The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index; 18 of the 31 sources its claims cite were checked for support.
Association of Triglyceride-Lowering LPL Variants and LDL-C–Lowering LDLR Variants With Risk of Coronary Heart Disease
Open accessAbstract
Importance: Triglycerides and cholesterol are both carried in plasma by apolipoprotein B (ApoB)-containing lipoprotein particles. It is unknown whether lowering plasma triglyceride levels reduces the risk of cardiovascular events to the same extent as lowering low-density lipoprotein cholesterol (LDL-C) levels. Objective: To compare the association of triglyceride-lowering variants in the lipoprotein lipase (LPL) gene and LDL-C-lowering variants in the LDL receptor gene (LDLR) with the risk of cardiovascular disease per unit change in ApoB. Design, Setting, and Participants: Mendelian randomization analyses evaluating the associations of genetic scores composed of triglyceride-lowering variants in the LPL gene and LDL-C-lowering variants in the LDLR gene, respectively, with the risk of cardiovascular events among participants enrolled in 63 cohort or case-control studies conducted in North America or Europe between 1948 and 2017. Exposures: Differences in plasma triglyceride, LDL-C, and ApoB levels associated with the LPL and LDLR genetic scores. Main Outcomes and Measures: Odds ratio (OR) for coronary heart disease (CHD)-defined as coronary death, myocardial infarction, or coronary revascularization-per 10-mg/dL lower concentration of ApoB-containing lipoproteins. Results: A total of 654 783 participants, including 91 129 cases of CHD, were included (mean age, 62.7 years; 51.4% women). For each 10-mg/dL lower level of ApoB-containing lipoproteins, the LPL score was associated with 69.9-mg/dL (95% CI, 68.1-71.6; P = 7.1 × 10-1363) lower triglyceride levels and 0.7-mg/dL (95% CI, 0.03-1.4; P = .04) higher LDL-C levels; while the LDLR score was associated with 14.2-mg/dL (95% CI, 13.6-14.8; P = 1.4 × 10-465) lower LDL-C and 1.9-mg/dL (95% CI, 0.1-3.9; P = .04) lower triglyceride levels. Despite these differences in associated lipid levels, the LPL and LDLR scores were associated with similar lower risk of CHD per 10-mg/dL lower level of ApoB-containing lipoproteins (OR, 0.771 [95% CI, 0.741-0.802], P = 3.9 × 10-38 and OR, 0.773 [95% CI, 0.747-0.801], P = 1.1 × 10-46, respectively). In multivariable mendelian randomization analyses, the associations between triglyceride and LDL-C levels with the risk of CHD became null after adjusting for differences in ApoB (triglycerides: OR, 1.014 [95% CI, 0.965-1.065], P = .19; LDL-C: OR, 1.010 [95% CI, 0.967-1.055], P = .19; ApoB: OR, 0.761 [95% CI, 0.723-0.798], P = 7.51 × 10-20). Conclusions and Relevance: Triglyceride-lowering LPL variants and LDL-C-lowering LDLR variants were associated with similar lower risk of CHD per unit difference in ApoB. Therefore, the clinical benefit of lowering triglyceride and LDL-C levels may be proportional to the absolute change in ApoB.
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Claims the paper makes
26 Own result · 9 Own interpretation · 7 Own method · 4 Partly supported · 2 Supported · 2 Supported so far · 2 Not supported · 2 No full text of the sources · 1 Sources not found · 1 No basis given · accuracy not yet measured
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“However, the mean reduction in plasma triglyceride concentration in the fibrate trials was only 20 mg/dL to 50 mg/dL, a fraction of what would be needed to significantly reduce the risk of major vascular events within a shortterm trial.”
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > Discussion
What the sources say
- Not checked — no full text of the sourcecites [29] Frick, 1987, Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia: safety of treatment, changes in risk factors, and incidence of coronary heart disease., N Engl J Med source
- Disputedcites [30] Rubins, 1999, Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol., N Engl J Med sourceExperimental — accuracy not yet measured
The Effects on Lipid Levels section reports triglycerides of 115 mg/dL with gemfibrozil versus 166 mg/dL with placebo, a 51 mg/dL difference. Contrary to the claim that a reduction of roughly this size was too small to yield a significant benefit in a trial, the Outcomes section reports a significant reduction in coronary death or nonfatal myocardial infarction, and the paper reports a significant reduction in the combined outcome including stroke. The paper does not isolate triglyceride lowering from the treatment’s other lipid effects as the cause of that benefit. (LLM, conf=0.86)
Checked by a reasoning model — may be wrong.
- Not checked — no full text of the sourcecites [31] Bezafibrate Infarction Prevention (BIP) Study, 2000, Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease., Circulation source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Every source the paper cites for this claim was checked and supports it.
In the 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”
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > Discussion
What the sources say
- Supportedcites [3] Baigent, 2010, Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials., Lancet source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Supportedcites [4] Silverman, 2016, Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: a systematic review and meta-analysis., JAMA source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“while rare, loss-of-function mutations in the APOC3, ANGPTL3, and ANGPTL4 genes, which encode for natural inhibitors of LPL, are associated with lower triglyceride levels and a corresponding lower risk of cardiovascular disease.[9][10][11][12][13]”
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > Abstract
What the sources say
- Not checked — no full text of the sourcecites [9] Nordestgaard, 1997, Heterozygous lipoprotein lipase deficiency: frequency in the general population, effect on plasma lipid levels, and risk of ischemic heart disease., Circulation source
- Partly supportedcites [10] Jørgensen, 2014, Loss-of-function mutations in APOC3 and risk of ischemic vascular disease., N Engl J Med sourceExperimental — accuracy not yet measured
The Results and Discussion report that APOC3 loss-of-function mutations are associated with lower nonfasting triglycerides and reduced risk of ischemic cardiovascular disease. The paper also describes apolipoprotein C3 as inhibiting lipoprotein lipase, but the passages do not establish the claimed associations for ANGPTL3 or ANGPTL4. Page numbers were not available in our copy. (LLM, conf=0.90)
- Partly supportedcites [11] Khera, 2017, Association of rare and common variation in the lipoprotein lipase gene with coronary artery disease., JAMA sourceExperimental — accuracy not yet measured
The Discussion (page not available in our copy) identifies APOC3 and ANGPTL4 as LPL inhibitors and says rare inactivating mutations in those genes confer substantial vascular protection. It does not make the corresponding claim about ANGPTL3 or establish lower triglyceride levels for mutations in all three genes; its triglyceride analysis concerns variants in LPL. (LLM, conf=0.87)
- Not checked yetcites [12] Dewey, 2016, Inactivating variants in ANGPTL4 and risk of coronary artery disease., N Engl J Med source
Checked before — its earlier verdict is held back until a new check runs.
- Partly supportedcites [13] Stitziel, 2016, Coding variation in ANGPTL4, LPL, and SVEP1 and the risk of coronary disease., N Engl J Med sourceExperimental — accuracy not yet measured
The ANGPTL4 Loss-of-Function Mutations section (page unavailable) reports lower triglyceride levels and lower coronary artery disease risk in ANGPTL4 mutation carriers. The Discussion and Figure 2 caption also describe APOC3 as an LPL inhibitor and discuss its loss-of-function variants, but identify ANGPTL3 only as an LPL regulator; they do not report the claimed triglyceride and disease-risk associations for ANGPTL3. (LLM, conf=0.87)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“The results of this study may also help to explain why prior randomized trials evaluating fibrates, which lower plasma triglyceride levels at least partially through the LPL pathway, have failed to consistently demonstrate that lowering triglyceride levels reduces the risk of cardiovascular events.[29][30][31][32][33]”
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > Discussion
What the sources say
- Not checked — no full text of the sourcecites [29] Frick, 1987, Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia: safety of treatment, changes in risk factors, and incidence of coronary heart disease., N Engl J Med source
- Supportedcites [30] Rubins, 1999, Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol., N Engl J Med source
This citation identifies one of the prior randomized fibrate trials discussed in the citing sentence. The Treatment Regimen and Follow-up section describes randomized assignment to gemfibrozil or placebo; Effects on Lipid Levels reports lower triglycerides, and Outcomes reports fewer coronary events. This trial found a benefit; the sentence’s observation about inconsistent results across trials concerns the cited trials collectively, not this trial alone. Page numbers were not available in our copy. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [31] Bezafibrate Infarction Prevention (BIP) Study, 2000, Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease., Circulation source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Every source the paper cites for this claim was checked and supports it.
