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|Objective:||To investigate which lipid markers best reflect residual cardiovascular risk in statin-treated patients: apolipoprotein (apo)B, non-high-density lipoprotein cholesterol (non-HDL-C) or low-density lipoprotein cholesterol (LDL-C).|
|Study design:||The Copenhagen General Population study is a prospective observational study.|
|Study population:||13,015 statin-treated patients from the Copenhagen General Population Study with 8 years median follow-up.|
|Main study variables:||• All-cause mortality cases, identified from the Danish Civil Registration System and myocardial infarction (MI) cases, identified from the Danish Patient Registry.
• Calculated non-HDL-C and measured apoB; LDL-C was calculated if triglycerides were <4.0 mmol/L or directly measured if above.
|Methods:||Cox regression analysis was used to assess the association of apoB, non-HDL-C, and LDL-C with all-cause mortality or MI. Data were analysed by categories of concordant and discordant values defined by median values.|
Over a median follow-up of 8 years, 2,499 subjects died and 537 experienced an MI.
The median values for lipids were 92 mg/dL for apoB, 3.1 mmol/L (120 mg/dL) for non-HDL-C and 2.3 mmol/L (89 mg/dL) for LDL-C. Individually, high apoB or non-HDL-C levels were associated with increased risk for all-cause mortality and MI.
Compared with concordant values below the median (i.e., both low apoB and low LDL-C values), a high apoB (above the median) with a low LDL-C (below the median) value was associated with increased risk for all-cause mortality and MI. Furthermore, both high non-HDL-C and low LDL-C values were also associated with increased risk for both outcomes, compared with concordant low values (Table 1).
In contrast, a high LDL-C value with either a low apoB or low non-HDL-C value was not associated with increased risk of either all-cause mortality or MI (Table 1).
Table 1. Risk for outcomes: low concordant lipid values versus discordant values.
|Authors’ conclusion:||In statin-treated patients, elevated apoB and non-HDL-C, but not LDL-C, are associated with residual risk of all-cause mortality and myocardial infarction. Discordance analysis demonstrates that apoB is a more accurate marker of all-cause mortality risk in statin-treated patients than LDL-C or non-HDL-C. ApoB is also a more accurate marker of risk of myocardial infarction than LDL cholesterol.|
The results of this study indicate that LDL-C may not be the best lipid marker for identifying residual cardiovascular risk in statin-treated patients. Instead, the authors propose either the use of either apoB or non-HDL-C as preferred biomarkers for this risk. This approach is also supported by expert consensus, which considered non-LDL lipoproteins (non-HDL-C, apoB, remnant cholesterol and lipoprotein(a)) as potential biomarkers of residual cardiovascular risk (1). Based on findings from this appraisal, non-HDL-C was proposed to better reflect the residual risk associated with atherogenic dyslipidemia, characterized by elevated triglycerides with or without low HDL-C, common in high-risk patients at LDL-C goal. Moreover, lipid guidelines recommend either apoB or non-HDL-C as secondary lipid targets, especially among individuals with cardiometabolic disease who may not necessarily have elevated LDL-C levels, due in particular to small and dense LDL (2).
The current study suggested that apoB may be the preferred marker. Such an approach makes sense, given current understanding of the integral role of apoB-containing lipoproteins in atherosclerosis. Each of these lipoproteins contains one molecule of apoB. Thus, apoB is likely to provide a more accurate estimate of residual atherogenic risk than other guideline-recommended lipid targets (3).
There is a possible misconception from this study that LDL-C may no longer be relevant in the context of residual risk. This relates to the finding from discordance analysis that a high LDL-C value with either a low apoB or low non-HDL-C value was not associated with increased risk of either all-cause mortality or MI in statin-treated patients. It should be emphasized, however, that LDL-C remains the primary lipid target for intervention to prevent cardiovascular events. Individuals with high LDL-C levels should receive intensified therapy, preferably combination therapy, to manage their LDL-related risk (2,4).
|References||1. Averna M, Stroes E; lipid alterations beyond LDL expert working group. How to assess and manage cardiovascular risk associated with lipid alterations beyond LDL. Atheroscler Suppl 2017;26:16-24.
2. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2020;41:111-88.
3. Sniderman AD, Thanassoulis G, Glavinovic T, et al. Apolipoprotein B particles and cardiovascular disease: a narrative review. JAMA Cardiol 2019;4:1287-95.
4. Packard CJ, Chapman MJ, Sibartie M, et al. Intensive low-density lipoprotein cholesterol lowering in cardiovascular disease prevention: opportunities and challenges. Heart 2021; https://heart.bmj.com/content/early/2021/03/31/heartjnl-2020-318760
|Key words||residual cardiovascular risk; apolipoprotein B; non-HDL cholesterol; lipid marker|