline and while in the study were estimated from total cholesterol levels (the Supplement provides additional details).”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > Methods
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Based purely on LDL-C lowering and given the number of events accrued, the statistical power for their primary end points was only approximately 51% for HPS2-Thrive, 19% for FIELD, and 3% for ACCORD.”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > 77 Full-text articles assessed for eligibility
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Two authors independently extracted and entered data into standardized data sheets and data were analyzed using meta-regression.”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“and background therapy has changed, which may account for some of the difference in absolute event rates between trials.”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > 77 Full-text articles assessed for eligibility
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Fourth, the studies included in the analysis were conducted over a span of 51 years”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > 77 Full-text articles assessed for eligibility
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Third, the data for statins are more extensive than the data for other interventions, with more than 20 000 events from statin trials vs several thousand events each for ezetimibe, niacin, fibrates, and CETP inhibitor trials; several hundred events each for diet, bile acid sequestrants, and ileal bypass trials; and only 2 trials with 111 events during a mean follow-up of 1.2 years for the PCSK9”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > 77 Full-text articles assessed for eligibility
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Sixth, hazard ratios were not available in all trials and risk ratios were used when they were not.”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > 77 Full-text articles assessed for eligibility
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“First, the meta-analysis was not performed on patient-level data.”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > 77 Full-text articles assessed for eligibility
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“by definition the analyses were at the trial level, examining the association between LDL-C reduction and the RR of major vascular events within a trial.”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > 77 Full-text articles assessed for eligibility
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
The paper relies on this without support.
The comparative clinical benefit of nonstatin therapies that reduce LDL-C remains uncertain.
“The comparative clinical benefit of nonstatin therapies that reduce low-density lipoprotein cholesterol (LDL-C) remains uncertain.”
The paper relies on this without support.
Major vascular event components (cardiovascular death, acute MI or other acute coronary syndrome, coronary revascularization, and stroke) have been shown to be reduced by therapies that lower LDL-C.
“because all these events have been shown to be reduced by therapies to lower LDL-C.”
The paper relies on this without support.
Fibrates substantially reduce levels of very low-density lipoprotein, an atherogenic particle that contains both cholesterol and triglycerides.
“Fibrates also substantially reduce levels of very low-density lipoprotein, an atherogenic particle that contains both cholesterol and triglycerides.”
The paper relies on this without support.
The therapies classified as acting predominantly via upregulation of LDL receptor expression indeed act predominantly through that mechanism.
“among the trials of statins and established nonstatin therapies that ultimately act predominantly via upregulation of LDL receptor expression”
The paper relies on this without support.
The absolute risk reduction observed in a given trial depends in part on the patient population, the end point, and the duration of follow-up.
“Second, the absolute risk reduction observed in a given trial will depend in part on the patient population, the end point, and the duration of follow-up”
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Numerous epidemiological studies, Mendelian randomization studies, and RCTs have consistently demonstrated a log-linear relationship between the absolute changes in plasma LDL-C and the risk of ASCVD [34,45-50].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [49]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Studies have shown that dyslipidemia, particularly elevated low-density lipoprotein cholesterol (LDL-C), is an independent risk factor for CHD (3–5).”
From Remnant cholesterol, lipid ratios, and the severity of coronary artery lesions: a retrospective cohort study in patients with coronary heart disease (2025) · cites this paper as [3]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The major limitation of this trial was a relatively short duration of follow-up as compared with that in other lipid-lowering trials, in which follow-up periods have averaged approximately 5 years.28”
From Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease (2017) · cites this paper as [28]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“elevated low-density lipoprotein cholesterol (LDL-C) maintains its position as the most significant risk factor associated with adverse cardiovascular results.”
From Inclisiran SiRNA therapy for durable LDL-C reduction: a systematic review and meta-analysis highlighting a breakthrough in long-term cardiovascular risk management (2026) · cites this paper as [3]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“LDLR plays a crucial role in the uptake of LDL-C from the circulation by hepatocytes 1,2,7 .”
From Dietary cholesterol activates a Ral-dependent pathway driving LDLR turnover (2026) · cites this paper as [7]
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The regulation of LDLR trafficking and turnover is essential for maintaining cholesterol homeostasis and remains a major focus of therapeutic strategies for CVD 1,2,7 .”
From Dietary cholesterol activates a Ral-dependent pathway driving LDLR turnover (2026) · cites this paper as [7]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Lipid-lowering therapy has transformed the landscape of cardiovascular disease (CVD) prevention, with low density lipoprotein cholesterol (LDL-C) firmly established as a central driver of atherosclerotic CVD (ASCVD) risk [1].”
From Targeting Triglycerides in Cardiovascular Disease Prevention: Evidence, Mechanisms, and Emerging Therapies (2026) · cites this paper as [1]
The cited source says what the claim attributes to it.
In the citing paper
“Like LDLC, non-HDLC is treatable with existing lipid-lowering agents and there is a direct, consistent relationship between the magnitude of non-HDLC lowering and cardiovascular risk reduction observed in meta-analyses and trials with statins and other lipid-lowering agents [56,57].”
From Quantifying atherogenic lipoproteins for lipid-lowering strategies: Consensus-based recommendations from EAS and EFLM (2020) · cites this paper as [57]
The cited source says what the claim attributes to it.
In the citing paper
“These observations are in accord with meta-analyses of data from clinical trials of different lipid-lowering interventions, which show consistent clinical benefits per unit reduction in LDL cholesterol.28”
From Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease (2017) · cites this paper as [28]
The cited source says what the claim attributes to it.
In the citing paper
“Therefore, if all ApoB-containing particles have approximately the same atherogenic effect as suggested by this study, then to reduce the risk of cardiovascular events by 20% as can be achieved by lowering LDL-C levels by 40 mg/dL, 3,4 triglyceride levels must be reduced by 5-fold this quantity, or approximately 200 mg/dL, to achieve the same corresponding reduction in ApoB-containing lipoproteins”
From Association of Triglyceride-Lowering LPL Variants and LDL-C–Lowering LDLR Variants With Risk of Coronary Heart Disease (2019) · cites this paper as [4]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Evidence suggests that atherosclerotic plaques are unlikely to further develop if LDL is at or below 70 mg/dL or 1.8 mmol/L [43].”