In the paper
“Furthermore, the results of this study are consistent with a recent mendelian randomization study that demonstrated that the causal effect of LDL particles on the risk of cardiovascular disease appears to be determined by the concentration of circulating LDL particles as measured by ApoB rather than by the mass of cholesterol carried by those particles as measured by LDL-C.23”
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > Discussion
What the sources say
- Supportedcites [23] Ference, 2017, Association of genetic variants related to CETP inhibitors and statins with lipoprotein levels and cardiovascular risk., JAMA source
The Study Design section says the mendelian randomization analysis compared LDL-C and apoB to assess whether cardiovascular risk tracks cholesterol mass or particle concentration. The Discussion states the paper’s conclusion in nearly the same terms as the citing sentence, including the qualifier “appears.” (LLM, conf=0.94)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The results of the current study extend those findings by suggesting that triglyceride-rich remnant particles have approximately the same effect on the risk of cardiovascular disease as LDL particles.”
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > Discussion
What the sources say
- Not checked — no full text of the sourcecites [27] Varbo, 2013, Remnant cholesterol as a causal risk factor for ischemic heart disease., J Am Coll Cardiol source
- Partly supportedcites [28] Sarwar, 2010, Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies, Lancet sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) describes VLDL and remnant lipoproteins as potentially proatherogenic, and reports findings consistent with a causal role for triglyceride-mediated pathways in coronary heart disease. It does not compare the effect of remnant particles with that of LDL particles or establish approximately equal effects; its reported outcome is coronary heart disease rather than cardiovascular disease broadly. (LLM, conf=0.85)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“Despite these differences in associated lipid levels, the LPL and LDLR scores were associated with similar lower risk of CHD per 10-mg/dL lower level of ApoB-containing lipoproteins (odds ratio [OR], 0.771 [95% CI, 0.741-0.802],P = 3.9 × 10 -38 for the LPL score and OR, 0.773 [95% CI, 0.747-0.801],P = 1.1 × 10 -46 for the LDLR score).”
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > Association of Genetic Scores With Lipids and CHD per Unit Change in ApoB
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 multivariable mendelian randomization analyses, the associations between triglyceride and LDL-C levels with the risk of CHD became null after adjusting for differences in ApoB”
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“and 1.9-mg/dL (95% CI, 0.1-3.9;P = .04)lower plasma triglyceride level”
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > Association of Genetic Scores With Lipids and CHD per Unit Change in ApoB
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 each 10-mg/dL lower level of ApoB-containing lipoproteins, the LPL score was associated with 69.9-mg/dL (95% CI, 68.1-71.6;P = 7.1 × 10 -1363 ) lower plasma triglyceride levels”
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > Association of Genetic Scores With Lipids and CHD per Unit Change in ApoB
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 11
- Probably not a substantial claim. 8
- The quote only partly states this claim. 1
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“By contrast, the guidelines do not recommend treatment to lower plasma triglyceride levels because randomized trials have not provided consistent evidence that lowering plasma triglyceride levels reduces the risk of cardiovascular events.1,2”
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > Abstract
What the sources say
- Disputedcites [1] Catapano, 2016, 2016 ESC/EAS guidelines for the management of dyslipidaemias., Eur Heart J sourceExperimental — accuracy not yet measured
Section 7.3 (p. 33) explicitly recommends considering drug treatment to lower triglycerides in high-risk patients with levels above 2.3 mmol/L, contrary to the claim that the guidelines do not recommend such treatment. The same section says evidence for benefit is modest, and section 9.5.2.2 (p. 42) describes mixed trial results; those qualifications do not negate the conditional recommendation. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
- Not checked — no full text of the sourcecites [2] Stone, 2014, 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines., J Am Coll Cardiol source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Disputed
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Several novel therapies that potently reduce triglyceride levels are currently in development.[6][7][8]”
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > Abstract
What the sources say
- Supportedcites [6] Dewey, 2017, Genetic and pharmacologic inactivation of ANGPTL3 and cardiovascular disease., N Engl J Med source
The Results report that evinacumab, an ANGPTL3 inhibitor, reduced fasting triglycerides by up to 76% in humans. The Discussion describes a clinical trial and calls for further investigation of ANGPTL3 inhibition as a therapy. This paper supports one therapy in the sentence’s collectively cited claim; it need not document all several therapies. (LLM, conf=0.87)
- Not checked — no full text of the sourcecites [7] Gaudet, 2017, ANGPTL3 inhibition in homozygous familial hypercholesterolemia., N Engl J Med source
- Supportedcites [8] Gaudet, 2015, Antisense inhibition of apolipoprotein C-III in patients with hypertriglyceridemia., N Engl J Med source
The Methods describe ISIS 304801 as a treatment being evaluated in a phase 2 study. The Discussion reports a dose-dependent mean triglyceride reduction of 71%. This paper supports the sentence by providing one example of a novel triglyceride-lowering therapy; the other citations need not be supported by this paper. (LLM, conf=0.90)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“rare loss-of-function mutations in the lipoprotein lipase (LPL) gene are associated with higher plasma triglyceride levels and a higher risk of cardiovascular disease”
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > Abstract
What the sources say
- Not checked — no full text of the sourcecites [9] Nordestgaard, 1997, Heterozygous lipoprotein lipase deficiency: frequency in the general population, effect on plasma lipid levels, and risk of ischemic heart disease., Circulation source
- Partly supportedcites [10] Jørgensen, 2014, Loss-of-function mutations in APOC3 and risk of ischemic vascular disease., N Engl J Med sourceExperimental — accuracy not yet measured
The Abstract (page unavailable) supports the general association between higher triglyceride levels and greater cardiovascular risk. It does not report an association for loss-of-function mutations in the LPL gene: the mutations studied are in APOC3, and they are associated with lower triglyceride levels and reduced risk. The Discussion mentions lipoprotein lipase as an enzyme inhibited by apolipoprotein C3, not as the mutated gene. (LLM, conf=0.82)
- Partly supportedcites [11] Khera, 2017, Association of rare and common variation in the lipoprotein lipase gene with coronary artery disease., JAMA sourceExperimental — accuracy not yet measured
The Results (page unavailable) associate rare damaging LPL mutations with higher plasma triglycerides and greater odds of early-onset coronary artery disease (CAD); the CAD association was most pronounced for loss-of-function mutations. However, the triglyceride finding pools loss-of-function and damaging missense mutations, rather than establishing it for loss-of-function mutations alone. The study also assessed early-onset CAD, not cardiovascular disease generally. (LLM, conf=0.84)
- Partly supportedcites [12] Dewey, 2016, Inactivating variants in ANGPTL4 and risk of coronary artery disease., N Engl J Med sourceExperimental — accuracy not yet measured
The paper’s background discussion (section labeled Abstract > Conclusions; page unavailable) says mutations that decrease LPL function increase serum triglycerides. It does not say those mutations increase cardiovascular disease risk; it reports lower risk for mutations that increase LPL activity instead. Its coronary artery disease results concern ANGPTL4, not LPL. (LLM, conf=0.86)
- Partly supportedcites [13] Stitziel, 2016, Coding variation in ANGPTL4, LPL, and SVEP1 and the risk of coronary disease., N Engl J Med sourceExperimental — accuracy not yet measured
The ‘Coding Variation in LPL and the Risk of Coronary Artery Disease’ section reports that one low-frequency, partial loss-of-function LPL variant (p.D36N) was associated with higher coronary artery disease risk. Figure 2 in the Discussion depicts higher triglycerides as an expected effect of LPL loss of function, but the paper does not report a measured triglyceride association for that variant. The claim presents that expected effect as an observed association and generalizes from one variant to mutations. (LLM, conf=0.86)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Second, genetic variants reflect the effect of lifelong changes in ApoB-containing lipoproteins on the risk of cardiovascular disease, which appear to be cumulative over time.5,34”
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > Limitations
What the sources say
- Partly supportedcites [5] Ference, 2017, Low-density lipoproteins cause atherosclerotic cardiovascular disease: 1, Evidence from genetic, epidemiologic, and clinical studies: a consensus statement from the European Atherosclerosis Society Consensus Panel., Eur Heart J sourceExperimental — accuracy not yet measured
The sections on Mendelian randomization and cumulative LDL exposure say that LDL-C–associated genetic variants reflect lifetime cardiovascular risk and that the effect depends on the duration of LDL-C exposure (page not available). The paper identifies LDL as an apoB-containing lipoprotein, but its genetic and cumulative-exposure findings concern LDL specifically; they do not establish the same finding for apoB-containing lipoproteins as a whole. (LLM, conf=0.85)
- Partly supportedcites [34] Ference, 2012, Effect of long-term exposure to lower low-density lipoprotein cholesterol beginning early in life on the risk of coronary heart disease: a mendelian randomization analysis., J Am Coll Cardiol sourceExperimental — accuracy not yet measured
The Discussion (page not provided) says genetically mediated differences in LDL-C reflect the cumulative effect of lifelong exposure, and the study links those differences to coronary heart disease risk. It does not establish the same claim for ApoB-containing lipoproteins as a whole or for cardiovascular disease beyond coronary heart disease. (LLM, conf=0.86)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- 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
“A total of 654 783 participants, including 91 129 cases of CHD, were included (mean age, 62.7 years; 51.4% women).”
