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Serum uric acid level and left ventricular hypertrophy in elderly male patients with nonvalvular atrial fibrillation
Nutrition, Metabolism & Cardiovascular Diseases (2016) xx, 1e6
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Serum uric acid level and left ventricular hypertrophy in elderly male patients with nonvalvular atrial fibrillation W.Y. Liang, W.W. Liu, M.L. Liu*, W. Xiang, X.R. Feng, B. Huang, X.H. Chen, Y.S. Sun Department of Geriatrics, Peking University First Hospital, Beijing, People’s Republic of China Received 24 August 2015; received in revised form 10 March 2016; accepted 15 March 2016 Available online - - -
KEYWORDS Serum uric acid; Left ventricular hypertrophy; Atrial fibrillation
Abstract Background and aims: Recent studies have suggested that serum uric acid (SUA) induces oxidative stress and inflammation, which are involved in the mechanism of cardiac hypertrophy. In patients with atrial fibrillation (AF), comorbidity of left ventricular hypertrophy (LVH) exacerbates cardiac function. In this study, we investigated the association between SUA and cardiac hypertrophy in AF patients. Methods and results: Initially, 1296 consecutive elderly patients (age >60) with nonvalvular AF were retrospectively selected from the inpatient clinic between January 2012 and April 2015. Demographic, clinical, and echocardiographic characteristics were carefully recorded. The final study population was 577 patients. The mean SUA level was significantly higher in patients with LVH than those without LVH. Compared with the non-LVH group, the LVH group was older, had a higher percentage of female patients, and had lower hemoglobin levels and estimated glomerular filtration rates. Patients in the LVH group also had a higher rate of coronary heart disease and fewer had history of radiofrequency ablation compared with the non-LVH group. In the hyperuricemia group, B-type natriuretic peptide levels, left atrial diameter, left ventricular mass index, and percentage of NYHA (New York Heart Association) class III/IV were significantly higher than the SUA normal group. Multivariate logistic regression analysis indicated the independent risk factors for LVH in elderly AF patients included SUA, age, male sex, the presence of coronary heart disease, and diuretic therapy. Subgroup analysis identified SUA as a significant risk factor associated with LVH in men. Conclusions: SUA was independently associated with LVH in elderly male patients with nonvalvular AF. ª 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
Abbreviations: LVH, left ventricular hypertrophy; AF, atrial fibrillation; SUA, serum uric acid; RFCA, radiofrequency catheter ablation; CHD, coronary heart disease; BNP, B-type natriuretic peptide; eGFR, estimated glomerular filtration rate; LVMI, left ventricular mass index; LAD, left atrial diameter; LVEDD, left ventricular end-diastolic dimension; IVST, interventricular septal thickness; PWT, posterior wall thickness; RWT, relative wall thickness; LVEF, left ventricular ejection fraction. * Corresponding author. Department of Geriatrics, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing 100034, People’s Republic of China. Tel.: þ86 10 83572022. E-mail address: [email protected] (M.L. Liu).
Introduction Left ventricular hypertrophy (LVH) is an important independent risk factor for cardiovascular complications and death. Patients with atrial fibrillation (AF) lose atrial pump function, resulting in hemodynamic deterioration and reduced cardiac output. Comorbidity of LVH further exacerbates cardiac malfunction. Factors associated with LVH have yet to be determined and preventive treatments are still required in AF patients.
http://dx.doi.org/10.1016/j.numecd.2016.03.011 0939-4753/ª 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: Liang WY, et al., Serum uric acid level and left ventricular hypertrophy in elderly male patients with nonvalvular atrial fibrillation, Nutrition, Metabolism & Cardiovascular Diseases (2016), http://dx.doi.org/10.1016/j.numecd.2016.03.011
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Regardless of whether serum uric acid (SUA) is a predictor or causative factor, it has been found to be increasingly associated with cardiovascular risk profiles [1e3]. Evidence suggests that SUA induces inflammatory and proliferative cytokines such as tumor necrosis factor-a [4], monocyte chemoattractant protein-1 [5], and endothelin-1 [6]. SUA induces oxidation stress, increases NADPH oxidase activity, and stimulates reactive oxygen species (ROS) formation [6e8], which promote cardiac hypertrophy. SUA also activates the renineangiotensinealdosterone system [9], which is a well-known system for cardiac hypertrophy, myocardial hyperplasia, and interstitial fibrosis [10]. SUA is strongly associated with the occurrence of AF, which is a common aging-related heart disease [11]. However, the association between SUA and cardiac hypertrophy in AF patients remains unclear. In this study, we investigated the association between SUA and LVH evaluated by echocardiography in an elderly AF population. Methods Study population A total of 1296 consecutive elderly patients (age >60) with nonvalvular AF were retrospectively selected from the inpatient clinic in our hospital between January 2012 and April 2015. Diagnosis of AF was based on 12-lead electrocardiography or 24-h Holter monitoring, and classification was based on the published guidelines. Diagnoses of other diseases were strictly based on clinical criteria, for example, coronary heart disease (CHD) was diagnosed using angiography. Patients without a history of rheumatic mitral stenosis, a mechanical or bioprosthetic heart valve, or mitral valve repair were eligible for the study. Exclusion criteria were cardiomyopathy, pulmonary heart disease, thyroid dysfunction, autoimmune diseases, chronic anemia (hemoglobin <90 g/L), severe kidney disease (defined as estimated glomerular filtration rate (eGFR) < 30 mL/ min/1.73 m2), chronic hepatic diseases, active inflammatory conditions, missing information on SUA or left ventricular mass index (LVMI), and those who were taking xanthine oxidase inhibitor or uricosuric drugs. Finally, 577 patients (age 74 8 years, 357 men and 220 women) with sufficient available clinical and echocardiographic information were selected for this study. SUA levels were measured by standard analytical methods (uricase enzymatic test) with routine laboratory testing at our hospital. For elderly people, hyperuricemia was defined as an SUA concentration >7 mg/dL (416.5 mmol/L). The left ventricular mass was calculated according to the formula proposed by Devereux et al.: left ventricular mass (g) Z 0.8 1.04 [(left ventricular enddiastolic dimension (LVEDD) þ end-diastolic interventricular septum thickness (IVST) þ end-diastolic left ventricular posterior wall thickness (PWT))3 (LVEDD)3] þ 0.6. Body surface area was calculated using the DuBois2 formula: body surface area (m2) Z (body weight)0.425 (height)0.725 0.007184. The LVMI was calculated by
W.Y. Liang et al.
