The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index; 19 of the 27 sources its claims cite were checked for support.
Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials
Open accessAbstract
Background: Randomized trials of therapies that primarily lowered triglycerides have not consistently shown reductions in cardiovascular events. Methods: We performed a systematic review and trial-level meta-regression analysis of 3 classes of lipid-lowering therapies that reduce triglycerides to a greater extent than they do low-density lipoprotein cholesterol (LDL-C): fibrates, niacin, and marine-derived omega-3 fatty acids. Key inclusion criteria were a randomized controlled trial that reported major vascular events. We also incorporated data from a previous meta-regression of 25 statin trials. The main outcome measure was the risk ratio (RR) for major vascular events associated with absolute reductions in lipid parameters. Results: A total of 197 270 participants from 24 trials of nonstatin therapy with 25 218 major vascular events and 177 088 participants from 25 trials of statin therapy with 20 962 major vascular events were included, for a total of 374 358 patients and 46 180 major cardiovascular events. Starting with non–high-density lipoprotein cholesterol, a surrogate for very-low-density lipoproteins and low-density lipoproteins, the RR per 1-mmol/L reduction in non–high-density lipoprotein cholesterol was 0.79 (95% CI, 0.76–0.82; P <0.0001; 0.78 per 40 mg/dL). In a multivariable meta-regression model that included terms for both LDL-C and triglyceride (surrogates for low-density lipoproteins and very-low-density lipoproteins, respectively), the RR was 0.80 (95% CI, 0.76–0.85; P <0.0001) per 1-mmol/L (0.79 per 40 mg/dL) reduction in LDL-C and 0.84 (95% CI, 0.75–0.94; P =0.0026) per 1-mmol/L (0.92 per 40 mg/dL) reduction in triglycerides. REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial) was a significant outlier and strongly influential trial in the meta-regression. When removed, the RRs became 0.79 (95% CI, 0.76–0.83; P <0.0001) per 1-mmol/L (0.78 per 40 mg/dL) reduction in LDL-C and 0.91 (95% CI, 0.81–1.006; P =0.06) per 1-mmol/L (0.96 per 40 mg/dL) reduction in triglycerides. In regard to omega-3 dose, each 1 g/d eicosapentaenoic acid administered was associated with a 7% relative risk reduction in major vascular events (RR, 0.93 [95% CI, 0.91–0.95]; P <0.0001), whereas there was no significant association between the dose of docosahexaenoic acid and the relative risk reduction in major vascular events (RR 0.96 [95% CI, 0.89–1.03]). Conclusions: In randomized controlled trials, triglyceride lowering is associated with a lower risk of major vascular events, even after adjustment for LDL-C lowering, although the effect is less than that for LDL-C and attenuated when REDUCE-IT is excluded. Furthermore, the benefits of marine-derived omega-3 fatty acids, particularly high-dose eicosapentaenoic acid, appear to exceed their lipid-lowering effects.
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Claims the paper makes
19 of 27 cited sources checked · 11 supported · 0 flagged · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The association between triglycerides and cardiovascular (CV) risk is well established from epidemiological studies,1-5 genome-wide analyses,6-8 and Mendelian randomization studies.9,10”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Background
What the sources say
- Not checked — no full text of the sourcecites [1] Nordestgaard BG, Benn M, Schnohr P, Tybjaerg-Hansen A. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA. 2007; 298: 299– 308. 17635890 source
- Not checked — no full text of the sourcecites [2] Sarwar N, Danesh J, Eiriksdottir G, Sigurdsson G, Wareham N, Bingham S, Boekholdt SM, Khaw KT, Gudnason V. Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies. Circulation. 2007; 115: 450– 458. 17190864 source
- Supportedcites [3] Miller M, Cannon CP, Murphy SA, Qin J, Ray KK, Braunwald E, Investigators PI-T. Impact of triglyceride levels beyond low-density lipoprotein cholesterol after acute coronary syndrome in the PROVE IT-TIMI 22 trial. J Am Coll Cardiol. 2008; 51: 724– 730. 18279736 source
The citation to this paper is among references 1–5, attached to the epidemiological-studies portion of the sentence, not the genome-wide or Mendelian-randomization portions. In the Discussion, the paper reports its own association between triglycerides and coronary risk and describes consistent findings from two prospective studies. (LLM, conf=0.90)