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > Abstract
plainn = 91,129- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“combined exposure to both the LPL and LDLR genetic scores was associated with linearly ad- ditive lower levels of triglyceride”
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > Association of Genetic Scores With Lipids and CHD per Unit Change in ApoB
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“For example, for each 10-mg/dL lower plasma ApoB concentration associated with a genetic score consisting of 51 variants associated with triglycerides but not LDL-C at genome-wide level of significance, there was a corresponding 41.3-mg/dL lower triglyceride level, 2.1-mg/dL lower LDL-C level, and a lower risk of CHD (odds ratio [OR], 0.762 [95% CI, 0.724-0.803]).”
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > APOB: rs1367117
plaincorrelationaln = 783- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For example, in multivariable mendelian randomization analyses involving these 186 genetic variants, both triglycerides (odds ratio [OR], 0.876 per 50-mg/dL lower triglycerides) and LDL-C (OR, 0.862 per 10-mg/dL lower LDL-C) were independently associated with a lower risk of CHD at genome-wide level of significance.”
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > APOB: rs1367117
plaincorrelationaln = 783- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, for the same 10-mg/dL lower plasma ApoB concentration associated with a genetic score consisting of 168 variants associated with either triglycerides or LDL-C at genome-wide level of significance, there was a corresponding 21.6-mg/dL lower triglyceride level, an 11.8-mg/dL lower LDL-C level, and a similar lower risk of CHD (OR, 0.770 [95% CI, 0.757-0.783]).”
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > APOB: rs1367117
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The associations between lower triglyceride level and lower LDL-C level with risk of CHD due to these variants appeared to be independent, additive, and proportional to the absolute change in ApoB.”
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > Discussion
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Both triglycerides and cholesterol are carried in plasma by ApoB-containing lipoprotein particles.
- Rests on an assumption: All ApoB-containing lipoproteins have a single ApoB molecule.
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
“The results of this study suggest that the clinical benefit of lowering triglyceride levels is similar to the clinical benefit of lowering LDL-C levels per unit change in ApoB and is proportional to the net absolute reduction in ApoB-containing lipoproteins.”
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > Discussion
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Both triglycerides and cholesterol are carried in plasma by ApoB-containing lipoprotein particles.
- Rests on an assumption: All ApoB-containing lipoproteins have a single ApoB molecule.
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 regression analyses were performed separately in each of the included studies adjusting for age, sex, and the first 5 principal components of ancestry.”
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > Study Design and Statistical Analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“The cholesterol, and perhaps triglyceride, content of the ApoB particles retained in the artery wall provokes an inflammatory response that leads to the initiation and progression of atherosclerotic plaque.25”
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > Discussion
What the sources say
- Not checked — no full text of the sourcecites [25] Nordestgaard, 2014, Triglycerides and cardiovascular disease., Lancet source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.”
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > Conflict
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.”
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > Acknowledgements
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Dr Ference had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.”
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > Contribution
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“First, this study compared triglyceride-and LDL-C-lowering genetic variants not lipidlowering therapies.”
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > Limitations
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
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 other disclosures were reported.”
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > Conflict
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
It is unknown whether lowering plasma triglyceride levels by targeting the LPL pathway will reduce the risk of cardiovascular events.
“However, it is unknown whether lowering plasma triglyceride levels by targeting the LPL pathway will reduce the risk of cardiovascular events.”
The paper relies on this without support.
Both triglycerides and cholesterol are carried in plasma by ApoB-containing lipoprotein particles.
“Both triglycerides and cholesterol are carried in plasma by apolipoprotein B (ApoB)-containing lipoprotein particles.”
The paper relies on this without support.
All ApoB-containing lipoproteins have a single ApoB molecule.
“Because all ApoB-containing lipoproteins, including triglyceriderich lipoprotein particles and LDL particles, have a single ApoB molecule”
The paper relies on this without support.
ApoB-containing particles are secreted by the liver as VLDL particles, which principally contain triglycerides, some cholesterol, and 1 molecule of ApoB.
“These particles are secreted by the liver as VLDL particles, which principally contain triglycerides, some cholesterol, and 1 molecule of ApoB.”
The paper relies on this without support.
Lipoprotein lipase removes most of the triglycerides from VLDL particles to convert them into triglyceride-depleted cholesterol-carrying LDL particles, which are then removed from plasma by hepatic LDL receptors.
“Lipoprotein lipase removes most of the triglycerides from these particles to convert the triglyceride-rich VLDL particles into triglyceridedepleted cholesterol-carrying LDL particles, which are then removed from plasma by hepatic LDL receptors.”
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
“Multiple epidemiological and genetic analyses have demonstrated an independent association with increased cardiovascular risk (14)”
From Effects of Icosapent Ethyl on Total Ischemic Events (2019) · cites this paper as [14]
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
“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 [20]
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
“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”
From 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 (2019) · cites this paper as [35]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Genetic studies and epidemiologic data increasingly implicate remnant lipoproteins as causal contributors to atherogenesis, providing a strong mechanistic and clinical rationale for targeted intervention [8–12].”
From Targeting Triglycerides in Cardiovascular Disease Prevention: Evidence, Mechanisms, and Emerging Therapies (2026) · cites this paper as [12]
The cited source says what the claim attributes to it.
In the citing paper
“Furthermore, Mendelian randomization studies demonstrated that the reduction in cardiovascular risk associated with genetic variation in clearance and processing of apoB-containing lipoproteins, including LDL particles as well as TG-rich VLDL particles and their remnants, was correlated with the change of concentration of these particles as measured by apoB rather than the cholesterol mass carried”
From Quantifying atherogenic lipoproteins for lipid-lowering strategies: Consensus-based recommendations from EAS and EFLM (2020) · cites this paper as [80]
The cited source says what the claim attributes to it.
