平均血小板体积在砷暴露与动脉粥样硬化性心血管疾病风险中的潜在作用
Potential role of mean platelet volume in association between arsenic exposure and risk of atherosclerotic cardiovascular disease
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摘要:
背景 动脉粥样硬化性心血管疾病（ASCVD）是我国居民致死致残的首要原因。研究表明砷暴露会增加ASCVD的发病风险。目前对于砷暴露和ASCVD十年风险间的关联以及其中可能的机制并不清楚。
目的 分析砷暴露与平均血小板体积（MPV）及ASCVD十年风险的相关性，探讨MPV在砷暴露与ASCVD十年风险间的潜在作用。
方法 在2011-2012年分别于武汉和珠海各选取两个社区，招募年龄在18~80岁的居民作为研究对象建立武汉-珠海社区队列，通过面对面的问卷调查和专业医生的体格检查收集研究对象的人口学信息和人体学指标，并采集其空腹血样和尿样。本次研究排除年龄不在35~74岁者、生物样本和人体测量学指标缺失者以及肾炎患者，最终纳入了3 081名研究对象。应用电感耦合等离子体质谱仪检测尿砷水平，应用全自动生化分析仪检测血中MPV水平。ASCVD十年风险得分采用由中国心血管疾病项目组改进的ASCVD风险预测研究模型计算，根据得分将研究对象分为高风险（≥ 0.05）和低风险（< 0.05）两类。采用logistic回归模型分析尿砷和ASCVD十年风险间的相关性，采用限制性立方样条回归分析尿砷和MPV以及MPV和ASCVD十年风险的相关性，并应用中介模型探讨MPV在尿砷和ASCVD十年风险间的中介作用。
结果 研究人群平均年龄54.05岁，尿砷和MPV的中位数水平分别为2.69 μg/mmol（经肌酐校正）、8.80 fL。logistic回归分析显示，在校正相关混杂因素后，尿砷和ASCVD十年风险呈正向的剂量-反应关系，尿砷每增加一个自然对数单位，研究对象进入ASCVD高风险组的概率增加16.3%（95% CI：0.8%~34.2%）。限制性立方样条回归分析显示，尿砷和MPV以及MPV和ASCVD十年风险均呈正向线性相关（非线性检验P>0.05）。此外，中介分析结果表明，MPV在尿砷和ASCVD十年风险间起中介作用，中介比例为20.9%。
结论 砷暴露可能与MPV升高和ASVD十年风险增加有关。MPV可能在砷暴露导致的ASCVD十年风险增加中起中介作用。
Abstract:Background Atherosclerotic cardiovascular disease (ASCVD) is one of the primary causes of death in Chinese residents. Research has shown that arsenic exposure could increase the incidence of ASCVD. However, the association between arsenic exposure and ASCVD 10-year risk and the possible mechanisms involved are still unclear.
Objective This study is conducted to evaluate the associations of arsenic exposure on mean platelet volume (MPV) and 10-year risk of ASCVD, and to investigate the potential role of MPV in the association between arsenic exposure and 10-year risk of ASCVD.
Methods The study participants were originated from the baseline survey of the Wuhan-Zhuhai Cohort, which was consisted of residents aged 18-80 years from two communities from each city in 2011 and 2012 respectively. Detailed socio-demographic characteristics and anthropometric indices were obtained from face-to-face questionnaire interviews and physical examinations, respectively. All participants were requested to provide fasting blood and urine samples. After excluding those not aged 35-74 years, those lacking biological samples and anthropometric indices, and those with nephritis, a total of 3 081 subjects were included. Urinary arsenic was detected by inductively coupled plasma mass spectrometry. MPV was detected with automatic biochemical analyzer. ASCVD 10-year risk scores were calculated using the China-PAR (Prediction for ASCVD Risk in China) equations improved by China Cardiovascular Disease Project. According to the scores, the participants were divided into two categories:high-risk (≥ 0.05) and low-risk (< 0.05). Logistic regression model was used to evaluate the association between urinary arsenic and 10-year risk of ASCVD. Restricted cubic spline regression was used to evaluate the associations between urinary arsenic and MPV and between MPV and 10-year risk of ASCVD. Furthermore, mediating model was used to assess the mediating effect of MPV on the association of urinary arsenic with 10-year risk of ASCVD.
Results The mean age of the study population was 54.05 years. The medians of urinary arsenic and MPV were 2.69 μg/mmol (corrected for creatinine) and 8.80fL respectively. After adjusting for potential confounders, there was a positive dose-response relationship between urinary arsenic and 10-year risk of ASCVD, and each 1-unit increase in ln-transformed value of urinary arsenic was associated with a 16.3% (95% CI:0.8%-34.2%) increase of being high-risk ASCVD. The results of restricted cubic spline regression analysis showed that urinary arsenic was positively linearly correlated with MPV, as well as MPV with 10-year risk of ASCVD. Besides, the results of mediation analysis indicated that MPV mediated 20.9% of the association between urinary arsenic and 10-year risk of ASCVD.
Conclusion Exposure to arsenic may be associated with increased MPV and increased 10-year risk of ASCVD. MPV might mediate the association of urinary arsenic with 10-year risk of ASCVD.
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