- Supportedcites [4] Triglyceride Coronary Disease Genetics C, Emerging Risk Factors C, Sarwar N, Sandhu MS, Ricketts SL, Butterworth AS, Di Angelantonio E, Boekholdt SM, Ouwehand W, Watkins H, Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies. Lancet. 2010; 375: 1634– 1639. 20452521 PMC2867029 source
The Discussion reports that an APOA5 variant associated with higher triglycerides was also associated with higher coronary heart disease risk, and that this genetic association was concordant with the association seen in prospective studies. The Introduction explicitly describes this genetic approach as Mendelian randomisation. The paper addresses coronary heart disease specifically, rather than all cardiovascular outcomes. (LLM, conf=0.91)
- Supportedcites [5] Miller M, Stone NJ, Ballantyne C, Bittner V, Criqui MH, Ginsberg HN, Goldberg AC, Howard WJ, Jacobson MS, Kris-Etherton PM, Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2011; 123: 2292– 2333. 21502576 source
The citation to this source falls within the epidemiological-studies group, so the genome-wide and Mendelian-randomization clauses are not attributed to it. Section 3.3 reports associations between triglycerides and cardiovascular disease in cohort studies and meta-analyses. It also cautions that an independent association is less certain after adjustment for other lipids; no page number is supplied in the passages. (LLM, conf=0.91)
- Supportedcites [6] Do R, Willer CJ, Schmidt EM, Sengupta S, Gao C, Peloso GM, Gustafsson S, Kanoni S, Ganna A, Chen J, Common variants associated with plasma triglycerides and risk for coronary artery disease. Nat Genet. 2013; 45: 1345– 1352. 24097064 PMC3904346 source
The Abstract reports that epidemiologic studies associate higher triglycerides with greater coronary artery disease risk. It also describes a genome-wide analysis of lipid-associated variants and coronary artery disease risk, finding that variants strongly associated with triglycerides are also associated with the disease. The paper cautions that establishing causality is more difficult, but the citing sentence claims an association, not proven causation. (LLM, conf=0.91)
- Supportedcites [7] Teslovich TM, Musunuru K, Smith AV, Edmondson AC, Stylianou IM, Koseki M, Pirruccello JP, Ripatti S, Chasman DI, Willer CJ, Biological, clinical and population relevance of 95 loci for blood lipids. Nature. 2010; 466: 707– 713. 20686565 PMC3039276 source
The citation is attached to the genome-wide analyses portion of the sentence. In “Clinical Relevance of GWAS Loci” (page unavailable), the paper reports TG-related loci associated with coronary artery disease and describes the direction of association as consistent with epidemiological relationships. It cautions that this does not establish TG as a causal risk factor, but the citing sentence claims an association, not causation. (LLM, conf=0.90)
- Supportedcites [8] Willer CJ, Schmidt EM, Sengupta S, Peloso GM, Gustafsson S, Kanoni S, Ganna A, Chen J, Buchkovich ML, Mora S, Discovery and refinement of loci associated with lipid levels. Nat Genet. 2013; 45: 1274– 1283. 24097068 PMC3838666 source
The citation is attached to the genome-wide analyses portion of the sentence. In Results (‘Association of individual lipids with coronary artery disease’), the paper reports that alleles at triglyceride-associated loci were associated with increased coronary artery disease risk and that triglyceride effect sizes correlated with effects on that risk. (LLM, conf=0.92)
- Not checked — no full text of the sourcecites [9] Varbo A, Benn M, Tybjaerg-Hansen A, Jorgensen AB, Frikke-Schmidt R, Nordestgaard BG. Remnant cholesterol as a causal risk factor for ischemic heart disease. J Am Coll Cardiol. 2013; 61: 427– 436. 23265341 source
- Partly supportedcites [10] Varbo A, Benn M, Tybjaerg-Hansen A, Nordestgaard BG. Elevated remnant cholesterol causes both low-grade inflammation and ischemic heart disease, whereas elevated low-density lipoprotein cholesterol causes ischemic heart disease without inflammation. Circulation. 2013; 128: 1298– 1309. 23926208 sourceExperimental — accuracy not yet measured
The Abstract describes a Mendelian randomization study and reports that triglycerides and remnant cholesterol are highly correlated. The Risk of IHD: Observational and Causal Associations section reports increased ischemic heart disease risk with genetically higher remnant cholesterol. The study tests remnant cholesterol, however, rather than a direct triglyceride–cardiovascular risk association; it therefore supports the Mendelian-randomization portion of the claim only indirectly. (LLM, conf=0.83)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe cited sources support only part of this claim — read each source’s verdict below.
