Gender differences in the relationship between serum uric acid and the long-term prognosis in heart failure: a nationwide study

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Abstract
Background: Serum uric acid (SUA) is an important pathogenetic and prognostic factor for heart failure (HF). Gender differences are apparent in HF. Furthermore, gender differences also exist in the association between SUA and prognosis in various cardiovascular diseases. However, the gender difference for SUA in the prediction of long-term prognosis in HF is still ambiguous. Methods: A total of 1593 HF patients (897 men, 696 women) from the National Health and Nutrition Examination Survey (NHANES) 1999–2018 cycle were enrolled in our final analysis. Participants were categorized according to gender-specific SUA tertile. We assessed the association between SUA and long-term prognosis of HF patients, defined as all-cause mortality and cardiovascular mortality, in different genders via Kaplan–Meier curve analysis, Cox proportional hazard model, and Fine-Gray competing risk model. The restricted cubic spline (RCS) was performed to investigate the dose-response relationship between SUA and outcomes. Results: Gender differences exist in demographic characteristics, clinical parameters, laboratory tests, and medication of HF patients. After a median follow-up of 127 months (95% CI 120–134 months), there were 853 all-cause deaths (493 events in men, 360 events in women) and 361 cardiovascular deaths (206 events in men, 155 events in women). Kaplan-Meier analysis showed that SUA had gender difference in the prediction of cardiovascular mortality (Log-rank p < 0.001, for male, Log-rank p = 0.150, for female), but not in all-cause mortality. Multivariate Cox regression analysis revealed that elevated SUA levels were associated with higher all-cause mortality and cardiovascular mortality in men (HR 1.11, 95% CI 1.05-1.18, p < 0.001, for all-cause death; HR 1.18, 95% CI 1.09-1.28, p < 0.001, for cardiovascular death), but not in women (HR 1.05, 95% CI 0.98-1.12, p = 0.186, for all-cause death; HR 1.01, 95% CI 0.91-1.12, p = 0.902, for cardiovascular death). Even using non-cardiovascular death as a competitive risk, adjusted Fine-Gray model also illustrated that SUA was an independent predictor of cardiovascular death in men (SHR 1.17, 95% CI 1.08-1.27, p < 0.001), but not in women (SHR 0.98, 95% CI 0.87 − 1.10, p = 0.690). Conclusions: Gender differences in the association between SUA and long-term prognosis of HF existed. SUA was an independent prognostic predictor for long-term outcomes of HF in men, but not in women.

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