dividing the left ventricular mass by the body surface area. LVH was defined as LVMI >115 g/m2 (in male) or 95 g/m2 (in female). Relative wall thickness (RWT) was calculated as 2 PWT/LVEDD with a partition value of 0.42 [12]. The study protocols were approved by the Peking University First Hospital Institutional Review Committee (PUFH2015-967) and conducted in accordance with the national legal requirements and the revised Declaration of Helsinki. Statistical analysis Distribution normality of each variable was tested using the KolmogoroveSmirnov test. Continuous variables were tested using the Student’s t-test or nonparametric test. Categorical variables were tested using the chi-square test or Fisher’s exact test. Log-transformed LVMI (log[LVMI]) and B-type natriuretic peptide (BNP) (log[BNP]) were confirmed to be normally distributed using the KolmogoroveSmirnov test. Relationships between variables were analyzed with Pearson correlation coefficients. In order to test the independence of risk factors for LVH, the main covariates were passed through a multivariate logistic regression model with backward selection of independent variables. Differences were considered significant at p < 0.05 (two-tailed). Results Clinical characteristics of study participants divided according to LVH are shown in Table 1. Age and sex differed between patients with and without LVH (median age: 76 vs. 68 years, p Z 0.004; 44.6% males vs. 68.9% males, p < 0.001). SUA level was significantly higher in patients with LVH (6.10 1.91 mg/dL) than those without LVH (5.73 1.56 mg/dL, p Z 0.018). Hemoglobin level and eGFR were significantly lower in the LVH group than the non-LVH group (p Z 0.003 and 0.013, respectively). Moreover, elderly AF patients with LVH had increased presence of CHD, and fewer had history of radiofrequency catheter ablation (RFCA) compared with the non-LVH group (p Z 0.001 and 0.022, respectively). Echocardiographic data showed that patients in the LVH group were characterized by a larger left atrial diameter (LAD), LVEDD, IVST, and PWT, but decreased left ventricular ejection fraction (LVEF) (all p values < 0.001). The percentage of NYHA class III/IV was significantly higher in the LVH group than the non-LVH group (p < 0.001), indicating poorer clinical heart function. Consistently, BNP level, an indicative marker of heart failure, was elevated in the LVH group compared with the non-LVH group (p < 0.001). Clinical characteristics of study participants divided according to SUA are shown in Table 2. Body mass index was significantly higher in the hyperuricemia group than the SUA normal group (26.1 4.2 kg/m2 vs. 24.7 3.7 kg/ m2, p Z 0.001). Patients in the hyperuricemia group also had higher levels of serum creatinine, blood urea, and triglycerides and lower levels of eGFR and high-density
Please cite this article in press as: Liang WY, et al., Serum uric acid level and left ventricular hypertrophy in elderly male patients with nonvalvular atrial fibrillation, Nutrition, Metabolism & Cardiovascular Diseases (2016), http://dx.doi.org/10.1016/j.numecd.2016.03.011
Serum uric acid level and left ventricular hypertrophy in elderly male patients
lipoprotein cholesterol (all p values < 0.001), indicating poorer renal function and metabolic profile than patients in the SUA normal group. CHD was the most evident cardiovascular condition in the hyperuricemia group compared with the SUA normal group (52.6% vs. 38.7%, p Z 0.004). Treatment with digoxin, diuretics, and angiotensin-converting enzyme inhibitors was more prevalent in the hyperuricemia group (all p values < 0.05). Interestingly, results showed that percentage of NYHA class III/IV in the hyperuricemia group was significantly higher than that in the SUA normal group (24.4% vs. 9.3%, p < 0.001), indicating poorer heart function in the hyperuricemia group. Consistently, BNP level in the hyperuricemia group was approximately 1.5 times higher than that in the SUA normal group (p < 0.001). Echocardiographic data showed that patients in the hyperuricemia group were characterized by higher LAD, LVEDD, IVST, PWT, LVMI, and LVEF (all p values < 0.05).
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With Pearson’s correlation tests, SUA was found to significantly correlate with log[LVMI] (r Z 0.234, p < 0.001) and log[BNP] (r Z 0.191, p < 0.001) for the entire study population. Multivariate regression analysis of LVH included the following independent variables in the model: age, male sex, body mass index, the presence of CHD, the presence of hypertension, RFCA history, pacemaker placement history, hemoglobin, eGFR, SUA, blood urea, triglycerides, highdensity lipoprotein cholesterol, drug therapy with digoxin, diuretics, and angiotensin-converting enzyme inhibitor. The independent risk factors were SUA (OR: 1.178, 95% CI: 1.048e1.323, p Z 0.006), age (OR: 1.028, 95% CI: 1.001e1.056, p Z 0.041), male sex (OR: 0.321, 95% CI: 0.214e0.480, p < 0.001), the presence of CHD (OR: 1.864, 95% CI: 1.252e2.777, p Z 0.002), and diuretic therapy (OR: 1.718, 95% CI: 1.087e2.717, p Z 0.021). Subgroup analysis identified SUA as a significant risk factor associated with
Table 1 Main characteristics of study participants with and without left ventricular hypertrophy. Variables
LVH (n Z 168)
Non-LVH (n Z 409)
P value
LVMI, g/m2 Age, years Male sex, n (%) Body mass index, Kg/m2 NYHA class III/IV, n (%) Medical history Paroxysmal AF, n (%) Duration of AF, years Pacemaker placement, n (%) RFCA, n (%) Hypertension, n (%) Coronary heart disease, n (%) Diabetes mellitus, n (%) Dyslipidemia, n (%) Smoking habits Never/Former/Current (n, %) Alcoholic habits Never/Former/Current (n, %) Laboratory data WBC, x103/mL Hemoglobin, g/L BNP, pg/mL eGFR, mL/min/1.73 m2 Serum uric acid, mg/dL Serum creatinine, mg/dL Blood urea, mg/dL Blood glucose, mg/dL Triglycerides, mg/dL Total cholesterol, mg/dL Echocardiographic data LAD, mm LVEDD, mm IVST, mm PWT, mm RWT LVEF, %
