The DOI matches its Crossref record; 81 of the 81 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
7 of 21 cited sources checked · 1 supported · 0 flagged · 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)
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
- 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)
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably 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
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably 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
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably 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
“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 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 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 measured
The 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
“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]
In 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.
IMPROVE-IT citation points to a different trial
MinorThe text cites reference 53 for IMPROVE-IT, but reference 53 in the provided list is the Lipid Research Clinics Coronary Primary Prevention Trial, not IMPROVE-IT.
“Ezetimibe was studied in the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) trial 53”
“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
Flagged first, then by citations
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 301–400 of 1,481
Tafolecimab in Chinese Patients With Hypercholesterolemia (CREDIT-4)
Qi, L., Liu, D., Qu, Y., Chen, B., Meng, H., Zhu, L., Li, L., Wang, S., Liu, C., Zheng, G., et al. (2023) · JACC Asia · doi:10.1016/j.jacasi.2023.04.011 · Cited by 37
Andersen, C. J., & Vance, T. M. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8030365 · Cited by 33
Haldar, S., Wong, L. H., Tay, S. L., Jacoby, J. J., He, P., Osman, F., Ponnalagu, S., Jiang, Y. R., Lian, H. P. R., & Henry, C. J. (2020) · The Journal of Nutrition · doi:10.1093/jn/nxaa274 · Cited by 31
“Given that a reduction of 1 mmol/L in LDL cholesterol through non–statin therapies is associated with a 25% reduction in CVD risk (5), dietary fatty acid (FA) composition and intrinsic bioactive phytonutrients within various cooking oils can play an important role in modulating LDL-cholesterol concentrations (6–8).”
BackgroundShah, N. N., Ghazi, L., Yamamoto, Y., Kumar, S., Martin, M. C., Simonov, M., Riello, R. J., Faridi, K. F., Ahmad, T., Wilson, F. P., et al. (2024) · Circulation Cardiovascular Quality and Outcomes · doi:10.1161/circoutcomes.123.010335 · Cited by 32
Plant Stanol Esters Reduce LDL (Low-Density Lipoprotein) Aggregation by Altering LDL Surface Lipids
Ruuth, M. K., Äikäs, L., Tigistu‐Sahle, F., Käkelä, R., Lindholm, H. J., Simonen, P. P., Kovanen, P. T., Gylling, H., & Öörni, K. (2020) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.120.314329 · Cited by 32
Ambrosy, A. P., Yang, J., Sung, S. H., Allen, A. R., Fitzpatrick, J. K., Rana, J. S., Wagner, J., Philip, S., Abrahamson, D., Granowitz, C., et al. (2021) · Journal of the American Heart Association · doi:10.1161/jaha.120.020377 · Cited by 32
Schremmer, J., Busch, L., Baasen, S., Heinen, Y., Sansone, R., Heiß, C., Kelm, M., & Stern, M. E. (2023) · Microvascular Research · doi:10.1016/j.mvr.2023.104513 · Cited by 34
Christensen, J. J., Arnesen, E., Rundblad, A., Telle‐Hansen, V. H., Narverud, I., Blomhoff, R., Bogsrud, M. P., Retterstøl, K., Ulven, S. M., & Holven, K. B. (2023) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2023.117433 · Cited by 31
Lipid Profiles After Changes in Alcohol Consumption Among Adults Undergoing Annual Checkups
Suzuki, T., Fukui, S., Shinozaki, T., Asano, T., Yoshida, T., Aoki, J., & Mizuno, A. (2025) · JAMA Network Open · doi:10.1001/jamanetworkopen.2025.0583 · Cited by 36
Drug Therapy of Dyslipidemia in the Elderly
Yandrapalli, S., Gupta, S., Andries, G., Cooper, H. A., & Aronow, W. S. (2019) · Drugs & Aging · doi:10.1007/s40266-018-00632-x · Cited by 31
Strilchuk, L. M., Tocci, G., Fogacci, F., & Cicero, A. F. G. (2020) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2020.1714028 · Cited by 31
“The impressive LDL-lowering effect of rosuvastatin/ezetimibe is expected to significantly reduce cardiovascular events, based on the available meta-analysis relating LDL-C reduction and cardiovascular risk reduction [95].”
