The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index; 10 of the 13 sources its claims cite were checked for support.
Association of Apolipoprotein B–Containing Lipoproteins and Risk of Myocardial Infarction in Individuals With and Without Atherosclerosis
Open accessAbstract
IMPORTANCE: Lipid management typically focuses on levels of low-density lipoprotein cholesterol (LDL-C) and, to a lesser extent, triglycerides (TG). However, animal models and genetic studies suggest that the atherogenic particle subpopulations (LDL and very-low-density lipoprotein [VLDL]) are both important and that the number of particles is more predictive of cardiac events than their lipid content. OBJECTIVE: To determine whether common measures of cholesterol concentration, TG concentration, or their ratio are associated with cardiovascular risk beyond the number of apolipoprotein B (apoB)-containing lipoproteins. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort analysis included individuals from the population-based UK Biobank and from 2 large international clinical trials, FOURIER and IMPROVE-IT. The median (IQR) follow-up was 11.1 (10.4-11.8) years in UK Biobank and 2.5 (2.0-4.7) years in the clinical trials. Two populations were studied in this analysis: 389 529 individuals in the primary prevention group who were not taking lipid-lowering therapy and 40 430 patients with established atherosclerosis who were receiving statin treatment. EXPOSURES: ApoB, non-high-density lipoprotein cholesterol (HDL-C), LDL-C, and TG. MAIN OUTCOME AND MEASURES: The primary study outcome was incident myocardial infarction (MI). RESULTS: Of the 389 529 individuals in the primary prevention group, 224 097 (58%) were female, and the median (IQR) age was 56.0 (49.5-62.5) years. Of the 40 430 patients with established atherosclerosis, 9647 (24%) were female, and the median (IQR) age was 63 (56.2-69.0) years. In the primary prevention cohort, apoB, non-HDL-C, and TG each individually were associated with incident MI. However, when assessed together, only apoB was associated (adjusted hazard ratio [aHR] per 1 SD, 1.27; 95% CI, 1.15-1.40; P < .001). Similarly, only apoB was associated with MI in the secondary prevention cohort. Adjusting for apoB, there was no association between the ratio of TG to LDL-C (a surrogate for the ratio of TG-rich lipoproteins to LDL) and risk of MI, implying that for a given concentration of apoB-containing lipoproteins, the relative proportions of particle subpopulations may no longer be a predictor of risk. CONCLUSIONS AND RELEVANCE: In this cohort study, risk of MI was best captured by the number of apoB-containing lipoproteins, independent from lipid content (cholesterol or TG) or type of lipoprotein (LDL or TG-rich). This suggests that apoB may be the primary driver of atherosclerosis and that lowering the concentration of all apoB-containing lipoproteins should be the focus of therapeutic strategies.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
In a large primary-prevention cohort and two secondary-prevention trial cohorts, apolipoprotein B (apoB) was the only lipid parameter independently associated with myocardial infarction after full adjustment. Neither lipid content nor lipoprotein type added risk beyond the number of apoB-containing particles.
Key findings
In 389,529 primary-prevention individuals not on lipid-lowering therapy, apoB, non–HDL-C, and TG were each individually associated with incident MI, but after full adjustment only apoB remained associated (aHR per 1 SD, 1.27; 95% CI, 1.15-1.40; P < .001).
- In the same cohort, TG was associated with MI in clinically adjusted models (aHR per 1 SD, 1.16; 95% CI, 1.13-1.19; P < .001), but not after full clinical and lipid adjustment (aHR per 1 SD, 1.00; 95% CI, 0.96-1.04; P = .71).
- In 40,430 patients with established atherosclerosis receiving statin treatment, only apoB was associated with MI; TG was not associated in clinically adjusted (aHR per 1 SD, 1.03; 95% CI, 0.99-1.07) or clinically and lipid-adjusted models (aHR per 1 SD, 0.94; 95% CI, 0.89-1.00).
- Adjusting for apoB, the TG/LDL-C ratio was not associated with MI (aHR per 1 SD, 1.04; 95% CI, 0.99-1.09; P = .12), suggesting that for a given concentration of apoB-containing lipoproteins, particle type did not confer additional risk.
Methods
Prospective cohort analysis using UK Biobank primary-prevention individuals without lipid-lowering therapy (n = 389,529) and pooled secondary-prevention patients with established atherosclerosis from FOURIER and IMPROVE-IT receiving lipid-lowering therapy (n = 40,430). Median follow-up was 11.1 years in UK Biobank and 2.5 years in the clinical trials.
- Exposures were apoB, non–HDL-C, LDL-C, and TG; the primary outcome was fatal or nonfatal MI.
- Cox proportional hazards models estimated adjusted hazard ratios per 1 SD higher lipid parameter, with clinical adjustment and further adjustment for HDL-C, TG, non–HDL-C, and apoB; the TG/LDL-C ratio was evaluated with adjustment for apoB.
Limitations
The paper states that lipid values were measured using conventional lipid profiles rather than nuclear magnetic resonance spectroscopy, which would more accurately determine the VLDL-to-LDL ratio than the TG/LDL-C surrogate used.
- The paper states that UK Biobank lipid values and lipid-lowering therapy data were collected at baseline and may have changed during follow-up; because individuals with higher lipid values would be most likely to start lipid-lowering therapy, this may have attenuated associations. The study was also not enriched for severe hypertriglyceridemia.
