McGraw Katlyn E, Schilling Kathrin, Glabonjat Ronald A, Galvez-Fernandez Marta, Domingo-Relloso Arce, Martinez-Morata Irene, Jones Miranda R, Post Wendy S, Kaufman Joel, Tellez-Plaza Maria, Valeri Linda, Brown Elizabeth R, Kronmal Richard A, Barr Graham R, Shea Steven, Navas-Acien Ana, Sanchez Tiffany R
Columbia University Mailman School of Public Health, Department of Environmental Health Science, 722 W 168th St, New York, NY 10032.
Columbia University Mailman School of Public Health, Department of Biostatistics, 722 W 168th St, New York, NY 10032.
medRxiv. 2023 Nov 1:2023.10.31.23297878. doi: 10.1101/2023.10.31.23297878.
OBJECTIVE: Growing evidence indicates that exposure to metals are risk factors for cardiovascular disease (CVD). We hypothesized that higher urinary levels of metals with prior evidence of an association with CVD, including non-essential (cadmium , tungsten, and uranium) and essential (cobalt, copper, and zinc) metals are associated with baseline and rate of change of coronary artery calcium (CAC) progression, a subclinical marker of atherosclerotic CVD. METHODS: We analyzed data from 6,418 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with spot urinary metal levels at baseline (2000-2002) and 1-4 repeated measures of spatially weighted coronary calcium score (SWCS) over a ten-year period. SWCS is a unitless measure of CAC highly correlated to the Agatston score but with numerical values assigned to individuals with Agatston score=0. We used linear mixed effect models to assess the association of baseline urinary metal levels with baseline SWCS, annual change in SWCS, and SWCS over ten years of follow-up. Urinary metals (adjusted to μg/g creatinine) and SWCS were log transformed. Models were progressively adjusted for baseline sociodemographic factors, estimated glomerular filtration rate, lifestyle factors, and clinical factors. RESULTS: At baseline, the median and interquartile range (25, 75) of SWCS was 6.3 (0.7, 58.2). For urinary cadmium, the fully adjusted geometric mean ratio (GMR) (95%Cl) of SWCS comparing the highest to the lowest quartile was 1.51 (1.32, 1.74) at baseline and 1.75 (1.47, 2.07) at ten years of follow-up. For urinary tungsten, uranium, and cobalt the corresponding GMRs at ten years of follow-up were 1.45 (1.23, 1.71), 1.39 (1.17, 1.64), and 1.47 (1.25, 1.74), respectively. For copper and zinc, the association was attenuated with adjustment for clinical risk factors; GMRs at ten years of follow-up before and after adjustment for clinical risk factors were 1.55 (1.30, 1.84) and 1.33 (1.12, 1.58), respectively, for copper and 1.85 (1.56, 2.19) and 1.57 (1.33, 1.85) for zinc. CONCLUSION: Higher levels of cadmium, tungsten, uranium, cobalt, copper, and zinc, as measured in urine, were associated with subclinical CVD at baseline and at follow-up. These findings support the hypothesis that metals are pro-atherogenic factors.
目的：越来越多的证据表明，接触金属是心血管疾病（CVD）的危险因素。我们假设，先前有证据表明与CVD相关的金属，包括非必需金属（镉、钨和铀）和必需金属（钴、铜和锌），其尿中水平较高与冠状动脉钙化（CAC）进展的基线水平和变化率相关，CAC是动脉粥样硬化性CVD的一种亚临床标志物。 方法：我们分析了动脉粥样硬化多族裔研究（MESA）中6418名参与者的数据，这些参与者在基线时（2000 - 2002年）有即时尿金属水平数据，并且在十年期间有1 - 4次重复测量的空间加权冠状动脉钙化评分（SWCS）。SWCS是一种与阿加斯顿评分高度相关的无单位CAC测量方法，但对于阿加斯顿评分为0的个体也赋予了数值。我们使用线性混合效应模型来评估基线尿金属水平与基线SWCS、SWCS的年度变化以及十年随访期间的SWCS之间的关联。尿金属（调整为μg/g肌酐）和SWCS进行了对数转换。模型逐步调整了基线社会人口统计学因素、估计肾小球滤过率、生活方式因素和临床因素。 结果：基线时，SWCS的中位数和四分位数间距（25%，75%）为6.3（0.7，58.2）。对于尿镉，在基线时，将最高四分位数与最低四分位数的SWCS进行比较，完全调整后的几何平均比（GMR）（95%CI）为1.51（1.32，1.74），在十年随访时为1.75（1.47，2.07）。对于尿钨、铀和钴，十年随访时相应的GMR分别为1.45（1.23，1.71）、1.39（1.17，1.64）和1.47（1.25，1.74）。对于铜和锌，在调整临床危险因素后关联减弱；在调整临床危险因素前后，铜在十年随访时的GMR分别为1.55（1.30，1.84）和1.33（1.12，1.58），锌分别为1.85（1.56，2.19）和1.57（1.33，1.85）。 结论：尿中测量的镉、钨、铀、钴、铜和锌水平较高与基线和随访时的亚临床CVD相关。这些发现支持了金属是促动脉粥样硬化因素的假设。
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