In the citing paper
“suggesting that the number of atherogenic particles may be the driver of cardiovascular risk, rather than cholesterol or TG content per se.4,5”
From Association of Apolipoprotein B–Containing Lipoproteins and Risk of Myocardial Infarction in Individuals With and Without Atherosclerosis (2022) · cites this paper as [4]
The cited source says what the claim attributes to it.
In the citing paper
“Mendelian randomization studies have shown that apoB is a better predictor of coronary artery disease risk than serum LDL-C or TG concentration”
From Association of Apolipoprotein B–Containing Lipoproteins and Risk of Myocardial Infarction in Individuals With and Without Atherosclerosis (2022) · cites this paper as [4]
The cited source says what the claim attributes to it.
In the citing 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”
The cited source says what the claim attributes to it.
In the citing 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”
The cited source says what the claim attributes to it.
In the citing 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”
The cited source says what the claim attributes to it.
In the citing paper
“However, genetic studies suggest that lower triglyceride levels, when accompanied by lower apolipoprotein B levels, are associated with lower CV risk”
The cited source says what the claim attributes to it.
In the citing 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.”
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Multiple disturbances in lipoprotein metabolism in individuals with prediabetes and T2D result from the combined effects of insulin deficiency, insulin resistance, and hyperglycemia.”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [308]
Experimental — accuracy not yet measuredIn the citing paper
“Over the past three decades, epidemiologic and genetic evidence has accumulated to support the concept that elevated levels of plasma TG, TRL, and TRL remnants are causally related to an increased risk of ASCVD-related events—myocardial infarction (MI), stroke, and aortic valve stenosis—and all-cause mortality.1,2,17,19,20,24–28”
In the citing paper
“Recent advances in human genetics, together with a large body of epidemiologic, preclinical, and clinical trial results, provide strong support for a causal association between triglycerides (TG), TG-rich lipoproteins (TRL), and TRL remnants, and increased risk of myocardial infarction, ischaemic stroke, and aortic valve stenosis.”
In the citing paper
“Atherosclerotic cardiovascular disease risk mediated by TRLs appears to be determined by the circulating concentration of apoB-containing particles rather than their TG content and that the clinical benefit of lowering TG correlates with the reduction in apoB, rather than the change in plasma TG concentration.”
From Clinical review on triglycerides (2020) · cites this paper as [24]
In the citing paper
“A recent Mendelian randomization study found that all apoB-containing lipoproteins have a similar effect on ASCVD risk.24”
From Clinical review on triglycerides (2020) · cites this paper as [24]
In the citing paper
“Furthermore, Mendelian randomization studies have demonstrated that long-term exposure to lower LDL-C levels is associated with a much lower risk of CV events as compared with shorter-term exposure to lower LDL-C (as achieved, for example, in randomized trials) [48,52].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [52]
In the citing paper
“Triglyceride elevation is a potent marker of residual cardiovascular risk in patients with well-controlled low-density lipoprotein cholesterol (LDL-C) on statin therapy, as shown in both randomized statin trials and observational studies.1–3”
From REDUCE-IT USA: Results From the 3146 Patients Randomized in the United States (2020) · cites this paper as [2]
In the citing paper
“For example, haemoglobin is a heterotetramer that is made up of alpha and beta globin polypeptides, each encoded by discrete genes 62 .”
From Integrating genomics with biomarkers and therapeutic targets to invigorate cardiovascular drug development (2021) · cites this paper as [62]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
“11.64-mg/dL (95% CI, 10.38-10.90;P = 8.3 × 10 -1365 ) lower plasma triglyceride level”
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > LPL and LDLR Genetic Scores
Reported 11.64 · recomputed 10.64
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > APOB: rs1367117
“there was a corresponding 41.3-mg/dL lower triglyceride level”
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > APOB: rs1367117
“| 51 Variants associated with triglycerides at P < 5.0×10 -8 , | -43.1 (-44.5 to -41.7) | -2.1 (-2.6 to -1.6) | 0.762 (0.724 to 0.803) |”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > Discussion
“there is a corresponding 14.1-mg/dL lower LDL-C level”
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > Association of Genetic Scores With Lipids and CHD per Unit Change in ApoB
“the LDLR score was associated with 14.2-mg/dL (95% CI, 13.6-14.8;P = 1.4 × 10 -465 ) lower plasma LDL-C level”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > Discussion
“-69.9 (-71.6 to -68.3)”
§ Association of Triglyceride-Lowering LPL Variants and LDL-C-Lowering LDLR Variants With Risk of Coronary Heart Disease > Discussion
“-69.9 (-71.6 to -68.1)”
Citations
Cites
Sudlow, C., Gallacher, J., Allen, N., Beral, V., Burton, P., Danesh, J., Downey, P., Elliott, P., Green, J., Landray, M., et al. (2015) · PLOS Medicine · doi:10.1371/journal.pmed.1001779 · Cited by 12,728
Self-citationStone, 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
Cholesterol Treatment Trialists' (CTT) Collaboration (2010) · The Lancet · doi:10.1016/s0140-6736(10)61350-5 · Cited by 6,550
Ference, B. A., Ginsberg, H. N., Graham, I., Ray, K. K., Packard, C. J., Bruckert, E., Hegele, R. A., Krauss, R. M., Raal, F. J., Schunkert, H., et al. (2017) · European Heart Journal · doi:10.1093/eurheartj/ehx144 · Cited by 3,962
Self-citationHelsinki 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
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) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.11.002 · Cited by 3,845
Rubins, H. B., Robins, S. J., Collins, D., Fye, C. L., Anderson, J. W., Elam, M. B., Faas, F. H., Linares, E., Schaefer, E. J., Schectman, G., et al. (1999) · New England Journal of Medicine · doi:10.1056/nejm199908053410604 · Cited by 3,439
Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia
Bhatt, D. L., Steg, P. G., Miller, M., Brinton, E. A., Jacobson, T. A., Ketchum, S. B., Doyle, R. T., Juliano, R. A., Jiao, L., Granowitz, C., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1812792 · Cited by 3,317
Self-citation2016 ESC/EAS Guidelines for the Management of Dyslipidaemias
Catapano, A. L., Graham, I., De Backer, G., Wiklund, O., Chapman, M. J., Drexel, H., Hoes, A. W., Jennings, C. S., Landmesser, U., Pedersen, T. R., et al. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehw272 · Cited by 3,162
Self-citation
Cited by
Sorted by citations
Items 201–300 of 693
Zuber, V., Lewin, A., Levin, M. G., Haglund, A., Ben‐Aicha, S., Emanueli, C., Damrauer, S. M., Burgess, S., Gill, D., & Bottolo, L. (2023) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2023.06.005 · Cited by 30
Feingold, K. R., & Grünfeld, C. (2023) · Contemporary cardiology · doi:10.1007/978-3-031-13177-6_14 · Cited by 35
Gonna, H., & Ray, K. K. (2019) · Diabetes Obesity and Metabolism · doi:10.1111/dom.13691 · Cited by 30
Self-citationRaman spectroscopy characterization of the major classes of plasma lipoproteins
Ricciardi, A., Piuri, G., Porta, M. G. D., Mazzucchelli, S., Bonizzi, A., Truffi, M., Sevieri, M., Allevi, R., Corsi, F., Cazzola, R., et al. (2020) · Vibrational Spectroscopy · doi:10.1016/j.vibspec.2020.103073 · Cited by 29
“LPs fractionation and quantification are a matter of primary interest in clinical medicine since several large-scale epidemiological studies showed that elevated concentrations of fasting cholesterol and triacylglycerols, stored in specific LPs, are associated with an increased incidence of cardiovascular events [9,10…”
BackgroundTriglyceride-Rich Lipoproteins: Their Role in Atherosclerosis
Castillo-Núñez, Y., Morales-Villegas, E., & Aguilar-Salinas, C. A. (2021) · Revista de investigaci�n Cl�nica · doi:10.24875/ric.21000416 · Cited by 35
Understanding Hypertriglyceridemia: Integrating Genetic Insights
Alves, M., Laranjeira, F., & Correia‐da‐Silva, G. (2024) · Genes · doi:10.3390/genes15020190 · Cited by 35
“Further support for TG-lowering variants in LPL and CVD risk came from a study by Ference et al. with participants enrolled in cohort or case–control studies between 1948 and 2017 [155].”
