Serum Calcium Levels Are Associated with Novel Cardiometabolic Risk Factors in the Population-Based CoLaus Study

BackgroundAssociations of serum calcium levels with the metabolic syndrome and other novel cardio-metabolic risk factors not classically included in the metabolic syndrome, such as those involved in oxidative stress, are largely unexplored. We analyzed the association of albumin-corrected serum calcium levels with conventional and non-conventional cardio-metabolic risk factors in a general adult population. Methodology/Principal FindingsThe CoLaus study is a population-based study including Caucasians from Lausanne, Switzerland. The metabolic syndrome was defined using the Adult Treatment Panel III criteria. Non-conventional cardio-metabolic risk factors considered included: fat mass, leptin, LDL particle size, apolipoprotein B, fasting insulin, adiponectin, ultrasensitive CRP, serum uric acid, homocysteine, and gamma-glutamyltransferase. We used adjusted standardized multivariable regression to compare the association of each cardio-metabolic risk factor with albumin-corrected serum calcium. We assessed associations of albumin-corrected serum calcium with the cumulative number of non-conventional cardio-metabolic risk factors. We analyzed 4,231 subjects aged 35 to 75 years. Corrected serum calcium increased with both the number of the metabolic syndrome components and the number of non-conventional cardio-metabolic risk factors, independently of the metabolic syndrome and BMI. Among conventional and non-conventional cardio-metabolic risk factors, the strongest positive associations were found for factors related to oxidative stress (uric acid, homocysteine and gamma-glutamyltransferase). Adiponectin had the strongest negative association with corrected serum calcium. Conclusions/SignificanceSerum calcium was associated with the metabolic syndrome and with non-conventional cardio-metabolic risk factors independently of the metabolic syndrome. Associations with uric acid, homocysteine and gamma-glutamyltransferase were the strongest. These novel findings suggest that serum calcium levels may be associated with cardiovascular risk via oxidative stress.背景 血清钙水平与代谢综合征（metabolic syndrome）以及经典代谢综合征范畴外的新型心血管代谢危险因素（如参与氧化应激过程的相关因素）之间的关联，目前尚未得到充分探索。本研究针对普通成人人群，分析了白蛋白校正血清钙（albumin-corrected serum calcium）与常规及非常规心血管代谢危险因素之间的关联。 方法与主要结果 CoLaus研究是一项基于人群的流行病学研究，纳入了瑞士洛桑的白人受试者。代谢综合征的诊断采用美国国家胆固醇教育计划成人治疗组第三次指南（Adult Treatment Panel III, ATP III）标准。本研究纳入的非常规心血管代谢危险因素包括：体脂量、瘦素（leptin）、低密度脂蛋白颗粒大小（LDL particle size）、载脂蛋白B（apolipoprotein B）、空腹胰岛素、脂联素（adiponectin）、超敏C反应蛋白（ultrasensitive CRP）、血清尿酸、同型半胱氨酸（homocysteine）以及γ-谷氨酰转移酶（gamma-glutamyltransferase）。本研究采用校正后的标准化多变量回归模型，对比各心血管代谢危险因素与白蛋白校正血清钙的关联；同时评估了白蛋白校正血清钙与非常规心血管代谢危险因素累计数量之间的关联。本研究共纳入4231名年龄介于35至75岁之间的受试者。校正后血清钙水平随代谢综合征组分数量及非常规心血管代谢危险因素数量的增加而升高，且该关联独立于代谢综合征及体质量指数（BMI）。在常规及非常规心血管代谢危险因素中，与氧化应激相关的因素（尿酸、同型半胱氨酸及γ-谷氨酰转移酶）呈现最强的正相关关系；脂联素与校正后血清钙则呈现最强的负相关关系。 结论与意义 血清钙水平与代谢综合征及非常规心血管代谢危险因素存在独立于代谢综合征的关联。其中与尿酸、同型半胱氨酸及γ-谷氨酰转移酶的关联最为显著。本研究的新发现提示，血清钙水平可能通过氧化应激途径参与心血管风险的发生发展。