Serum uric acid is associated with cardiac diastolic dysfunction among women with preserved ejection fraction

Abstract

N. Serum uric acid is associated with cardiac diastolic dysfunction among women with preserved ejection fraction. Am J Physiol Heart Circ Physiol 309: H986 -H994, 2015. First published July 25, 2015 doi:10.1152/ajpheart.00402.2015.-Serum uric acid (SUA) is associated with the severity and prognosis of systolic heart failure. We investigated the potential association between SUA and cardiac diastolic dysfunction among total of 744 cardiac patients (202 women and 542 men) who had preserved left ventricular ejection fraction. Presence of diastolic dysfunction was assessed by echocardiographic data, plasma B-type natriuretic peptide concentration, and left ventricular hypertrophy. Univariate analysis showed that the prevalence of diastolic dysfunction increased with increasing SUA value in women, but not in men. When sex-nonspecific SUA quartiles were used, multivariate logistic regression analysis, among female patients who were not taking uric acid lowering medication, showed that the third (SUA, 5.7-6.4 mg) and the fourth (SUA, Ն6.5 mg/dl) SUA quartiles were associated with diastolic dysfunction with an odds ratio of 3.25 (P Ͻ 0.05) and 8.06 (P Ͻ 0.001), respectively, when compared with the first SUA quartile (Յ4.7 mg/dl). When sex-specific SUA quartiles were used among these population, multivariate logistic regression analysis showed that the fourth SUA quartile (Ն5.7 mg/dl) was associated with diastolic dysfunction with an odds ratio of 5.34 (P Ͻ 0.05) when compared with the first SUA quartile (Յ4.1 mg/dl). By contrast, the relationship between SUA and diastolic dysfunction was not significant in men, irrespective of which of the sex-nonspecific or sex-specific SUA quartiles were used. These data indicated that among cardiac patients with preserved ejection fraction, SUA was significantly associated with diastolic dysfunction in women but not in men. ALONGSIDE THE AGING POPULATION, the prevalence of heart failure with preserved ejection fraction, or diastolic heart failure, is increasing, and this increase is more prominent in women than in men, who demonstrate striking disparity with regard to heart failure with reduced ejection fraction (2,3,25). This disparity might be explained by the fact that aging-associated concentric ventricular remodeling is greater in the female heart (35). In addition to sex difference, several clinical characteristics are known to be associated with heart failure with preserved ejection fraction including older age, hypertension, obesity, diabetes, and potassium concentration (23). The prognosis for diastolic heart failure may be as poor as that for systolic heart failure (11, 31), and most therapies that have been shown to be effective for systolic heart failure seem to be least effective for diastolic heart failure (11,15,26,32,42). Thus factors that are not only related to diastolic dysfunction risk but also potentially modifiable by lifestyle interventions or certain medication need to be identified for the better management of diastolic cardiac dysfunction, especially in wom...

Is Serum Uric Acid Independently Associated With Left Ventricular Mass Index, Ejection Fraction, and B-Type Natriuretic Peptide Among Female and Male Cardiac Patients?

“…There may be other mechanisms linking elevated BNP and SUA at least in female patients. We showed that SUA is positively associated with diastolic dysfunction exclusively in women, 21) therefore, diastolic dysfunction might be one of the candidates to explain the observed link.…”

“…In addition, the strength of the association between SUA and certain cardiac abnormalities might differ between women and men. 3,[20][21][22] We found that among patients with sinus rhythm, SUA was independently associated with diastolic dysfunction only in women. 21) In a previous study, by analyzing the data from male patients, we showed that SUA is associated with cardiac hypertrophy.…”

“…3,[20][21][22] We found that among patients with sinus rhythm, SUA was independently associated with diastolic dysfunction only in women. 21) In a previous study, by analyzing the data from male patients, we showed that SUA is associated with cardiac hypertrophy. In the current study, we have analyzed the possible association between SUA and cardiac hypertrophy, cardiac systolic dysfunction, and the marker of heart failure B-type natriuretic peptide (BNP), in a gender-specific manner.…”

“…Study population: Between 2012 January and 2014 June, among 240 female cardiac inpatients, sufficient clinical and echocardiographic information was available were enrolled in the current study. Among these patients, 21 were taking a xanthine oxidase inhibitor (either allopurinol or febuxostat) and/or a uricosuric drug, respectively, and were subsequently excluded. Although we analyzed SUA data from 116 male patients in our previous paper, 14) to compare the data between female and male patients over the same study period, here we further analyzed data from 519 male patients selected by the same inclusion and exclusion criteria used for female patients.…”

Redox Control of Vascular Function

“…For example, females have been shown to have a higher incidence of vascular stiffness and increased levels of plasma uric acid. 67,68,69,70 Pharmacological inhibition of xanthine oxidase was shown to increase vasoreactivity and reduce aortic hardening in female mice fed a western diet. 71 In a similar manner, COX-2 is a responsive element to other forms of ROS and can exacerbate hypertension through feed-forward chronic production of inflammatory or vasoconstrictive prostaglandin synthesis and increase the magnitude of hypertension and ROS production in patients with ROS-induced vasculopathy.…”