- Evident from the text: the analysis is observational, limiting causal inference; the trial cohorts excluded patients with TG ≥400 mg/dL in FOURIER and ≥350 mg/dL in IMPROVE-IT, so severe hypertriglyceridemia is not represented.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
35 Own result · 9 Own interpretation · 8 Own method · 5 No basis given · 4 Supported · 2 Partly supported · 2 No full text of the sources · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“Mendelian randomization studies have shown that apoB is a better predictor of coronary artery disease risk than serum LDL-C or TG concentration”
What the sources say
- Supportedcites [4] Ference, 2019, Association of triglyceride-lowering LPL variants and LDL-C–lowering LDLR variants with risk of coronary heart disease., JAMA source
The Abstract reports that, in multivariable Mendelian randomization analyses, the associations of triglycerides and LDL-C with coronary heart disease risk became null after adjustment for ApoB, while the ApoB association remained. The Discussion likewise says risk appears to be determined by ApoB-containing particle concentration rather than the cholesterol or triglyceride mass those particles carry. The supplied passages do not give page numbers. (LLM, conf=0.92)
- Supportedcites [5] Richardson, 2020, Evaluating the relationship between circulating lipoprotein lipids and apolipoproteins with risk of coronary heart disease: a multivariable mendelian randomisation analysis., PLoS Med source
The Results section (“Appraisal of LDL cholesterol, triglycerides, and apolipoprotein B”) reports that only apoB retained a robust association with coronary heart disease when all three traits were assessed together in multivariable Mendelian randomisation. The Introduction also describes apoB as having a stronger association with cardiovascular risk than LDL cholesterol and notes a modest improvement in predictive performance when apoB-related measures are included. (LLM, conf=0.87)
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“This study builds on prior work showing that apoB concentration is the most predictive parameter of CV risk,13,14,15”
What the sources say
- Partly supportedcites [13] Lawler, 2017, Discordance between circulating atherogenic cholesterol mass and lipoprotein particle concentration in relation to future coronary events in women., Clin Chem sourceExperimental — accuracy not yet measured
The Discussion (page not supplied) reports that, among women whose apoB and non-HDL cholesterol measurements were discordant, coronary heart disease risk tracked more closely with lipoprotein particle concentration, particularly apoB. It does not establish that apoB is the most predictive parameter of cardiovascular risk generally, across populations and risk measures. (LLM, conf=0.88)
- Partly supportedcites [14] Johannesen, 2021, Apolipoprotein B and non-HDL Cholesterol better reflect residual risk than LDL cholesterol in statin-treated patients., J Am Coll Cardiol sourceExperimental — accuracy not yet measured
The Conclusions report that apoB was a more accurate marker of all-cause mortality risk than LDL or non-HDL cholesterol in statin-treated patients, and of myocardial infarction risk than LDL cholesterol. The claim broadens those comparisons to call apoB the most predictive parameter of cardiovascular risk generally; the cited paper does not establish that broader ranking. (LLM, conf=0.87)
- Partly supportedcites [15] Sniderman, 2019, Apolipoprotein B particles and cardiovascular disease: a narrative review., JAMA Cardiol sourceExperimental — accuracy not yet measured
The Introduction reports that discordance analyses found apoB more accurate than LDL-C and non-HDL-C for predicting cardiovascular risk attributable to apoB lipoprotein particles. It does not establish apoB as the most predictive parameter of cardiovascular risk overall; it also notes studies finding apoB and non-HDL-C equivalent predictors. (LLM, conf=0.84)
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.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the primary prevention cohort, apoB, non–HDL-C, and TG each individually were associated with incident MI.”
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
“and while this was maintained after adding TG to the model”
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
“This significant positive association was maintained after full adjustment for lipid parameters, including TG, non–HDL-C, and HDL-C (HR, 1.27; 95% CI, 1.15-1.40; P < .001) (Figure 1B).”
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
“ApoB, LDL-C, and non–HDL-C were correlated (ρ ≥ 0.95).”
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
“In the primary prevention cohort, apoB, non–HDL-C, and TG each individually were associated with incident MI.”
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
“In the primary prevention cohort, apoB, non–HDL-C, and TG each individually were associated with incident MI.”
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
“Similarly, only apoB was associated with MI in the secondary prevention cohort.”
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
“non–HDL-C was no longer associated with MI when adjusted for apoB (Table 2).”
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. 19
- It may state two separate claims as one. 14
Every source the paper cites for this claim was checked and supports it.
In the 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”
What the sources say
- Supportedcites [4] Ference, 2019, Association of triglyceride-lowering LPL variants and LDL-C–lowering LDLR variants with risk of coronary heart disease., JAMA source
The Discussion states that cardiovascular risk appears to be determined by the circulating concentration of ApoB-containing particles rather than the mass of cholesterol or triglyceride they carry. It also explains that particle concentration determines how many particles become retained in the artery wall. This supports the citing sentence’s hedged claim. (LLM, conf=0.94)
- Supportedcites [5] Richardson, 2020, Evaluating the relationship between circulating lipoprotein lipids and apolipoproteins with risk of coronary heart disease: a multivariable mendelian randomisation analysis., PLoS Med source
The Discussion states that apolipoprotein B indexes the number of atherogenic particles and that this number, rather than circulating cholesterol or triglycerides per se, is the important driver of coronary heart disease. The claim’s cautious wording is consistent with the paper’s conclusion. (LLM, conf=0.95)
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.
Probably not a substantial claim.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“These studies have suggested that TG and remnant cholesterol may be more potent risk factors for myocardial infarction (MI) than LDL-C is.2,3”
What the sources say
- Not checked — no full text of the sourcecites [2] Castañer, 2020, Remnant cholesterol, not LDL cholesterol, is associated with incident cardiovascular disease., J Am Coll Cardiol source
- Partly supportedcites [3] Balling, 2020, VLDL cholesterol accounts for one-half of the risk of myocardial infarction associated with apoB-containing lipoproteins., J Am Coll Cardiol sourceExperimental — accuracy not yet measured
The paper’s Abstract (page unavailable) reports that VLDL cholesterol explained 50% of the myocardial-infarction risk associated with apoB-containing lipoproteins, compared with 29% for IDL plus LDL cholesterol. This supports the remnant-cholesterol portion of the claim. It does not support the triglyceride portion: the same passage says VLDL triglycerides did not explain that risk. (LLM, conf=0.88)
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.
Probably not a substantial claim.
Every source the paper cites for this claim was checked and supports it.
In the paper
“However, it should be recognized that these measures do not identify the number of apoB-containing lipoprotein particles as reliably and have been shown to not always accurately predict CV risk.17”
What the sources say
- Supportedcites [17] Mora, 2014, Discordance of low-density lipoprotein (LDL) cholesterol with alternative LDL-related measures and future coronary events., Circulation source
The Discussion explains that LDL-C and non-HDL-C measure cholesterol carried by particles, whereas apoB reflects the number of apoB-containing particles. The Results and Discussion report that relying on LDL-C alone can under- or overestimate coronary risk when LDL-related measures are discordant. The study assessed coronary events in initially healthy women. (LLM, conf=0.88)
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.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“While such an approach can specifically measure the number and particle size of lipoprotein particles, prior studies have shown that they are not superior to conventional lipid profiles.22”
What the sources say
- Supportedcites [22] Mora, 2009, Lipoprotein particle profiles by nuclear magnetic resonance compared with standard lipids and apolipoproteins in predicting incident cardiovascular disease in women., Circulation source
The Discussion reports that, in a prospective cohort of initially healthy women, NMR-measured lipoproteins predicted incident cardiovascular disease comparably to, but not better than, standard lipids. This supports the cited comparison for CVD risk prediction; the paper does not establish that NMR is inferior for every clinical use or population. (LLM, conf=0.91)
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
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
“TG was positively correlated with these 3 parameters (ρ = 0.38-0.52).”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and negatively correlated with TG (ρ = −0.49).”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“HDL-C was correlated with apoB, LDL-C, and non–HDL-C (ρ ≤ |0.12|)”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“First, apoB was the only independent driver of lipid-associated MI risk, confirming the importance of particle concentration.”
boosteddirect- 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: ApoB is in a 1:1 association with atherogenic lipoprotein particles.