In the paper
“but also that, on a mg/dL basis, the association of triglycerides with major vascular events is less strong as that for LDL-C.6,8,35”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Background
What the sources say
- Partly supportedcites [6] Do R, Willer CJ, Schmidt EM, Sengupta S, Gao C, Peloso GM, Gustafsson S, Kanoni S, Ganna A, Chen J, Common variants associated with plasma triglycerides and risk for coronary artery disease. Nat Genet. 2013; 45: 1345– 1352. 24097064 PMC3904346 sourceExperimental — accuracy not yet measured
The paper reports associations of both triglycerides and LDL-C with coronary artery disease across lipid-associated SNPs (Abstract; page unavailable). It does not compare their association strengths per mg/dL or assess the broader outcome of major vascular events. The Online Methods specify that lipid effects were measured in standard-deviation units, not mg/dL. (LLM, conf=0.86)
- Partly supportedcites [8] Willer CJ, Schmidt EM, Sengupta S, Peloso GM, Gustafsson S, Kanoni S, Ganna A, Chen J, Buchkovich ML, Mora S, Discovery and refinement of loci associated with lipid levels. Nat Genet. 2013; 45: 1274– 1283. 24097068 PMC3838666 sourceExperimental — accuracy not yet measured
In Results, under “Association of individual lipids with coronary artery disease” (page unavailable), the correlation between lipid-locus effects and CAD effects is lower for triglycerides (r=0.46) than for LDL cholesterol (r=0.74). This supports a narrower comparison of genetic associations, not the claimed difference in association per mg/dL with major vascular events; the paper reports CAD rather than that broader outcome. (LLM, conf=0.82)
- Supportedcites [35] Ference BA, Kastelein JJP, Ray KK, Ginsberg HN, Chapman MJ, Packard CJ, Laufs U, Oliver-Williams C, Wood AM, Butterworth AS, Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease. JAMA. 2019; 321: 364– 373. 30694319 PMC6439767 source
The Discussion explains that an approximately 200-mg/dL triglyceride reduction would be needed to achieve the cardiovascular-risk reduction associated with a 40-mg/dL LDL-C reduction. This supports the claim that, per mg/dL, the triglyceride association is weaker, although the paper presents the comparison as conditional on its ApoB-particle interpretation. (LLM, conf=0.89)
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
“Indeed, recent genetic data highlight that lower levels of apoB-containing particles, be it cholesterol-rich LDL or triglyceride-rich VLDL, are associated with similar lower risk of major vascular events.35”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Discussion
What the sources say
- Partly supportedcites [35] Ference BA, Kastelein JJP, Ray KK, Ginsberg HN, Chapman MJ, Packard CJ, Laufs U, Oliver-Williams C, Wood AM, Butterworth AS, Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease. JAMA. 2019; 321: 364– 373. 30694319 PMC6439767 sourceExperimental — accuracy not yet measured
The Discussion reports similar lower coronary heart disease (CHD) risk per unit lower ApoB for triglyceride-lowering and LDL-C-lowering genetic variants, and describes triglyceride-rich VLDL remnants and LDL as ApoB-containing particles. But the Study Outcomes section defines the measured outcome as CHD, not the broader category of major vascular events. (LLM, conf=0.86)
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
“Recent data from the CANTOS trial showed that a 1.6-1.7 mg/dL reduction in hs-CRP was associated with a 17% reduction in major vascular events.50”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Discussion
What the sources say
- Partly supportedcites [50] Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N Engl J Med. 2017; 377: 1119– 1131. 28845751 sourceExperimental — accuracy not yet measured
The Results report a 17% lower risk for the key secondary cardiovascular end point with 150-mg canakinumab versus placebo (hazard ratio 0.83). They also report a greater reduction in hs-CRP, but express it as 37 percentage points, not a 1.6–1.7 mg/dL reduction. The paper does not establish the claimed association between that specific hs-CRP reduction and the event reduction. (LLM, conf=0.90)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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
“Examining individual classes, the RR (95%CI) per 1 mmol/L reduction in non-HDL-C was 0.80 (0.77-0.82) (0.79 per 40 mg/dl) for statins, 0.79 (0.71-0.88) (0.78 per 40 mg/dl) for fibrates, 0.84 (0.75-0.95) (0.83 per 40 mg/dl) for niacin, and 0.51 (0.40-0.64) (0.50 per 40 mg/dl) for omega-3 fatty acid trials (Supplemental Figure 2).”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Results > Non-HDL-C Lowering and Major Vascular Events
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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 a meta-regression by EPA dose, for each 1 gram/day of EPA administered there was a 7% relative lower risk in major vascular events (RR 0.93 [0.91-0.95], p<0.0001, Figure 3a).”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Results > Omega-3 Dose and Major Vascular Events
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“Examining individual classes, the RR (95%CI) per 1 mmol/L reduction in non-HDL-C was 0.80 (0.77-0.82) (0.79 per 40 mg/dl) for statins, 0.79 (0.71-0.88) (0.78 per 40 mg/dl) for fibrates, 0.84 (0.75-0.95) (0.83 per 40 mg/dl) for niacin, and 0.51 (0.40-0.64) (0.50 per 40 mg/dl) for omega-3 fatty acid trials (Supplemental Figure 2).”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Results > Non-HDL-C Lowering and Major Vascular Events
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA 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 removed, the RRs became 0.79 (0.76-0.83, P<0.0001) per 1 mmol/L (0.78 per 40 mg/dl) reduction in LDL-C”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Abstract > Results
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- The authors state this as an assumption: As the dose of a drug goes to zero, the lipid effect goes to zero and the treatment effect goes to zero (the origin).
