Association between serum zinc levels and new-onset hypertension: A 5-year retrospective cohort study

The relationship between zinc deficiency and incident hypertension remains poorly characterized in humans. We examined the association between zinc deficiency and new-onset hypertension and related complications. This retrospective cohort study utilized the TriNetX Research Network to analyze adult patients with serum zinc measurements between January 2010 and December 2023. The zinc-deficient group had concentrations below 0.7 µg/mL, while controls ranged from 0.70 to 1.20 µg/mL. Following propensity score matching, 47,843 pairs were analyzed over 5 years. The primary outcome was new-onset primary hypertension. Secondary outcomes included secondary hypertension, hypertension-related cardiac and renal complications, and hypertensive crisis. Zinc deficiency was significantly associated with primary hypertension (hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.14-1.25; P < .001), secondary hypertension (HR 1.82, 95% CI 1.45-2.29; P < .001), hypertension-related cardiac and renal complications (HR 1.69, 95% CI 1.49-1.92; P < .001), and hypertensive crisis (HR 1.09, 95% CI 1.01-1.18; P = .028). Dose-response analyses revealed a J-shaped association for primary hypertension, with elevated hazards at both low and high zinc concentrations. The association between zinc deficiency and primary hypertension was significantly stronger in men than in women (HR 1.28 vs 1.13; P for interaction = .021). Zinc deficiency was associated with incident hypertension and related complications, particularly secondary hypertension. Further prospective studies are warranted to determine whether correction of zinc deficiency modifies hypertension risk.