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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...

Aim: Fibroblast growth factor 23 (FGF23) and -Klotho have been recently identified to play a crucial role in calcium/phosphate metabolism. We herein investigated the possible relation between serum FGF23/ -Klotho levels and coronary artery calcification (CAC) and aortic valve calcification (AVC). Methods: Among subjects with diagnosed or suspected coronary artery disease (CAD), CAC and AVC were estimated via the Agatston score of 320-detector computed tomography images, and serum FGF23 and -Klotho levels were measured. Results: In total, 157 subjects were enrolled (75 women and 82 men). We performed logistic regression using CAC as a dependent variable; the highest FGF23 tertile ( 52.5 pg/mL) was significantly positively associated with CAC with an odds ratio of 6.61 versus the lowest FGF23 tertile ( 35.3 pg/mL) in women after the adjustment for potential confounding variables including age, renal function, hypertension, statin use, diuretic use, and calcium/phosphate metabolism related factors. In addition, the highest -Klotho tertile ( 561 pg/mL) was significantly associated with AVC with an odds ratio of 6.31 versus the lowest -Klotho tertile ( 306 pg/mL) in men after adjusting for the same variables. On the other hand, the association between FGF23 and CAC/AVC in men or that between -Klotho and CAC/AVC in women was nonsignificant. Conclusion: Among subjects with diagnosed or suspected CAD, serum FGF23 was positively associated with CAC in women and serum -Klotho was positively associated with AVC in men independent of the confounding variables, including the renal function and calcium/phosphate metabolismrelated factors. J Atheroscler Thromb, 2015; 22: 1338-1346.

Besides regulating calcium-phosphate metabolism, fibroblast growth factor-23 (FGF23) and Klotho have been proposed to have other roles in heart and vasculature. For example, FGF23 has been associated with cardiac hypertrophy and reduced left ventricular ejection fraction among patients with chronic kidney disease and cardiovascular disorders. The purpose of the study was to investigate whether serum FGF23 and α-Klotho concentrations are associated with cardiac diastolic dysfunction and related parameters among cardiac patients with preserved left ventricular ejection fraction. The current study enrolled 269 patients (69 women, 200 men) who were admitted to our cardiology department between October 2012 and January 2014 and had a left ventricular ejection fraction of >50%. Cardiac diastolic function was assessed by blood flow and tissue Doppler velocities, plasma B-type natriuretic peptide (BNP) concentration, and cardiac hypertrophy. After adjusting for sex, and age, logistic regression analysis showed that log(α-Klotho), but not log(FGF23), was significantly associated with diastolic dysfunction. After further adjustment for renal function, blood hemoglobin, and serum albumin levels, the negative association between log(α-Klotho) and diastolic dysfunction retained statistical significance with an odds ratio of 0.50 (95% confidence interval 0.31-0.81, P = 0.005, per 1 standard deviation). Among patients with preserved LVEF, serum α-Klotho concentrations were negatively associated with diastolic dysfunction. Whether modulation of serum levels α-Klotho will ameliorate cardiac diastolic function among patients with this disorder awaits further investigation.