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 individuals not receiving lipid-lowering therapy, the median (IQR) TG/LDL-C ratio was 0.39 (0.29-0.55).”
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 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
“Each of these findings was consistent across both primary and secondary populations and in those receiving and not receiving lipid lowering therapy.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This flat association was seen up to TG/LDL-C ratios of 2 in the clinical trials, where LDL-C lowering therapies lowered LDL-C, resulting in much higher TG/LDL-C ratios (eFigure 2 in the Supplement).”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and further advances our understanding by demonstrating that LDL-C and TG levels do not have predictive value beyond apoB.”
boosted- 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
“LDL-C and non–HDL-C are correlated with apoB, and therefore can be used to approximate lipoprotein particle concentration and CV risk when apoB is not available.”
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.
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
“A sensitivity analysis using a broader composite atherosclerotic cardiovascular disease end point was performed in each cohort.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In FOURIER and IMPROVE-IT, MI was a component of the trials’ primary end points and was therefore adjudicated by the Thrombolysis in Myocardial Infarction (TIMI) central clinical end points committee. Adjudicators were blinded to lipid levels and treatment arm.”
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
“Nonetheless, nuclear magnetic resonance spectroscopy would offer a more accurate method for determining the VLDL-to-LDL ratio compared with the surrogate of TG to LDL-C used in this study.”
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A 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
“Because individuals with higher lipid values would be most likely to start lipid-lowering therapy, we anticipate this may have attenuated the association for each lipid parameter.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Rests on an assumption: Individuals with higher lipid values are most likely to start lipid-lowering therapy.
In the paper
“but the American Association of Clinical Chemistry has stated that apoB is standardized and can be measured with more accuracy than LDL-C and non–HDL-C.21”
What the sources say
- Not checked — no full text of the sourcecites [21] Cole, 2013, Association of apolipoprotein B and nuclear magnetic resonance spectroscopy-derived LDL particle number with outcomes in 25 clinical studies: assessment by the AACC Lipoprotein and Vascular Diseases Division Working Group on Best Practices., Clin Chem source
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
“Lipid values in these cohorts were measured using conventional lipid profiles rather than nuclear magnetic resonance spectroscopy.”
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
“Moreover, our study was not enriched for patients with severe hypertriglyceridemia, so we cannot comment on risk associations in such individuals.”
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.
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
“Conversely, 2 individuals can have the same apoB levels (and hence the same number of atherogenic lipoproteins). An individual with lower LDL-C, the metric on which the field currently focuses, may be perceived as being at lower risk, but that is not necessarily the case.”
hedgedn = 2- 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: ApoB is in a 1:1 association with atherogenic lipoprotein particles.
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
“However, these studies have limitations that include incomplete model adjustment, residual confounding, and not accounting for the concentration of lipoprotein particles as measured by apoB.”
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. It may state two separate claims as one.
In the paper
“These findings are of increased relevance as recent publications have reported that TG, rather than LDL-C, most strongly predict CV risk.2”
What the sources say
- Not checked — no full text of the sourcecites [2] Castañer, 2020, Remnant cholesterol, not LDL cholesterol, is associated with incident cardiovascular disease., J Am Coll Cardiol source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A 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
“ApoB allows for accurate assessment of particle concentration, and when it is held constant, the measurements of TG and LDL-C reflect particle type and content.”
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.
- Rests on an assumption: ApoB is in a 1:1 association with atherogenic lipoprotein particles.
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
“Additionally, lipid values and lipid-lowering therapy data were collected at baseline in UK Biobank, but may have changed in some individuals during the follow-up period.”
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. 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
“Indeed, LDL-C is often calculated by laboratories rather than directly measured, which may contribute to less accurate measurements compared with those for apoB and support more widespread use of apoB.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“we addressed the issue by running a bootstrapped version of an adjusted Cox regression for the risk of MI, including all the lipids under examination (apoB, TG, non–HDL-C, and HDL).”
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.
The paper relies on this without support.
There is exactly one apoB-100 molecule on each atherogenic apoB-containing particle (LDL, IDL, and VLDL).
“As there is exactly 1 apoB-100 on each of the atherogenic apoB-containing particles (ie, LDL, IDL, and VLDL)”
The paper relies on this without support.
Measures of cholesterol and triglycerides provide information on the lipids in the blood and thus only indirectly on the types of lipoproteins and their composition, and not on the number of lipoproteins.
“However, measures of cholesterol and TG provide information on the lipids in the blood and thus only indirectly on the types of lipoproteins and their composition, and not on the number of lipoproteins.”
The paper relies on this without support.
Fatal or nonfatal myocardial infarction can be known with high precision and is strongly associated with dyslipidemia.
“The end point of interest in both cohorts was fatal or nonfatal MI, a cardiovascular outcome that can be known with high precision and is strongly associated with dyslipidemia.”
The paper relies on this without support.
The ratio of triglycerides to LDL-C is a surrogate for the ratio of triglyceride-rich lipoproteins to LDL.
“the ratio of TG to LDL-C (a surrogate for the ratio of TG-rich lipoproteins to LDL)”
The paper relies on this without support.
ApoB is in a 1:1 association with atherogenic lipoprotein particles.
“given the 1:1 association between apoB and atherogenic lipoprotein particles.”
The paper relies on this without support.
TG estimates TG-rich lipoproteins (VLDL and IDL) and LDL-C estimates LDL particles.
“TG-rich lipoproteins (ie, VLDL and IDL, estimated by TG) or LDL particle (estimated by LDL-C).”
The paper relies on this without support.
Individuals with higher lipid values are most likely to start lipid-lowering therapy.
“Because individuals with higher lipid values would be most likely to start lipid-lowering therapy”
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
§ Conclusions
“eTable 4. Baseline lipid parameters and adjusted hazard ratios for the composite endpoint myocardial infarction, stroke or cv death in the secondary prevention cohort without lipid lowering therapy”
§ Methods
“The second group included 40 430 patients with established atherosclerosis disease who were receiving lipid-lowering therapy”
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
§ Discussion
“In this study, all lipid-adjusted analyses included adjustment for apoB, thereby accounting for lipoprotein particle concentration in the risk assessment.”
§ Results
“Non–HDL-C had similar MI association with clinical adjustment, and while this was maintained after adding TG to the model, non–HDL-C was no longer associated with MI when adjusted for apoB (Table 2).”