BackgroundChapman, M. J., Packard, C. J., Björnson, E., Ginsberg, H. N., & Borén, J. (2025) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2025.120529 · Cited by 36
Self-citationInhibition of angiopoietin-like 3 for the management of severe hypercholesterolemia
Mohamed, F., Botha, T. C., & Raal, F. J. (2021) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000755 · Cited by 29
The Effect of Diet on Cardiovascular Disease and Lipid and Lipoprotein Levels
Feingold, K. R. (2021) · Europe PMC (PubMed Central) · Cited by 30
Colaco, K., Lee, K., Akhtari, S., Winer, R., Welsh, P. I., Sattar, N. A., McInnes, I. B., Chandran, V., Harvey, P., Cook, R. J., et al. (2021) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2021-220168 · Cited by 30
A new phenotypic classification system for dyslipidemias based on the standard lipid panel
Sampson, M. L., Ballout, R. A., Soffer, D. E., Wolska, A. T., Wilson, S. R., Meeusen, J. W., Donato, L. J., Fatica, E. M., Otvos, J. D., Brinton, E. A., et al. (2021) · Lipids in Health and Disease · doi:10.1186/s12944-021-01585-8 · Cited by 34
“Although it is clear from genetic studies that many of the causes of hypertriglyceridemia increase the risk for ASCVD [61, 63, 64]; it is not known at this time if lowering TG will Sampson et al.”
BackgroundLiu, J., Fan, F., Liu, B., Li, K., Jiang, Y., Jia, J., Chen, C., Zheng, B., & Zhang, Y. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.993097 · Cited by 29
“It is reported that TG lowering brings similar benefit to LDL-C levels per unit change in ApoB (26).”
BackgroundFappi, A., & Mittendorfer, B. (2019) · Proceedings of The Nutrition Society · doi:10.1017/s0029665119001022 · Cited by 29
[Incisional hernia after surgery for abdominal aortic aneurysm].
Augestad, K. M., Wilsgaard, T., & Solberg, S. K. (2002) · PubMed · Cited by 29
Atherosclerosis Regression and Cholesterol Efflux in Hypertriglyceridemic Mice
Josefs, T., Basu, D., Vaisar, T., Arets, B., Kanter, J. E., Huggins, L.-A., Hu, Y., Liu, J., Clouet-Foraison, N., Heinecke, J. W., et al. (2021) · Circulation Research · doi:10.1161/circresaha.120.317458 · Cited by 26
Jo, S., Nam, H., Lee, J., Park, S., Lee, J., & Kyoung, D. (2021) · Diabetes Care · doi:10.2337/dc20-1533 · Cited by 30
Drexel, H., Tamargo, J. L., Kaski, J. C., Lewis, B. S., Saely, C. H., Fraunberger, P., Dobrev, D., Komiyama, M., PLATTNER, T., Agewall, S., et al. (2023) · European Heart Journal - Cardiovascular Pharmacotherapy · doi:10.1093/ehjcvp/pvad044 · Cited by 32
Muro, F. M. D., Vogel, B., Sartori, S., Bay, B., Oliva, A., Feng, Y., Krishnan, P., Sweeny, J. M., Gitto, M., Smith, K. F., et al. (2025) · European Journal of Preventive Cardiology · doi:10.1093/eurjpc/zwaf112 · Cited by 31
Self-citationLambadiari, V., Korakas, E., & Tsimihodimos, V. (2020) · Nutrients · doi:10.3390/nu12082204 · Cited by 29
“However, measuring Apo-B particles is not easy in everyday practice, so triglycerides and non-HDL-C could act as good markers of atherogenic lipoprotein levels indirectly [22].”
BackgroundLi, M., Zhao, J. V., Kwok, M. K., & Schooling, C. M. (2021) · Scientific Reports · doi:10.1038/s41598-021-88256-x · Cited by 26
Fang, S., Holmes, M. V., Gaunt, T. R., Smith, G. D., & Richardson, T. G. (2022) · eLife · doi:10.7554/elife.73951 · Cited by 27
Coronavirus accessory protein ORF3 biology and its contribution to viral behavior and pathogenesis
Si, F., Song, S., Yu, R., Li, Z., Wei, W., & Wu, C. (2023) · iScience · doi:10.1016/j.isci.2023.106280 · Cited by 27
“Human LDLR NM_000527 TM-LKNINSINFDNPVYQKTTEDEVHICHN-COOH (Ference et al.(159))”
Li, D., Cai, H., Liu, G., Han, Y., Qiu, K., Liu, W., Meng, K., & Yang, P. (2024) · Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · doi:10.1186/s40104-023-00982-6 · Cited by 30
“VLDLR, LPL, and microsomal triglyceride transfer protein (MTTP) usually play a crucial role in transport and metabolism of lipoprotein and lipid [23, 24].”
BackgroundNew approaches to triglyceride reduction: is there any hope left?
Filtz, A., Parihar, S., Greenberg, G. S., Park, C. M., Scotti, A., Lorenzatti, D., Badimon, J. J., Soffer, D. E., Toth, P. P., Lavie, C. J., et al. (2024) · American Journal of Preventive Cardiology · doi:10.1016/j.ajpc.2024.100648 · Cited by 26
“Both variants were associated with a lower risk of CHD per unit change in apolipoprotein B (apoB) (OR 0.771 [95 % CI, 0.741-0.802], p = 3.9 × 10 (cid:0) 38 and OR 0.773 [95 % CI, 0.747-0.801], p = 1.1 × 10 (cid:0) 46 , respectively) [47].”
InfluentialParhofer, 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
Self-citationClimax, J., Newsome, P. N., Hamza, M., Weissbach, M., Coughlan, D., Sattar, N. A., McGuire, D. K., & Bhatt, D. L. (2020) · Journal of the American Heart Association · doi:10.1161/jaha.119.016334 · Cited by 26
Self-citationSkudder‐Hill, L., Sequeira, I. R., Ko, J., Cho, J., Poppitt, S. D., & Petrov, M. S. (2023) · Diabetes Obesity and Metabolism · doi:10.1111/dom.15233 · Cited by 26
Jin, Q., Lau, E. S. H., Luk, A. O. Y., Tam, C. H. T., Ozaki, R., Lim, C. K. P., Wu, H., Chow, E., Kong, A. P. S., Lee, H. M., et al. (2024) · Diabetologia · doi:10.1007/s00125-024-06108-5 · Cited by 29
“…CVD in people with DKD is not yet fully understood, Mendelian randomisation studies have suggested TRLs and ApoB are causally associated with CVD [14, 15]; phenylalanine has been associated with type 2 diabetes [16], impaired kidney function [9], heart failure [17] and CVD [18] in large cohort…”
BackgroundManaging dyslipidemia in patients with Type 2 diabetes
Tomlinson, B., Patil, N. G., Fok, M., & Lam, C. W. K. (2021) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2021.1912734 · Cited by 25
Suchowerska, A. K., Stokman, G., Palmer, J. T., Coghlan, P. A., Pieterman, E. J., Keijzer, N., Lambert, G. C., Chemello, K., Jaafar, A. K., Parmar, J., et al. (2022) · Journal of Lipid Research · doi:10.1016/j.jlr.2022.100293 · Cited by 30
“For many individuals at risk of CVD, statin monotherapy is often insufficient to achieve their LDL-C targets (50, 51).”
