High-Density Lipoprotein Anti-Inflammatory Capacity and Incident Cardiovascular Events

<jats:sec> <jats:title>Background:</jats:title> <jats:p>The role of high-density lipoprotein (HDL) function in cardiovascular disease represents an important emerging concept. The present study investigated whether HDL anti-inflammatory capacity is prospectively associated with first cardiovascular events in the general population.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods:</jats:title> <jats:p>HDL anti-inflammatory capacity was determined as its ability to suppress TNFα (tumor necrosis factor α)–induced VCAM-1 (vascular cell adhesion molecule-1) mRNA expression in endothelial cells in vitro (results expressed as achieved percent reduction by individual HDL related to the maximum TNFα effect with no HDL present). In a nested case-control design of the PREVEND (Prevention of Renal and Vascular End Stage Disease) study, 369 cases experiencing a first cardiovascular event (combined end point of death from cardiovascular causes, ischemic heart disease, nonfatal myocardial infarction, and coronary revascularization) during a median of 10.5 years of follow-up were identified and individually matched to 369 controls with respect to age, sex, smoking status, and HDL cholesterol. Baseline samples were available in 340 cases and 340 matched controls.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p> HDL anti-inflammatory capacity was not correlated with HDL cholesterol or hsCRP (high-sensitivity C-reactive protein). HDL anti-inflammatory capacity was significantly lower in cases compared with controls (31.6% [15.7–44.2] versus 27.0% [7.4–36.1]; <jats:italic>P</jats:italic> <0.001) and was inversely associated with incident CVD in a fully adjusted model (odds ratio [OR] per 1 SD, 0.74 [CI, 0.61–0.90]; <jats:italic>P</jats:italic> =0.002). Furthermore, this association was approximately similar with all individual components of the cardiovascular disease end point. The HDL anti-inflammatory was not correlated with cholesterol efflux capacity ( <jats:italic>r</jats:italic> =−0.02; <jats:italic>P</jats:italic> >0.05). When combining these 2 HDL function metrics in 1 model, both were significantly and independently associated with incident cardiovascular disease in a fully adjusted model (efflux: OR per 1 SD, 0.74; <jats:italic>P</jats:italic> =0.002; anti-inflammatory capacity: OR per 1 SD, 0.66; <jats:italic>P</jats:italic> <0.001). Adding HDL anti-inflammatory capacity improved risk prediction by the Framingham risk score, with a model likelihood-ratio statistic increase from 10.50 to 20.40 ( <jats:italic>P</jats:italic> =0.002). </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>The HDL anti-inflammatory capacity, reflecting vascular protection against key steps in atherogenesis, was inversely associated with incident cardiovascular events in a general population cohort, independent of HDL cholesterol and HDL cholesterol efflux capacity. Adding HDL anti-inflammatory capacity to the Framingham risk score improves risk prediction.</jats:p> </jats:sec>