BackgroundMultitrait GWAS to connect disease variants and biological mechanisms
Julienne, H., Laville, V., McCaw, Z. R., He, Z., Guillemot, V., Lasry, C., Ziyatdinov, A., Nerin, C., Vaysse, A., Lechat, P., et al. (2021) · PLoS Genetics · doi:10.1371/journal.pgen.1009713 · Cited by 35
“The associations of clusters 4 and 6 with CAD add to the evidence of a causal effect of LDL-C on CAD[46], which has been established by prospective epidemiological studies[47], Mendelian randomization [48] and randomized clinical trials evaluating the effect of LDL-C reducing therapies[49].”
BackgroundVolpe, M., Gallo, G., Modena, M. G., Ferri, C., Desideri, G., Tocci, G., Members of the Board of the Italian Society of Cardiovascular Prevention, Bellone, S., Bertolotti, M., Biffi, A., et al. (2022) · High Blood Pressure & Cardiovascular Prevention · doi:10.1007/s40292-021-00503-4 · Cited by 30
“Another fundamental intervention for CV prevention consists in the effective treatment of dyslipidaemias (mostly hypercholesterolemia), since the linear relationship between the reduction of low density lipoproteins cholesterol (LDLc) and CV risk is well established [37].”
BackgroundZheutlin, A. R., Derington, C. G., Herrick, J. S., Rosenson, R. S., Poudel, B., Safford, M. M., Brown, T. M., Jackson, E. A., Woodward, M., Reading, S. R., et al. (2022) · Circulation Cardiovascular Quality and Outcomes · doi:10.1161/circoutcomes.121.008861 · Cited by 31
Harm, T., Dittrich, K., Brun, A., Fu, X., Frey, M., Petersen-Uribe, Á., Schwarz, F.-J., Rohlfing, A., Castor, T., Geisler, T., et al. (2023) · Clinical Research in Cardiology · doi:10.1007/s00392-023-02260-x · Cited by 31
“Beyond conventional cardiovascular risk factors, plasmatic lipoproteins such as low-density lipoprotein (LDL) are strongly associated with poor prognosis in CAD [23, 24].”
BackgroundThe clinical relevance of the reversal of coronary atherosclerotic plaque
Cesaro, A., Acerbo, V., Indolfi, C., Filardi, P. P., & Calabrò, P. (2024) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2024.08.010 · Cited by 30
Desai, N. R., Giugliano, R. P., Wasserman, S. M., Gibbs, J. P., Liu, T., Scott, R. C., & Sabatine, M. S. (2017) · JAMA Cardiology · doi:10.1001/jamacardio.2016.5395 · Cited by 30
Self-citationBreuker, C., Clément, F., Mura, T., Macioce, V., Castet‐Nicolas, A., Audurier, Y., Boegner, C., Morcrette, E., Jalabert, A., Villiet, M., et al. (2018) · International Journal of Cardiology · doi:10.1016/j.ijcard.2018.04.068 · Cited by 30
Gonna, H., & Ray, K. K. (2019) · Diabetes Obesity and Metabolism · doi:10.1111/dom.13691 · Cited by 30
Ying, H., Wang, J., Shen, Z., Wang, M., & Zhou, B. (2020) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-020-07045-2 · Cited by 31
Fledderus, J., Vanchin, B., Rots, M. G., & Krenning, G. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11020103 · Cited by 31
“Interestingly, and given that lipid-lowering drugs reduce the incidence of severe cardiovascular events [62,82], the sole treatment of dyslipidaemia does not prevent atherogenesis [83,84], underscoring the need for additional therapies.”