119 (106e132) 76 (71e81) 75 (44.6) 25.2 4.0 39 (23.2)
85 (74e95) 68 (74e80) 282 (68.9) 25.0 3.8 35 (8.6)
<0.001*** 0.004** <0.001*** 0.515 <0.001***
107 (64.1) 3.0 (0.3e9.8) 15 (8.9) 3 (1.8) 133 (79.2) 89 (53.0) 51 (30.4) 72 (42.9)
250 (61.1) 3.5 (0.45e10.0) 20 (4.9) 26 (6.4) 300 (73.3) 153 (37.4) 134 (32.8) 160 (39.1)
0.509 0.502 0.065 0.022* 0.142 0.001** 0.574 0.406
115/35/18 (68/21/11)
270/82/57 (66/20/14)
0.579
139/11/18 (83/7/11)
323/34/52 (79/8/13)
0.583
5.63 (4.80e6.90) 131.3 16.8 326 (194e575) 67.9 (57.0e82.2) 6.10 1.87 1.04 (0.86e1.18) 38.5 (32.5e48.0) 93.6 (82.8e111.6) 105.3 (70.8e134.5) 151.6 37.9
5.85 (4.80e7.12) 135.2 17.3 246 (131e418) 73.0 (61.3e86.5) 5.71 1.57 1.00 (0.89e1.18) 37.9 (30.7e44.5) 97.2 (84.6e118.8) 102.7 (73.5e137.2) 154.7 41.0
0.284 0.013* <0.001*** 0.003** 0.018* 0.720 0.063 0.244 0.795 0.379
43 (40e47) 50 (47e55) 11 (10e12) 10 (10e11) 0.416 0.090 60 (53e69)
41 (37e45) 46 (42e49) 10 (9e11) 9 (9e10) 0.418 0.074 65 (59e71)
<0.001*** <0.001*** <0.001*** <0.001*** 0.798 <0.001***
LVMI, left ventricular mass index; AF, atrial fibrillation; RFCA, radiofrequency catheter ablation; WBC, white blood cells; eGFR, estimated glomerular filtration rate; BNP, B-type natriuretic peptide; LAD, left atrial diameter; LVEDD, left ventricular end-diastolic dimension; IVST, interventricular septal thickness; PWT, posterior wall thickness; RWT, relative wall thickness; LVEF, left ventricular ejection fraction. *: p < 0.05; **: p < 0.01; ***: p < 0.001.
Please cite this article in press as: Liang WY, et al., Serum uric acid level and left ventricular hypertrophy in elderly male patients with nonvalvular atrial fibrillation, Nutrition, Metabolism & Cardiovascular Diseases (2016), http://dx.doi.org/10.1016/j.numecd.2016.03.011
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W.Y. Liang et al.
LVH (OR: 1.213, 95% CI: 1.017e1.446, p Z 0.031) in male patients only. Discussion The results of this study suggest that this population of hyperuricemia patients showed poorer renal function, heart function, and metabolic profiles than the control group. SUA was independently associated with LVH in elderly patients with nonvalvular AF, particularly in men. The relationship between SUA and LVH has been shown in hypertensive patients, chronic kidney disease patients,
and the general population [13e15]. To the best of the authors’ knowledge, this is the first study of its kind to investigate the relationship between SUA and LVH in nonvalvular AF patients. The results suggest a malespecific association between SUA and LVH. The sexrelated differences identified in this study may reflect different sensitivities to metabolic processes of uric acid [16]. Previous population-based studies reported that SUA was associated with metabolic syndrome components [17,18]. In this study, the hyperuricemia group also exhibited an increased BMI, paralleling higher triglyceride
Table 2 Main characteristics of study participants with and without hyperuricemia. Variables
Hyperuricemia (n Z 135)
SUA normal (n Z 442)
P value
SUA, mg/dL Age, years Male sex, n (%) Body mass index, kg/m2 NYHA class III/IV, n (%) Medical history Paroxysmal AF, n (%) Duration of AF, years Hypertension, n (%) Coronary heart disease, n (%) Diabetes mellitus, n (%) Dyslipidemia, n (%) Smoking habits Never/Former/Current (n, %) Alcoholic habits Never/Former/Current (n, %) Laboratory data WBC, 103/mL Hemoglobin, g/L BNP, pg/mL eGFR, mL/min/1.73 m2 Serum creatinine, mg/dL Blood urea, mg/dL Blood glucose, mg/dL Triglycerides, mg/dL Total cholesterol, mg/dL HDL-C, mg/dL LDL-C, mg/dL Echocardiographic data LAD, mm LVEDD, mm IVST, mm PWT, mm LVMI, g/m2 RWT LVEF, % Drug therapy Digoxin, n (%) Beta-blockers, n (%) Diuretics, n (%) ACEI, n (%) ARB, n (%) CCB, n (%)
8.08 1.08 76 (69e82) 93 (68.9) 26.1 4.2 33 (24.4)
5.14 1.12 75 (69e80) 264 (59.7) 24.7 3.7 41 (9.3)
<0.001*** 0.071 0.055 0.001** <0.001***
75 (55.6) 3.0 (0.4e10.0) 105 (77.8) 71 (52.6) 42 (31.1) 60 (44.4)
282 (63.9) 3.0 (0.3e10.0) 328 (74.2) 171 (38.7) 143 (32.4) 172 (38.9)
0.079 0.816 0.402 0.004** 0.787 0.251
87/30/18 (65/22/14)
298/87/57 (67/20/13)
0.786
99/15/21 (73/11/16)
363/30/49 (82/7/11)
0.075
6.00 (5.14e7.24) 133.8 19.3 349.0 (197.0e672.0) 59.6 (51.2e73.5) 1.16 (1.02e1.32) 45.0 (37.9e54.7) 95.4 (82.8e115.2) 116.0 (82.3e168.2) 154.7 39.4 35.2 (30.9e41.8) 87.4 (73.5e105.6)
5.64 (4.76e7.10) 134.1 16.6 247.8 (134.0e429.0) 74.8 (63.0e87.1) 0.98 (0.85e1.12) 36.7 (30.1e42.0) 95.4 (82.8e118.8) 100.0 (69.0e129.2) 153.5 40.2 40.2 (34.4e48.0) 89.3 (69.6e110.2)
0.061 0.846 <0.001*** <0.001*** <0.001*** <0.001*** 0.969 <0.001*** 0.746 <0.001*** 0.726
43 (40e48) 49 (45e53) 10 (10e11) 10 (9e11) 100 (85e116) 0.414 0.086 60 (53e67)
41 (37e45) 47 (43e50) 10 (9e11) 10 (9e10) 92 (78e106) 0.418 0.077 65 (59e71)
<0.001*** <0.001*** 0.011* 0.004** <0.001*** 0.148 <0.001***
17 83 47 32 46 45
30 (6.8) 248 (56.1) 75 (17.0) 49 (11.1) 127 (28.7) 143 (32.4)
0.031* 0.269 <0.001*** <0.001*** 0.236 0.832
(12.6) (61.5) (34.8) (23.7) (34.1) (33.3)
SUA, serum uric acid; AF, atrial fibrillation; WBC, white blood cells; eGFR, estimated glomerular filtration rate; BNP, B-type natriuretic peptide; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; LAD, left atrial diameter; LVEDD, left ventricular enddiastolic dimension; IVST, interventricular septal thickness; PWT, posterior wall thickness; LVMI, left ventricular mass index; RWT, relative wall thickness; LVEF, left ventricular ejection fraction; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor-blocking agent; CCB, calcium channel blocker. *: p < 0.05; **: p < 0.01; ***: p < 0.001.