BackgroundInfluentialMa, M., Hou, C. J., & Liu, J. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2023.1148486 · Cited by 26
“LDL-C-lowering LDLR variants are associated with lower risk of CHD (64).”
BackgroundDose-Response Associations of Lipid Traits With Coronary Artery Disease and Mortality
Yang, G., Mason, A. M., Wood, A., Schooling, C. M., & Burgess, S. (2024) · JAMA Network Open · doi:10.1001/jamanetworkopen.2023.52572 · Cited by 27
Self-citationKraaijenhof, J. M., Kerkvliet, M., Nurmohamed, N. S., Grefhorst, A., Kroon, J., Wareham, N. J., Hovingh, G. K., Stroes, E. S. G., Boekholdt, S. M., & Reeskamp, L. F. (2025) · European Journal of Preventive Cardiology · doi:10.1093/eurjpc/zwaf037 · Cited by 28
Koohi, F., Khalili, D., Mansournia, M. A., Hadaegh, F., & Soori, H. (2021) · Journal of Translational Medicine · doi:10.1186/s12967-021-02966-4 · Cited by 26
“Evidence from some genetic studies suggested that the risk associated with elevated TGs might be because of their association with elevations in non– HDL-C or apolipoprotein B (apo B)-containing lipoproteins [43].”
BackgroundZhou, L., Liu, J., An, Y., Wang, Y., & Wang, G. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.898305 · Cited by 24
“Another study showed that RCinduced ASCVD was proportional to apolipoprotein B (ApoB) concentrations (23).”
BackgroundResultDyslipidemia in Transplant Patients: Which Therapy?
Iannuzzo, G., Cuomo, G., Lorenzo, A. D., Tripaldella, M., Mallardo, V., Idelson, P. I., Sagnelli, C., Sica, A., Creta, M., Baltar, J., et al. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11144080 · Cited by 31
“Very low-density lipoproteins (VLDL) and their remnants are rich in triglycerides and are also associated with ASCVD; however, this association seems to be related to the blood concentration of ApoB-containing particles rather than the concentration of triglycerides itself [18].”
BackgroundPersonalised 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
“Numerous variants through the LPL pathway and current therapies that lower LDL-C levels through the LDLR pathway were also associated with similar lower CHD risk per unit lower plasma ApoB levels [61].”
BackgroundAlsayed, N., Almahmeed, W. A., Alnouri, F., Al-Waili, K., Sabbour, H. M., Sulaiman, K., Zubaid, M., Ray, K. K., & Al‐Rasadi, K. (2021) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2021.11.022 · Cited by 23
Self-citationFolwaczny, A., Waldmann, E., Altenhofer, J., Henze, K., & Parhofer, K. G. (2021) · Nutrients · doi:10.3390/nu13051737 · Cited by 23
“Data derived from Mendelian randomization studies indicate that this association is causal in nature [11,12].”
BackgroundMa, J., Joehanes, R., Liu, C., Keshawarz, A., Hwang, S., Bui, H., Tejada, B., Sooda, M., Munson, P. J., Demirkale, C. Y., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-24100-0 · Cited by 22
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
Taskinen, M., Matikainen, N., Björnson, E., Söderlund, S., Inkeri, J., Hakkarainen, A., Parviainen, H., Sihlbom, C., Thorsell, A., Andersson, L. K., et al. (2023) · Diabetologia · doi:10.1007/s00125-023-06008-0 · Cited by 23
Self-citationManagement of Lipid Abnormalities in Patients with Diabetes
Sillars, A., & Sattar, N. A. (2019) · Current Cardiology Reports · doi:10.1007/s11886-019-1246-1 · Cited by 24
Feng, L.-S., Wang, Y., Liu, H., Ning, B., Yu, H.-B., Li, S., Wang, Y., Zhao, M., & Ma, J. (2024) · Journal of Integrative Neuroscience · doi:10.31083/j.jin2312222 · Cited by 22
“A Mendelian randomization study found that the presence of depressive symptoms at different times during the course of CHD doubles the risk of death, and clinical depression is associated with an even higher risk [9].”
Beyond LDL-C levels, does remnant cholesterol estimation matter?
Pirillo, A., Norata, G. D., & Catapano, A. L. (2020) · European Journal of Preventive Cardiology · doi:10.1177/2047487319899622 · Cited by 22
“In agreement with these observations, Mendelian randomization studies have suggested that the clinical benefit of lowering LDL-C may be better explained by the absolute reduction in apoB-containing lipoproteins.(6,7) In their study, Elshazly et al.”
BackgroundResultSelf-citationGrupp, C., Beckermann, J., Köster, E., Zewinger, S., Knittel, M., Walek, T., Hohenstein, B., Jaeger, B. R., Spitthöver, R., Klingel, R., et al. (2020) · Blood Purification · doi:10.1159/000506506 · Cited by 22
“J Clin Endocrinol Metab 2016; 101(12):45004511 7.”
Dong, X. Y., Zhuang, Z., Zhao, Y., Song, Z., Xiao, W., Wang, W., Li, Y., Huang, N., Jia, J., Liu, Z., et al. (2023) · Journal of the American Heart Association · doi:10.1161/jaha.122.027934 · Cited by 22
Gaundal, L., Myhrstad, M. C. W., Leder, L., Byfuglien, M. G., Gjøvaag, T. F., Rud, I., Retterstøl, K., Holven, K. B., Ulven, S. M., & Telle‐Hansen, V. H. (2020) · British Journal Of Nutrition · doi:10.1017/s0007114520003402 · Cited by 22
“Small changes in cholesterol levels implemented early are associated with reduced risk of CVD later in life.”
InfluentialUsing Mendelian randomization study to assess the renal effects of antihypertensive drugs
Zhao, J. V., & Schooling, C. M. (2021) · BMC Medicine · doi:10.1186/s12916-021-01951-4 · Cited by 23
“As genetic variants are randomly allocated at conception and unlikely affected by socioeconomic position or other confounders, the study design minimizes residual confounding and has been successfully applied previously to assess the cardiovascular effects of several drugs such as antihypertensives and lipid-lowering…”
BackgroundSweeney, T. E., Quispe, R., Das, T. M., Juraschek, S. P., Martin, S. S., & Michos, E. D. (2021) · Expert Review of Precision Medicine and Drug Development · doi:10.1080/23808993.2021.1930531 · Cited by 24
Molecular Regulation and Therapeutic Targeting of VLDL Production in Cardiometabolic Disease
Burks, K. H., Stitziel, N. O., & Davidson, N. O. (2024) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2024.101409 · Cited by 24
Ballantyne, C. M., & Norata, G. D. (2025) · European Heart Journal · doi:10.1093/eurheartj/ehaf606 · Cited by 23
Genomics of hypertriglyceridemia
Tada, H., Takamura, M., & Kawashiri, M. (2020) · Advances in clinical chemistry · doi:10.1016/bs.acc.2019.12.005 · Cited by 22
León‐Mimila, P., Villamil‐Ramírez, H., Kauffer, L. R. M., Jacobo‐Albavera, L., López-Contreras, B. E., Posadas‐Sánchez, R., Posadas‐Romero, C., Romero‐Hidalgo, S., Morán‐Ramos, S., Domínguez‐Pérez, M., et al. (2021) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.120.315391 · Cited by 25
Triglycerides and cardiovascular risk: Apolipoprotein B holds the key
Stock, J. K. (2019) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2019.03.004 · Cited by 21
Jin, J., Zhang, H., Cao, Y., Liu, H., Hua, Q., Li, Y., Zhang, Y., Guo, Y., Wu, N., Zhu, C., et al. (2020) · Cardiovascular Diabetology · doi:10.1186/s12933-020-01125-1 · Cited by 20
Apolipoprotein B: the Rosetta Stone of lipidology
Glavinovic, T., & Sniderman, A. D. (2020) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000596 · Cited by 22
New Insights in the Control of Low-Density Lipoprotein Cholesterol to Prevent Cardiovascular Disease
Katzmann, J. L., & Laufs, U. (2019) · Current Cardiology Reports · doi:10.1007/s11886-019-1159-z · Cited by 19
Self-citationThe year in cardiology: cardiovascular prevention
Ray, K. K., Laufs, U., Cosentino, F., Lobo, M. D., & Landmesser, U. (2019) · European Heart Journal · doi:10.1093/eurheartj/ehz929 · Cited by 20
Self-citationThe role of remnant cholesterol in patients with ST-segment elevation myocardial infarction
Zhou, Y., Madsen, J. M., Özbek, B. T., Køber, L., Bang, L. E., Lønborg, J. T., & Engstrøm, T. (2024) · European Journal of Preventive Cardiology · doi:10.1093/eurjpc/zwae102 · Cited by 20
Xiao, L., Li, Y., Chang, H., Ma, P., Zhu, H., Cui, H., Zou, X., Wang, J., Li, R., He, J., et al. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-024-05478-z · Cited by 21
“LPL variants have also been shown to significantly contribute to dyslipidemia, being associated with several conditions including obesity, metabolic syndrome, and atherosclerosis [40–43].”