From The Effect of Exercise Training on Blood Lipids: A Systematic Review and Meta-analysis (2025) · cites this paper as [43]
Experimental — accuracy not yet measuredIn the citing paper
“In contrast, Mendelian randomization studies do not provide compelling evidence that HDL-C is causally associated with the risk of ASCVD [49,61,62].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [49]
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.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > 77 Full-text articles assessed for eligibility
“Ezetimibe was studied in the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) trial 53”
§ Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions A Systematic Review and Meta-analysis > References
“53. The Lipid Research Clinics Coronary Primary Prevention Trial results, 1: reduction in incidence of coronary heart disease.”
Citations
Cites
Conducting Meta-Analyses in R with the metafor Package
Viechtbauer, W. (2010) · Journal of Statistical Software · doi:10.18637/jss.v036.i03 · Cited by 20,464
OLSSON, A. G., McMurray, J. J. V., Thorgeirsson, G., Spaulding, C. M., Slattery, J., Pyörälà, K., Færgeman, O., Wright, R. S., Berg, K. M., Wilhelmsen, L., et al. (1994) · The Lancet · Cited by 8,467
Prevention of Coronary Heart Disease with Pravastatin in Men with Hypercholesterolemia
Shepherd, J., Cobbe, S. M., Ford, I., Isles, C. G., Lorimer, A. R., Macfarlane, P. W., McKillop, J. H., & Packard, C. J. (1995) · New England Journal of Medicine · doi:10.1056/nejm199511163332001 · Cited by 7,449
Sacks, F. M., Pfeffer, M. A., Moye, L. A., Rouleau, J. L., Rutherford, J. D., Cole, T. G., Brown, L., Warnica, J. W., Arnold, J. M. O., Wun, C.-C., et al. (1996) · New England Journal of Medicine · doi:10.1056/nejm199610033351401 · Cited by 7,439
Stone, N. J., Robinson, J. G., Lichtenstein, A. H., Bairey Merz, C. N., Blum, C. B., Eckel, R. H., Goldberg, A. C., Gordon, D., Levy, D., Lloyd-Jones, D. M., et al. (2014) · Circulation · doi:10.1161/01.cir.0000437738.63853.7a · Cited by 7,081
Grundy, S. M., Cleeman, J. I., Merz, C. N. B., Brewer, H. B., Clark, L. T., Hunninghake, D. B., Pasternak, R. C., Smith, S. C., & Stone, N. J. (2004) · Circulation · doi:10.1161/01.cir.0000133317.49796.0e · Cited by 6,902
Self-citationRosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein
Ridker, P. M., Danielson, E., Fonseca, F. A. H., Genest, J., Gotto, A. M., Kastelein, J. J. P., Koenig, W., Libby, P., Lorenzatti, A. J., MacFadyen, J. G., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0807646 · Cited by 6,674
Cholesterol Treatment Trialists' (CTT) Collaboration (2010) · The Lancet · doi:10.1016/s0140-6736(10)61350-5 · Cited by 6,550
Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project
Conroy, R. (2003) · European Heart Journal · doi:10.1016/s0195-668x(03)00114-3 · Cited by 5,290
(1998) · New England Journal of Medicine · doi:10.1056/nejm199811053391902 · Cited by 5,261
Research works printed but not linked: 13
- [7]7. Hegele RA, Gidding SS, Ginsberg HN, et al. Nonstatin low-density lipoprotein-lowering therapy and cardiovascular risk reduction. Arterioscler Thromb Vasc Biol. 2015;35(11):2269-2280.
- [8]8. US Food and Drug Administration. Withdrawal of approval of indications related to the coadministration with statins in applications for niacin extended-release tablets and fenofibric acid delayed-release capsules. Fed Regist. 2016;81(74): 22612-22613.
- [22]22. GISSI Prevenzione Investigators. Results of the low-dose (20 mg) pravastatin GISSI Prevenzione trial in 4271 patients with recent myocardial infarction. Ital Heart J. 2000;1(12):810-820.
- [25]25. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease. Lancet. 1994;344(8934):1383-1389.
- [33]33. Shepherd J, Blauw GJ, Murphy MB, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER). Lancet. 2002;360(9346): 1623-1630.
- [34]34. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care. JAMA. 2002;288(23):2998-3007.
- [37]37. Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS). Lancet. 2004;364(9435):685-696.
- [41]41. Pedersen TR, Faergeman O, Kastelein JJ, et al. High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction. JAMA. 2005;294(19):2437-2445.
- [44]44. Nakamura H, Arakawa K, Itakura H, et al. Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study). Lancet. 2006; 368(9542):1155-1163.
- [46]46. Armitage J, Bowman L, Wallendszus K, et al. Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction. Lancet. 2010;376(9753): 1658-1669.
- [50]50. Dorr AE, Gundersen K, Schneider JC Jr, et al. Colestipol hydrochloride in hypercholesterolemic patients. J Chronic Dis. 1978;31(1):5-14.
- [53]53. The Lipid Research Clinics Coronary Primary Prevention Trial results, 1: reduction in incidence of coronary heart disease. JAMA. 1984;251(3):351-364.
- [63]63. Grundy SM. Dyslipidaemia in 2015. Nat Rev Cardiol. 2016;13(2):74-75.
