Gender-related differences in the association between serum uric acid and left ventricular mass index in patients with obstructive hypertrophic cardiomyopathy

Zhang et al. Biology of Sex Differences (2016) 7:22 DOI 10.1186/s13293-016-0074-x RESEARCH Open Access Gender-related differences in the association between serum uric acid and left ventricular mass index in patients with obstructive hypertrophic cardiomyopathy Changlin Zhang1, Rong Liu1, Jiansong Yuan1, Jingang Cui1, Fenghuan Hu1, Weixian Yang1, Yan Zhang2, Chengzhi Yang1 and Shubin Qiao1* Abstract Background: Serum uric acid (SUA) is associated with left ventricular hypertrophy in a wide spectrum of study population. However, whether this association exists in patients with hypertrophic cardiomyopathy (HCM, including obstructive HCM), and if present, whether gender has any impact on this association, remains unknown. Methods: A total of 161 patients with obstructive HCM (age 47.2 ± 10.8 years, 99 (62 %) men) were included in this study. All patients underwent extensive clinical, laboratory, echocardiographic, and cardiac magnetic resonance (CMR) imaging examinations. Left ventricular mass index (LVMI) was assessed using CMR. Results: The mean value of SUA was 353.4 ± 87.5 μmol/L. Both SUA levels (381.2 ± 86.4 vs. 309.0 ± 69.3 μmol/L, p < 0.001) and LVMI (96.2 ± 32.1 vs. 84.4 ± 32.4 g/m2, p = 0.025) were significantly higher in men than in women. LVMI increased progressively across sex-specific tertiles of SUA in women (p = 0.030), but not in men (p = 0.177). SUA was positively correlated with LVMI in female patients (r = 0.372, p = 0.003), but not in males (r = 0.112, p = 0.269). On multivariate linear regression analysis, SUA was independently associated with LVMI in females (β = 0.375, p = 0.002), but not in males. Conclusions: SUA levels are significantly and independently associated with LVMI in women with obstructive HCM, but not in men. Our findings imply the potential significance of urate-lowering regimens in female patients with obstructive HCM. Keywords: Gender difference, Uric acid, Left ventricular mass index, Obstructive hypertrophic cardiomyopathy Background Serum uric acid (SUA), as an end metabolite of purine degradation, is associated with multiple established cardiovascular risk factors, including hypertension, diabetes mellitus, dyslipidemia, obesity, and metabolic syndrome [1–5]. Although its importance in cardiovascular conditions remains controversial [6], elevated SUA has been shown to be an independent predictor for the incidence and adverse cardiovascular outcomes of coronary heart disease, myocardial infarction, heart failure, stroke, atrial * Correspondence: 1 Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, No.167 Beilishi Road, Xicheng District, Beijing 100037, China Full list of author information is available at the end of the article fibrillation, and chronic kidney disease (CKD) [7–12]. Baseline SUA levels are also related to an increased risk for cardiovascular and all-cause mortality in the general population [13]. Multiple studies, although not all, have demonstrated that SUA levels are significantly and independently associated with left ventricular hypertrophy (LVH) and left ventricular mass index (LVMI) in the general population and in patients with essential hypertension, CKD, and renal transplant [14–24]. Moreover, divergent sex differences in the relationship between SUA and LVH have been observed. Some studies found this relationship only present in males [14, 16, 18, 25], while others only in females [17, 20, 22]. Hypertrophic cardiomyopathy (HCM) is a common inherited heart disease, mainly with an autosomal © 2016 Zhang et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Zhang et al. Biology of Sex Differences (2016) 7:22 dominant pattern, and caused by more than 1500 individual mutations in 11 or more genes encoding cardiac sarcomere proteins [26, 27]. It can lead to heterogeneous clinical presentations, ranging from asymptomatic status with normal longevity to progressive heart failure, atrial fibrillation with risk for embolic stroke, and sudden death [27, 28]. HCM is characterized by unexplained LVH, as well as myocyte disarray, replacement fibrosis, and small vessel disease [29]. Quite recently, uric acid has been reported to be independently associated with adverse prognosis in patients with HCM [30]. However, the pathophysiological mechanisms underlying this association have not been elucidated. There are scanty data regarding the relationship between SUA and LVH in patients with HCM [30]. In addition, it is well known that the majority of HCM patients (about 70 %) have left ventricular outflow tract (LVOT) obstruction present at rest or with physiologic exercise [31]. Accordingly, the aim of our study was to examine in patients with obstructive HCM the association between SUA and LVMI (as assessed by cardiac magnetic resonance (CMR) imaging) and to evaluate whether gender has any impact on this association. Page 2 of 12 agents. Patients with a history of alcohol septal ablation, septal myectomy, or permanent mechanical device implantation were also excluded. Eventually, 161 patients were included in the current study. The study protocol was approved by the Ethics Committee of Fuwai Hospital and conducted in accordance with the Declaration of Helsinki. All patients gave their written informed consent. Echocardiography TTE was performed by an experienced cardio-sonographer using the Phillips iE33 Color Doppler Ultrasound System (Philips Healthcare, Andover, MA, USA). M-mode, twodimensional, and pulsed and continuous-wave Doppler studies were utilized in the standard evaluation according to the guidelines of the American Society of Echocardiography [32]. All patients underwent resting LVOT gradient measurements with continuous-wave Doppler echocardiography, while LVOT gradient after provocation was only determined in those with a resting LVOT gradient <50 mmHg. The severity of mitral regurgitation (MR), graded from mild to severe in accordance with European association of echocardiography criteria, was evaluated semi-quantitatively using color Doppler flow imaging [33]. Methods Patients CMR protocol and image analysis Between November 2008 and August 2013, consecutive patients with obstructive HCM who were referred to Fuwai Hospital (Beijing, China) for a comprehensive cardiac evaluation were enrolled in this study. (...truncated)