BackgroundDefining the Place of Ezetimibe/Atorvastatin in the Management of Hyperlipidemia
Ferreira, A. M., & da Silva, P. M. (2016) · American Journal of Cardiovascular Drugs · doi:10.1007/s40256-016-0205-0 · Cited by 33
Development and Population Results of a Fully Automated Homogeneous Assay for LDL Triglyceride
Ito, Y., Ohta, M., Ikezaki, H., et al. (2018) · The Journal of Applied Laboratory Medicine · doi:10.1373/jalm.2017.024554 · Cited by 30
Causal Effect of Lipids and Lipoproteins on Atherosclerosis
Ference, B. A. (2018) · Cardiology Clinics · doi:10.1016/j.ccl.2017.12.001 · Cited by 28
Self-citationMa, X., Wang, Q., Hu, X., Wang, X., Zhao, Y., Liu, X. L., Li, J., Du, Y., Wang, M., Qiu, C., et al. (2024) · Stroke · doi:10.1161/strokeaha.123.045601 · Cited by 33
Drugs for dyslipidaemia: the legacy effect of the Scandinavian Simvastatin Survival Study (4S)
Strandberg, T. E., Kovanen, P. T., Lloyd‐Jones, D. M., Raal, F. J., Santos, R. D., & Watts, G. F. (2024) · The Lancet · doi:10.1016/s0140-6736(24)02089-0 · Cited by 29
Shin, J., Chung, J., Jang, H.-S., Lee, J., Hong, K., Bang, O. Y., Kim, G., & Seo, W. (2019) · European Journal of Preventive Cardiology · doi:10.1177/2047487319830503 · Cited by 31
Okeke, N. L., Webel, A. R., Bosworth, H. B., Aifah, A. A., Bloomfield, G. S., Choi, E. W., Gonzales, S. E., Hale, S. L., Hileman, C. O., Lopez‐Kidwell, V., et al. (2019) · American Heart Journal · doi:10.1016/j.ahj.2019.07.005 · Cited by 29
Molavi, F., Namazi, N., Asadi, M., Sanjari, M., Motlagh, M. E., Shafiee, G., Qorbani, M., Heshmat, R., & Kelishadi, R. (2020) · Lipids in Health and Disease · doi:10.1186/s12944-020-01306-7 · Cited by 29
Hsu, H., Lin, C., Lee, Y.-S., Wu, T., & Chien, K. (2020) · BMC Cardiovascular Disorders · doi:10.1186/s12872-020-01567-1 · Cited by 30
The Effect of Diet on Cardiovascular Disease and Lipid and Lipoprotein Levels
Feingold, K. R. (2021) · Europe PMC (PubMed Central) · Cited by 30
Fogacci, F., Rizzoli, E., Giovannini, M., Bove, M., D’Addato, S., Borghi, C., & Cicero, A. F. G. (2022) · Nutrients · doi:10.3390/nu14102099 · Cited by 29
“Moreover, unlike the other nutraceuticals specifically inhibiting cholesterol synthesis or absorption [35], bergamot polyphenolic fraction and artichoke extracts have an impact on both lipid and glucose metabolism [33,36].”
BackgroundGoldberg, R. B. (2022) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2022.02.011 · Cited by 31
Gavina, C., Seabra, D., Pardal, M., Afonso-Silva, M., Grangeia, D., Dinis‐Oliveira, R. J., Araujo, F. P., & Taveira‐Gomes, T. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11226825 · Cited by 29
Dron, J. S., Patel, A. P., Zhang, Y., Jurgens, S. J., Maamari, D. J., Wang, M., Boerwinkle, E., Morrison, A. C., de Vries, P. S., Fornage, M., et al. (2023) · JAMA Cardiology · doi:10.1001/jamacardio.2022.5271 · Cited by 30
Farrah, T. E., Anand, A., Gallacher, P. J., Kimmitt, R. A., Carter, E., Dear, J. W., Mills, N. L., Webb, D. J., & Dhaun, N. (2019) · Hypertension · doi:10.1161/hypertensionaha.119.12919 · Cited by 28
Furtado, R. H. M., & Giugliano, R. P. (2020) · Cardiology and Therapy · doi:10.1007/s40119-020-00163-w · Cited by 29
Self-citationCholesterol and Inflammation in Atherosclerosis: An Immune-Metabolic Hypothesis
Mauricio, D., Castelblanco, E., & Alonso, N. (2020) · Nutrients · doi:10.3390/nu12082444 · Cited by 29
“There is no doubt from epidemiological studies that deranged lipid metabolism, primarily low-density lipoprotein cholesterol (LDL) and other atherogenic lipoproteins, is a significant contributor to the development of atherosclerosis [14].”