Cited by
Sorted by citations
Items 101–200 of 1,481
Kumar, S. U., Kumar, D. T., Bithia, R., Sankar, S., Magesh, R., Sidenna, M., Doss, C. G. P., & Zayed, H. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.00734 · Cited by 114
Treat-to-Target or High-Intensity Statin in Patients With Coronary Artery Disease
Hong, S., Lee, Y., Lee, S., Hong, B., Kang, W. C., Lee, J., Lee, J., Yang, T., Yoon, J., Ahn, C., et al. (2023) · JAMA · doi:10.1001/jama.2023.2487 · Cited by 122
Byrne, P., Demasi, M., Jones, M., Smith, S. M., O’Brien, K. K., & DuBroff, R. (2022) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2022.0134 · Cited by 114
The role of nutraceuticals in the prevention of cardiovascular disease
Sosnowska, B., Penson, P. E., & Banach, M. (2017) · Cardiovascular Diagnosis and Therapy · doi:10.21037/cdt.2017.03.20 · Cited by 117
“In particular, low LDL-C levels are associated with lower rates of major coronary events (20).”
BackgroundGlycogen Synthase Kinase-3α Promotes Fatty Acid Uptake and Lipotoxic Cardiomyopathy
Nakamura, M., Liu, T., Husain, S., Zhai, P., Warren, J. S., Hsu, C., Matsuda, T., Phiel, C. J., Cox, J. E., Tian, B., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.01.005 · Cited by 115
“Although a recent meta analysis showed that fibrates have an additive cardioprotective effect upon statin therapy in humans (Silverman et al., 2016), the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial had previously showed little or no effect of combination therapy with fenofibrate and simvastatin co…”
BackgroundCardiometabolic risk factors in vegans; A meta-analysis of observational studies
Benatar, J. R., & Stewart, R. (2018) · PLoS ONE · doi:10.1371/journal.pone.0209086 · Cited by 121
The Role of Lipids and Lipoproteins in Atherosclerosis
Linton, M. F., Yancey, P. G., Davies, S. S., Jerome, W. G., Linton, E. F., Song, W., Doran, A. C., & Vickers, K. C. (2015) · Europe PMC (PubMed Central) · Cited by 108
2023 China Guidelines for Lipid Management
Li, J., Zhao, S., Zhao, D., Lü, G., Peng, D., Liu, J., Chen, Z., Guo, Y., Wu, N., Yan, S.-K., et al. (2023) · 老年心脏病学杂志：英文版 · doi:10.26599/1671-5411.2023.09.008 · Cited by 120
Robinson, J. G., Williams, K. J., Gidding, S. S., Borén, J., Tabas, I. A., Fisher, E. A. A., Packard, C. J., Pencina, M. J., Fayad, Z. A., Mani, V., et al. (2018) · Journal of the American Heart Association · doi:10.1161/jaha.118.009778 · Cited by 109
“Indeed, progressively greater magnitudes of reduction in the relative risk of cardiovascular disease correlate with progressively larger absolute reductions in LDL-C, non-HDL-C, and apoB lipoprotein levels.(74,76) Non-HDL-C differs from LDL-C in that non-HDL cholesterol encompasses VLDL and remnant lipoprotein cholest…”
BackgroundMichael, D. R., Jack, A. A., Masetti, G., Davies, T. S., Loxley, K. E., Kerry-Smith, J., Plummer, J. F., Marchesi, J. R., Mullish, B. H., McDonald, J. A. K., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-60991-7 · Cited by 106
A gut-derived hormone regulates cholesterol metabolism
Hu, X., Chen, F., Jia, L., 隆爱军, Peng, Y. C., Li, X., Huang, J., Wei, X., Fang, X., Gao, Z., et al. (2024) · Cell · doi:10.1016/j.cell.2024.02.024 · Cited by 109
Chinese Guideline on the Primary Prevention of Cardiovascular Diseases
Chinese Society of Cardiology of Chinese Medical Association, C. D. P. A. R. C. O. C. A. O. R. M. (2021) · Cardiology Discovery · doi:10.1097/cd9.0000000000000025 · Cited by 109
Mineral oil: safety and use as placebo in REDUCE-IT and other clinical studies
Olshansky, B., Chung, M. K., Budoff, M. J., Philip, S., Jiao, L., Doyle, Jr., Copland, C., Giaquinto, A., Juliano, R. A., & Bhatt, D. L. (2020) · European Heart Journal Supplements · doi:10.1093/eurheartj/suaa117 · Cited by 103
Burgess, S. (2018) · Apollo (University of Cambridge) · doi:10.17863/cam.26250 · Cited by 118
Cardiovascular Risk and Statin Therapy Considerations in Women
Gheorghe, G., Toth, P. P., BUNGAU, S. G., Behl, T., Ilie, M., Stoian, A. P., Bratu, O. G., Bacalbaşa, N., Rus, M., & Diaconu, C. C. (2020) · Diagnostics · doi:10.3390/diagnostics10070483 · Cited by 106
“Meta-analyses confirmed that atherosclerotic CVD reduction is dose dependent with LDL-C-lowering agents, and the higher the LDL-C reduction, the greater the CV risk reduction [32].”
BackgroundThe Effect of Exercise Training on Blood Lipids: A Systematic Review and Meta-analysis
Smart, N. A., Downes, D., van der Touw, T., Hada, S., Dieberg, G., Pearson, M. J., Wolden, M., King, N., & Goodman, S. P. J. (2025) · Sports Medicine · doi:10.1007/s40279-024-02115-z · Cited by 126
Integrated Guidance for Enhancing the Care of Familial Hypercholesterolaemia in Australia
Watts, G. F., SULLIVAN, D. R., Hare, D. L., Kostner, K., Horton, A., Bell, D. A., Brett, T., Trent, R. J., Poplawski, N. K., Martin, A. C., et al. (2020) · Heart Lung and Circulation · doi:10.1016/j.hlc.2020.09.943 · Cited by 103
“…c guidelines on FH [11,14 – 19], our recommendations have also been based on new international guidelines for the primary and secondary prevention of ASCVD [49 – 52], as well as on meta-analyses and systematic reviews on the role of LDL-cholesterol in the inception and development of ASCVD [2,53].”