- Rests on an assumption: Non-HDL-C is a surrogate for VLDL and LDL, and LDL-C and triglyceride are surrogates for LDL and VLDL.
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 a multivariable meta-regression model that included terms for both LDL-C and triglyceride (surrogates for LDL and VLDL), the RR (95%CI) was 0.80 (0.76-0.85, P<0.0001) per 1 mmol/L (0.79 per 40 mg/dl) reduction in LDL-C”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Abstract > Results
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- The authors state this as an assumption: As the dose of a drug goes to zero, the lipid effect goes to zero and the treatment effect goes to zero (the origin).
- Rests on an assumption: Non-HDL-C is a surrogate for VLDL and LDL, and LDL-C and triglyceride are surrogates for LDL and VLDL.
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 pooling 44 trials with necessary lipid data (nine fibrate, three niacin, eight omega-3 fatty acid, and 25 statin trials), the RR (95%CI) was 0.80 (0.76-0.85, P<0.0001) per 1 mmol/L (0.79 per 40 mg/dl) reduction in LDL-C and 0.84 (0.75-0.94, P=0.0026) per 1 mmol/L (0.92 per 40 mg/dl) reduction in triglycerides (Figure 2a, 2b).”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Results > LDL-C Lowering and Triglyceride Lowering and Major Vascular Events
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- It may state two separate claims as one. 29
- Probably not a substantial claim. 15
- The quote only partly states this claim. 1
Every source the paper cites for this claim was checked and supports it.
In the paper
“We demonstrate that triglyceride-lowering is associated with about half the CV risk reduction per mmol/L and therefore closer to ¼ the benefit per mg/dL (1 mmol/L = 38.67 mg/dl of LDL-C and 88.57 mg/dL of TG), a ratio congruent with our Mendelian randomization study data.35”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Discussion
What the sources say
- Supportedcites [35] Ference BA, Kastelein JJP, Ray KK, Ginsberg HN, Chapman MJ, Packard CJ, Laufs U, Oliver-Williams C, Wood AM, Butterworth AS, Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease. JAMA. 2019; 321: 364– 373. 30694319 PMC6439767 source
The Discussion (page unavailable) estimates that a 200-mg/dL triglyceride reduction would be needed for the cardiovascular-risk reduction associated with a 40-mg/dL LDL-C reduction. That implies about one-fifth as much benefit per mg/dL of triglyceride lowering and, using the citing sentence’s unit conversions, about half as much per mmol/L. The paper presents this as an inference from genetic associations, consistent with the citing sentence’s association language. (LLM, conf=0.90)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“However, genetic studies suggest that lower triglyceride levels, when accompanied by lower apolipoprotein B levels, are associated with lower CV risk”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Background
What the sources say
- Partly supportedcites [6] Do R, Willer CJ, Schmidt EM, Sengupta S, Gao C, Peloso GM, Gustafsson S, Kanoni S, Ganna A, Chen J, Common variants associated with plasma triglycerides and risk for coronary artery disease. Nat Genet. 2013; 45: 1345– 1352. 24097064 PMC3904346 sourceExperimental — accuracy not yet measured
The paper reports that variants associated with lower triglycerides and lower LDL cholesterol tend to be associated with lower coronary artery disease risk (results passage, page unavailable). It does not report the claimed condition of lower apolipoprotein B levels; LDL cholesterol is not the same measurement. (LLM, conf=0.87)
- Partly supportedcites [8] Willer CJ, Schmidt EM, Sengupta S, Peloso GM, Gustafsson S, Kanoni S, Ganna A, Chen J, Buchkovich ML, Mora S, Discovery and refinement of loci associated with lipid levels. Nat Genet. 2013; 45: 1274– 1283. 24097068 PMC3838666 sourceExperimental — accuracy not yet measured
The Results section (‘Association of individual lipids with coronary artery disease’; page not provided) reports that triglyceride-related genetic effects correlate with CAD risk, supporting the lower-triglyceride portion of the claim. It does not establish that the association depends on accompanying lower apolipoprotein B levels; the paper’s APOB mention concerns a protein-interaction network, not measured apolipoprotein B levels. (LLM, conf=0.88)
- Supportedcites [35] Ference BA, Kastelein JJP, Ray KK, Ginsberg HN, Chapman MJ, Packard CJ, Laufs U, Oliver-Williams C, Wood AM, Butterworth AS, Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease. JAMA. 2019; 321: 364– 373. 30694319 PMC6439767 source
The Discussion reports that triglyceride-lowering genetic variants were associated with lower coronary heart disease risk per unit reduction in ApoB-containing lipoproteins. It also says the benefit of lowering triglycerides may be proportional to the reduction in those particles. No page number is provided in our copy. (LLM, conf=0.93)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Moreover, triglycerides per se may not be atherogenic, but rather may be a marker for the concentration of atherogenic very low density lipoprotein (VLDL) particles.35”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Background
What the sources say
- Supportedcites [35] Ference BA, Kastelein JJP, Ray KK, Ginsberg HN, Chapman MJ, Packard CJ, Laufs U, Oliver-Williams C, Wood AM, Butterworth AS, Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease. JAMA. 2019; 321: 364– 373. 30694319 PMC6439767 source
The Discussion (page unavailable in our copy) says cardiovascular risk appears to depend on the concentration of ApoB-containing particles, including triglyceride-rich VLDL particles, rather than the mass of triglyceride they carry. It also says plasma triglycerides can be used to estimate the concentration of triglyceride-rich lipoproteins. This supports the claim’s cautious distinction between triglycerides themselves and the atherogenic particles they mark. (LLM, conf=0.89)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Proposed non-lipid lowering mechanisms for icosapent ethyl include anti-inflammatory, anti-arrhythmic, and anti-platelet properties.49”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Discussion
What the sources say
- Partly supportedcites [49] Preston Mason R New Insights into Mechanisms of Action for Omega-3 Fatty Acids in Atherothrombotic Cardiovascular Disease. Curr Atheroscler Rep. 2019; 21: 2. 30637567 PMC6330561 sourceExperimental — accuracy not yet measured