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
Mach, F., Baigent, C., Catapano, A. L., Koskinas, K. C., Casula, M., Badimon, L., Chapman, M. J., De Backer, G. G., Delgado, V., Ference, B. A., et al. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehz455 · Cited by 8,961
Self-citationThe UK Biobank resource with deep phenotyping and genomic data
Bycroft, C., Freeman, C., Petkova, D., Band, G., Elliott, L. T., Sharp, K., Motyer, A., Vukcevic, D., Delaneau, O., O’Connell, J., et al. (2018) · Nature · doi:10.1038/s41586-018-0579-z · Cited by 8,876
Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease
Sabatine, M. S., Giugliano, R. P., Keech, A. C., Honarpour, N., Wiviott, S. D., Murphy, S. A., Kuder, J. F., Wang, H., Liu, T., Wasserman, S. M., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1615664 · Cited by 6,138
Self-citationMach, F., Baigent, C., Catapano, A. L., Koskinas, K. C., Casula, M., Badimon, L., Chapman, M. J., De Backer, G. G., Delgado, V., Ference, B. A., et al. (2019) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2019.08.014 · Cited by 4,854
Self-citationEzetimibe Added to Statin Therapy after Acute Coronary Syndromes
Cannon, C. P., Blazing, M. A., Giugliano, R. P., McCagg, A., White, J. A., Theroux, P., Darius, H., Lewis, B. S., Ophuis, T. O., Jukema, J. W., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1410489 · Cited by 4,487
Self-citationKANNEL, W. B., DAWBER, T. R., KAGAN, A., REVOTSKIE, N., & STOKES, J. (1961) · Annals of Internal Medicine · doi:10.7326/0003-4819-55-1-33 · Cited by 1,837
Elliott, P., Peakman, T. C., & Biobank, O. B. O. U. (2008) · International Journal of Epidemiology · doi:10.1093/ije/dym276 · Cited by 1,004
Richardson, T. G., Sanderson, E., Palmer, T. M., Ala-Korpela, M., Ference, B. A., Davey Smith, G., & Holmes, M. V. (2020) · PLOS Medicine · doi:10.1371/journal.pmed.1003062 · Cited by 843
Self-citationBoekholdt, S. M., Arsenault, B. J., Mora, S., Pedersen, T. R., LaRosa, J. C., Nestel, P. J., Simes, R. J., Durrington, P., Hitman, G. A., Welch, K. M. A., et al. (2012) · JAMA · doi:10.1001/jama.2012.366 · Cited by 795
Cited by
Sorted by citations
Palaniappan, L. P., Allen, N. B., Almarzooq, Z., Anderson, C. A. M., Arora, P. K., Avery, C. L., Baker-Smith, C. M., Bansal, N., Currie, M. E., Earlie, R. S., et al. (2026) · Circulation · doi:10.1161/cir.0000000000001412 · Cited by 343
2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Dyslipidemia
Blumenthal, R. S., Morris, P. B., Gaudino, M., Johnson, H. M., Anderson, T. S., Bittner, V. A., Blankstein, R., Brewer, L. C., Cho, L., de Ferranti, S. D., et al. (2026) · JACC · doi:10.1016/j.jacc.2025.11.016 · Cited by 304
Non-HDL-cholesterol in dyslipidemia: Review of the state-of-the-art literature and outlook
Raja, V., Aguíar, C., Al-Sayed, N., Chibber, Y. S., ElBadawi, H., Владиславович, Е. М., Hermans, M. P., Pandey, R. C., Ray, K. K., Tokgözoğlu, L. S., et al. (2023) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2023.117312 · Cited by 221
Friend or Foe? The Role of Animal-Source Foods in Healthy and Environmentally Sustainable Diets
Beal, T., Gardner, C. D., Herrero, M., Iannotti, L. L., Merbold, L., Nordhagen, S., & Mottet, A. (2023) · Journal of Nutrition · doi:10.1016/j.tjnut.2022.10.016 · Cited by 228
Björnson, E., Adiels, M., Taskinen, M.-R., Burgess, S., Rawshani, A., Borén, J., & Packard, C. J. (2023) · European Heart Journal · doi:10.1093/eurheartj/ehad337 · Cited by 183
“10, 22 In contrast, extensive reports from the Copenhagen General Population Study 1, 11–13, 23,21 and other cohorts 12 indicated that TRL cholesterol or remnant cholesterol was associated with a higher CHD risk per mmol/l increase than LDL-C, and since remnants have a higher cholesterol/apoB ratio…”
Cheeley, M. K., Saseen, J. J., Agarwala, A., Ravilla, S., Ciffone, N., Jacobson, T. A., Dixon, D. L., & Maki, K. C. (2022) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2022.05.068 · Cited by 197
Glavinovic, T., Thanassoulis, G., Graaf, J. D., Couture, P., Hegele, R. A., & Sniderman, A. D. (2022) · Journal of the American Heart Association · doi:10.1161/jaha.122.025858 · Cited by 182
Burgess, S., Mason, A. M., Grant, A. J., Slob, E. A. W., Gkatzionis, A., Zuber, V., Patel, A. R., Tian, H., Liu, C., Haynes, W. G., et al. (2023) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2022.12.017 · Cited by 157
World Heart Federation Cholesterol Roadmap 2022
Ray, K. K., Ference, B. A., Séverin, T., Blom, D. J., Nicholls, S. J., Shiba, M. H., Almahmeed, W. A., Rodrigo Alonso, K., Daccord, M., Владиславович, Е. М., et al. (2022) · Global Heart · doi:10.5334/gh.1154 · Cited by 159
Self-citationWriting Committee Members, Blumenthal, R. S., Morris, P. B., Gaudino, M., Johnson, H. M., Anderson, T. S., Bittner, V. A., Blankstein, R., Brewer, L. C., Cho, L., et al. (2026) · Circulation · doi:10.1161/cir.0000000000001423 · Cited by 122
Kirkpatrick, C. F., Sikand, G., Petersen, K. S., Anderson, C. A. M., Aspry, K. E., Bolick, J. P., Kris‐Etherton, P. M., & Maki, K. C. (2023) · Journal of clinical lipidology · doi:10.1016/j.jacl.2023.05.099 · Cited by 137
Sniderman, A. D., Dufresne, L., Pencina, K. M., Bilgic, S., Thanassoulis, G., & Pencina, M. J. (2024) · European Heart Journal · doi:10.1093/eurheartj/ehae258 · Cited by 139
“26 However, given that apoB is a more accurate measure of the adequacy of lipid-lowering therapy than LDL-C or non-HDL-C, 1,3–13 , 27 there In summary, the present prospective discordance analysis adds to the evidence that apoB is a more accurate marker of cardiovascular risk than LDL-C, non-HDL-C,…”
BackgroundResultSoffer, D. E., Marston, N. A., Maki, K. C., Jacobson, T. A., Bittner, V. A., Peña, J. M., Thanassoulis, G., Martin, S. S., Kirkpatrick, C. F., Virani, S. S., et al. (2024) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2024.08.013 · Cited by 115
Self-citationHansen, C. D., Gram-Kampmann, E.-M., Hansen, J. K., Hugger, M. B., Madsen, B. S., Jensen, J. M., Olesen, S., Torp, N., Rasmussen, D. N., Kjærgaard, M., et al. (2023) · Annals of Internal Medicine · doi:10.7326/m22-1787 · Cited by 110
Hagström, E., Steg, P. G., Szarek, M., Bhatt, D. L., Bittner, V. A., Danchin, N., Diaz, R., Goodman, S. G., Harrington, R. A., Jukema, J. W., et al. (2022) · Circulation · doi:10.1161/circulationaha.121.057807 · Cited by 118
Emerging Evidence of Pathological Roles of Very-Low-Density Lipoprotein (VLDL)
Huang, J.-K., & Lee, H. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23084300 · Cited by 115
“Increased Apo C-III, Apo E-III, and E-IV of VLDL in MetS exhibit reduced LPL activity and function [8,27,104,105].”