Cardiometabolic Comorbidities in Cancer Survivors
Zullig, L. L., Sung, A. D., Khouri, M. G., Jazowski, S. A., Shah, N. P., Sitlinger, A. P., Blalock, D. V., Whitney, C. A., Kikuchi, R., Bosworth, H. B., et al. (2022) · JACC CardioOncology · doi:10.1016/j.jaccao.2022.03.005 · Cited by 105
Amrock, S. M., Duell, P. B., Knickelbine, T., Martin, S. S., O'Brien, E. C., Watson, K. E., Mitri, J., Kindt, I., Shrader, P., Baum, S. J., et al. (2017) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2017.10.006 · Cited by 99
Gender-Related Factors in Medication Adherence for Metabolic and Cardiovascular Health
Venditti, V., Bleve, E., Morano, S., & Filardi, T. (2023) · Metabolites · doi:10.3390/metabo13101087 · Cited by 118
“Strong evidence from epidemiological studies and randomized controlled trials (RCTs) supports a logarithmic relationship between LDL-c variations and CVD risk [73–75].”
BackgroundAssessment of the Role of Niacin in Managing Cardiovascular Disease Outcomes
D’Andrea, E., Hey, S. P., Ramirez, C. L., & Kesselheim, A. S. (2019) · JAMA Network Open · doi:10.1001/jamanetworkopen.2019.2224 · Cited by 99
Steed, L., Sohanpal, R., Todd, A., Madurasinghe, V., Rivas, C. A., Edwards, E. A., Summerbell, C. D., Taylor, S. J., & Walton, R. T. (2019) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd011207.pub2 · Cited by 96
A new dawn for managing dyslipidemias: The era of rna-based therapies
Macchi, C., Sirtori, C. R., Corsini, A., Santos, R. D., Watts, G. F., & Ruscica, M. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.104413 · Cited by 95
“The relative risk reduction of major vascular events was similar for all drug classes (statins, bile acid sequestrants, ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and fibrates), and the achieved lowering of LDL-C was directly associated with a reduced incidence of major ASCVD events (7…”
BackgroundCognition After Lowering LDL-Cholesterol With Evolocumab
Gencer, B., Mach, F., Guo, J., Im, K., Ruzza, A., Wang, H., Kurtz, C. E., Pedersen, T. R., KEECH, A. C., Ott, B. R., et al. (2020) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2020.03.039 · Cited by 94
Self-citationPhysiological and therapeutic regulation of PCSK9 activity in cardiovascular disease
Glerup, S., Schulz, R., Laufs, U., & Schlüter, K. (2017) · Basic Research in Cardiology · doi:10.1007/s00395-017-0619-0 · Cited by 95
D’Onofrio, N., Prattichizzo, F., Marfella, R., Sardu, C., Martino, E., Scisciola, L., Marfella, L., Grotta, R. L., Frigé, C., Paolisso, G., et al. (2023) · Theranostics · doi:10.7150/thno.80289 · Cited by 93
“These data further sustain the argument that PCSK9i might provide CV benefit also beyond LDL-cholesterol lowering, providing an additional rationale for its use in patients with high cardiovascular risk independently of their LDL-cholesterol levels [2,47,48].”
Toth, P. P., Worthy, G., Gandra, S. R., Sattar, N. A., Bray, S. L., Cheng, L., Bridges, I. M., Worth, G. M., Dent, R. E., Forbes, C. A., et al. (2017) · Journal of the American Heart Association · doi:10.1161/jaha.116.005367 · Cited by 93
Goldstein, L. B., Toth, P. P., Dearborn, J. L., Giugliano, R. P., Hirsh, B. J., Peña, J. M., Selim, M. H., & Woo, D. (2023) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atv.0000000000000164 · Cited by 99
Self-citationZarić, B. L., Radovanović, J., Gluvic, Z. M., Stewart, A. J., Essack, M., Motwalli, O., Gojobori, T., & Isenović, E. R. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.551758 · Cited by 94
Rubino, J., MacDougall, D. E., Sterling, L. R., Hanselman, J. C., & Nicholls, S. J. (2020) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2020.12.023 · Cited by 96
Role of diet and exercise in aging, Alzheimer’s disease, and other chronic diseases
Khemka, S., Reddy, A., Garcia, R. I., Jacobs, M., Reddy, R. P., Roghani, A. K., Pattoor, V., Basu, T., Sehar, U., & Reddy, P. H. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102091 · Cited by 88
Genetic Predisposition Impacts Clinical Changes in a Lifestyle Coaching Program
Zubair, N., Conomos, M. P., Hood, L., Omenn, G. S., Price, N. D., Spring, B. J., Magis, A. T., & Lovejoy, J. C. (2019) · Scientific Reports · doi:10.1038/s41598-019-43058-0 · Cited by 85
Lipid Lowering Therapy: An Era Beyond Statins
Abdul‐Rahman, T., Bukhari, S. M. A., Cantu‐Herrera, E., Awuah, W. A., Lawrence, J. A., de Andrade, H., Patel, N., Shah, R. M., Shaikh, R., Capriles, C. A. A., et al. (2022) · Current Problems in Cardiology · doi:10.1016/j.cpcardiol.2022.101342 · Cited by 94
Genetics, Dyslipidemia, and Cardiovascular Disease: New Insights
Stein, R., Ferrari, F., & Scolari, F. (2019) · Current Cardiology Reports · doi:10.1007/s11886-019-1161-5 · Cited by 83
Kent, S. T., Rosenson, R. S., Avery, C. L., Chen, Y.-D. I., Correa, A., Cummings, S. R., Cupples, L. A., Cushman, M., Evans, D. S., Gudnason, V., et al. (2017) · Circulation: Cardiovascular Genetics · doi:10.1161/circgenetics.116.001632 · Cited by 86
“Previous meta-analyses of ezetimibe and other nonstatin LDL-C–lowering medication trials have also found greater LDL-C lowering to be associated with larger CHD risk reduction.(17,18) The association between PCSK9 LOF variants and stroke has not been extensively studied.”
