TY - JOUR T1 - Circulating Soluble CD163, Associations With Cardiovascular Outcomes and Mortality, and Identification of Genetic Variants in Older Individuals: The Cardiovascular Health Study. JF - J Am Heart Assoc Y1 - 2022 A1 - Durda, Peter A1 - Raffield, Laura M A1 - Lange, Ethan M A1 - Olson, Nels C A1 - Jenny, Nancy Swords A1 - Cushman, Mary A1 - Deichgraeber, Pia A1 - Grarup, Niels A1 - Jonsson, Anna A1 - Hansen, Torben A1 - Mychaleckyj, Josyf C A1 - Psaty, Bruce M A1 - Reiner, Alex P A1 - Tracy, Russell P A1 - Lange, Leslie A KW - Aged KW - Antigens, CD KW - Antigens, Differentiation, Myelomonocytic KW - Asialoglycoprotein Receptor KW - Biomarkers KW - Cardiovascular Diseases KW - Female KW - Genome-Wide Association Study KW - Heart Failure KW - Humans KW - Longitudinal Studies KW - Male AB -

Background Monocytes/macrophages participate in cardiovascular disease. CD163 (cluster of differentiation 163) is a monocyte/macrophage receptor, and the shed sCD163 (soluble CD163) reflects monocyte/macrophage activation. We examined the association of sCD163 with incident cardiovascular disease events and performed a genome-wide association study to identify sCD163-associated variants. Methods and Results We measured plasma sCD163 in 5214 adults (aged ≥65 years, 58.7% women, 16.2% Black) of the CHS (Cardiovascular Health Study). We used Cox regression models (associations of sCD163 with incident events and mortality); median follow-up was 26 years. Genome-wide association study analyses were stratified on race. Adjusted for age, sex, and race and ethnicity, sCD163 levels were associated with all-cause mortality (hazard ratio [HR], 1.08 [95% CI, 1.04-1.12] per SD increase), cardiovascular disease mortality (HR, 1.15 [95% CI, 1.09-1.21]), incident coronary heart disease (HR, 1.10 [95% CI, 1.04-1.16]), and incident heart failure (HR, 1.18 [95% CI, 1.12-1.25]). When further adjusted (eg, cardiovascular disease risk factors), only incident coronary heart disease lost significance. In European American individuals, genome-wide association studies identified 38 variants on chromosome 2 near (top result rs62165726, =3.3×10),19 variants near chromosome 17 gene (rs55714927, =1.5×10), and 18 variants near chromosome 11 gene . These regions replicated in the European ancestry ADDITION-PRO cohort, a longitudinal cohort study nested in the Danish arm of the Anglo-Danish-Dutch study of Intensive Treatment Intensive Treatment In peOple with screeNdetcted Diabetes in Primary Care. In Black individuals, we identified 9 variants on chromosome 6 (rs3129781 =7.1×10) in the region, and 3 variants (rs115391969 =4.3×10) near the chromosome 16 gene Conclusions Monocyte function, as measured by sCD163, may be predictive of overall and cardiovascular-specific mortality and incident heart failure.

VL - 11 IS - 21 ER -