BackgroundGuerrero-Bonmatty, R., Fernández, G. G., Rodríguez-Velasco, F. J., & Espadaler, J. (2021) · Nutrients · doi:10.3390/nu13041206 · Cited by 30
“Cardiovascular diseases (CVDs) are the number one cause of death globally, representing 31% of all global deaths [1].”
BackgroundInfluentialClinical significance of subclinical atherosclerosis in retinal vein occlusion
Lyu, M., Lee, Y., Kim, B. S., Kim, H., Hong, R., Shin, Y. U., Cho, H., & Shin, J. (2021) · Scientific Reports · doi:10.1038/s41598-021-91401-1 · Cited by 28
Bellis, A., Gioia, G. D., Mauro, C., Mancusi, C., Barbato, E., Izzo, R., Trimarco, B., & Morisco, C. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10132968 · Cited by 28
Kexin, W., Yaodong, D., Wen, G., Rui, W., Jiaxin, Y., Xiaoli, L., Hua, S., & Hailong, G. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.740596 · Cited by 28
Vicente-Valor, J., García‐González, X., Ibáñez-García, S., Durán-García, M. E., de Lorenzo‐Pinto, A., Rodríguez, C., Méndez, I., Percovich-Hualpa, J. C., Alonso, A. H., & Sanjurjo‐Sáez, M. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.112519 · Cited by 29
Zhang, Y., Bai, Y., Xie, J., Wang, J., He, L., Huang, M., & Xu, F. (2022) · Journal of Stroke and Cerebrovascular Diseases · doi:10.1016/j.jstrokecerebrovasdis.2022.106857 · Cited by 33
Durairaj, A., Sabates, A., Nieves, J., Moraes, B., & Baum, S. (2017) · Current Treatment Options in Cardiovascular Medicine · doi:10.1007/s11936-017-0556-0 · Cited by 27
Luo, Y., & Peng, D. (2023) · Journal of Cardiovascular Pharmacology and Therapeutics · doi:10.1177/10742484231189597 · Cited by 30
“3,16,17 Although LDL-C levels are used to estimate circulating LDL in plasma, 3 LDL-C only re fl ects the level of cholesterol carried by LDL particles and not the number of LDL particles.”
MethodThe functions of apolipoproteins and lipoproteins in health and disease
Ma, Z., Zhong, J., Tu, W., Li, S., & Chen, J. (2024) · Molecular Biomedicine · doi:10.1186/s43556-024-00218-7 · Cited by 36
Nanna, M. G., Návar, A. M., Wang, T. Y., Li, S., Virani, S. S., Li, Z., Robinson, J. G., Roger, V. L., Wilson, P. W. F., Goldberg, A. C., et al. (2019) · American Heart Journal · doi:10.1016/j.ahj.2019.05.009 · Cited by 27
Lee, J., Egolum, U. O., Parihar, H. S., Cooley, M., & Ling, H. (2021) · Cardiology Research · doi:10.14740/cr1224 · Cited by 29
“While other factors also play an important role in influencing the cardiovascular outcome, the percentage reduction in LDL-C levels from baseline was linearly correlated with ASCVD rates [31].”
BackgroundResultRNA-based therapy in the management of lipid disorders: a review
Blom, D. J., Marais, A. D., Moodley, R., van der Merwe, N., van Tonder, A., & Raal, F. J. (2022) · Lipids in Health and Disease · doi:10.1186/s12944-022-01649-3 · Cited by 29
“002) for established non-statin interventions that act primarily via upregulation of LDL receptor expression [24].”
