U-Shaped Relationship Between Cardiovascular Mortality and Serum Uric Acid May Be Attributed to Stroke- and Heart-Specific Mortality, Respectively, Among Hypertensive Patients: A Nationally Representative Cohort Study

BACKGROUND: Serum uric acid (UA) is involved in the development of hypertension. However, its impact on mortality in hypertension remains unclear. We aimed to assess the association of cardiovascular and all-cause mortality with UA in a hypertensive population. MATERIAL/METHODS: This study included 15 583 hypertensive patients from the NHANES study during 1999–2014. Weighted Cox regression analyses and cubic spline fitting were used to assess the relationship between UA and mortality risk. RESULTS: Over a median follow-up of 7.4 years (116 351 person-years), a total of 3291 deaths occurred. Mortality was examined according to 5 predefined UA levels: ≤3.5, 3.5–5, 5–6, 6–7.5, and >7.5 mg/dL. In multivariable analysis with 5–6 mg/dL as a reference, the hazard ratios (95% confidence interval) of total mortality across the 5 groups were 1.40 (1.05–1.88), 1.08 (0.95–1.21), 1.00 (reference), 1.14 (1.02–1.29), and 1.74 (1.50–2.02), respectively. According to a restricted cubic spline, we noted a U-shaped relationship between UA and total mortality. The U-shaped relationship between UA and cardiovascular mortality remained in both females and males. The increased cardiovascular mortality in the lowest and highest UA groups was attributed to stroke and heart-specific mortality, respectively. However, serum UA was not significantly associated with cancer mortality. CONCLUSIONS: Our findings showed a U-shaped relationship between serum UA levels and total and cardiovascular mortality in patients with hypertension. Furthermore, low UA was associated with stroke mortality, while higher UA was associated with heart-related mortality. Further research is needed to identify the potential mechanisms of UA in hypertension.