InfluentialPCSK9 Inhibitors: Mechanisms of Action, Metabolic Effects, and Clinical Outcomes
Hess, C. N., Wang, C. C. L., & Hiatt, W. R. (2017) · Annual Review of Medicine · doi:10.1146/annurev-med-042716-091351 · Cited by 87
Rong, S., Li, B., Chen, L., Sun, Y., Du, Y., Liu, B., Robinson, J. G., & Bao, W. (2022) · Journal of the American Heart Association · doi:10.1161/jaha.121.023690 · Cited by 88
Low-Density Lipoprotein Cholesterol, Cardiovascular Disease Risk, and Mortality in China
Chen, L., Chen, S., Bai, X., Su, M., He, L., Li, G., He, G., Yang, Y., Zhang, X., Cui, J., et al. (2024) · JAMA Network Open · doi:10.1001/jamanetworkopen.2024.22558 · Cited by 83
Paciullo, F., Momi, S., & Gresele, P. (2019) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1676863 · Cited by 83
Ghavami, A., Ziaei, R., Talebi, S., Barghchi, H., Nattagh-Eshtivani, E., Moradi, S., Rahbarinejad, P., Mohammadi, H., Ghasemi-Tehrani, H., Marx, W., et al. (2023) · Advances in Nutrition · doi:10.1016/j.advnut.2023.01.005 · Cited by 86
Lotta, L. A., Stewart, I. D., Sharp, S. J., Day, F. R., Burgess, S., Luan, J., Bowker, N., Cai, L., Li, C., Wittemans, L. B. L., et al. (2018) · JAMA Cardiology · doi:10.1001/jamacardio.2018.2866 · Cited by 72
“This result suggeststhatANGPTL3inhibitionmaybeanexceptiontotheLDL paradigm, themechanism-independent log-linear relationship between LDL-C lowering and coronary disease protection that has been consistently found in genetic studies and clinical trials.(42,46) Inphase 1 trials,ANGPTL3 inhibitors reducedLDL-C levelsbyam…”
BackgroundResultUnderberg, J. A., Toth, P. P., & Rodríguez, F. (2022) · Postgraduate Medicine · doi:10.1080/00325481.2022.2117498 · Cited by 81
“Larger reductions in LDL-C produce larger reductions in CV risk [23].”
BackgroundPetersen, K. S., Maki, K. C., Calder, P. C., Belury, M. A., Messina, M. J., Kirkpatrick, C. F., & Harris, W. S. (2024) · British Journal Of Nutrition · doi:10.1017/s0007114524002459 · Cited by 85
“Specifically, per 1 mmol/l (39 mg/dl) decrease in LDL-cholesterol, the RR of a major vascular event was reduced by 23 % (RR 0 · 77; 95 % CI 0 · 75, 0 · 79) (76) .”
Small molecules as inhibitors of PCSK9: Current status and future challenges
Xu, S., Luo, S., Zhu, Z., & Xu, J. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.11.011 · Cited by 85
“[1] Hypercholesterolemia has long been considered as an independent risk factor for CVD, and lowering low-density lipoprotein cholesterol (LDL-C) has been shown to reduce cardiovascular risk in clinical trials.[2] Several agents have been widely applied for reducing LDL-C levels in the treatment of hypercholesterolemi…”
BackgroundMehta, S. R., Paré, G., Lonn, E., Jolly, S. S., Natarajan, M. K., Pinilla‐Echeverri, N., Schwalm, J.-D., Sheth, T., Sibbald, M., Tsang, M., et al. (2022) · EuroIntervention · doi:10.4244/eij-d-22-00735 · Cited by 79
Zoungas, S., Curtis, A. J., Spark, S., Wolfe, R. S., McNeil, J. J., Beilin, L. J., Chong, T. T. ‐., CLOUD, G. C., Hopper, I., Kost, A., et al. (2023) · BMJ Open · doi:10.1136/bmjopen-2022-069915 · Cited by 80
Statins for Primary Prevention of Cardiovascular Disease
Kazi, D. S., Penko, J. M., & Bibbins-Domingo, K. B. (2017) · Medical Clinics of North America · doi:10.1016/j.mcna.2017.03.001 · Cited by 76
Luo, M., Lim, W. Y., Tan, C. S., Ning, Y., Chia, K. S., van Dam, R. M., Tang, W. E., Tan, N. C., Chen, R., Tai, E. S., et al. (2017) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2017.08.013 · Cited by 74
Triglyceride and Triglyceride-Rich Lipoproteins in Atherosclerosis
Zhang, B., Yin, F., Qiao, Y.-N., & Guo, S. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.909151 · Cited by 83
“The first line lipid-lowering drug, statins, can significantly reduce LDL-C levels, leading to a reduction in CVD events by 25%–40% (Michos et al., 2012; Silverman et al., 2016; Toth et al., 2019a).”
BackgroundLamprea-Montealegre, J. A., Staplin, N., Herrington, W. G., Haynes, R., Emberson, J., Baigent, C., de Boer, I. H., & on behalf of the SHARP Collaborative Group (2019) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.07320619 · Cited by 75
Masana, L., Girona, J., Ibarretxe, D., Rodríguez‐Calvo, R., Rosales, R., Vallvé, J.-C., Rodríguez-Borjabad, C., Guardiola, M., Rodríguez, M. M., Guaita‐Esteruelas, S., et al. (2018) · Journal of clinical lipidology · doi:10.1016/j.jacl.2017.12.018 · Cited by 71
“Indeed, current evidence shows that cardiovascular benefit is dependent on the absolute magnitude of LDL-C reduction regardless of the LDL-lowering therapy, provided that it increases LDLR activity.(9,10) What, then, is the evidence that these VLDL-C levels are safe?”