BackgroundExpanding the triglyceride range in clinical trials: therapeutic opportunities
Nordestgaard, A. T., Pradhan, A. D., Everett, B. M., MacFadyen, J. G., Bhatt, D. L., Visseren, F. L. J., Libby, P., Santos, R. D., Nissen, S. E., Nordestgaard, B. G., et al. (2025) · European Heart Journal · doi:10.1093/eurheartj/ehaf074 · Cited by 20
Self-citationLiao, L., Li, W., Liu, Y., Li, J.-P., Zhuang, X., & Liao, X. (2019) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2019.09.013 · Cited by 19
Jin, D., Trichia, E., Islam, N., Bešević, J., Lewington, S., & Lacey, B. (2023) · Journal of the American Heart Association · doi:10.1161/jaha.123.029552 · Cited by 19
Doi, T., Langsted, A., & Nordestgaard, B. G. (2024) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2024.117556 · Cited by 23
Impact of Remnant Cholesterol on Cardiovascular Risk in Diabetes
Elías-López, D., Wadström, B. N., Vedel‐Krogh, S., Kobylecki, C. J., & Nordestgaard, B. G. (2024) · Current Diabetes Reports · doi:10.1007/s11892-024-01555-1 · Cited by 18
“Indeed, genetic variation in LPL , which leads to increased levels of plasma triglycerides, is associated with increased risk of ASCVD in the general population [50, 56–59].”
Eicosapentaenoic acid vs. docosahexaenoic acid for the prevention of cardiovascular disease
Sweeney, T. E., Gaine, S. P., & Michos, E. D. (2023) · Current Opinion in Endocrinology, Diabetes & Obesity · doi:10.1097/med.0000000000000796 · Cited by 18
“All rights rese Copyright © 2023 Wolters Kluwe tested icosapentethyl (IPE) – ahighly-purified formof EPA – at a dose of 2g twice daily in patients on statintherapywith established ASCVDor diabeteswith one other cardiovascular risk factor who remained with elevated fasting TG levels >135mg/dl despite well controlled LD…”
BackgroundInfluentialThe LDL-C/ApoB ratio predicts cardiovascular and all-cause mortality in the general population
Xiao, L., Zhang, K., Wang, F., Wang, M., Huang, Q., Wei, C., & Gou, Z. (2023) · Lipids in Health and Disease · doi:10.1186/s12944-023-01869-1 · Cited by 18
“Studies [47, 48] have suggested that each LDL particle has a single ApoB molecule and more than 90% of all ApoB is found in LDL; of course, a minor fraction of ApoB is also carried on other atherogenic particles (e.”
BackgroundRuhanen, H., Haridas, P. A. N., Jauhiainen, M., & Olkkonen, V. M. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2020.158791 · Cited by 18
Impact of loss-of-function in angiopoietin-like 4 on the human phenome
Gagnon, E., Bourgault, J., Gobeil, É., Thériault, S., & Arsenault, B. J. (2024) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2024.117558 · Cited by 17
Modder, M., Panhuis, W. I. H., Li, M., Afkir, S., Dorn, A. L., Pronk, A. C. M., Streefland, T. C. M., Lalai, R. A., Pierrou, S. E., Nilsson, S. K., et al. (2024) · Cardiovascular Research · doi:10.1093/cvr/cvae195 · Cited by 17
Statin therapy in primary and secondary cardiovascular disease prevention
Paparodis, R. D., Bantouna, D., Livadas, S., & Angelopoulos, N. (2024) · Current Atherosclerosis Reports · doi:10.1007/s11883-024-01265-9 · Cited by 17
“Similarly, genetically defined LDL-C lowering variants of the LDL receptor [3], cases of familial hypobetalipoproteinemia, and PCSK9 or ANGPTL3 loss-of-function mutations [4] were associated with lower risk for cardiovascular events due to low LDL-C concentrations.”
N-3 polyunsaturated fatty acids for cardiovascular risk
Goff, Z. D., & Nissen, S. E. (2022) · Current Opinion in Cardiology · doi:10.1097/hco.0000000000000962 · Cited by 17
Zhang, Y., Pei, Z., Chen, B., Qu, Y., Dong, X., Yu, B., Wang, G., Xu, F., Lu, D., He, Z., et al. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107340 · Cited by 17
Trinder, M., & Brunham, L. R. (2020) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000737 · Cited by 17
Ibrahim, M. A., Thanigaimani, S., Singh, T. P., Morris, D., & Golledge, J. (2021) · IJC Heart & Vasculature · doi:10.1016/j.ijcha.2021.100836 · Cited by 17
Sex-specific trajectories of molecular cardiometabolic traits from childhood to young adulthood
O’Keeffe, L. M., Tilling, K. M., Bell, J. A., Walsh, P. T., Lee, M. A., Lawlor, D. A., Smith, G. D., & Kearney, P. M. (2023) · Heart · doi:10.1136/heartjnl-2022-321347 · Cited by 17
Postprandial hyperlipidemia as a risk factor in patients with type 2 diabetes
Tomlinson, B., Chan, P., & Lam, C. W. K. (2020) · Expert Review of Endocrinology & Metabolism · doi:10.1080/17446651.2020.1750949 · Cited by 20
A Comparison of Lipids and apoB in Asian Indians and Americans
Singh, K., Thanassoulis, G., Dufresne, L., Nguyen, A., Gupta, R., Narayan, K. M. V., Tandon, N., Sniderman, A. D., & Prabhakaran, D. (2021) · Global Heart · doi:10.5334/gh.882 · Cited by 16
Deng, J., Tang, R., Chen, J., Zhou, Q., Zhan, X., Haibo, L., Peng, F., Wang, X., Wen, Y., Feng, X., et al. (2023) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2023.02.009 · Cited by 16
Colesterol remanente, riesgo vascular y prevención de la arteriosclerosis
Pintó, X., Fanlo‐Maresma, M., Esteve, V., Millán, J., Blanco, A., Blasco, M., Díaz-Díaz, J. L., Rodríguez, Á. D., Mangas, A., Pascual, V., et al. (2023) · Clínica e Investigación en Arteriosclerosis · doi:10.1016/j.arteri.2023.02.001 · Cited by 18
Lipid profile and lipoprotein(a) testing
Parhofer, K. G., & Laufs, U. (2023) · Deutsches Ärzteblatt international · doi:10.3238/arztebl.m2023.0150 · Cited by 16
Self-citationLDL-Cholesterol-Lowering Therapy
Pirillo, A., Norata, G. D., & Catapano, A. L. (2020) · Handbook of experimental pharmacology · doi:10.1007/164_2020_361 · Cited by 17
Self-citationSilbernagel, G., Scharnagl, H., Kleber, M. E., Hoffmann, M. M., Delgado, G., Stojaković, T., Gary, T., Zeng, L., Ritsch, A., Zewinger, S., et al. (2020) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2020.08.017 · Cited by 16
Taba, N., Valge, H.-K., Metspalu, A., Esko, T., Wilson, J. F., Fischer, K., & Pirastu, N. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.738265 · Cited by 17
Yao, T., Lu, W., Ke, J., Zhang, H., Zhao, X., Song, B., Liu, T., Ke, Q., & Liu, C. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.865863 · Cited by 16
Wang, J., Sun, Q., An, Y., Liu, J., Leng, S., & Wang, G. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.951635 · Cited by 15
Fogacci, F., ALGhasab, N. S., Micoli, V. D., Giovannini, M., & Cicero, A. F. G. (2024) · Nutrients · doi:10.3390/nu16101526 · Cited by 17
“Optimal low-density lipoprotein cholesterol and/or triglyceride plasma levels significantly protect against cardiovascular disease (CVD) development, and higher levels are associated with an increased risk [1,2].”