Please cite this article in press as: Liang WY, et al., Serum uric acid level and left ventricular hypertrophy in elderly male patients with nonvalvular atrial fibrillation, Nutrition, Metabolism & Cardiovascular Diseases (2016), http://dx.doi.org/10.1016/j.numecd.2016.03.011
Serum uric acid level and left ventricular hypertrophy in elderly male patients
and lower high-density lipoprotein cholesterol levels. In a population-based prospective study, adjusting for age, sex, blood pressure, history of hypertension, insulin resistance, central adiposity, and eGFR confirmed that incident metabolic syndrome was associated with a higher baseline SUA. However, the association disappeared when body composition assessed by fat-free mass was taken into account [19]. The role of SUA in cardiovascular disease was largely ignored until the mid-1950s and early 1960s, when it was rediscovered. The mean SUA levels in humans increased gradually from <3.5 mg/dL (210 mmol/L) in the 1920s to 6.0e6.5 mg/dL (360e390 mmol/L) in the 1970s [20]. Elevated SUA is associated with fructose or purine-rich food intake, alcohol intake, diabetes, obesity, metabolic syndrome, renal failure, drug therapy such as diuretics, and genetic factors. Experimental studies have reported that elevated SUA induces inflammation and oxidation stress and activates the renineangiotensinealdosterone system, which may result in cardiac hypertrophy and interstitial fibrosis [4e10]. A rat model of hyperuricemia has been reported to develop all the hemodynamic findings observed in essential hypertension, including prominent vasoconstriction of the afferent arteriole, with a reduction in renal blood flow and a relative preservation of the GFR [21,22]. Cardiac hypertrophy compensates the pressure overload seen in hypertension [23]. In this study, a medical history of hypertension was more prevalent in patients with hyperuricemia, but this finding was not statistically significant. The influence of additional hormonal, hemodynamic, and metabolic factors also predisposes these patients to develop structural and functional abnormalities of the heart. Further, hypertrophic myocardium with anoxia leads to an increase in the degradation of adenosine triphosphatase, which increases the production of xanthine and uric acid. Thus, it is a difficult task to distinguish the causeeeffect relationship between uric acid and cardiac hypertrophy. The results of this study suggest that further attention be given to the therapeutic control of high SUA levels in AF patients. However, there was a U-shaped association between uric acid levels and cardiovascular mortality observed [24]. Thus, we recommend using appropriate intervention strategies, rather than assuming that “lower is better.” This study had some limitations. First, the sample size was relatively small. Second, the observational study design allowed for only determining an association and not causality. Third, paroxysmal, persistent, and permanent AF patients are quite heterogeneous in terms of symptoms and arrhythmia burden, yet these patients were not analyzed separately in this study. Finally, the mechanisms behind the results obtained require further investigation.
Disclosures The authors have no conflict of interest to disclose.
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Acknowledgment This study was supported by the National Science and Technology Support Program, whose topic is Translational Medicine Research of Treatment Risk and Strategy in the Old Population (2012BAI37B05). The funding agency did not play any role in the collection, analysis, and interpretation of data or the preparation of the manuscript. References [1] Kanbay M, Segal M, Afsar B, Kang DH, Rodriguez-Iturbe B, Johnson RJ. The role of uric acid in the pathogenesis of human cardiovascular disease. Heart 2013;99:759e66. [2] Fenech G, Rajzbaum G, Mazighi M, Blacher J. Serum uric acid and cardiovascular risk: state of the art and perspectives. Jt Bone Spine 2014;81:392e7. [3] Zhao G, Huang L, Song M, Song Y. Baseline serum uric acid level as a predictor of cardiovascular disease related mortality and allcause mortality: a meta-analysis of prospective studies. Atherosclerosis 2013;231:61e8. [4] Peracoli MT, Bannwart CF, Cristofalo R, Borges VT, Costa RA, Witkin SS, et al. Increased reactive oxygen species and tumor necrosis factor-alpha production by monocytes are associated with elevated levels of uric acid in pre-eclamptic women. Am J Reprod Immunol 2011;66:460e7. [5] Liang WY, Zhu XY, Zhang JW, Feng XR, Wang YC, Liu ML. Uric acid promotes chemokine and adhesion molecule production in vascular endothelium via nuclear factor-kappa B signaling. Nutr Metab Cardiovasc Dis 2015;25:187e94. [6] Cheng TH, Lin JW, Chao HH, Chen YL, Chen CH, Chan P, et al. Uric acid activates extracellular signal-regulated kinases and thereafter endothelin-1 expression in rat cardiac fibroblasts. Int J Cardiol 2010;139:42e9. [7] Corry DB, Eslami P, Yamamoto K, Nyby MD, Makino H, Tuck ML. Uric acid stimulates vascular smooth muscle cell proliferation and oxidative stress via the vascular renin-angiotensin system. J Hypertens 2008;26:269e75. [8] Yu MA, Sanchez-Lozada LG, Johnson RJ, Kang DH. Oxidative stress with an activation of the renin-angiotensin system in human vascular endothelial cells as a novel mechanism of uric acidinduced endothelial dysfunction. J Hypertens 2010;28:1234e42. [9] Kanbay M, Sanchez-Lozada LG, Franco M, Madero M, Solak Y, Rodriguez-Iturbe B, et al. Microvascular disease and its role in the brain and cardiovascular system: a potential role for uric acid as a cardiorenal toxin. Nephrol Dial Transpl 2011;26:430e7. [10] Yoshimura A, Adachi H, Hirai Y, Enomoto M, Fukami A, Kumagai E, et al. Serum uric acid is associated with the left ventricular mass index in males of a general population. Int Heart J 2014;55:65e70. [11] Chuang SY, Wu CC, Hsu PF, Chia-Yu CR, Liu WL, Hsu YY, et al. Hyperuricemia and incident atrial fibrillation in a normotensive older population in Taiwan. Nutr Metab Cardiovasc Dis 2014;24: 1020e6. [12] Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, et al. Recommendations for chamber quantification: a report from the American society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 2005;18:1440e63. [13] Catena C, Colussi G, Capobianco F, Brosolo G, Sechi LA. Uricaemia and left ventricular mass in hypertensive patients. Eur J Clin Invest 2014;44:972e81. [14] Yoshitomi R, Fukui A, Nakayama M, Ura Y, Ikeda H, Oniki H, et al. Sex differences in the association between serum uric acid levels and cardiac hypertrophy in patients with chronic kidney disease. Hypertens Res 2014;37:246e52. [15] Cicero AF, Rosticci M, Reggi A, Derosa G, Parini A, Grandi E, et al. Relationship between serum uric acid and electrocardiographic alterations in a large sample of general population: data from the Brisighella Heart Study. High Blood Press Cardiovasc Prev 2015;22: 129e34.
