Circulating Soluble CD163, Associations With Cardiovascular Outcomes and Mortality, and Identification of Genetic Variants in Older Individuals: The Cardiovascular Health Study
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Circulating Soluble CD163, Associations With Cardiovascular Outcomes and Mortality, and Identification of Genetic Variants in Older Individuals : The Cardiovascular Health Study. / Durda, Peter; Raffield, Laura M.; Lange, Ethan M.; Olson, Nels C.; Jenny, Nancy Swords; Cushman, Mary; Deichgraeber, Pia; Grarup, Niels; Jonsson, Anna; Hansen, Torben; Mychaleckyj, Josyf C.; Psaty, Bruce M.; Reiner, Alex P.; Tracy, Russell P.; Lange, Leslie A.
In: Journal of the American Heart Association, Vol. 11, No. 21, e024374, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Circulating Soluble CD163, Associations With Cardiovascular Outcomes and Mortality, and Identification of Genetic Variants in Older Individuals
T2 - The Cardiovascular Health Study
AU - Durda, Peter
AU - Raffield, Laura M.
AU - Lange, Ethan M.
AU - Olson, Nels C.
AU - Jenny, Nancy Swords
AU - Cushman, Mary
AU - Deichgraeber, Pia
AU - Grarup, Niels
AU - Jonsson, Anna
AU - Hansen, Torben
AU - Mychaleckyj, Josyf C.
AU - Psaty, Bruce M.
AU - Reiner, Alex P.
AU - Tracy, Russell P.
AU - Lange, Leslie A.
N1 - Publisher Copyright: © 2022, American Heart Association Inc. All rights reserved.
PY - 2022
Y1 - 2022
N2 - BACKGROUND: Monocytes/macrophages participate in cardiovascular disease. CD163 (cluster of differentiation 163) is a mono-cyte/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 mor-tality); 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 MGAT5 (top result rs62165726, P=3.3×10−18),19 variants near chromosome 17 gene ASGR1 (rs55714927, P=1.5×10−14), and 18 variants near chromosome 11 gene ST3GAL4. 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 P=7.1×10−9) in the HLA region, and 3 variants (rs115391969 P=4.3×10−8) near the chromosome 16 gene MYLK3. CONCLUSIONS: Monocyte function, as measured by sCD163, may be predictive of overall and cardiovascular-specific mortality and incident heart failure.
AB - BACKGROUND: Monocytes/macrophages participate in cardiovascular disease. CD163 (cluster of differentiation 163) is a mono-cyte/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 mor-tality); 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 MGAT5 (top result rs62165726, P=3.3×10−18),19 variants near chromosome 17 gene ASGR1 (rs55714927, P=1.5×10−14), and 18 variants near chromosome 11 gene ST3GAL4. 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 P=7.1×10−9) in the HLA region, and 3 variants (rs115391969 P=4.3×10−8) near the chromosome 16 gene MYLK3. CONCLUSIONS: Monocyte function, as measured by sCD163, may be predictive of overall and cardiovascular-specific mortality and incident heart failure.
KW - cardiovascular diseases
KW - CD163 antigen
KW - genome-wide association study
KW - humans
KW - monocytes
KW - risk factors
U2 - 10.1161/JAHA.121.024374
DO - 10.1161/JAHA.121.024374
M3 - Journal article
C2 - 36314488
AN - SCOPUS:85140940927
VL - 11
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
SN - 2047-9980
IS - 21
M1 - e024374
ER -
ID: 325638028