Strontium and Lead Accelerate, Calcium Protects: Arterial Stiffness Progression in an 11-Year Prospective Cohort Study

Abstract Arterial stiffness measured by estimated pulse wave velocity (ePWV) is an established predictor of cardiovascular disease. Long-term metal exposure may drive arterial stiffness progression, but prior studies largely relied on single-time assessments of exposure or outcome, overlooking heterogeneity in ePWV progression and its longitudinal links to long-term metal exposure. In an 11-year prospective study of 707 participants from the Manganese-Exposed Workers Healthy Cohort, we repeatedly quantified blood cell metals and computed cumulative exposure indices (CEIs). Latent class mixed models identified low and high ePWV trajectories. A one-quantile increase in CEI of a five-metal mixture [strontium (Sr), calcium (Ca), lead (Pb), magnesium, and manganese] was associated with belonging to the high ePWV trajectory (OR = 1.62; 95% CI: 1.14–2.31), with CEI_Sr and CEI_Pb as positive drivers and CEI_Ca inversely associated. The stronger CEI_Sr and CEI_Pb effects were observed in participants with high body mass index or smokers. The distinct trajectories of metal exposure were further identified; we found that the high-decreasing Pb trajectory was associated with higher odds of the high ePWV trajectory compared with the low-decreasing Pb trajectory (OR = 3.98; 95% CI: 1.28–13.26). We provided insights into the longitudinal links between long-term metal exposure and arterial stiffness progression, emphasizing the critical role of metal biomonitoring and primary prevention of arteriosclerosis in high-risk populations.