Please cite this article in press as: Liang WY, et al., Serum uric acid level and left ventricular hypertrophy in elderly male patients with nonvalvular atrial fibrillation, Nutrition, Metabolism & Cardiovascular Diseases (2016), http://dx.doi.org/10.1016/j.numecd.2016.03.011
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Please cite this article in press as: Liang WY, et al., Serum uric acid level and left ventricular hypertrophy in elderly male patients with nonvalvular atrial fibrillation, Nutrition, Metabolism & Cardiovascular Diseases (2016), http://dx.doi.org/10.1016/j.numecd.2016.03.011
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Nutrition, Metabolism & Cardiovascular Diseases journal homepage: www.elsevier.com/locate/nmcd
Serum uric acid level and left ventricular hypertrophy in elderly male patients with nonvalvular atrial fibrillation W.Y. Liang, W.W. Liu, M.L. Liu*, W. Xiang, X.R. Feng, B. Huang, X.H. Chen, Y.S. Sun Department of Geriatrics, Peking University First Hospital, Beijing, People’s Republic of China Received 24 August 2015; received in revised form 10 March 2016; accepted 15 March 2016 Available online - - -
KEYWORDS Serum uric acid; Left ventricular hypertrophy; Atrial fibrillation
Abstract Background and aims: Recent studies have suggested that serum uric acid (SUA) induces oxidative stress and inflammation, which are involved in the mechanism of cardiac hypertrophy. In patients with atrial fibrillation (AF), comorbidity of left ventricular hypertrophy (LVH) exacerbates cardiac function. In this study, we investigated the association between SUA and cardiac hypertrophy in AF patients. Methods and results: Initially, 1296 consecutive elderly patients (age >60) with nonvalvular AF were retrospectively selected from the inpatient clinic between January 2012 and April 2015. Demographic, clinical, and echocardiographic characteristics were carefully recorded. The final study population was 577 patients. The mean SUA level was significantly higher in patients with LVH than those without LVH. Compared with the non-LVH group, the LVH group was older, had a higher percentage of female patients, and had lower hemoglobin levels and estimated glomerular filtration rates. Patients in the LVH group also had a higher rate of coronary heart disease and fewer had history of radiofrequency ablation compared with the non-LVH group. In the hyperuricemia group, B-type natriuretic peptide levels, left atrial diameter, left ventricular mass index, and percentage of NYHA (New York Heart Association) class III/IV were significantly higher than the SUA normal group. Multivariate logistic regression analysis indicated the independent risk factors for LVH in elderly AF patients included SUA, age, male sex, the presence of coronary heart disease, and diuretic therapy. Subgroup analysis identified SUA as a significant risk factor associated with LVH in men. Conclusions: SUA was independently associated with LVH in elderly male patients with nonvalvular AF. ª 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
Abbreviations: LVH, left ventricular hypertrophy; AF, atrial fibrillation; SUA, serum uric acid; RFCA, radiofrequency catheter ablation; CHD, coronary heart disease; BNP, B-type natriuretic peptide; eGFR, estimated glomerular filtration rate; LVMI, left ventricular mass index; LAD, left atrial diameter; LVEDD, left ventricular end-diastolic dimension; IVST, interventricular septal thickness; PWT, posterior wall thickness; RWT, relative wall thickness; LVEF, left ventricular ejection fraction. * Corresponding author. Department of Geriatrics, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing 100034, People’s Republic of China. Tel.: þ86 10 83572022. E-mail address: [email protected] (M.L. Liu).
Introduction Left ventricular hypertrophy (LVH) is an important independent risk factor for cardiovascular complications and death. Patients with atrial fibrillation (AF) lose atrial pump function, resulting in hemodynamic deterioration and reduced cardiac output. Comorbidity of LVH further exacerbates cardiac malfunction. Factors associated with LVH have yet to be determined and preventive treatments are still required in AF patients.
