Excess Apolipoprotein B and Cardiovascular Risk in Women and Men

BACKGROUND Low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB) are highly correlated measures of atherogenic lipoproteins. OBJECTIVES The study investigators hypothesized that excess apoB is associated with an increased risk of myocardial infarction (MI), atherosclerotic cardiovascular disease (ASCVD), and all-cause mortality. METHODS The study included 53,484 women and 41,624 men not taking statins from the Copenhagen General Population Study. Associations of excess apoB with the risk of MI, ASCVD, and all-cause mortality were estimated by Cox proportional hazards regressions with 95% CIs. Excess apoB was de fined as measured levels of apoB minus expected levels of apoB from LDL-C alone; expected levels were de fined by linear regressions of LDL-C levels vs apoB levels in individuals with triglycerides #1 mmol/L (89 mg/dL). RESULTS During a median follow-up of 9.6 years, 2,048 MIs, 4,282 ASCVD events, and 8,873 deaths occurred. There was a dose-dependent association between excess apoB and the risk of MI and ASCVD in both women and men, as well as an association with the risk of all-cause mortality in women. For ASCVD in women compared with those with excess apoB <11 mg/dL, the multivariable adjusted HR was 1.08 (95% CI: 0.97-1.21) for excess apoB 11 to 25 mg/dL, 1.30 (95% CI: 1.14-1.48) for 26 to 45 mg/dL, 1.34 (95% CI: 1.14-1.58) for 46 to 100 mg/dL, and 1.75 (95% CI: 1.08-2.83) for excess apoB >100 mg/dL. Corresponding HRs in men were 1.14 (95% CI: 1.02-1.26), 1.41 (95% CI: 1.26-1.57), 1.41 (95% CI: 1.25-1.60), and 1.52 (95% CI: 1.13-2.05), respectively. Results were robust across the entire LDL-C spectrum. CONCLUSIONS Excess apoB (ie, the value of apoB above that contributed by LDL-C levels alone) is associated dose-dependently with an increased risk of MI and ASCVD in women and men. This finding demonstrates that apoB provides important predictive value beyond LDL-C across the entire LDL-C spectrum.