03432nas a2200457 4500008004100000022001400041245018200055210006900237260001300306300001200319490000700331520203700338653000902375653001702384653004602401653003202447653001502479653002802494653001102522653003402533653001802567653001102585653002502596653000902621100001702630700002302647700002002670700001902690700002502709700001802734700002202752700001802774700001802792700001902810700002602829700002002855700002002875700002202895700002102917856003602938 2022 eng d a2047-998000aCirculating Soluble CD163, Associations With Cardiovascular Outcomes and Mortality, and Identification of Genetic Variants in Older Individuals: The Cardiovascular Health Study.0 aCirculating Soluble CD163 Associations With Cardiovascular Outco c2022 Nov ae0243740 v113 a
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.
10aAged10aAntigens, CD10aAntigens, Differentiation, Myelomonocytic10aAsialoglycoprotein Receptor10aBiomarkers10aCardiovascular Diseases10aFemale10aGenome-Wide Association Study10aHeart Failure10aHumans10aLongitudinal Studies10aMale1 aDurda, Peter1 aRaffield, Laura, M1 aLange, Ethan, M1 aOlson, Nels, C1 aJenny, Nancy, Swords1 aCushman, Mary1 aDeichgraeber, Pia1 aGrarup, Niels1 aJonsson, Anna1 aHansen, Torben1 aMychaleckyj, Josyf, C1 aPsaty, Bruce, M1 aReiner, Alex, P1 aTracy, Russell, P1 aLange, Leslie, A uhttps://chs-nhlbi.org/node/9245