BackgroundChang, H., Wei, J., Chen, K., Zhang, S., Han, F., Lu, L., Xiao, W., & Gao, Y. (2018) · Journal of Cancer · doi:10.7150/jca.22836 · Cited by 27
“Serum lipid profiles are a group of practical indexes which can now be tested routinely and interfered easily in the daily clinical works [11,12].”
BackgroundParhofer, K. G., Aguíar, C., Banach, M., Drexel, H., Gouni‐Berthold, I., de Isla, L. P., Rietzschel, E. R., Zambon, A., & Ray, K. K. (2025) · European Heart Journal - Cardiovascular Pharmacotherapy · doi:10.1093/ehjcvp/pvaf007 · Cited by 31
“C is associated with a decrease in the relative risk of a major CV event by up to 23%, 12 , 13 regardless of the initial CV risk.”
Alder, M., Bavishi, A. A., Zumpf, K. B., Peterson, J., & Stone, N. J. (2020) · The American Journal of Medicine · doi:10.1016/j.amjmed.2020.03.056 · Cited by 26
van Bruggen, F. H., Nijhuis, G. B. J., Zuidema, S. U., & Luijendijk, H. J. (2020) · Expert Review of Clinical Pharmacology · doi:10.1080/17512433.2020.1787832 · Cited by 27
Takahashi, D., Wada, H., Ogita, M., Yasuda, K., Nishio, R., Takeuchi, M., Shitara, J., Tsuboi, S., Dohi, T., Suwa, S., et al. (2022) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2021.12.014 · Cited by 26
Mollace, R., Macrì, R., Tavernese, A., Gliozzi, M., Musolino, V., Carresi, C., Maiuolo, J., Fini, M., Volterrani, M., & Mollace, V. (2022) · Nutrients · doi:10.3390/nu14030477 · Cited by 26
New Therapeutic Approaches for Familial Hypercholesterolemia
Ajufo, E., & Rader, D. J. (2018) · Annual Review of Medicine · doi:10.1146/annurev-med-051215-030943 · Cited by 26
The Highs and Lows of Cholesterol: A Paradox of Healthy Aging?
Orkaby, A. R. (2020) · Journal of the American Geriatrics Society · doi:10.1111/jgs.16302 · Cited by 27
“Nevertheless, a meta-analysis of 312 175 individuals (mean age = 62 y) enrolled in clinical trials of cholesterollowering medications demonstrated that reduction in LDL was associated with a linear reduction in the relative risk of major CV events including CV mortality.(3) LDL has inflammatory effects beyond the buil…”
BackgroundSafety and Lipid-Lowering Efficacy of Inclisiran Monotherapy in Patients Without ASCVD
Taub, P. R., Gutierrez, A., Wewers, D., Garcia Cantu, E., Cao, H., Deck, C., Lesogor, A., Ott, D., Mena-Madrazo, J., Zang, X., et al. (2025) · JACC · doi:10.1016/j.jacc.2025.04.049 · Cited by 25
Broader Perspective on Atherosclerosis—Selected Risk Factors, Biomarkers, and Therapeutic Approach
Fularski, P., Czarnik, W., Dąbek, B., Lisińska, W., Radzioch, E., Witkowska, A., Młynarska, E., Rysz, J., & Franczyk, B. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25105212 · Cited by 26
Page, M. M., & Watts, G. F. (2017) · Diabetes Obesity and Metabolism · doi:10.1111/dom.13070 · Cited by 27
“A prima facie case for new agents that lower atherogenic lipoproteins more than statin therapy is established by the continuous relationship between plasma LDL cholesterol-lowering and cardiovascular risk.(25)”
BackgroundGiorgi, M. D., Jarrett, K. E., Burton, J. C., Doerfler, A. M., Hurley, A. E., Li, A., Hsu, R. H., Furgurson, M. N., Patel, K. R., Han, J., et al. (2020) · Journal of Lipid Research · doi:10.1194/jlr.ra120001006 · Cited by 25
“HMGCR is an integral glycoprotein localized in the ER and is the target of statins, the most widely used cholesterol-lowering drugs in the world (2).”