BackgroundYang, X. H., Zhang, B. L., Cheng, Y., Fu, S. K., & Jin, H. M. (2023) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2023.03.012 · Cited by 83
Sniderman, A. D., Návar, A. M., & Thanassoulis, G. (2021) · JAMA Cardiology · doi:10.1001/jamacardio.2021.5080 · Cited by 78
Apolipoprotein B: Bridging the Gap Between Evidence and Clinical Practice
Oliveira-Gomes, D. D., Joshi, P. H., Peterson, E. D., Rohatgi, A. K., Khera, A., & Návar, A. M. (2024) · Circulation · doi:10.1161/circulationaha.124.068885 · Cited by 85
Excess Apolipoprotein B and Cardiovascular Risk in Women and Men
Johannesen, C. D. L., Langsted, A., Nordestgaard, B. G., & Mortensen, M. B. (2024) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2024.03.423 · Cited by 81
Nelson, A. J., Sniderman, A. D., Ditmarsch, M., Dicklin, M. R., Nicholls, S. J., Davidson, M. H., & Kastelein, J. J. P. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23169417 · Cited by 72
Dai, H., Hou, T., Wang, Q., Hou, Y., Wang, T., Zheng, J., Lin, H., Zhao, Z., Li, M., Wang, S., et al. (2023) · European Journal of Preventive Cardiology · doi:10.1093/eurjpc/zwad171 · Cited by 65
Best practice for LDL-cholesterol: when and how to calculate
Martins, J., Steyn, N., Rossouw, H. M., & Pillay, T. S. (2023) · Journal of Clinical Pathology · doi:10.1136/jcp-2022-208480 · Cited by 61
“In a recent cohort study by Marston et al , 48 association with MI was best captured by the number of apoB-containing lipoproteins, independent from lipid content (cholesterol or TG) or type of lipoprotein (LDL or TG-rich).”
BackgroundSarraju, A., Brennan, D. M., Hayden, K., Stronczek, A., Goldberg, A. C., Michos, E. D., McGuire, D. K., Mason, D., Tercek, G., Nicholls, S. J., et al. (2025) · The Lancet · doi:10.1016/s0140-6736(25)00721-4 · Cited by 64
Standardization of Apolipoprotein B, LDL‐Cholesterol, and Non‐HDL‐Cholesterol
Contois, J. H., Langlois, M. R., Cobbaert, C. M., & Sniderman, A. D. (2023) · Journal of the American Heart Association · doi:10.1161/jaha.123.030405 · Cited by 57
Hansen, M. K., Mortensen, M. B., Warnakula Olesen, K. K., Thrane, P. G., & Maeng, M. (2024) · The Lancet Regional Health - Europe · doi:10.1016/j.lanepe.2023.100774 · Cited by 57
Galimberti, F., Casula, M., & Olmastroni, E. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.106873 · Cited by 63
“More recently, Marston et al. [36] conducted a prospective cohort study that included 389,529 participants in the primary prevention group and 40,430 participants in the secondary prevention group.”
Role of Treg cell subsets in cardiovascular disease pathogenesis and potential therapeutic targets
Xia, Y., Gao, D., Wang, X., Liu, B., Shan, X., Sun, Y., & Ma, D. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1331609 · Cited by 58
Karwatowska‐Prokopczuk, E., Tardif, J., Gaudet, D., Ballantyne, C. M., Shapiro, M. D., Moriarty, P. M., Baum, S. J., Amour, E. S., Alexander, V. J., Xia, S., et al. (2022) · Journal of clinical lipidology · doi:10.1016/j.jacl.2022.06.005 · Cited by 51
Elliott, P. S., Kharaty, S. S., & Phillips, C. M. (2022) · Nutrients · doi:10.3390/nu14245371 · Cited by 53
Intracellular tPA–PAI-1 interaction determines VLDL assembly in hepatocytes
Dai, W., Zhang, H., Lund, H., Zhang, Z., Castleberry, M., Rodriguez, M., Kuriakose, G., Gupta, S. K., Lewandowska, M., Powers, H. R., et al. (2023) · Science · doi:10.1126/science.adh5207 · Cited by 52
Brunham, L. R., Lonn, E., & Mehta, S. R. (2024) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2024.04.017 · Cited by 54
Nicholls, S. J., Nelson, A. J., Ditmarsch, M., Kastelein, J. J. P., Ballantyne, C. M., Ray, K. K., Návar, A. M., Nissen, S. E., Goldberg, A. C., Brunham, L. R., et al. (2024) · American Heart Journal · doi:10.1016/j.ahj.2024.05.002 · Cited by 46
Self-citationApoB100 and Atherosclerosis: What’s New in the 21st Century?
Kounatidis, D. C., Vallianou, N. G., Poulaki, A., Evangelopoulos, A. A., Panagopoulos, F., Stratigou, T., Geladari, E. V., Karampela, Ι., & Dalamaga, Μ. (2024) · Metabolites · doi:10.3390/metabo14020123 · Cited by 49
“The authors concluded that the number of ApoB-containing lipoproteins may be superior in reflecting MI risk, independent of the type of lipoprotein or lipid content [41].”
BackgroundApoB-containing lipoproteins: count, type, size, and risk of coronary artery disease
Morze, J., Melloni, G. E. M., Wittenbecher, C., Ala‐Korpela, M., Rynkiewicz, A., Guasch‐Ferré, M., Ruff, C. T., Hu, F. B., Sabatine, M. S., & Marston, N. (2025) · European Heart Journal · doi:10.1093/eurheartj/ehaf207 · Cited by 46
“4 Similarly, Mendelian randomization studies have demonstrated equivalent atherogenicity of VLDL and LDL. 5,6 However, this view was challenged by a recent gen-etic analysis suggesting that the per-particle risk of VLDL carries twice the atherogenic risk compared with LDL particles.”
