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
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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
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L’apolipoprotéine B dans l’évaluation du risque cardiovasculaire
Ahmad, M., Sniderman, A. D., & Hegele, R. A. (2023) · Canadian Medical Association Journal · doi:10.1503/cmaj.230048-f
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ApoB and prognosis of patients with chronic coronary syndrome
Cordero, A., & Olmo, R. F. (2024) · Revista Española de Cardiología (English Edition) · doi:10.1016/j.rec.2024.10.003
ApoB y pronóstico de los pacientes con síndrome coronario crónico
Cordero, A., & Olmo, R. F. (2024) · Revista Española de Cardiología · doi:10.1016/j.recesp.2024.10.004
Stationary screen time, blood lipids, and atherosclerotic cardiovascular disease incidence
Liu, Y., Xu, L., Liu, P., Liao, X., & Liao, J. (2025) · BMC Cardiovascular Disorders · doi:10.1186/s12872-025-04568-0
“In addition, the measurement of ApoB provides more information about particle types, including LDL-C and VLDL-C, than the measurement of LDL-C alone [35].”
Bedre risikoprediksjon med ApoB eller non-HDL-kolesterol
Kalleklev, T., Larstorp, A. C. K., & Retterstøl, K. (2025) · Tidsskrift for Den norske legeforening · doi:10.4045/tidsskr.25.0139
Current opinions on the role of apolipoprotein B in the clinical management of cardiovascular risk
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Evans, J., Dales, R., Mitchell, K., & Cakmak, S. (2026) · Environmental Pollution · doi:10.1016/j.envpol.2026.127671
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Expanded Lipid Biomarkers and Estimating Risk Beyond PREVENT
Davis, J. W., & Manson, J. E. (2026) · JAMA Network Open · doi:10.1001/jamanetworkopen.2026.5207
ApoB and Resilient Cost-Effectiveness of Statin Intensity
Pandya, A., & Zhu, J. (2026) · JAMA · doi:10.1001/jama.2026.3531
Zhang, F., & Liao, Q. (2026) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2026.1790509 · Cited by 1
“Molecular imaging approaches remain largely research tools due to cost and standardization barriers (16, 17, 43, 46, 47), but they are conceptually important for validating inflammatory targets and bridging mechanisms to clinical phenotypes.”
InfluentialMirskaya, T. A., Rodionova, V. V., & Lysenko, L. A. (2025) · Biochemistry (Moscow) Supplement Series B Biomedical Chemistry · doi:10.1134/s1990750825601237
“The most pronounced correlation was observed with apolipoprotein B ( ρ = 0.218), which is consistent with its role as an integral marker of atherogenic lipoproteins [20].”
InfluentialShapiro, M. D. (2026) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2026.02.5131
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Geng, H., Sun, Y. W., Kong, X., et al. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1733766
“This fi nding aligns with studies suggesting that ApoB re fl ects atherogenic lipid burden (16), which has been implicated in both metabolic and psychological disorders (17).”
Pan, A., Zhao, H., Wang, J., Zhang, J., Zheng, H., Zhang, C. J., Chen, W., & Zhang, T. (2026) · Mass Spectrometry Reviews · doi:10.1002/mas.70035
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Zheng, C., Jia, M., & Ning, B. (2026) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2026.1915694
“Several studies (1 – 4) have found that ApoB/ApoA1 more effectively identifies risks linked to coronary atherosclerotic disease, myocardial infarction, and ischemic stroke.”
Genedy, N., & Zouwail, S. (2026) · Journal of clinical lipidology · doi:10.1016/j.jacl.2026.07.022
Sarti, A., Sciaramenti, G., Camaiti, G., Cioci, P., Rizza, C., Tezze, R., Vocale, L. R., Hoxha, K., Maccaferri, I., Paparazzo, F., et al. (2026) · Journal of Clinical Medicine · doi:10.3390/jcm15166358
“…that apoB is a more accurate marker of residual atherothrombotic risk than LDL-C in patients treated with statins, statin-ezetimibe combination therapy, or PCSK9 inhibitors, as well as in individuals with obesity, metabolic syndrome, type 2 diabetes mellitus, or insulin resistance [7–9].”
Siddiqi, A. K., Jacob, J., Khan, M. S., & Kulkarni, A. (2026) · Current Atherosclerosis Reports · doi:10.1007/s11883-026-01465-5
Dragomir, T. L., Branea, H. S., Andor, M., Citu, I. M., Căruntu, F. R., Șușan, M. M., Oprean, C. M., Dragomir, R.-T., Șușan, R. M., Huțanu, D., et al. (2026) · Diagnostics · doi:10.3390/diagnostics16193245 · Cited by 1
“Serial imaging, statin-treated cohorts, and contemporary discordance analyses support ApoB as a marker of residual risk when the cholesterol content of atherogenic particles and particle number diverge [5,14,15,26–29].”
Higher APOB is associated with poor renal outcome in lupus nephritis
Wang, Q., Wu, W., & Jiang, Z. (2026) · Clinical Rheumatology · doi:10.1007/s10067-026-08479-z
Helgadottir, A., Thorleifsson, G., Snaebjarnarson, A., Stefansdottir, L., Sveinbjornsson, G., Tragante, V., Björnsson, E., Steinthorsdottir, V., Gretarsdottir, S., Helgason, H., et al. (2022) · European Journal of Preventive Cardiology · doi:10.1093/eurjpc/zwac219 · Cited by 30
A Translational Tool to Facilitate Use of Apolipoprotein B for Clinical Decision-Making
Cole, J., Otvos, J. D., & Remaley, A. T. (2023) · Clinical Chemistry · doi:10.1093/clinchem/hvac161 · Cited by 22
Is hypertriglyceridemia a reliable indicator of cholesterol-depleted Apo B particles?
De Marco, D., Pencina, K., Pencina, M., Dufresne, L., Thanassoulis, G., & Sniderman, A. D. (2023) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2023.05.093 · Cited by 15
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 ›
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