BackgroundCainzos‐Achirica, M., Bittencourt, M. S., Osei, A. D., Haque, W. Z., Bhatt, D. L., Blumenthal, R. S., Blankstein, R., Ray, K. K., Blaha, M. J., & Nasir, K. (2020) · JACC. Cardiovascular imaging · doi:10.1016/j.jcmg.2020.10.016 · Cited by 25
Bjornsson, E., Gunnarsdottir, K., Halldorsson, G. H., Sigurdsson, A., Arnadottir, G. A., Jonsson, H., Olafsdottir, E. F., Niehus, S., Kehr, B., Sveinbjörnsson, G., et al. (2021) · Circulation: Genomic and Precision Medicine · doi:10.1161/circgen.120.003029 · Cited by 23
Lipid-lowering therapy and percutaneous coronary interventions
Koskinas, K. C., Mach, F., & Räber, L. (2021) · EuroIntervention · doi:10.4244/eij-d-20-00999 · Cited by 26
Wen, J., & Su, M. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18105480 · Cited by 26
“It is another major risk factor for IHD and IS [6,7].”
BackgroundBanach, M., Shekoohi, N., Mikhailidis, D. P., Lip, G. Y. H., Hernández, A. V., & Mazidi, M. (2022) · Archives of Medical Science · doi:10.5114/aoms/145970 · Cited by 30
“Arch Med Sci 4, 1st July / 2022 925 vascular outcomes (including stroke) was found [84].”
BackgroundCold shock domain-containing protein E1 is a posttranscriptional regulator of the LDL receptor
Smith, G. A., Padmanabhan, A., Lau, B. H., Pampana, A., Li, L., Lee, C. Y., Pelonero, A., Nishino, T., Sadagopan, N., Xia, V. Q., et al. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.abj8670 · Cited by 23
Peng, K., Li, X., Wang, Z., Li, M., & Yang, Y. (2022) · Medicine · doi:10.1097/md.0000000000032003 · Cited by 25
“In a defined population, reducing elevated LDL-C level is a crucial strategy in primary and secondary prevention for CVD event.[43,44] Many clinical trials have demonstrated an increased risk of CVD-relevant morbidity correlated with elevation of LDL-C level.”
Ma, M., Hou, C. J., & Liu, J. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2023.1148486 · Cited by 26
Stroes, E. S. G., Bays, H. E., Banach, M., Catapano, A. L., Duell, P. B., Laufs, U., Mancini, G. B. J., Ray, K. K., Sasiela, W. J., Zhang, Y., et al. (2023) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2023.03.020 · Cited by 26
Reduction of Vascular Inflammation, LDL-C, or Both for the Protection from Cardiovascular Events?
Reklou, A., Doumas, M. N., Imprialos, K. P., Stavropoulos, K., Patoulias, D., & Athyros, V. G. (2018) · The Open Cardiovascular Medicine Journal · doi:10.2174/1874192401812010029 · Cited by 26
“Finally, a meta-regression analysis of 312,175 participants from 49 trials with 39,645 major CVD events [24] showed that statin use and non-statin therapies that reduce LDL-C to the same degree were associated with similar relative risk reductions in CVD events per mmol/l change in LDL-C, both in primary and in second…”
MethodReprint of: Impact of Lipids on Cardiovascular Health
Ference, B. A., Graham, I. M., Tokgözoğlu, L. S., & Catapano, A. L. (2018) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.10.021 · Cited by 26
Self-citationRimbert, A., Dalila, N., Wolters, J. C., Huijkman, N., Smit, M., Kloosterhuis, N., Riemsma, M., van der Veen, Y., Singla, A., van Dijk, F., et al. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehz727 · Cited by 24
Lyu, X., Liu, J., Gou, Y., Sun, S., Hao, J., & Cui, Y. (2024) · Open Research (University of Surrey) · doi:10.1002/viw.20240059 · Cited by 24
Ruscica, M., Loh, W. J., Sirtori, C. R., & Watts, G. F. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.107681 · Cited by 25