Self-citationWilliams, K. J. (2023) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.123.320065 · Cited by 41
“44,86 Post hoc analyses of PCSK9i trials have implicated residual circulating apoB-lipoproteins in residual ASCVD event risk, 90,91 as would be expected.”
BackgroundRuscica, M., Macchi, C., Giuliani, A., Rizzuto, A. S., Ramini, D., Sbriscia, M., Carugo, S., Bonfigli, A. R., Corsini, A., Olivieri, F., et al. (2023) · Cardiovascular Diabetology · doi:10.1186/s12933-023-01948-8 · Cited by 40
Tybjærg‐Hansen, A., Nordestgaard, B. G., & Christoffersen, M. (2023) · European Heart Journal · doi:10.1093/eurheartj/ehad419 · Cited by 37
Khan, S. S., Greenland, P., Hayman, L. L., Khera, R., Návar, A. M., Pencina, M. J., Reza, N., Shah, S. H., Shanbhag, S. M., Weber, B., et al. (2026) · Circulation · doi:10.1161/cir.0000000000001401 · Cited by 45
Menopausal hormone therapy in women with dyslipidemia and nonalcoholic fatty liver disease
Pοlyzos, S. A., Lambrinoudaki, I. V., & Goulis, D. G. (2022) · HORMONES · doi:10.1007/s42000-022-00369-8 · Cited by 31
European guidelines for the treatment of dyslipidaemias: New concepts and future challenges
Pirillo, A., Casula, M., & Catapano, A. L. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.106936 · Cited by 38
Risk factors for clonal hematopoiesis of indeterminate potential and mosaic chromosomal alterations
Jakubek, Y. A., Reiner, A. P., & Honigberg, M. C. (2022) · Translational research · doi:10.1016/j.trsl.2022.11.009 · Cited by 30
Sayed, A., Peterson, E. D., Virani, S. S., Sniderman, A. D., & Návar, A. M. (2024) · JAMA Cardiology · doi:10.1001/jamacardio.2024.1310 · Cited by 30
Sampson, M. L., Wolska, A. T., Meeusen, J. W., Donato, L. J., Jaffe, A. S., & Remaley, A. T. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.935257 · Cited by 29
Kristensen, F., Christensen, D. H., Mortensen, M. B., Mæng, M., Kahlert, J. A., Sørensen, H. T., & Thomsen, R. W. (2023) · Cardiovascular Diabetology · doi:10.1186/s12933-023-01921-5 · Cited by 29
Liang, X., Zhang, J., Yu, J., Zhao, J., & Yang, S.-S. (2025) · European journal of medical research · doi:10.1186/s40001-025-02562-y · Cited by 33
“When occurring in the coronary arteries, it may lead to local clots that thoroughly block the blood flow, causing myocardial infarction [6, 7].”
Valproate-Induced Metabolic Syndrome
Shnayder, N. A., Владимировна, Г. В., Trefilova, V. V., Efremov, I. S., Dontceva, E. A., Narodova, E. A., Петрова, М. М., Soloveva, I. A., Tepnadze, L. E., Reznichenko, P. A., et al. (2023) · Biomedicines · doi:10.3390/biomedicines11051499 · Cited by 25
Zimerman, A., Wiviott, S. D., Park, J., Murphy, S. A., Ran, X., Bramson, C., Curto, M., Ramos, V., Jevne, A., Kuder, J., et al. (2024) · European Journal of Preventive Cardiology · doi:10.1093/eurjpc/zwae090 · Cited by 28
Self-citationUse of Apolipoprotein B in the Era of Precision Medicine: Time for a Paradigm Change?
Cole, J., Zubirán, R., Wolska, A. T., Jialal, I., & Remaley, A. T. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12175737 · Cited by 23
“[9] performed a similar analysis on 40,430 statin-treated patients from the FOURIER and IMPROVE-IT studies, who were followed up for a median of 2.”
BackgroundMethodInfluentialDyslipidemia: A Narrative Review on Pharmacotherapy
de Oliveira, L. D., de Assis, A. C. R., Giraldez, V. Z. R., Scudeler, T. L., & Soares, P. R. (2024) · Pharmaceuticals · doi:10.3390/ph17030289 · Cited by 26
“In recent years, the value of apoB (an essential structural component of LDL-C) as a marker of CV risk has increased through epidemiological studies, clinical trials, and Mendelian randomization analyses [154–161].”
BackgroundKraaijenhof, 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
Self-citationShen, Y., Gu, H.-M., Zhai, L., Wang, B., Qin, S., & Zhang, D. (2022) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2022.159196 · Cited by 24
Ma, 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
Chen, K.-S., Chan, H.-C., & Chan, C.-M. (2024) · International Journal of Retina and Vitreous · doi:10.1186/s40942-024-00606-9 · Cited by 22
“MI is often caused by the natural progression of coronary atherosclerosis, with coronary artery occlusion resulting from plaques prone to rupture or erosion being the most common cause of MI [49].”
Yun, S. Y., Rim, J. H., Kang, H., Lee, S., & Lim, J. (2022) · Annals of Laboratory Medicine · doi:10.3343/alm.2023.43.3.237 · Cited by 22
“Studies have compared these three lipid markers in ASCVD [10-12, 15-17 15-17]; however, identifying the most potent marker of ASCVD is challenging.”
Ballantyne, C. M., & Norata, G. D. (2025) · European Heart Journal · doi:10.1093/eurheartj/ehaf606 · Cited by 23
Triglyceride-Rich Lipoproteins and Atherosclerotic Cardiovascular Disease Risk
Duell, P. B. (2023) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2022.11.013 · Cited by 22
The Causal-Benefit Model to Prevent Cardiovascular Events
Kohli-Lynch, C. N., Thanassoulis, G., Pencina, M. J., Sehayek, D., Pencina, K. M., Moran, A. E., & Sniderman, A. D. (2024) · JACC Advances · doi:10.1016/j.jacadv.2023.100825 · Cited by 23
ApoB, LDL-C, and non-HDL-C as markers of cardiovascular risk
Sehayek, D., Cole, J., Björnson, E., Wilkins, J. T., Mortensen, M. B., Dufresne, L., Pencina, K. M., Pencina, M. J., Thanassoulis, G., & Sniderman, A. D. (2025) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2025.05.024 · Cited by 20
Koba, S., Satoh, N., Ito, Y., Yokota, Y., Tsunoda, F., Sakai, K., Nakamura, Y., Shoji, M., Hirano, T., & Shinke, T. (2024) · Clinical Chemistry · doi:10.1093/clinchem/hvae061 · Cited by 20
Zaheen, M., Pender, P., Dang, Q., Sinha, E., Chong, J. J. H., Chow, C. K., & Zaman, S. J. (2025) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd12040148 · Cited by 27
“This suggests that apolipoprotein B may be a key factor in the development of atherosclerosis, but these findings were not specific to young MI patients [105].”
