Gender differences in the predictive value of serum uric acid for major adverse cardiovascular events in patients with acute coronary syndromes: a retrospective cohort study

Abstract

Background: Serum uric acid(SUA) is proinflammatory and increases the risk of cardiovascular events in patients with coronary artery disease. SUA levels differ between men and women, and it is unclear whether there are gender differences in the correlation between SUA levels and major adverse cardiovascular events (MACE) in patients with acute coronary syndromes (ACS). In this paper, we analyze the correlation between SUA and MACE in men and women with ACS respectively, to achieve a more accurate prognosis prediction and to determine the optimal level of SUA control in ACS patients of different genders.

Methods: This was a retrospective cohort study that ultimately selected 2799 ACS patients who were hospitalized in the Department of Cardiology of the Affiliated Hospital of Jining Medical College from May 2013 to October 2015, and grouped the patients according to the gender-specific criteria for hyperuricemia(HUA). With a mean follow-up of 4.42 years after discharge, MACE were collected, and the correlation between SUA and MACE risk in patients of different genders was investigated using the Cox proportional risk regression model. Smooth curve fitting was used to analyze the nonlinear relationship between SUA and MACE, and sensitivity and subgroup analyses were performed to investigate further the correlation between SUA and MACE in different populations.

Results: A total of 309 patients developed MACE during the follow-up period. Kaplan-Meier curves showed that patients with HUA had a higher risk of MACE (p < 0.01). Multivariate Cox proportional risk regression modeling analysis revealed a significant correlation between SUA and MACE risk. In crude Cox analyses, SUA levels were associated with higher risk of MACE (total: HR 1.22,95% CI 1.13, 1.31, p < 0.0001, men: HR 1.24, 95% CI 1.14, 1.35, p < 0.0001, women: HR 1.16, 95% CI 1.00, 1.34, p = 0.0477). However, after adjusting for various covariates including SYNTAX scores(SS), the prediction of MACE risk by SUA was clinically significant only in men (HR 1.21, 95% CI 1.03, 1.42, p = 0.0191), and the incidence of MACE events was elevated with elevated uric acid in women but was not clinically significant (HR 1.06, 95% CI 0.82, 1.38, p = 0.6633). In addition, when results were analyzed according to SUA tertiles and gender, men with higher SUA tertiles had a higher risk of MACE (p < 0.0001). After adjusting for variables, smoothed-fit curve analysis similarly showed a trend toward higher MACE occurrence with elevated uric acid in a variety of populations. The inflection points present in the threshold effect analysis in the whole population, men and women curve fits were 7.11 mg/dL, 7.13 mg/dL, and 6.31 mg/dL, respectively, and for every 1-unit increase in uric acid to the right of the inflection point, the risk of MACE increased by 1.48-fold, 1.24-fold, and 1.48-fold, respectively. (( HR (95%) CI: 2.48 (1.57, 3.90) p < 0.0001, in total; 2.24 (1.37, 3.65) p = 0.0013, in men; 2.48 (1.02, 6.01) p = 0.0442, in women)). Subgroup analyses and interaction tests showed that the association between uric acid and MACE was more significant in men in the high triglyceride and high LDL population, whereas in women it was more significant in patients with high BMI, mild coronary artery stenosis, high creatinine, and normoglycemia (interaction p-value < 0.05).

Conclusions: There is a gender difference in the risk of MACE and uric acid levels in patients with ACS, with elevated uric acid levels being more likely to lead to cardiovascular events in men patients, whereas there was no significant difference in women patients.

Keywords: Acute coronary syndromes; Gender differences; Major adverse cardiovascular events; Uric acid.