Martinez-Morata Irene, Domingo-Relloso Arce, Mayer Melanie, Schilling Kathrin, Glabonjat Ronald A, McGraw Katlyn, Sanchez Tiffany R, Kaufman Joel D, Vaidya Dhananjay, Post Wendy, Jones Miranda, Shimbo Daichi, Zhang Ying, Fretts Amanda M, Pichler Gernot, Umans Jason G, Garcia Pinilla Jose Manuel, Cole Shelley A, Martin-Escudero Juan C, Redon Josep, Grau-Perez Maria, Barr R Graham, Valeri Linda, Shea Steven, Tellez-Plaza Maria, Devereux Richard B, Navas-Acien Ana
Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, New York, USA.
Department of Biostatistics, Columbia University Mailman School of Public Health, New York, New York, USA.
JACC Heart Fail. 2025 Jun 17;13(8):102510. doi: 10.1016/j.jchf.2025.03.046.
Environmental metals are recognized cardiovascular disease risk factors, yet the role of metal exposure in heart failure (HF) risk remains understudied.
This study aims to evaluate the prospective association of urinary metals with incident HF across 3 geographically and ethnically/racially diverse cohorts: MESA (Multi-Ethnic Study of Atherosclerosis) and SHS (Strong Heart Study) in the United States, and the Hortega Study in Spain.
Adults 18-85 years of age in MESA (n = 6,601), SHS (n = 2,917), and Hortega (n = 1,300) were followed up to 20 years. Urinary levels of a multi-metal panel were measured at baseline and corrected for urine dilution. Cox proportional hazards and Cox elastic-net models were used to estimate the multi-adjusted (sociodemographic/clinical/lifestyle covariates) HR of incident HF by individual metals and the mixture of 5 metals available in all cohorts, respectively. The pooled HR (95% CI) of HF by 1-unit increase in log2-transformed levels of individual metals (ie, doubling of the dose) across cohorts was estimated using a fixed effects meta-analysis. Analyses by left ventricular ejection fraction were conducted in a subset.
A total of 1,001 participants developed HF. In adjusted models, significant associations (pooled HRs [95% CI] per doubling of urinary metal) were identified for cadmium (HR: 1.15 [95% CI: 1.07-1.24]) molybdenum (HR: 1.13 [95% CI: 1.05-1.22]), and zinc (HR: 1.22 [95% CI: 1.14-1.32]). The HRs (95% CIs) for the association of 1 IQR increase in the multi-metal mixture levels and incident HF were 1.38 (95% CI: 1.00-1.86) in MESA, HR: 1.55 (95% CI: 1.28-1.97) in SHS, and HR: 1.08 (95% CI: 0.85-1.63) in Hortega in fully adjusted models. Stratified models by left ventricular ejection fraction were consistent with the pooled results.
Urinary metals are risk factors of HF across 3 diverse populations, supporting the role of reducing metal exposures to lower HF risk.
环境金属被认为是心血管疾病的危险因素，但金属暴露在心力衰竭（HF）风险中的作用仍未得到充分研究。
本研究旨在评估在3个地理、种族/民族不同的队列中，尿金属与新发HF之间的前瞻性关联：美国的动脉粥样硬化多民族研究（MESA）和强心脏研究（SHS），以及西班牙的奥尔特加研究。
对MESA（n = 6601）、SHS（n = 2917）和奥尔特加（n = 1300）中18 - 85岁的成年人进行了长达20年的随访。在基线时测量了多种金属的尿水平，并对尿液稀释进行了校正。分别使用Cox比例风险模型和Cox弹性网模型，按个体金属以及所有队列中均可获得的5种金属混合物，估计新发HF的多因素调整（社会人口统计学/临床/生活方式协变量）风险比（HR）。使用固定效应荟萃分析估计各队列中个体金属的log2转换水平每增加1个单位（即剂量加倍）时HF的合并HR（95%置信区间）。在一个亚组中按左心室射血分数进行了分析。
共有1001名参与者发生了HF。在调整模型中，确定了镉（HR：1.15 [95%置信区间：1.07 - 1.24]）、钼（HR：1.13 [95%置信区间：1.05 - 1.22]）和锌（HR：1.22 [95%置信区间：1.14 - 1.32]）存在显著关联（尿金属每加倍的合并HRs [95%置信区间]）。在完全调整模型中，多金属混合物水平每增加1个四分位数间距（IQR）与新发HF关联的HRs（95%置信区间）在MESA中为1.38（95%置信区间：1.00 - 1.86），在SHS中为HR：1.55（95%置信区间：1.28 - 1.97），在奥尔特加中为HR：1.08（95%置信区间：0.85 - 1.63）。按左心室射血分数分层的模型与合并结果一致。
尿金属是3个不同人群中HF的危险因素，支持减少金属暴露以降低HF风险的作用。