The paper identifies icosapent ethyl as a purified EPA preparation. In “Omega-3 Fatty Acids and Atherothrombotic Disease” (page unavailable), it reports reduced inflammatory markers with prescription EPA; Table 2 in “Distinct Roles of EPA and DHA in Cellular Function and Atherosclerosis” (page unavailable) lists reduced platelet activation. It does not propose an anti-arrhythmic mechanism: its REDUCE-IT discussion instead reports a higher rate of hospitalization for atrial fibrillation or flutter with EPA. (LLM, conf=0.87)
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.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Nonetheless, it is important to note that our recent Mendelian randomization study35 would suggest that it is simply the number of atherogenic apoB-containing lipoproteins that is the true determinant of cardiovascular risk and not the cholesterol or triglyceride content per se, which are surrogate biomarkers.”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Discussion
What the sources say
- Supportedcites [35] Ference BA, Kastelein JJP, Ray KK, Ginsberg HN, Chapman MJ, Packard CJ, Laufs U, Oliver-Williams C, Wood AM, Butterworth AS, Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease. JAMA. 2019; 321: 364– 373. 30694319 PMC6439767 source
The Discussion states that the effect of ApoB-containing lipoprotein particles on cardiovascular disease risk appears to depend on their circulating concentration rather than the mass of cholesterol or triglyceride they carry. It also reports that associations of triglycerides and LDL-C with coronary heart disease became null after adjustment for ApoB. Page numbers are not provided in the supplied copy. (LLM, conf=0.94)
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- 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
“These trials included a total of 197,270 patients with an average age of 63 years old and a mean baseline triglyceride level of 163 mg/dL (median 151, IQR 143-165 mg/dL).”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Results
Strength:plain· not yet calibratedn = 197,270Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one. The quote only partly states this 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
“Three non-statin trials were outliers and significantly deviated from the regression line: a fibrate trial, VA-HIT (p=0.02), and two omega-3 fatty acid trials, JELIS (p=0.0495) and REDUCE-IT (p=0.0002).”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Results > Non-HDL-C Lowering and Major Vascular Events
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 average median trial follow-up was 4.8 years during which there were 25,218 major CV events (Table).”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Results
Strength:plain· not yet calibratedn = 197,270Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ 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
“Of these, 24 triglyceride lowering trials were included in the meta-regression analyses.”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Results
Tests✓ 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
“Based on the observed meta-regression relationship between non-HDL-C lowering and reduction in major vascular events and the actual non-HDL-C lowering in non-statin trials, the power to detect a significant clinical benefit given the number of events in each of the non-statin trials was quite limited, being ≤20% in 14 trials, 21-50% in two trials, 51-79% in two trials and ≥80% in only one trial (S”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Results > Non-HDL-C Lowering and Major Vascular Events
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 contrast, the RR for omega-3 fatty acid trials differed significantly from the RRs seen in fibrate (p=0.008), niacin (p=0.004), and statin (p=0.005) trials.”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Results > Non-HDL-C Lowering and Major Vascular Events
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
“REDUCE-IT was a significant outlier and strongly influential trial in the meta-regression.”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Abstract > 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
“Once again, REDUCE-IT was a significant outlier (P=0.007) and had strong influence on the meta-regression (D = 2.27, if D >1.39 relatively influential) (Supplement Figure 5).”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Results > LDL-C Lowering and Triglyceride Lowering and Major Vascular Events
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
“As a check, models with terms for intercept were also created, and showed that the intercept terms were close to the origin and not significant.”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > 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. 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 significantly higher dose of 4 grams/day of EPA in REDUCE-IT gave the trial high leverage, but was not influential on the regression line (D = 0.27, if D >0.45 relatively influential).”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Results > Omega-3 Dose and Major Vascular Events
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ 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 nine fibrate trials (Supplemental Table 2), three niacin trials (Supplemental Table 3) and 13 omega-3 fatty acids trials (Supplemental Table 4) (one trial had both fibrate and niacin experimental arms).”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Results
Strength:plain· not yet calibratedn = 197,270Tests✓ 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.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“JELIS and DOIT were the only other two trials to test >1 gram/day of EPA and both had CV risk reduction beyond what was expected based on non-HDL-C lowering, supporting the potential pleiotropic benefits of higher-dose EPA.”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Publication bias was also assessed by funnel plots and Egger’s regression test.48”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Methods
What the sources say
- Not checked — no full text of the sourcecites [48] Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997; 315: 629– 634. 9310563 PMC2127453 source
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.