BackgroundYang, G., Mason, A. M., Gill, D., Schooling, C. M., & Burgess, S. (2024) · European Journal of Epidemiology · doi:10.1007/s10654-024-01141-5 · Cited by 17
“…targets of each therapy (i.e., HMGCR for statins, PCSK9 for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, NPC1L1 for ezetimibe, ACLY for ATP citrate lyase inhibitors, LDLR for targeting LDL receptors, and APOB for targeting apolipoprotein B (apoB)), as previously [25, 26 ].”
Cojocaru, E., Leon, M. M., Ungureanu, C., et al. (2021) · Medicina · doi:10.3390/medicina57030239 · Cited by 15
“The mechanism by which lowering the level of plasma triglycerides leads to a decrease of the total cardiovascular risk appears to be the apoB (apolipoprotein B) reduction [9].”
BackgroundO’Keeffe, L. M., Bell, J. A., O’Neill, K. N., Lee, M., Woodward, M., Peters, S. A. E., Smith, G. D., & Kearney, P. M. (2022) · PLoS Medicine · doi:10.1371/journal.pmed.1003636 · Cited by 15
“In addition, several of the traits that were higher in males in these studies [3,29] and more strongly associated with adiposity in males in our study such as LDL cholesterol [30], VLDL triglycerides [31], and apolipoprotein B [32–34] are very likely causal for CHD.”
BackgroundIs hypertriglyceridemia atherogenic?
Huet, F., Roubille, C., & Roubille, F. (2019) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000622 · Cited by 15
Pharmacokinetics of current and emerging treatments for hypercholesterolemia
Tomlinson, B., Chan, P., Zhang, Y., Liu, Z., & Lam, C. W. K. (2020) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2020.1749261 · Cited by 16
“portional to the absolute change in apo B [11].”
BackgroundKomiya, I., Yamamoto, A., Sunakawa, S., & Wakugami, T. (2021) · Lipids in Health and Disease · doi:10.1186/s12944-021-01434-8 · Cited by 16
Preventing Diabetes and Atherosclerosis in the Cardiometabolic Syndrome
Ahmad, M. I., & Shapiro, M. D. (2021) · Current Atherosclerosis Reports · doi:10.1007/s11883-021-00913-8 · Cited by 14
Proteomic studies on apoB-containing lipoprotein in cardiovascular research: A comprehensive review.
Gianazza, E., Zoanni, B., Mallia, A., Brioschi, M., Colombo, G., & Banfi, C. (2021) · Mass spectrometry reviews (Print) · doi:10.1002/mas.21747 · Cited by 10
The role of adiposity, diet and inflammation on the discordance between LDL-C and apolipoprotein B
Webb, R. J., Mazidi, M., Lip, G. Y. H., Kengne, A. P., Banach, M., & Davies, I. G. (2021) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2021.12.004 · Cited by 14
Lipoprotein(a) and risk-weighted apolipoprotein B: a novel metric for atherogenic risk
Rehman, M. B., & Tudrej, B. V. (2024) · Lipids in Health and Disease · doi:10.1186/s12944-024-02307-6 · Cited by 15
“This strongly implied that the atherogenicity of TRL and LDL was broadly the same on a per apoB particle basis [13].”
BackgroundOhukainen, P., Kuusisto, S. M., Kettunen, J., Perola, M., Järvelin, M., Mäkinen, V., & Ala‐Korpela, M. (2019) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2019.12.009 · Cited by 14
“[13], comparing the effects of genetic modification of lowering triglycerides with the lowering of LDL cholesterol, convincingly showed that the clinical benefit of lowering triglycerides as well as LDL cholesterol is proportional to the absolute change in the circulating apoB concentration.”
BackgroundLi, J., Yang, Y., Jiao, X., Yu, H., Du, Y., Zhang, M., Hu, C., Wei, Y., & Qin, Y. (2020) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-020-06991-1 · Cited by 15
Metadata
- Authors
- Ference, B. A., Kastelein, J. J. P., Ray, K. K., Ginsberg, H. N., Chapman, M. J., Packard, C. J., Laufs, U., Oliver-Williams, C., Wood, A. M., Butterworth, A. S., Di Angelantonio, E., Danesh, J., Nicholls, S. J., Bhatt, D. L., Sabatine, M. S., & Catapano, A. L.
- Affiliations
- University of Cambridge (GB)
- Amsterdam UMC Location University of Amsterdam (NL)
- Imperial College London (GB)
- Columbia University (US)
- Inserm (FR)
- University of Glasgow (GB)
- Leipzig University (DE)
- MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
- Monash University (AU)
- Brigham and Women's Hospital (US)
- University of Milan (IT)
- Corresponding author
- Ference, Brian A.
- ORCID
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2019-01-29
- Volume
- 321
- Issue
- 4
- Pages
- 364
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC6439767
- OpenAlex
- W2911290113
- Semantic Scholar
- 79708784ea168e7e24e1ab47deffcd9005c32cfd
- Cited by
- 703
- References
- 39
- Citations by year
- 2026: 59 · 2025: 83 · 2024: 119 · 2023: 88 · 2022: 69 · 2021: 111 · 2020: 100 · 2019: 72
- FWCI
- 63.33
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- Locations
- JAMA (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- Explore Bristol Research (acceptedVersion, other-oa)
- Bristol Research (University of Bristol) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- Amgen
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Sanofi
- Biogen
- CSL Behring
- NHS Blood and Transplant
- Regeneron Pharmaceuticals
- Wellcome Trust
- Ironwood Pharmaceuticals, Incorporated
- Amarin Corporation
- Anthera
- InfraRedx
- National Institute for Health and Care Research (NF-SI-0617-10113)
- British Heart Foundation (RG/18/13/33946, RG/13/13/30194)
- Bupa Foundation
- European Commission
- Eisai
- Evelyn Trust
- Esperion Therapeutics
- Medical Research Council
- Homerton College, University of Cambridge
- National Heart, Lung, and Blood Institute
- Fogarty International Center
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- lipoprotein lipase, LDL receptor, apolipoprotein B, triglycerides, LDL cholesterol, coronary artery disease, cardiovascular risk, genetic score, lipoprotein particles, cardiovascular events, myocardial infarction, coronary revascularization, coronary death
- MeSH terms
- Loss of Function Mutation, Apolipoproteins B, Coronary Disease, Female, Humans, Lipoprotein Lipase, Cholesterol, LDL, Male, Middle Aged, Prospective Studies, Receptors, LDL, Risk Factors, Triglycerides, Genetic Variation, Case-Control Studies, Genetic Predisposition to Disease, Metabolic Networks and Pathways, Mendelian Randomization Analysis
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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