Lipoprotein(a), family history of cardiovascular disease, and incidence of heart failure
Wang, H., Zhang, N., Liu, Y., Xia, T.-L., Chen, G., Yang, J., & Li, F. (2023) · Journal of Lipid Research · doi:10.1016/j.jlr.2023.100398 · Cited by 20
“Sensitivity analysis was also performed by further adjusting for apolipoprotein B [(apo) B], as previous studies have reported that apoB may be the primary driver of atherosclerosis beyond other lipids (30, 31).”
MethodJin, 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
Johannesen, C. D. L., Mortensen, M. B., Nordestgaard, B. G., & Langsted, A. (2025) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2025.119139 · Cited by 22
Sampson, M. L., Zubirán, R., Wolska, A. T., Meeusen, J. W., Donato, L. J., Jaffe, A. S., Melloni, G. E. M., Giugliano, R. P., Sabatine, M. S., Marston, N., et al. (2025) · Clinical Chemistry · doi:10.1093/clinchem/hvaf073 · Cited by 18
Self-citationCandás‐Estébanez, B., Fernández‐Cidón, B., Corbella, E., Tebé, C., Fanlo‐Maresma, M., Esteve-Luque, V., Salas‐Salvadó, J., Fitó, M., Riera‐Mestre, A., Ros, E., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25021338 · Cited by 19
“The er-MedDiet+PA intervention also induced a decrease in VLDL-TG, and, as a consequence, lVLDL-P was also reduced, and LDL particle size increased—changes that are recognized as anti-atherogenic [21].”
BackgroundCascade testing for elevated lipoprotein(a) in relatives of probands with high lipoprotein(a)
Chakraborty, A., Chan, D. C., Ellis, K. L., Pang, J., Barnett, W., Woodward, A. M., Vorster, M., Norman, R., Moses, E. K., & Watts, G. F. (2022) · American Journal of Preventive Cardiology · doi:10.1016/j.ajpc.2022.100343 · Cited by 18
Kalra, D. K., Ray, K. K., Bajaj, A., Kushner, P. R., Wilcox, M. L., Dicklin, M. R., Kirkpatrick, C. F., & Maki, K. C. (2026) · Journal of clinical lipidology · doi:10.1016/j.jacl.2026.02.006 · Cited by 18
Residual lipid risk in atherosclerotic cardiovascular disease
Nordestgaard, B. G., & Hegele, R. A. (2026) · European Heart Journal · doi:10.1093/eurheartj/ehag087 · Cited by 29
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
Apolipoprotein B in cardiovascular risk assessment
Ahmad, M., Sniderman, A. D., & Hegele, R. A. (2023) · Canadian Medical Association Journal · doi:10.1503/cmaj.230048 · Cited by 16
APOB is a potential prognostic biomarker in hepatocellular carcinoma
Lin, Z., Ji, X., Tian, N., Gan, Y., & Ke, L. (2024) · Discover Oncology · doi:10.1007/s12672-024-00877-6 · Cited by 16
“Among the apolipoprotein family members, APOB consists of tiny particles that carry dietary lipids through the blood-stream from the intestines to the liver [22, 23].”
BackgroundBlood-Based DNA Methylation Biomarkers to Identify Risk and Progression of Cardiovascular Disease
Willmer, T., Mabasa, L., Sharma, J. R., Muller, C. J. F., & Johnson, R. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26052355 · Cited by 16
“Some of these genes, including APOB , have been previously reported to be strong drivers of myocardial infarction risk [130].”
Li, J.-N., Wang, M., Tan, Y., & Wang, L.-L. (2024) · The American Journal of Chinese Medicine · doi:10.1142/s0192415x24500381 · Cited by 15
Cargo Receptor-Mediated ER Export in Lipoprotein Secretion and Lipid HomeostasisPreprint
Wang, X., & Chen, X. (2022) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a041260 · Cited by 14
Colchicine promotes atherosclerotic plaque stability independently of inflammationPreprint
Li, W., Lin, A., Hutton, M., Dhaliwal, H., Nadel, J., Rodor, J., Tumanov, S., Örd, T., Hadden, M. K., Mokrý, M., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.10.03.560632 · Cited by 14
“low-density lipoproteins (LDLs), very low-density lipoproteins, and chylomicron remnants) (29, 30).”
Girona, J., Guardiola, M., Barroso, E., García‐Altares, M., Ibarretxe, D., Plana, N., Ribalta, J., Amigó, N., Correig, X., Vázquez‐Carrera, M., et al. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26052039 · Cited by 13
“Although the mechanisms by which VLDL are related to the atherosclerosis physiopathology are still unclear, these lipoproteins have been proposed as a causal risk factor for atherosclerotic CV disease, showing a atherogenic risk per particle than LDL [11,12,37].”
Novel Biomarkers for Atherosclerotic Disease: Advances in Cardiovascular Risk Assessment
Jigoranu, A. R., Roca, M., Costache, A. D., Mitu, O., Oancea, A. F., Miftode, R.-Ş., Haba, M. Ș. C., Botnariu, G., Maștaleru, A., Gavril, R. S., et al. (2023) · Life · doi:10.3390/life13081639 · Cited by 17
“They evaluated the triglyceride/LDL-C ratio while adjusting for apoB and clinical risk factors and concluded that the type of apoB-containing lipoprotein brought no additional risk-assessment value [86].”
MethodAssociations between apolipoprotein B and bone mineral density: a population-based study
Zhao, X., Tan, N., Zhang, Y., et al. (2023) · BMC Musculoskeletal Disorders · doi:10.1186/s12891-023-06990-x · Cited by 13
Liao, K. P., Rist, P. M., Giles, J. T., Santacroce, L. M., Connelly, M. A., Glynn, R. J., Ridker, P. M., Tawakol, A. A., Bathon, J. M., & Solomon, D. H. (2024) · Arthritis Research & Therapy · doi:10.1186/s13075-024-03352-3 · Cited by 14
“Apolipoprotein B (apoB), a more direct measurement of atherogenic lipid particles has the strongest association with CV outcomes compared to other lipid and lipoprotein measurements [16].”
BackgroundBilgic, S., Pencina, K. M., Pencina, M. J., Cole, J., Dufresne, L., Thanassoulis, G., & Sniderman, A. D. (2024) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.124.321165 · Cited by 15
Anderson, J. L., Knight, S., May, H. T., Le, V. T., Almajed, J., Bair, T. L., Knowlton, K. U., & Muhlestein, J. B. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm12010075 · Cited by 13
Papathanasiou, K. A., Roussos, C. E., Armylagos, S., Rallidis, S. L., & Rallidis, L. S. (2024) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd11100316 · Cited by 13
“ApoB-containing lipoproteins are the main drivers for atherosclerosis progression among patients with established CAD and are predictive of new MI [26,27].”