In the paper
“Most of the fibrate trials, both of the statin-era niacin trials, and all but two of the omega-3 trials have failed to show a statistically significant reduction in major vascular events.”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Background
What the sources say
- Not matchedcites 11-34
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Not matched
In the paper
“All results are reported in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines.41”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Methods
What the sources say
- Not checked — no full text of the sourcecites [41] Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009; 151: 264– 269, W264. 19622511 source
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 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
“Specifically, developing drugs that achieve large reductions in VLDL and triglycerides and/or targeting patients with high baseline levels of VLDL or triglycerides would likely increase the probability of showing a meaningful clinical benefit.”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Discussion
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
“In randomized controlled trials, triglyceride lowering is associated with lower risk of major vascular events, even after adjusting for LDL-C lowering, although the effect is attenuated when REDUCE-IT is excluded.”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Abstract > Conclusion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- The authors state this as an assumption: As the dose of a drug goes to zero, the lipid effect goes to zero and the treatment effect goes to zero (the origin).
- Rests on an assumption: Non-HDL-C is a surrogate for VLDL and LDL, and LDL-C and triglyceride are surrogates for LDL and VLDL.
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
“Specifically, a decrease in 40 mg/dl of LDL-C should translate into an approximately 20% lower CV risk, but a similar 40 mg/dL reduction in triglycerides is associated with only around 4-5% lower CV risk.”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Discussion
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
“Fifth, REDUCE-IT may have been an outlier because of the type of omega-3 fatty acid and/or the dose that was used.”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Discussion
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.
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
“Second, triglyceride lowering (a surrogate of triglyceride-rich VLDL) is associated with lower risk of cardiovascular events, but to a lesser extent per absolute amount of reduction than with LDL-C (a surrogate for cholesterol-rich LDL).”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Discussion
Tests✓ 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
“Each trial was reviewed independently by 2 of the authors (N.A.M. and M.S.S.).”
- Also stated in: § Methods · plain
“All disagreements were discussed and resolved by consensus.”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > 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. It may state two separate claims as one.
- Also stated in: § Methods · plain
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
“Fourth, REDUCE-IT was the most significant outlier and influencer of the meta-regression, and removing it attenuated the effect estimate for triglyceride lowering with an upper bound of the 95% CIs that just crosses 1.0.”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Discussion
Tests✓ 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
“Sensitivity analyses including terms for duration of follow up and proportion of background statin use (in trials of non-statin therapy) were performed but showed no significant interactions (p values for interaction of 0.53 and 0.55, respectively).”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Results > Non-HDL-C Lowering and Major Vascular Events
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Risk-of-bias assessments were performed for each trial using the Cochrane’s Collaboration tool.53”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Methods
What the sources say
- Not matchedcites [53]
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
“No significant bias was detected across trials although it was notable that JELIS was the only trial with an open-label design.”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Methods
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ 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
“It should also be noted that very few of these trials included a substantial proportion of patients with very high triglyceride levels (ie, >400 mg/dl), a group in whom triglyceride lowering would be expected to associate with the largest clinical benefit.”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Discussion > Limitations
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
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
“Thus, it is possible the magnitude of clinical benefit observed in REDUCE-IT could reflect a combination of both lower triglycerides and lower hs-CRP in the EPA arm vs. the comparator arm of mineral oil, but even those two factors together seem insufficient.”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Discussion
Tests✓ 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
“The meta-analysis was not performed on patient-level data.”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Discussion > Limitations
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
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
“In randomized controlled trials, triglyceride lowering is associated with lower risk of major vascular events, even after adjusting for LDL-C lowering, but that relationship was attenuated when REDUCE-IT is excluded.”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Discussion > Conclusions
Tests✓ 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
“There was visual evidence of publication bias (less small negative trials than expected) but this was not statistically significant.”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Discussion > Limitations
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
“Finally, few omega-3 trials used high doses, giving REDUCE-IT greater influence on the meta-regression line.”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Discussion > Limitations
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ 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
“All lipid measurements were not available in every trial and almost no trials had data on apoB.”
