EditorialDid the ACC/AHA/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA cholesterol guidelines get apoB right?
Section snippets
Why was LDL-C maintained as the primary measure on, which to base therapeutic decisions?
Low-density lipoprotein cholesterol (LDL-C) remains the primary measure in these guidelines to assess the adequacy of lipid-lowering therapy.1 But this recommendation is not consistent with Section 2.1.1 (page 13) of the ACC/AHA Guidelines, which states that non–high-density lipoprotein cholesterol (non–HDL-C) and apoB are both stronger indicators of the risk of atherogenicity than LDL-C. If both non–HDL-C and apoB are more accurate measures of atherogenic risk, why is neither the primary
How thorough and how accurate is the review of the evidence on which the ACC/AHA recommendations regarding apoB are based?
The relevant section is short enough to reproduce in its entirety.
“Because apoB is the major apolipoprotein embedded in LDL and very-low-density lipoprotein (VLDL), several investigators identify strength of association between apoB and ASCVD (S2.3-1). Others report a high correlation between apoB and non–HDL-C (S2.3-2). Under certain circumstances, particularly in patients with hypertriglyceridemia, the measurement of apoB may have advantages (S2.3-3). Nevertheless, apoB measurement carries
Why were the discordance analyses of apoB vs LDL-C and non–HDL-C not cited?
Grundy et al base their argument for the equivalence of apoB and non–HDL-C on the high correlation between the two markers.3, 6 ApoB and non–HDL-C are highly correlated, but they are also moderately discordant, that is, for any given value of one, there can be a substantial range of values for the other.20 Differences in the cholesterol content of the apoB particles are due to transfers and exchanges of core lipids—cholesterol ester and triglycerides—mediated by cholesterol ester transfer
Why was type III hyperlipoproteinemia not considered?
Type III hyperlipoproteinemia is a highly atherogenic dyslipoproteinemia, which generally appears in midlife.35, 36 Cardiovascular risk is sufficiently high that treatment is mandated once the diagnosis is made. The incidence of type III in the population and among subjects with hypertriglyceridemia is not known with precision but the available estimates suggest it is at least as common as familial hypercholesterolemia.35 Moreover, just as in familial hypercholesterolemia, calculated 10-year
References (41)
- et al.
Correlation of non-high-density lipoprotein cholesterol and low-density lipoprotein cholesterol with apolipoprotein B during simvastatin + fenofibrate therapy in patients with combined hyperlipidemia (a subanalysis of the SAFARI trial)
Am J Cardiol
(2009) Differential response of cholesterol and particle measures of atherogenic lipoproteins to LDL-lowering therapy: implications for clinical practice
J Clin Lipidol
(2008)- et al.
Phenotypes of hypertriglyceridemia caused by excess very-low-density lipoprotein
J Clin Lipidol
(2012) - et al.
Comparisons of apolipoprotein B levels estimated by immunoassay, nuclear magnetic resonance, vertical auto profile, and non-high-density lipoprotein cholesterol in subjects with hypertriglyceridemia (SAFARI Trial)
Am J Cardiol
(2011) - et al.
A comparison of three apolipoprotein B methods and their associations with incident coronary heart disease risk over a 12-year follow-up period: the Multi-ethnic study of atherosclerosis
J Clin Lipidol
(2018) - et al.
A failure of standardization or a failure of the process of standardization
J Clin Lipidol
(2018) - et al.
Apolipoprotein B measurement: need for standardization
J Clin Lipidol
(2018) - et al.
Rapid isolation of low density lipoprotein (LDL) subfractions from plasma by density gradient ultracentrifugation
Atherosclerosis
(1990) - et al.
Concordance/discordance between plasma apolipoprotein B levels and the cholesterol indexes of atherosclerotic risk
Am J Cardiol
(2003) - et al.
Hypertriglyceridemia and cardiovascular risk: a cautionary note about metabolic confounding
J Lipid Res
(2018)
An evidence-based analysis of the National Lipid Association recommendations concerning non-HDL-C and apoB
J Clin Lipidol
LDL particle number and risk of future cardiovascular disease in the Framingham Offspring Study - implications for LDL management
J Clin Lipidol
Clinical implications of discordance between low-density lipoprotein cholesterol and particle number
J Clin Lipidol
Discordance analysis of apolipoprotein B and non-high density lipoprotein cholesterol as markers of cardiovascular risk in the INTERHEART study
Atherosclerosis
Discordance between apolipoprotein B and LDL-cholesterol in young adults predicts coronary artery calcification: the CARDIA Study
J Am Coll Cardiol
The spectrum of type III hyperlipoproteinemia
J Clin Lipidol
Diagnosis of type III hyperlipoproteinemia from plasma total cholesterol, triglyceride, and apolipoprotein B
J Clin Lipidol
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol
Circulation
A meta-analysis of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk
Circ Cardiovasc Qual Outcomes
Apolipoprotein B and cardiovascular disease risk: position statement from the AACC Lipoproteins and Vascular Diseases Division Working Group on Best Practices
Clin Chem
Cited by (10)
A More Atherogenic Lipoprotein Status Is Present in Adults With Type 2 Diabetes Mellitus Than in Those Without With Equivalent Degrees of Hypertriglyceridemia
2022, Canadian Journal of DiabetesCitation Excerpt :Whereas non-HDLC and apoB are clearly separate entities, their use for CVD risk prediction and as alternate targets for lipid-lowering pharmacotherapy are often discussed as if they give similar information. Mounting evidence suggests that non-HDLC and apoB should not be viewed as interchangeable biomarkers (4–10). From a lipoprotein pathophysiology perspective, the difference between non-HDLC and apoB is likely to be most important when there is heterogeneity in the size of TRL.
Does variation in serum LDL-cholesterol response to dietary fatty acids help explain the controversy over fat quality and cardiovascular disease risk?
2021, AtherosclerosisCitation Excerpt :Moreover, serum apo B can be measured directly, inexpensively, and with greater accuracy and precision than LDL-C, which is mostly calculated indirectly from the Friedewald equation [10]. While these advantages confer greater all-round clinical utility upon serum apo B [11,12], LDL-C has remained the primary target for lipid-lowering drug therapy, in part, because of its relatively greater prominence in the mechanism to explain the regulation of serum LDL and whole-body cholesterol homeostasis [13]. The lowering of serum LDL-C is also the main target for the dietary management of ASCVD risk, by approaches such as the Portfolio Diet [14], though subtle differences exist between this approach and the dietary management of elevated serum apo B [15].
Relative effect of hypertriglyceridemia on non-HDLC and apolipoprotein B as cardiovascular disease risk markers
2020, Journal of Clinical LipidologyCitation Excerpt :By placing the TG-related trajectories of non-HDLC and apoB onto comparative risk equivalent categories, we have demonstrated that the two markers in our cohort share the same intermediate-risk category for TG up to 2-3 mmol/L (177-266 mg/dL), beyond which the two markers occupy different risk zones. Our selection of non-HDLC ≥ 5.7 mmol/L (220 mg/dL), and apoB ≥ 1.4 g/L (140 mg/dL) to be high CVD risk equivalents is based on observational epidemiological studies.25,30,31,54,55 As is the case with many cut-off values, they are not absolute but are useful for general reference.
From the editor: Atherosclerosis in different flavors
2019, Journal of Clinical LipidologySaturated fat and cardiovascular disease: Importance of inter-individual variation in the response of serum low-density lipoprotein cholesterol
2024, Proceedings of the Nutrition SocietyWhat should be the goal of cholesterol-lowering treatment? A quantitative evaluation dispelling guideline myths
2022, Current Opinion in Lipidology
Conflict of interest: None.