BackgroundLiu, C., Shen, Y., Tu, Q., Zhao, Y., Guo, H., Wang, J., Zhang, L., Shi, H., & Sun, Y. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.02.131 · Cited by 73
Zhang, X., Centurion, F., Misra, A., Patel, S., & Gu, Z. (2023) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2023.114709 · Cited by 76
Khan, S. U., Rahman, H., Okunrintemi, V., Riaz, H., Khan, M. S., Sattur, S., Kaluski, E., Lincoff, A. M., Martin, S. S., & Blaha, M. J. (2019) · Journal of the American Heart Association · doi:10.1161/jaha.118.011581 · Cited by 70
Khan, S. U., Khan, M. U., Valavoor, S., Khan, M. S., Okunrintemi, V., Mamas, M. A., Leucker, T. M., Blaha, M. J., & Michos, E. D. (2020) · European Journal of Preventive Cardiology · doi:10.1177/2047487319871733 · Cited by 67
Messina, M. J., Shearer, G. C., & Petersen, K. S. (2021) · Nutrition · doi:10.1016/j.nut.2021.111343 · Cited by 75
Plant Sterols and Plant Stanols in Cholesterol Management and Cardiovascular Prevention
Barkas, F., Bathrellou, E., Nomikos, T., Panagiotakos, D. B., Liberopoulos, E. N., & Kontogianni, M. D. (2023) · Nutrients · doi:10.3390/nu15132845 · Cited by 77
“Indeed, a few meta-analyses have confirmed that any LDL-C lowering intervention, either dietary or pharmaceutical, effectively reduces CVD risk [3].”
BackgroundGlycaemic Control and Vascular Complications in Diabetes Mellitus Type 2
Maranta, F., Cianfanelli, L., & Cianflone, D. (2020) · Advances in experimental medicine and biology · doi:10.1007/5584_2020_514 · Cited by 74
Langlois, M. R., & Sniderman, A. D. (2020) · Current Cardiology Reports · doi:10.1007/s11886-020-01323-z · Cited by 69
How low is safe? The frontier of very low (<30 mg/dL) LDL cholesterol
Karagiannis, A. D., Mehta, A., Dhindsa, D. S., Virani, S. S., Orringer, C. E., Blumenthal, R. S., Stone, N. J., & Sperling, L. S. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehaa1080 · Cited by 70
“a log linear correlation has been found between LDL-C and CAD risk.(2) Randomized controlled trials (RCTs) unequivocally show that”
BackgroundTuñón, J., Bäck, M., Badimón, L., Bochaton‐Piallat, M., Cariou, B., Daemen, M. J. A. P., Egido, J., Evans, P. C., Francis, S., Ketelhuth, D. F. J., et al. (2018) · European Journal of Preventive Cardiology · doi:10.1177/2047487318773384 · Cited by 70
Khan, S. U., Talluri, S., Riaz, H., Rahman, H., Nasir, F., Bin Riaz, I., Sattur, S., Ahmed, H., Kaluski, E., & Krasuski, R. (2018) · European Journal of Preventive Cardiology · doi:10.1177/2047487318766612 · Cited by 61
“Email: safinmc@gmail.com 1mmol/L reduction in LDL-C.2 The addition of ezetimibe to statin therapy can result in additional LDL-C reduction accompanied by exponential cardiovascular risk reduction.3 Similarly, PCSK9 inhibitors have shown to generate incremental reductions in LDL-C compared with ezetimibe or placebo.4,5…”
BackgroundMethodInfluentialPouwer, M. G., Pieterman, E. J., Worms, N., Keijzer, N., Jukema, J. W., Gromada, J., Gusarova, V., & Princen, H. M. G. (2020) · Journal of Lipid Research · doi:10.1194/jlr.ra119000419 · Cited by 66
“LDL-C is associated with a 23% CVD risk reduction (3).”
BackgroundMitchell, R. E., Hartley, A. E., Walker, V. M., Gkatzionis, A., Yarmolinsky, J., Bell, J. A., Chong, A., Paternoster, L., Tilling, K. M., & Smith, G. D. (2023) · PLoS Genetics · doi:10.1371/journal.pgen.1010596 · Cited by 73
“For example, these assumptions would not be met in cardiovascular disease; given that lowering LDL cholesterol reduces risk of major vascular events in both primary and secondary prevention trials [39], and thus for SNPs influencing LDL cholesterol, there will be a very strong positive correlation between their associ…”
BackgroundTang, Y., Shah, H., Bueno Junior, C. R., Sun, X., Mitri, J., Sambataro, M., Sambado, L., Gerstein, H. C., Fonseca, V., Doria, A., et al. (2021) · Diabetes Care · doi:10.2337/dc20-1842 · Cited by 60
Giugliano, R. P., Mach, F., Zavitz, K. H., Kurtz, C. E., Schneider, J., Wang, H., KEECH, A. C., Pedersen, T. R., Sabatine, M. S., Sever, P. S., et al. (2017) · Clinical Cardiology · doi:10.1002/clc.22678 · Cited by 64
Self-citationMinno, A. D., Lupoli, R., Calcaterra, I. L., Poggio, P., Forte, F., Spadarella, G., Ambrosino, P., Iannuzzo, G., & Minno, M. N. D. D. (2020) · Journal of the American Heart Association · doi:10.1161/jaha.119.016262 · Cited by 68
Lipid Management in Patients Presenting With Acute Coronary Syndromes: A Review
Claessen, B. E. P. M., Guedeney, P., Gibson, C. M., Angiolillo, D. J., Cao, D., Lepor, N. E., & Mehran, R. (2020) · Journal of the American Heart Association · doi:10.1161/jaha.120.018897 · Cited by 67
