Association Between Zinc-to-Copper Ratio and Hypertension in Populations with Differential Environmental Heavy Metal...

The zinc-to-copper ratio (ZCR) reflects essential metal balance and may be relevant to cardiovascular regulation, yet its association with hypertension in populations exposed to environmental heavy metals remains unclear. We conducted a cross-sectional study of 966 adults (≥ 30 years, recruited in 2008) comprising an exposed group (n = 564) residing within 4 km of the Janghang copper smelter and a non-exposed control group (n = 402) from a rural area approximately 15 km away. Serum zinc, copper, and nickel, along with blood lead, mercury, and urinary cadmium and arsenic were measured. Associations between ZCR and blood pressure were examined using multivariable linear regression, logistic regression, Bayesian kernel machine regression (BKMR), and restricted cubic spline (RCS) analyses, with sensitivity analyses. Higher ZCR was associated with increased systolic and diastolic blood pressure in fully adjusted linear models (SBP: β = 1.75, p = 0.002; DBP: β = 1.47, p < 0.001), with consistent associations in both exposed and control groups. In logistic regression, participants in the highest ZCR tertile had higher odds of hypertension than those in the lowest tertile (adjusted OR = 1.91; 95% CI: 1.25-2.93; p = 0.003). When stratified, the association was more pronounced in the non-exposed group (OR = 2.29; 95% CI: 1.18-4.45; p = 0.014) and somewhat attenuated but still suggestive in the exposed group (OR = 1.71; 95% CI: 0.96-3.06; p = 0.069); the formal interaction test was not statistically significant (p = 0.561). Sensitivity analyses, including exclusion of antihypertensive medication users, yielded consistent findings (OR = 1.83; 95% CI: 1.19-2.80), and the E-value (1.97) indicated limited-to-moderate robustness to unmeasured confounding. Higher ZCR is consistently associated with hypertension across analytical approaches and subgroups, with a suggestive but not statistically significant pattern of effect modification by environmental metal exposure. These findings support ZCR as a potentially informative indicator of essential metal imbalance relevant to blood pressure, warranting further investigation in prospective settings.