§ Association Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials > Discussion > Limitations
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
The authors state this as an assumption.
As the dose of a drug goes to zero, the lipid effect goes to zero and the treatment effect goes to zero (the origin).
“In each analysis the intercept was set at 0 to reflect the clinical assumption that as the dose of a drug goes to zero, the lipid effect goes to zero and the treatment effect goes to zero (ie, the origin).”
The paper relies on this without support.
Non-HDL-C is a surrogate for VLDL and LDL, and LDL-C and triglyceride are surrogates for LDL and VLDL.
“Starting with non-HDL-C, a surrogate for VLDL and LDL”
“In a multivariable meta-regression model that included terms for both LDL-C and triglyceride (surrogates for LDL and VLDL)”
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
“Increasing evidence now shows that older persons gain significant benefits from lipid lowering for primary prevention, and these benefits are even more impactful in persons with DM.”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [361]
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
“Neither linear assumption‐driven meta‐regressions 38 , 39 , 40 , 41 , 42 nor stratified dose analyses 42 , 43 have conclusively estimated the dose–response relationship between ω3 PUFA intake and relative risk reduction, raising the possibility of a nonlinear dose–response curve. 30”
From Association Between Omega-3 Fatty Acid Intake and Dyslipidemia: A Continuous Dose-Response Meta-Analysis of Randomized Controlled Trials (2023) · cites this paper as [38]
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
“H ypertriglyceridemia is common and is associated with an increased risk of atherosclerosis, 1-4”
From Targeting APOC3 with Olezarsen in Moderate Hypertriglyceridemia (2025) · cites this paper as [1]
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 association between triglyceride‐lowering and ω3 PUFA intake could causally lead to the reduction of cardiovascular risks in patients with high triglyceride, as previously reported in trials 18 , 19 and meta‐analyses. 38”
From Association Between Omega-3 Fatty Acid Intake and Dyslipidemia: A Continuous Dose-Response Meta-Analysis of Randomized Controlled Trials (2023) · cites this paper as [38]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“The mechanisms for end point prevention appear to be attributed to the pleiotropic effects in addition to serum lipid regulation. 38 , 148”
From Association Between Omega-3 Fatty Acid Intake and Dyslipidemia: A Continuous Dose-Response Meta-Analysis of Randomized Controlled Trials (2023) · cites this paper as [38]
The cited source says what the claim attributes to it.
In the citing paper
“Moderate elevations in triglyceride levels are associated with an increased risk of atherosclerotic cardiovascular disease, 1,2,19,20”
From Targeting APOC3 with Olezarsen in Moderate Hypertriglyceridemia (2025) · cites this paper as [1]
In the citing paper
“There is also evidence that reductions in plasma TG are associated with reduction in the risk of ASCVD events after adjustment for statin-induced LDL-C lowering.39–42”
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.
DHA trials include a zero-DHA dose
MinorThe reported range for the 11 trials with DHA starts at 0 mg. A trial receiving 0 mg of DHA cannot be one of the trials with DHA.
“In the 11 trials with DHA, the mean dose was 411 mg (median 380 mg) with a range of 0 mg to 950 mg.”
“Among the 13 omega-3 fatty acids trials, all but two used a combination of EPA + DHA.”
