Low HDL-C is associated with increased risk of cardiovascular illness. However recent trials have not been able to demonstrate that raising HDL-C leads to lower CV outcomes. This research looks deeper at nuances of HDL pathophysiology for answers; such as HDL-cholesterol itself, apoA-I, HDL particle number and cholesterol efflux capacity. Study finds HDL particle number as the best inverse predictor of CVD. More research to come on full significance of such findings.
Background: Recent failures of drugs that raise HDL-cholesterol levels to reduce cardiovascular events in clinical trials have led to increased interest in alternative indices of HDL quality, such as cholesterol efflux capacity, and HDL quantity, such as HDL particle number. However, no studies have directly compared these metrics in a contemporary population that includes potent statin therapy and low LDL cholesterol.
Methods: HDL-cholesterol levels, apolipoprotein A-I (apoA-I), cholesterol efflux capacity, and HDL particle number were assessed at baseline and 12 months in a nested case-control study of the JUPITER trial, a randomized primary prevention trial that compared rosuvastatin treatment to placebo in individuals with normal LDL cholesterol but increased C-reactive protein levels. A total of 314 cases of incident cardiovascular disease (myocardial infarction, unstable angina, arterial revascularization, stroke, or cardiovascular death) were compared to age- and gender-matched controls. Conditional logistic regression models adjusting for risk factors evaluated associations between HDL-related biomarkers and incident CVD.
Results: Cholesterol efflux capacity was moderately correlated with HDL cholesterol, apoA-I, and HDL particle number (Spearman r= 0.39, 0.48, and 0.39 respectively; P<0.001). Baseline HDL particle number was inversely associated with incident CVD (adjusted odds ratio per SD increment [OR/SD] 0.69, p< 0.001), while no significant association was found for baseline cholesterol efflux capacity (OR/SD 0.89, p=0.28), HDL cholesterol (OR/SD 0.82; 95%CI 0.66-1.02; P = 0.08), or apoA-I (OR/SD 0.83, p=0.08). 12 months of rosuvastatin (20mg/day) did not change cholesterol efflux capacity (average percent change -1.5%, p=0.80), but increased HDL cholesterol (+7.7%), apoA-I (+4.3%), and HDL particle number (+5.2%). On-statin cholesterol efflux capacity was inversely associated with incident CVD (OR/SD 0.62, p=0.02), although HDL particle number again emerged as the strongest predictor (OR/SD 0.51, p< 0.001).
Conclusions: In JUPITER, cholesterol efflux capacity was associated with incident CVD in individuals on potent statin therapy but not at baseline. For both baseline and on-statin analyses, HDL particle number was the strongest of four HDL-related biomarkers as an inverse predictor of incident events and biomarker of residual risk.