González‐Sarrías, A., Combet, E., Pinto, P., Mena, P. R., Dall’Asta, M., Garcia‐Aloy, M., Rodriguez‐Mateos, A., Gibney, E. R., Dumont, J., Massaro, M., et al. (2017) · Nutrients · doi:10.3390/nu9070746 · Cited by 64
“These results are very relevant considering that the reduction of LDL-cholesterol by 1 mmol/L has been associated with a 23% reduction of CVDs risk [168] and reinforce the interest in understanding the influence of different factors on the regulatory efficiency of plant bioactive compounds, in general, and of flavanol…”
BackgroundDiet, exercise and weight loss and dyslipidaemia
Clifton, P. M. (2018) · Pathology · doi:10.1016/j.pathol.2018.10.013 · Cited by 66
Riaz, H., Khan, S. U., Rahman, H., Shah, N. P., Kaluski, E., Lincoff, A. M., & Nissen, S. E. (2019) · European Journal of Preventive Cardiology · doi:10.1177/2047487318816495 · Cited by 61
Gerl, M. J., Vaz, W. L. C., Domingues, N. S., Klose, C. D., Surma, M. A., Sampaio, J. L., Almeida, M. S., Rodrigues, G., Gonçalves, P. D. A., Ferreira, J., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-33116-4 · Cited by 66
Barkas, F., Nomikos, T., Liberopoulos, E. N., & Panagiotakos, D. B. (2020) · Nutrients · doi:10.3390/nu12082436 · Cited by 66
Richardson, T. G., Wang, Q., Sanderson, E. C. M., Mahajan, A., McCarthy, M. I., Frayling, T. M., Ala‐Korpela, M., Sniderman, A. D., Smith, G. D., & Holmes, M. V. (2021) · The Lancet Healthy Longevity · doi:10.1016/s2666-7568(21)00086-6 · Cited by 61
Sarraju, A., Brennan, D. M., Hayden, K., Stronczek, A., Goldberg, A. C., Michos, E. D., McGuire, D. K., Mason, D., Tercek, G., Nicholls, S. J., et al. (2025) · The Lancet · doi:10.1016/s0140-6736(25)00721-4 · Cited by 64
Björnsson, E., Þorleifsson, G., Helgadóttir, A., Guðnason, Þ., Guðbjartsson, T., Andersen, K. K., Grétarsdóttir, S., Ólafsson, Í., Tragante, V., Ólafsson, Ó., et al. (2019) · JAMA Cardiology · doi:10.1001/jamacardio.2019.2946 · Cited by 59
The Impact of Coronary Artery Disease and Statins on Survival After Liver Transplantation
Patel, S. S., Rodríguez, V., Siddiqui, M. B., Faridnia, M., Lin, F., Chandrakumaran, A., Laurenzano, J., Clinton, J. W., Kowlgi, G. N., Kirkman, D. L., et al. (2019) · Liver Transplantation · doi:10.1002/lt.25613 · Cited by 59
“(9,10) Dyslipidemia is a strong, independent, and, more importantly, modifiable risk factor for CAD and CVD-associated mortality.(29,30) In the present study, we defined a time-dependent increase in the prevalence of dyslipidemia in LTR that varied with the etiology of end-stage liver disease requiring LT.”
BackgroundKang, S., Eum, S., Chang, Y., Koyanagi, A., Jacob, L., Smith, L., Shin, J. I., Song, T., & Song, T. (2022) · BMJ Open · doi:10.1136/bmjopen-2021-059548 · Cited by 60
Beyond statins: New pharmacological targets to decrease LDL-cholesterol and cardiovascular events
Raschi, E., Casula, M., Cicero, A. F. G., Corsini, A., Borghi, C., & Catapano, A. L. (2023) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2023.108507 · Cited by 67
Lee, H., Park, J.-B., Hwang, I.-C., Yoon, Y. E., Park, H. E., Choi, S.-Y., Kim, Y.-J., Cho, G.-Y., Han, K., & Kim, H.-K. (2020) · European Journal of Preventive Cardiology · doi:10.1177/2047487319898571 · Cited by 56
Cornelis, M. C., & van Dam, R. M. (2020) · Journal of Nutrition · doi:10.1093/jn/nxaa212 · Cited by 58
“%) higher LDL-cholesterol concentration, which could be associated with a 5% higher risk of major CVDs (28).”
BackgroundAdvancements in risk stratification and management strategies in primary cardiovascular prevention
Barkas, F., Şener, Y. Z., Golforoush, P. A., Kheirkhah, A., Rodríguez‐Sánchez, E., Novák, J., Apellániz-Ruiz, M., Akyea, R. K., Bianconi, V., Ceasovschih, A., et al. (2024) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2024.117579 · Cited by 61
Schubert, J. R., Leósdóttir, M., Lindahl, B., Westerbergh, J., Melhus, H., Modica, A., Cater, N. B., Brinck, J. W., Ray, K. K., & Hagström, E. (2024) · European Heart Journal · doi:10.1093/eurheartj/ehae576 · Cited by 67
“…associated with 20% reduction in relative risk for major vascular events, similar to the relative risk reductions with LDL-C reduction of 1 mmol/L. 34 This finding suggests that non–HDL-C is a reasonable alternative to LDL-C to assess response to lipid-lowering treatment and provide useful…”
Hypercholesterolaemia – practical information for non-specialists
Soran, H., Adam, S., Mohamad, J. B., Ho, J. H., Schofield, J. D., Kwok, S., Siahmansur, T. J., Liu, Y., Syed, A. A., Dhage, S. S., et al. (2018) · Archives of Medical Science · doi:10.5114/aoms.2018.72238 · Cited by 59
“The risk reduction for every 1 mmol/l absolute reduction in LDL-C was 24% which is consistent with previous meta-analyses [21, 74, 82, 83].”