http://dx.doi.org/10.1016/j.numecd.2016.03.011 0939-4753/ª 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: Liang WY, et al., Serum uric acid level and left ventricular hypertrophy in elderly male patients with nonvalvular atrial fibrillation, Nutrition, Metabolism & Cardiovascular Diseases (2016), http://dx.doi.org/10.1016/j.numecd.2016.03.011
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Regardless of whether serum uric acid (SUA) is a predictor or causative factor, it has been found to be increasingly associated with cardiovascular risk profiles [1e3]. Evidence suggests that SUA induces inflammatory and proliferative cytokines such as tumor necrosis factor-a [4], monocyte chemoattractant protein-1 [5], and endothelin-1 [6]. SUA induces oxidation stress, increases NADPH oxidase activity, and stimulates reactive oxygen species (ROS) formation [6e8], which promote cardiac hypertrophy. SUA also activates the renineangiotensinealdosterone system [9], which is a well-known system for cardiac hypertrophy, myocardial hyperplasia, and interstitial fibrosis [10]. SUA is strongly associated with the occurrence of AF, which is a common aging-related heart disease [11]. However, the association between SUA and cardiac hypertrophy in AF patients remains unclear. In this study, we investigated the association between SUA and LVH evaluated by echocardiography in an elderly AF population. Methods Study population A total of 1296 consecutive elderly patients (age >60) with nonvalvular AF were retrospectively selected from the inpatient clinic in our hospital between January 2012 and April 2015. Diagnosis of AF was based on 12-lead electrocardiography or 24-h Holter monitoring, and classification was based on the published guidelines. Diagnoses of other diseases were strictly based on clinical criteria, for example, coronary heart disease (CHD) was diagnosed using angiography. Patients without a history of rheumatic mitral stenosis, a mechanical or bioprosthetic heart valve, or mitral valve repair were eligible for the study. Exclusion criteria were cardiomyopathy, pulmonary heart disease, thyroid dysfunction, autoimmune diseases, chronic anemia (hemoglobin <90 g/L), severe kidney disease (defined as estimated glomerular filtration rate (eGFR) < 30 mL/ min/1.73 m2), chronic hepatic diseases, active inflammatory conditions, missing information on SUA or left ventricular mass index (LVMI), and those who were taking xanthine oxidase inhibitor or uricosuric drugs. Finally, 577 patients (age 74 8 years, 357 men and 220 women) with sufficient available clinical and echocardiographic information were selected for this study. SUA levels were measured by standard analytical methods (uricase enzymatic test) with routine laboratory testing at our hospital. For elderly people, hyperuricemia was defined as an SUA concentration >7 mg/dL (416.5 mmol/L). The left ventricular mass was calculated according to the formula proposed by Devereux et al.: left ventricular mass (g) Z 0.8 1.04 [(left ventricular enddiastolic dimension (LVEDD) þ end-diastolic interventricular septum thickness (IVST) þ end-diastolic left ventricular posterior wall thickness (PWT))3 (LVEDD)3] þ 0.6. Body surface area was calculated using the DuBois2 formula: body surface area (m2) Z (body weight)0.425 (height)0.725 0.007184. The LVMI was calculated by
W.Y. Liang et al.
dividing the left ventricular mass by the body surface area. LVH was defined as LVMI >115 g/m2 (in male) or 95 g/m2 (in female). Relative wall thickness (RWT) was calculated as 2 PWT/LVEDD with a partition value of 0.42 [12]. The study protocols were approved by the Peking University First Hospital Institutional Review Committee (PUFH2015-967) and conducted in accordance with the national legal requirements and the revised Declaration of Helsinki. Statistical analysis Distribution normality of each variable was tested using the KolmogoroveSmirnov test. Continuous variables were tested using the Student’s t-test or nonparametric test. Categorical variables were tested using the chi-square test or Fisher’s exact test. Log-transformed LVMI (log[LVMI]) and B-type natriuretic peptide (BNP) (log[BNP]) were confirmed to be normally distributed using the KolmogoroveSmirnov test. Relationships between variables were analyzed with Pearson correlation coefficients. In order to test the independence of risk factors for LVH, the main covariates were passed through a multivariate logistic regression model with backward selection of independent variables. Differences were considered significant at p < 0.05 (two-tailed). Results Clinical characteristics of study participants divided according to LVH are shown in Table 1. Age and sex differed between patients with and without LVH (median age: 76 vs. 68 years, p Z 0.004; 44.6% males vs. 68.9% males, p < 0.001). SUA level was significantly higher in patients with LVH (6.10 1.91 mg/dL) than those without LVH (5.73 1.56 mg/dL, p Z 0.018). Hemoglobin level and eGFR were significantly lower in the LVH group than the non-LVH group (p Z 0.003 and 0.013, respectively). Moreover, elderly AF patients with LVH had increased presence of CHD, and fewer had history of radiofrequency catheter ablation (RFCA) compared with the non-LVH group (p Z 0.001 and 0.022, respectively). Echocardiographic data showed that patients in the LVH group were characterized by a larger left atrial diameter (LAD), LVEDD, IVST, and PWT, but decreased left ventricular ejection fraction (LVEF) (all p values < 0.001). The percentage of NYHA class III/IV was significantly higher in the LVH group than the non-LVH group (p < 0.001), indicating poorer clinical heart function. Consistently, BNP level, an indicative marker of heart failure, was elevated in the LVH group compared with the non-LVH group (p < 0.001). Clinical characteristics of study participants divided according to SUA are shown in Table 2. Body mass index was significantly higher in the hyperuricemia group than the SUA normal group (26.1 4.2 kg/m2 vs. 24.7 3.7 kg/ m2, p Z 0.001). Patients in the hyperuricemia group also had higher levels of serum creatinine, blood urea, and triglycerides and lower levels of eGFR and high-density
Please cite this article in press as: Liang WY, et al., Serum uric acid level and left ventricular hypertrophy in elderly male patients with nonvalvular atrial fibrillation, Nutrition, Metabolism & Cardiovascular Diseases (2016), http://dx.doi.org/10.1016/j.numecd.2016.03.011
Serum uric acid level and left ventricular hypertrophy in elderly male patients
lipoprotein cholesterol (all p values < 0.001), indicating poorer renal function and metabolic profile than patients in the SUA normal group. CHD was the most evident cardiovascular condition in the hyperuricemia group compared with the SUA normal group (52.6% vs. 38.7%, p Z 0.004). Treatment with digoxin, diuretics, and angiotensin-converting enzyme inhibitors was more prevalent in the hyperuricemia group (all p values < 0.05). Interestingly, results showed that percentage of NYHA class III/IV in the hyperuricemia group was significantly higher than that in the SUA normal group (24.4% vs. 9.3%, p < 0.001), indicating poorer heart function in the hyperuricemia group. Consistently, BNP level in the hyperuricemia group was approximately 1.5 times higher than that in the SUA normal group (p < 0.001). Echocardiographic data showed that patients in the hyperuricemia group were characterized by higher LAD, LVEDD, IVST, PWT, LVMI, and LVEF (all p values < 0.05).