Zamora, A., Masana, L., Comas‐Cufí, M., Plana, N., Vila, À., García-Gil, M., Alves‐Cabratosa, L., Elosúa, R., Marrugat, J., & Ramos, R. (2017) · Revista Española de Cardiología · doi:10.1016/j.recesp.2017.11.006 · Cited by 24
“Individuos sin HF con ECV 7,3 [4,1-9,2] 148 93 35,5 1,9 73,0”
Kodera, S., Morita, H., Kiyosue, A., Ando, J., Takura, T., & Komuro, I. (2018) · Circulation Journal · doi:10.1253/circj.cj-17-1455 · Cited by 24
Soran, H., Adam, S., & Durrington, P. N. (2018) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2018.08.040 · Cited by 23
Cheng, Y., Qiao, L., Jiang, Z., Dong, X., Feng, H., Gui, Q., Lu, Y., & Liang, Y. (2020) · PubMed Central · Cited by 25
Lycopene Inhibit IMQ-Induced Psoriasis-Like Inflammation by Inhibiting ICAM-1 Production in Mice
Shih, C., Hsieh, C.-K., Huang, C., Huang, C., Wang, K.-H., Fong, T.-H., Trang, N. T. T., Liu, K.-T., & Lee, A.-W. (2020) · Polymers · doi:10.3390/polym12071521 · Cited by 24
“Dyslipid mia is the elevation in plasma chol st r l and riglycerid s that contrib te to the development of atherosclerosis [18].”
BackgroundCainzos-Achirica, M., Quispe, R., Dudum, R., Greenland, P., Lloyd-Jones, D., Rana, J. S., Lima, J. A. C., Doria de Vasconcellos, H., Joshi, P. H., Khera, A., et al. (2022) · JACC: Cardiovascular Imaging · doi:10.1016/j.jcmg.2021.10.017 · Cited by 24
Bibliometric and Visual Analysis on Metabolomics in Coronary Artery Disease Research
Yu, N., Wang, R., Liu, B., & Zhang, L. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.804463 · Cited by 24
Personalised medicine in hypercholesterolaemia: the role of pharmacogenetics in statin therapy
Ahangari, N., Doosti, M., Ghayour‐Mobarhan, M., Sahebkar, A., Ferns, G. A., & Pasdar, A. (2020) · Annals of Medicine · doi:10.1080/07853890.2020.1800074 · Cited by 25
Palacio-Portilla, E. J., Roquer, J., Amaro, S., Arenillas, J. F., Martín, Ó. A., Castellanos, M., Freijo, M. D. M., Fuentes, B., Pastor, Á. G., Gomis, M., et al. (2020) · Neurología · doi:10.1016/j.nrl.2020.07.027 · Cited by 22
Lecis, D., Prandi, F. R., Barone, L., Belli, M., Sergi, D., Longo, S., Muscoli, S., Romeo, F., Federici, M., Lerakis, S., et al. (2023) · Biomolecules · doi:10.3390/biom13121695 · Cited by 23
“…controlled trials demonstrated a log-linear relationship between the absolute changes in plasma LDL and the risk of atherosclerotic cardiovascular diseases (ASCVDs) [14,15], which include coronary heart disease, cerebrovascular disease, peripheral artery disease, and aortic atherosclerotic disease.”
Patti, G., Cumitini, L., Bosco, M., Marengo, A., D’Amario, D., Mennuni, M. G., Solli, M., & Grisafi, L. (2025) · European Heart Journal - Cardiovascular Pharmacotherapy · doi:10.1093/ehjcvp/pvaf004 · Cited by 23
“3 –7 Accordingly, in 2019, the ESC/EAS updated the recommendations indicating an even more stringent LDL-C goal ( 55 mg/dL) in patients at very high cardio-vascular risk, including those with acute MI. 8 To achieve this lower goal, the 2019 ESC/EAS guidelines continued to support a stepwise…”
Best Treatment Strategies With Statins to Maximize the Cardiometabolic Benefits
Cho, K. I., Sakuma, I., Sohn, I. S., Hayashi, T., Shimada, K., & Koh, K. K. (2018) · Circulation Journal · doi:10.1253/circj.cj-17-1445 · Cited by 23
Li, C., Chen, Q., Zhang, M., Liu, Y., Chu, Y., Meng, F., Wang, J., Tang, J. T., Luo, J., Niu, X., et al. (2021) · BMC Cardiovascular Disorders · doi:10.1186/s12872-021-01861-6 · Cited by 22
“A meta-analysis of 49 clinical trials, over 312,000 patients, showed a great 23% MACE risk reduction achievement with 1 mmol/L LDL-C reduction in statin therapy [18].”