ResultFlint, A. C., Conell, C., Ren, X., Kamel, H., Chan, S. L., Rao, V. A., & Johnston, S. C. (2017) · Stroke · doi:10.1161/strokeaha.117.017343 · Cited by 56
Pleotropic effects of statins: the dilemma of wider utilization of statin
Choudhary, A., Rawat, U., Kumar, P., & Mittal, P. (2023) · The Egyptian Heart Journal · doi:10.1186/s43044-023-00327-8 · Cited by 61
Ruscica, M., Banach, M., Sahebkar, A., Corsini, A., & Sirtori, C. R. (2019) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2019.1583209 · Cited by 56
“studies and from RCTs has shown that any mechanism leading to LDL lowering, can reduce the risk of ASCVD events, proportional to the absolute LDL-C reduction [62,65].”
BackgroundCasula, M., Olmastroni, E., Gazzotti, M., Galimberti, F., Zambon, A., & Catapano, A. L. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.105060 · Cited by 54
Jacobson, T. A., Cheeley, M. K., Jones, P. H., Forge, R. L., Maki, K. C., López, J. A. G., Xiang, P., Bushnell, D. M., Martin, M. L., & Cohen, J. D. (2019) · Journal of clinical lipidology · doi:10.1016/j.jacl.2019.04.011 · Cited by 57
Milinkovic, A., Berger, F., Arenas‐Pinto, A., & Mauss, S. (2019) · AIDS · doi:10.1097/qad.0000000000002350 · Cited by 55
“Research studies also show that lowering cholesterol has a clinical impact on cardiovascular events [1].”
BackgroundPPAR-α agonists are still on the rise: an update on clinical and experimental findings
Ferri, N., Corsini, A., Sirtori, C. R., & Ruscica, M. (2017) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2017.1312339 · Cited by 59
“significant association between the degree of TG lowering and the RR of major vascular events after fibrates [81].”
BackgroundMasana, L., Ibarretxe, D., & Plana, N. (2020) · Current Cardiology Reports · doi:10.1007/s11886-020-01326-w · Cited by 57
Pleiotropic Effects of PCSK-9 Inhibitors
Basiak, M., Kosowski, M., Cyrnek, M., Bułdak, Ł., Maligłówka, M., Machnik, G., & Okopień, B. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22063144 · Cited by 56
“However, this view was changed by a recent meta-analysis in which it was shown on a group of 300,000 patients that the reduction of cardiovascular events is greater in patients using PCSK-9 inhibitors compared to patients using statins with the same level of LDLc reduction [36].”
ResultContemporary Management of Dyslipidemia
Ferraro, R., Leucker, T. M., Martin, S. S., Banach, M., Jones, S. R., & Toth, P. P. (2022) · Drugs · doi:10.1007/s40265-022-01691-6 · Cited by 59
Gong, Y., Ma, Y., Ye, Z., Fu, Z., Yang, P., Gao, B., Guo, W., Hu, D., Ye, J., Ma, S., et al. (2017) · Metabolism · doi:10.1016/j.metabol.2017.07.006 · Cited by 54
Comparative efficacy and safety of lipid-lowering agents in patients with hypercholesterolemia
Zhao, Z., Du, S., Shen, S., Luo, P., Ding, S., Wang, G., & Wang, L. (2019) · Medicine · doi:10.1097/md.0000000000014400 · Cited by 55
“Collectively, given the uncertain CV benefit of ezetimibe in the absence of statins and its low intensity lipidlowering effect, combination data from previous SEAS([41]) and SHARP([42]) trials and current analyses, in accordance with”
BackgroundMethodGardouh, A. R., Nasef, A. M., Mostafa, Y., & Gad, S. (2020) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2020.102093 · Cited by 60
Mok, Y., Sang, Y., Ballew, S. H., Rebholz, C. M., Rosamond, W. D., HEISS, G. M., Folsom, A. R., Coresh, J., & Matsushita, K. (2018) · Journal of the American Heart Association · doi:10.1161/jaha.117.007658 · Cited by 53
“DOI: 10.1161/JAHA.117.007658 Journal of the American Heart Association 7 Life’s Simple 7 and Prognosis After MI Mok et al O R IG IN A L R E S E A R C H activity at baseline were not individually associated with adverse outcomes after incident MI.”
BackgroundInfluentialDevelopment of small-molecule PCSK9 inhibitors for the treatment of hypercholesterolemia
Ahamad, S., Mathew, S., Khan, W. A., & Mohanan, K. (2022) · Drug Discovery Today · doi:10.1016/j.drudis.2022.01.014 · Cited by 60
Baumgartner, S., Bruckert, É., Gallo, A., & Plat, J. (2020) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2020.07.019 · Cited by 57
Metadata
- Authors
- Silverman, M. G., Ference, B. A., Im, K., Wiviott, S. D., Giugliano, R. P., Grundy, S. M., Braunwald, E., & Sabatine, M. S.
- Affiliations
- Brigham and Women's Hospital (US)
- Wayne State University (US)
- The University of Texas Southwestern Medical Center (US)
- TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
- Corresponding author
- Sabatine, Marc S.
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2016-09-27
- Volume
- 316
- Issue
- 12
- Pages
- 1289
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W2465758073
- Cited by
- 1,483
- References
- 79
- Citations by year
- 2026: 111 · 2025: 163 · 2024: 182 · 2023: 202 · 2022: 152 · 2021: 151 · 2020: 170 · 2019: 152 · 2018: 115 · 2017: 70 · 2016: 13
- FWCI
- 23.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (T32HL007604)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- LDL cholesterol lowering, cardiovascular risk reduction, statins, non-statin lipid-lowering therapy, LDL receptor upregulation, ezetimibe, bile acid sequestrants, ileal bypass, dietary intervention, myocardial infarction, major vascular events, coronary revascularization, stroke, cardiovascular mortality, acute coronary syndrome, LDL cholesterol targets
- MeSH terms
- Hypolipidemic Agents, Cardiovascular Diseases, Female, Humans, Cholesterol, LDL, Male, Middle Aged, Myocardial Infarction, Niacin, Receptors, LDL, Up-Regulation, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Stroke, Risk Reduction Behavior
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.
A language model drew the claims from the paper on 2026-10-19, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-19 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
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.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
