High‐Sensitivity C‐Reactive Protein Discordance With Atherogenic Lipid Measures and Incidence of Atherosclerotic Cardiovascular Disease in Primary Prevention: The ARIC Study

BACKGROUND: Inflammation is an independent causal risk factor for atherosclerotic cardiovascular diseases (ASCVDs). However, whether hsCRP (high‐sensitivity C‐reactive protein) is prognostic across various levels of atherogenic lipid measures such as low‐density lipoprotein cholesterol, non–high‐density lipoprotein cholesterol, apolipoprotein B and total cholesterol/high‐density lipoprotein cholesterol in primary prevention is unknown. METHODS AND RESULTS: We studied 9748 ARIC (Atherosclerosis Risk in Communities) study participants who were free of ASCVD at baseline (visit 4, 1996–1998) and had measurements of lipids, apolipoprotein B, and hsCRP. We used multivariable adjusted Cox models to estimate the risk of incident ASCVD events associated with hsCRP levels (less than/greater than or equal to median) in individuals where triple lipid measures combined (low‐density lipoprotein cholesterol + non–high‐density lipoprotein cholesterol + apolipoprotein B) or quadruple measures combined [triple + total cholesterol/high‐density lipoprotein cholesterol] were less than versus greater than or equal to median cut points. Mean age of participants was 62.6±5.6 years; 59% women, 22% black. There were 1574 ASCVD events over median (interquartile range) follow‐up of 18.4 (12.8–19.5) years, and discordance between hsCRP and lipid measures was prevalent in 50% of the population. hsCRP greater than or equal to median (2.4 mg/L), compared with less than median, was associated with an increased risk of ASCVD in individuals with less than median levels of the triple (adjusted hazard ratio, 1.33; 95% CI, 1.09–1.60) and quadruple (adjusted hazard ratio,1.47; 95% CI, 1.18–1.85) lipid measures. Such increased risk was consistent among individuals with low (<7.5%) or high (≥7.5%) estimated risk by the pooled cohort equation. There were no interactions by sex, diabetes mellitus, or statin use. CONCLUSIONS: Our findings suggest that inflammation is independently associated with ASCVD regardless of atherogenic lipid levels and pooled cohort equation risk score in individuals without known ASCVD.