Department of Pathology and Laboratory Medicine Larner College of Medicine, University of Vermont Burlington VT.
Department of Genetics University of North Carolina Chapel Hill NC.
J Am Heart Assoc. 2022 Nov;11(21):e024374. doi: 10.1161/JAHA.121.024374. Epub 2022 Oct 31.
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.
单核细胞/巨噬细胞参与心血管疾病。CD163（分化群 163）是单核细胞/巨噬细胞受体，而可溶性 CD163（sCD163）的释放反映了单核细胞/巨噬细胞的激活。我们研究了 sCD163 与心血管疾病事件的关系，并进行了全基因组关联研究，以鉴定与 sCD163 相关的变异。
我们测量了 CHS（心血管健康研究）中 5214 名成年人（年龄≥65 岁，58.7%为女性，16.2%为黑人）的血浆 sCD163。我们使用 Cox 回归模型（sCD163 与事件和死亡率的关系）；中位随访时间为 26 年。全基因组关联研究分析按种族分层。经年龄、性别和种族/民族调整后，sCD163 水平与全因死亡率相关（每标准差增加，危险比[HR]为 1.08[95%置信区间，1.04-1.12]），心血管疾病死亡率（HR，1.15[95%CI，1.09-1.21]），冠心病发病率（HR，1.10[95%CI，1.04-1.16]）和心力衰竭发病率（HR，1.18[95%CI，1.12-1.25]）。当进一步调整（例如，心血管疾病危险因素）时，只有冠心病发病率失去了意义。在欧洲裔美国人中，全基因组关联研究在染色体 2 附近（最高结果 rs62165726，=3.3×10），染色体 17 基因附近（rs55714927，=1.5×10）和染色体 11 基因附近（rs16172486，=2.2×10）鉴定出 19 个变体。这些区域在丹麦人手臂的丹麦-英荷-荷兰强化治疗糖尿病筛查试验的丹麦队列研究 ADDITION-PRO 中复制。在黑人中，我们在染色体 6 上发现了 9 个变体（rs3129781，=7.1×10）在 区域中，在染色体 16 基因附近发现了 3 个变体（rs115391969，=4.3×10）。
单核细胞功能，如 sCD163 测量，可以预测总死亡率、心血管特异性死亡率和心力衰竭发病率。