BackgroundNacarelli, G. S., Fasolino, T. K., & Davis, S. C. (2023) · Nutrition Reviews · doi:10.1093/nutrit/nuad102 · Cited by 12
Roles of O-GlcNAcylation in Mitochondrial Homeostasis and Cardiovascular Diseases
Qiu, Z., Cui, J., Huang, Q., Qi, B., & Xia, Z. (2024) · Antioxidants · doi:10.3390/antiox13050571 · Cited by 13
“Atherosclerosis is a key predisposing factor in the development of CHD and leads to much morbidity and mortality worldwide, including most myocardial infarction and many strokes, as well as disabling peripheral artery disease [23,175,176].”
BackgroundTale of two systems: the intertwining duality of fibrinolysis and lipoprotein metabolism
Dai, W., Castleberry, M., & Zheng, Z. (2023) · Journal of Thrombosis and Haemostasis · doi:10.1016/j.jtha.2023.08.004 · Cited by 14
Wu, J., Fan, Q., He, Q., Zhong, Q., Zhu, X., Cai, H., He, X., Xu, Y., Huang, Y., & Di, X. (2023) · Medicine · doi:10.1097/md.0000000000036284 · Cited by 14
“[33] The enrichment analysis results revealed that the KEGG pathway primarily focuses on cholesterol metabolism, the PPAR signaling pathway, and vitamin digestion and absorption.”
BackgroundRemnant cholesterol, vascular risk, and prevention of atherosclerosis
Pintó, X., Fanlo‐Maresma, M., Esteve-Luque, V., & Millán, J. (2023) · Clínica e Investigación en Arteriosclerosis (English Edition) · doi:10.1016/j.artere.2023.07.005 · Cited by 13
Remnant cholesterol: a reliable prognostic marker?
Pirillo, A., & Catapano, A. L. (2023) · European Journal of Preventive Cardiology · doi:10.1093/eurjpc/zwad107 · Cited by 11
Rehman, M. B., Björnson, E., Adiels, M., Morze, J., Bergström, G. M. L., Gummesson, A., Erlinge, D., Fall, T., Matic, L. P., Söderberg, S., et al. (2026) · European Heart Journal · doi:10.1093/eurheartj/ehaf1124 · Cited by 12
“Early studies suggested that all apoB-containing lipoproteins had approximately equal atherogenicity, 28,29 but recent investigations have revealed this not to be the case.”
Li, T., Zhu, P., Song, Y., Tang, X., Gao, Z., Run-Lin, G. A. O., & Yuan, J. (2023) · 老年心脏病学杂志：英文版 · doi:10.26599/1671-5411.2023.12.001 · Cited by 12
Maidman, S. D., Hegele, R. A., & Rosenson, R. S. (2024) · Current Atherosclerosis Reports · doi:10.1007/s11883-024-01258-8 · Cited by 13
Fujino, M., Giovanni, G. D., Butters, J., Kataoka, Y., Hucko, T., Nelson, A. J., Nissen, S. E., Psaltis, P. J., & Nicholls, S. J. (2025) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2025.119145 · Cited by 10
Faquih, T. O., Aziz, N. A., Gardiner, S. L., Li‐Gao, R., de Mutsert, R., Milaneschi, Y., Trompet, S., Jukema, J. W., Rosendaal, F. R., Vlieg, A. V. H., et al. (2023) · Human Molecular Genetics · doi:10.1093/hmg/ddad020 · Cited by 10
Reijnders, E., van der Laarse, A., Ruhaak, L. R., & Cobbaert, C. M. (2024) · Clinical Proteomics · doi:10.1186/s12014-024-09465-w · Cited by 10
“In particular, apolipoprotein B (ApoB) has been identified as a strong independent predictor of CVD risk, with several studies demonstrating its superiority over traditional lipids such as LDL-c, and non-HDL-c [17–19].”
BackgroundVelilla, T. A., Guijarro, C., Ruíz, R. C., Piñero, M. R., Marcos, J. F. V., Pérez, A., López, M. A. B., López, A. M., Donaire, J. A. G., Obaya, J. C., et al. (2023) · Neurology Perspectives · doi:10.1016/j.neurop.2023.100126 · Cited by 11
Bilgic, S., & Sniderman, A. D. (2023) · Current Opinion in Cardiology · doi:10.1097/hco.0000000000001100 · Cited by 9
Pikkemaat, M., Woodward, M., af Geijerstam, P., Harrap, S. B., Hamet, P., Mancia, G., Marre, M., Poulter, N. R., Chalmers, J. P., & Harris, K. (2024) · Diabetes Obesity and Metabolism · doi:10.1111/dom.15935 · Cited by 9
Metadata
- Authors
- Marston, N. A., Giugliano, R. P., Melloni, G. E. M., Park, J.-G., Morrill, V., Blazing, M. A., Ference, B., Stein, E., Stroes, E. S., Braunwald, E., Ellinor, P. T., Lubitz, S. A., Ruff, C. T., & Sabatine, M. S.
- Affiliations
- Brigham and Women's Hospital (US)
- Broad Institute (US)
- Duke University (US)
- University of Cambridge (GB)
- Metabolic and Atherosclerosis Research Center, Cincinnati, Ohio
- Amsterdam University Medical Centers (NL)
- Thrombolysis in Myocardial Infarction (TIMI) Study Group, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
- Corresponding author
- Marston, Nicholas A.
- ORCID
- Venue
- JAMA Cardiology
- Publisher
- American Medical Association (AMA)
- Published
- 2022-03-01
- Volume
- 7
- Issue
- 3
- Pages
- 250
- ISSN
- 2380-6583 (ISSN-L)
- PMC
- PMC8590731
- OpenAlex
- W3213895219
- Semantic Scholar
- a8dd33ed82854a233b2e5383c88457332240ec72
- Cited by
- 262
- References
- 23
- Citations by year
- 2026: 43 · 2025: 50 · 2024: 67 · 2023: 68 · 2022: 32
- FWCI
- 35.66
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JAMA Cardiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Funders
- British Heart Foundation (CH/1996001/9454)
- Medical Research Council (MC_PC_17228)
- National Heart, Lung, and Blood Institute (K08HL153950)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Keywords
- apolipoprotein B, apoB-containing lipoproteins, myocardial infarction, atherosclerosis, non-HDL cholesterol, triglycerides, LDL cholesterol, VLDL, cardiovascular risk, statin therapy, primary prevention, lipid control, FOURIER trial, IMPROVE-IT trial, UK Biobank
- MeSH terms
- Apolipoproteins B, Cholesterol, Female, Humans, Lipoproteins, Cholesterol, LDL, Male, Myocardial Infarction, Prospective Studies, Cohort Studies, Atherosclerosis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-19, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-19 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