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With Pearson’s correlation tests, SUA was found to significantly correlate with log[LVMI] (r Z 0.234, p < 0.001) and log[BNP] (r Z 0.191, p < 0.001) for the entire study population. Multivariate regression analysis of LVH included the following independent variables in the model: age, male sex, body mass index, the presence of CHD, the presence of hypertension, RFCA history, pacemaker placement history, hemoglobin, eGFR, SUA, blood urea, triglycerides, highdensity lipoprotein cholesterol, drug therapy with digoxin, diuretics, and angiotensin-converting enzyme inhibitor. The independent risk factors were SUA (OR: 1.178, 95% CI: 1.048e1.323, p Z 0.006), age (OR: 1.028, 95% CI: 1.001e1.056, p Z 0.041), male sex (OR: 0.321, 95% CI: 0.214e0.480, p < 0.001), the presence of CHD (OR: 1.864, 95% CI: 1.252e2.777, p Z 0.002), and diuretic therapy (OR: 1.718, 95% CI: 1.087e2.717, p Z 0.021). Subgroup analysis identified SUA as a significant risk factor associated with
Table 1 Main characteristics of study participants with and without left ventricular hypertrophy. Variables
LVH (n Z 168)
Non-LVH (n Z 409)
P value
LVMI, g/m2 Age, years Male sex, n (%) Body mass index, Kg/m2 NYHA class III/IV, n (%) Medical history Paroxysmal AF, n (%) Duration of AF, years Pacemaker placement, n (%) RFCA, n (%) Hypertension, n (%) Coronary heart disease, n (%) Diabetes mellitus, n (%) Dyslipidemia, n (%) Smoking habits Never/Former/Current (n, %) Alcoholic habits Never/Former/Current (n, %) Laboratory data WBC, x103/mL Hemoglobin, g/L BNP, pg/mL eGFR, mL/min/1.73 m2 Serum uric acid, mg/dL Serum creatinine, mg/dL Blood urea, mg/dL Blood glucose, mg/dL Triglycerides, mg/dL Total cholesterol, mg/dL Echocardiographic data LAD, mm LVEDD, mm IVST, mm PWT, mm RWT LVEF, %
119 (106e132) 76 (71e81) 75 (44.6) 25.2 4.0 39 (23.2)
85 (74e95) 68 (74e80) 282 (68.9) 25.0 3.8 35 (8.6)
<0.001*** 0.004** <0.001*** 0.515 <0.001***
107 (64.1) 3.0 (0.3e9.8) 15 (8.9) 3 (1.8) 133 (79.2) 89 (53.0) 51 (30.4) 72 (42.9)
250 (61.1) 3.5 (0.45e10.0) 20 (4.9) 26 (6.4) 300 (73.3) 153 (37.4) 134 (32.8) 160 (39.1)
0.509 0.502 0.065 0.022* 0.142 0.001** 0.574 0.406
115/35/18 (68/21/11)
270/82/57 (66/20/14)
0.579
139/11/18 (83/7/11)
323/34/52 (79/8/13)
0.583
5.63 (4.80e6.90) 131.3 16.8 326 (194e575) 67.9 (57.0e82.2) 6.10 1.87 1.04 (0.86e1.18) 38.5 (32.5e48.0) 93.6 (82.8e111.6) 105.3 (70.8e134.5) 151.6 37.9
5.85 (4.80e7.12) 135.2 17.3 246 (131e418) 73.0 (61.3e86.5) 5.71 1.57 1.00 (0.89e1.18) 37.9 (30.7e44.5) 97.2 (84.6e118.8) 102.7 (73.5e137.2) 154.7 41.0
0.284 0.013* <0.001*** 0.003** 0.018* 0.720 0.063 0.244 0.795 0.379
43 (40e47) 50 (47e55) 11 (10e12) 10 (10e11) 0.416 0.090 60 (53e69)
41 (37e45) 46 (42e49) 10 (9e11) 9 (9e10) 0.418 0.074 65 (59e71)
<0.001*** <0.001*** <0.001*** <0.001*** 0.798 <0.001***
LVMI, left ventricular mass index; AF, atrial fibrillation; RFCA, radiofrequency catheter ablation; WBC, white blood cells; eGFR, estimated glomerular filtration rate; BNP, B-type natriuretic peptide; LAD, left atrial diameter; LVEDD, left ventricular end-diastolic dimension; IVST, interventricular septal thickness; PWT, posterior wall thickness; RWT, relative wall thickness; LVEF, left ventricular ejection fraction. *: p < 0.05; **: p < 0.01; ***: p < 0.001.
Please cite this article in press as: Liang WY, et al., Serum uric acid level and left ventricular hypertrophy in elderly male patients with nonvalvular atrial fibrillation, Nutrition, Metabolism & Cardiovascular Diseases (2016), http://dx.doi.org/10.1016/j.numecd.2016.03.011
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W.Y. Liang et al.