MethodNakamura, M., Ako, J., Arai, H., Hirayama, A., Nohara, A., Murakami, Y., Ozaki, A., & Harada‐Shiba, M. (2021) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.59543 · Cited by 24
Bempedoic Acid for Heterozygous Familial Hypercholesterolemia: From Bench to Bedside
Agarwala, A., Quispe, R., Goldberg, A. C., & Michos, E. D. (2021) · Drug Design Development and Therapy · doi:10.2147/dddt.s251865 · Cited by 23
“75).(42) Since bempedoic acid is a non-statin that also similarly works through a mechanism of upregulation of LDL-C receptor, we anticipate similar degrees of reduction in vascular events proportional to that same degree of LDL-C lowering.”
BackgroundEvaluating pharmacokinetics of bempedoic acid in the treatment of hypercholesterolemia
Cicero, A. F. G., Fogacci, F., & Cincione, R. I. (2021) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2021.1951222 · Cited by 23
Anudeep, P. P., Kumari, S., Rajasimman, A. S., Nayak, S., & Priyadarsini, P. (2021) · Annals of Clinical Biochemistry International Journal of Laboratory Medicine · doi:10.1177/00045632211046805 · Cited by 24
“LDL-C being a strong marker of CAD and the primary target for therapy, estimation of accurate LDL-C value is crucial.(28) Our effort was to validate the performance of ML models in predicting LDL-C.”
MethodObesity Partially Mediates the Diabetogenic Effect of Lowering LDL Cholesterol
Wu, P., Moon, J., Daghlas, I., Giulianini, F., Porneala, B., Ahmadizar, F., Richardson, T. G., Isaksen, J. L., Hindy, G., Yao, J., et al. (2021) · Diabetes Care · doi:10.2337/dc21-1284 · Cited by 24
Ennezat, P. V., Guerbaaï, R.-A., Maréchaux, S., Jemtel, T. H. L., & François, P. (2022) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0000000000001345 · Cited by 24
Platelet Redox Imbalance in Hypercholesterolemia: A Big Problem for a Small Cell
Morotti, A., Barale, C., Melchionda, E., & Russo, I. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911446 · Cited by 25
“Data from randomized controlled trials showed a clinical benefit in terms of a dramatic decrease of LDL-C and a positive impact on CV events for both evolocumab [210] and alirocumab [211], even more than for statins, despite the same LDL-C reduction [212].”
New Therapeutic Approaches to the Treatment of Dyslipidemia 1: ApoC-III and ANGPTL3
Kim, J. Y., & Kim, N. H. (2023) · Journal of Lipid and Atherosclerosis · doi:10.12997/jla.2023.12.1.23 · Cited by 23
Koh, K. K., Sakuma, I., Shimada, K., Hayashi, T., & Quon, M. J. (2016) · Korean Circulation Journal · doi:10.4070/kcj.2016.0406 · Cited by 24
Ikezaki, H., Fisher, V. A., Lim, E., Ai, M., Liu, C., Cupples, L. A., Nakajima, K., Asztalos, B. F., Furusyo, N., & Schaefer, E. J. (2019) · Clinical Chemistry · doi:10.1373/clinchem.2019.304600 · Cited by 23
Khan, S. U., & Michos, E. D. (2020) · American Journal of Preventive Cardiology · doi:10.1016/j.ajpc.2020.100013 · Cited by 23
“Although similar methods have been previously used [6], this approach is not ideal given substantial heterogeneity in the definition of primary endpoint across the trials.”
Method
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