Citations
Cites
Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement
Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G., & for the PRISMA Group (2009) · BMJ · doi:10.1136/bmj.b2535 · Cited by 83,823
Bias in meta-analysis detected by a simple, graphical test
Egger, M., Smith, G. D., Schneider, M., & Minder, C. (1997) · BMJ · doi:10.1136/bmj.315.7109.629 · Cited by 56,722
Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement
Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G., & the PRISMA Group* (2009) · Annals of Internal Medicine · doi:10.7326/0003-4819-151-4-200908180-00135 · Cited by 37,554
The Cochrane Collaboration's tool for assessing risk of bias in randomised trials
Higgins, J. P. T., Altman, D. G., Gotzsche, P. C., Juni, P., Moher, D., Oxman, A. D., Savovic, J., Schulz, K. F., Weeks, L., Sterne, J. A. C., et al. (2011) · BMJ · doi:10.1136/bmj.d5928 · Cited by 33,817
Dermyshi, E., Wang, Y., Yan, C., Hong, W., Qiu, G., Gong, X., & Zhang, T. (2017) · Neonatology · doi:10.1159/000454668 · Cited by 24,586
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
Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease
Ridker, P. M., Everett, B. M., Thuren, T., MacFadyen, J. G., Chang, W. H., Ballantyne, C., Fonseca, F., Nicolau, J., Koenig, W., Anker, S. D., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1707914 · Cited by 9,482
Helsinki Heart Study: Primary-Prevention Trial with Gemfibrozil in Middle-Aged Men with Dyslipidemia
Frick, M. H., Elo, O., Haapa, K., Heinonen, O. P., Heinsalmi, P., Helo, P., Huttunen, J. K., Kaitaniemi, P., Koskinen, P., Manninen, V., et al. (1987) · New England Journal of Medicine · doi:10.1056/nejm198711123172001 · Cited by 3,881
Biological, clinical and population relevance of 95 loci for blood lipids
Teslovich, T. M., Musunuru, K., Smith, A. V., Edmondson, A. C., Stylianou, I. M., Koseki, M., Pirruccello, J. P., Ripatti, S., Chasman, D. I., Willer, C. J., et al. (2010) · Nature · doi:10.1038/nature09270 · Cited by 3,487
Flagged first, then by citations
Cited by
Sorted by citations
Heart Disease and Stroke Statistics—2023 Update: A Report From the American Heart Association
Tsao, C. W., Aday, A. W., Almarzooq, Z. I., Anderson, C. A. M., Arora, P., Avery, C. L., Baker-Smith, C. M., Beaton, A. Z., Boehme, A. K., Buxton, A. E., et al. (2023) · Circulation · doi:10.1161/cir.0000000000001123 · Cited by 8,300
Heart Disease and Stroke Statistics—2022 Update: A Report From the American Heart Association
Tsao, C. W., Aday, A. W., Almarzooq, Z. I., Alonso, A., Beaton, A. Z., Bittencourt, M. S., Boehme, A. K., Buxton, A. E., Carson, A. P., Commodore-Mensah, Y., et al. (2022) · Circulation · doi:10.1161/cir.0000000000001052 · Cited by 5,987
Heart Disease and Stroke Statistics—2021 Update: A Report From the American Heart Association
Virani, S. S., Alonso, A., Aparicio, H. J., Benjamin, E. J., Bittencourt, M. S., Callaway, C. W., Carson, A. P., Chamberlain, A. M., Cheng, S., Delling, F. N., et al. (2021) · Circulation · doi:10.1161/cir.0000000000000950 · Cited by 5,784
Martin, S. S., Aday, A. W., Almarzooq, Z. I., Anderson, C. A. M., Arora, P., Avery, C. L., Baker-Smith, C. M., Barone Gibbs, B., Beaton, A. Z., Boehme, A. K., et al. (2024) · Circulation · doi:10.1161/cir.0000000000001209 · Cited by 2,800
Martin, S. S., Aday, A. W., Allen, N. B., Almarzooq, Z., Anderson, C. A. M., Arora, P. K., Avery, C. L., Baker-Smith, C. M., Bansal, N., Beaton, A., et al. (2025) · Circulation · doi:10.1161/cir.0000000000001303 · Cited by 1,284
Metadata
- Authors
- Marston, N. A., Giugliano, R. P., Im, K., Silverman, M. G., O’Donoghue, M. L., Wiviott, S. D., Ference, B. A., & Sabatine, M. S.
- Affiliations
- Brigham and Women's Hospital (US)
- Harvard University (US)
- University of Cambridge (GB)
- ORCID
- Venue
- Circulation
- Published
- 2019-10-15
- Volume
- 140
- Issue
- 16
- Pages
- 1308-1317
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- PMC
- PMC6791781
- OpenAlex
- W2973983647
- Cited by
- 301
- References
- 55
- Citations by year
- 2026: 19 · 2025: 58 · 2024: 51 · 2023: 45 · 2022: 42 · 2021: 51 · 2020: 32 · 2019: 3
- FWCI
- 30.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (L30 HL143770, K08HL153950, F32HL144029)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- triglyceride lowering, cardiovascular risk reduction, lipid-lowering therapy, fibrates, nicotinic acid, omega-3 fatty acids, non-HDL cholesterol, LDL cholesterol, major vascular events, REDUCE-IT trial, icosapent ethyl, statins, surrogate endpoints, meta-regression, cardiovascular disease prevention, hypertriglyceridemia, VLDL
- MeSH terms
- Cardiovascular Diseases, Humans, Cholesterol, LDL, Niacin, Risk, Triglycerides, Fatty Acids, Omega-3, Randomized Controlled Trials as Topic, Hydroxymethylglutaryl-CoA Reductase Inhibitors
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 ›
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