LVH (OR: 1.213, 95% CI: 1.017e1.446, p Z 0.031) in male patients only. Discussion The results of this study suggest that this population of hyperuricemia patients showed poorer renal function, heart function, and metabolic profiles than the control group. SUA was independently associated with LVH in elderly patients with nonvalvular AF, particularly in men. The relationship between SUA and LVH has been shown in hypertensive patients, chronic kidney disease patients,
and the general population [13e15]. To the best of the authors’ knowledge, this is the first study of its kind to investigate the relationship between SUA and LVH in nonvalvular AF patients. The results suggest a malespecific association between SUA and LVH. The sexrelated differences identified in this study may reflect different sensitivities to metabolic processes of uric acid [16]. Previous population-based studies reported that SUA was associated with metabolic syndrome components [17,18]. In this study, the hyperuricemia group also exhibited an increased BMI, paralleling higher triglyceride
Table 2 Main characteristics of study participants with and without hyperuricemia. Variables
Hyperuricemia (n Z 135)
SUA normal (n Z 442)
P value
SUA, mg/dL Age, years Male sex, n (%) Body mass index, kg/m2 NYHA class III/IV, n (%) Medical history Paroxysmal AF, n (%) Duration of AF, years Hypertension, n (%) Coronary heart disease, n (%) Diabetes mellitus, n (%) Dyslipidemia, n (%) Smoking habits Never/Former/Current (n, %) Alcoholic habits Never/Former/Current (n, %) Laboratory data WBC, 103/mL Hemoglobin, g/L BNP, pg/mL eGFR, mL/min/1.73 m2 Serum creatinine, mg/dL Blood urea, mg/dL Blood glucose, mg/dL Triglycerides, mg/dL Total cholesterol, mg/dL HDL-C, mg/dL LDL-C, mg/dL Echocardiographic data LAD, mm LVEDD, mm IVST, mm PWT, mm LVMI, g/m2 RWT LVEF, % Drug therapy Digoxin, n (%) Beta-blockers, n (%) Diuretics, n (%) ACEI, n (%) ARB, n (%) CCB, n (%)
8.08 1.08 76 (69e82) 93 (68.9) 26.1 4.2 33 (24.4)
5.14 1.12 75 (69e80) 264 (59.7) 24.7 3.7 41 (9.3)
<0.001*** 0.071 0.055 0.001** <0.001***
75 (55.6) 3.0 (0.4e10.0) 105 (77.8) 71 (52.6) 42 (31.1) 60 (44.4)
282 (63.9) 3.0 (0.3e10.0) 328 (74.2) 171 (38.7) 143 (32.4) 172 (38.9)
0.079 0.816 0.402 0.004** 0.787 0.251
87/30/18 (65/22/14)
298/87/57 (67/20/13)
0.786
99/15/21 (73/11/16)
363/30/49 (82/7/11)
0.075
6.00 (5.14e7.24) 133.8 19.3 349.0 (197.0e672.0) 59.6 (51.2e73.5) 1.16 (1.02e1.32) 45.0 (37.9e54.7) 95.4 (82.8e115.2) 116.0 (82.3e168.2) 154.7 39.4 35.2 (30.9e41.8) 87.4 (73.5e105.6)
5.64 (4.76e7.10) 134.1 16.6 247.8 (134.0e429.0) 74.8 (63.0e87.1) 0.98 (0.85e1.12) 36.7 (30.1e42.0) 95.4 (82.8e118.8) 100.0 (69.0e129.2) 153.5 40.2 40.2 (34.4e48.0) 89.3 (69.6e110.2)
0.061 0.846 <0.001*** <0.001*** <0.001*** <0.001*** 0.969 <0.001*** 0.746 <0.001*** 0.726
43 (40e48) 49 (45e53) 10 (10e11) 10 (9e11) 100 (85e116) 0.414 0.086 60 (53e67)
41 (37e45) 47 (43e50) 10 (9e11) 10 (9e10) 92 (78e106) 0.418 0.077 65 (59e71)
<0.001*** <0.001*** 0.011* 0.004** <0.001*** 0.148 <0.001***
17 83 47 32 46 45
30 (6.8) 248 (56.1) 75 (17.0) 49 (11.1) 127 (28.7) 143 (32.4)
0.031* 0.269 <0.001*** <0.001*** 0.236 0.832
(12.6) (61.5) (34.8) (23.7) (34.1) (33.3)
SUA, serum uric acid; AF, atrial fibrillation; WBC, white blood cells; eGFR, estimated glomerular filtration rate; BNP, B-type natriuretic peptide; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; LAD, left atrial diameter; LVEDD, left ventricular enddiastolic dimension; IVST, interventricular septal thickness; PWT, posterior wall thickness; LVMI, left ventricular mass index; RWT, relative wall thickness; LVEF, left ventricular ejection fraction; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor-blocking agent; CCB, calcium channel blocker. *: p < 0.05; **: p < 0.01; ***: p < 0.001.
Please cite this article in press as: Liang WY, et al., Serum uric acid level and left ventricular hypertrophy in elderly male patients with nonvalvular atrial fibrillation, Nutrition, Metabolism & Cardiovascular Diseases (2016), http://dx.doi.org/10.1016/j.numecd.2016.03.011
Serum uric acid level and left ventricular hypertrophy in elderly male patients
and lower high-density lipoprotein cholesterol levels. In a population-based prospective study, adjusting for age, sex, blood pressure, history of hypertension, insulin resistance, central adiposity, and eGFR confirmed that incident metabolic syndrome was associated with a higher baseline SUA. However, the association disappeared when body composition assessed by fat-free mass was taken into account [19]. The role of SUA in cardiovascular disease was largely ignored until the mid-1950s and early 1960s, when it was rediscovered. The mean SUA levels in humans increased gradually from <3.5 mg/dL (210 mmol/L) in the 1920s to 6.0e6.5 mg/dL (360e390 mmol/L) in the 1970s [20]. Elevated SUA is associated with fructose or purine-rich food intake, alcohol intake, diabetes, obesity, metabolic syndrome, renal failure, drug therapy such as diuretics, and genetic factors. Experimental studies have reported that elevated SUA induces inflammation and oxidation stress and activates the renineangiotensinealdosterone system, which may result in cardiac hypertrophy and interstitial fibrosis [4e10]. A rat model of hyperuricemia has been reported to develop all the hemodynamic findings observed in essential hypertension, including prominent vasoconstriction of the afferent arteriole, with a reduction in renal blood flow and a relative preservation of the GFR [21,22]. Cardiac hypertrophy compensates the pressure overload seen in hypertension [23]. In this study, a medical history of hypertension was more prevalent in patients with hyperuricemia, but this finding was not statistically significant. The influence of additional hormonal, hemodynamic, and metabolic factors also predisposes these patients to develop structural and functional abnormalities of the heart. Further, hypertrophic myocardium with anoxia leads to an increase in the degradation of adenosine triphosphatase, which increases the production of xanthine and uric acid. Thus, it is a difficult task to distinguish the causeeeffect relationship between uric acid and cardiac hypertrophy. The results of this study suggest that further attention be given to the therapeutic control of high SUA levels in AF patients. However, there was a U-shaped association between uric acid levels and cardiovascular mortality observed [24]. Thus, we recommend using appropriate intervention strategies, rather than assuming that “lower is better.” This study had some limitations. First, the sample size was relatively small. Second, the observational study design allowed for only determining an association and not causality. Third, paroxysmal, persistent, and permanent AF patients are quite heterogeneous in terms of symptoms and arrhythmia burden, yet these patients were not analyzed separately in this study. Finally, the mechanisms behind the results obtained require further investigation.
Disclosures The authors have no conflict of interest to disclose.
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Please cite this article in press as: Liang WY, et al., Serum uric acid level and left ventricular hypertrophy in elderly male patients with nonvalvular atrial fibrillation, Nutrition, Metabolism & Cardiovascular Diseases (2016), http://dx.doi.org/10.1016/j.numecd.2016.03.011