Predictive Value of Uric Acid Regarding Cardiometabolic Disease in a Community-Dwelling Older Population in Shanghai: A Cohort Study.

Aim: This study aimed to test the predictive power of serum uric acid (UA) levels on new-onset cardiometabolic risk in the Chinese population. Methods: Older people who visited a community health center for a yearly health check (N = 5,000; men: 47%, women: 53%) were enrolled. Participants were followed for 4 years from baseline (median: 48 months), with the endpoints being development of heart failure, atrial fibrillation, diabetes, hypertension, metabolic syndrome, or kidney disease. Results: During follow-up, 342 men (7.4%) and 360 women (8.6%) developed hypertension; 98 men (2.48%) and 135 women (3.06%) developed diabetes; and 175 men (5.04%) and 214 women (4.51%) developed metabolic syndrome. Incident diabetes, hypertension, and metabolic syndrome increased with increased UA levels at baseline (P < 0.001). A multivariate Cox proportional hazards analysis revealed a significant, independent association between the baseline UA level and the onset and future hypertension and/or diabetes in both men and women. However, UA is associated with the development of metabolic syndrome in men, but not in women. Conclusion: UA is an independent predictor of new-onset diabetes and hypertension in both women and men and a predictor of new-onset metabolic syndrome only in men.

Distinct Circulating Expression Profiles of Long Noncoding RNAs in Heart Failure Patients With Ischemic and Nonischemic Dilated Cardiomyopathy.

Ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM), with distinct long-term prognosis and responses to treatment, are two major problems that lead to heart failure (HF) ultimately. In this study, we investigated the long noncoding RNA (lncRNA) and messenger RNA (mRNA) expressions in the plasma of patients with DCM and ICM and analyzed the different lncRNA profile between the two groups. The microarray analysis identified 3,222 and 1,911 significantly differentially expressed lncRNAs and mRNAs between DCM and ICM group. The most enriched upregulated functional terms included positive regulation of I-kappaB kinase/nuclear factor-kappaB signaling and regulation of cellular localization, while the top 10 downregulated genes mainly consisted of acid secretion and myosin heavy chain binding. Furthermore, the Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the differentially expressed lncRNA-coexpressed mRNAs between DCM and ICM group were significantly enriched in the natural killer cell mediated cytotoxicity and ras signaling pathway respectively. Quantitative real-time PCR confirmed 8 of 12 lncRNAs were upregulated in DCM group compared to ICM group which was consistent with the initial microarray results. The lncRNA/mRNA coexpression network indicated the possible functions of the validated lncRNAs. These findings revealed for the first time the specific expression pattern of both protein-coding RNAs and lncRNAs in plasma of HF patients due to DCM and ICM which may provide some important evidence to conveniently identify the etiology of myocardial dysfunctions and help to explore a better strategy for future HF prognosis evaluation.

Fasudil preserves lung endothelial function and reduces pulmonary vascular remodeling in a rat model of end­stage pulmonary hypertension with left heart disease.

Pulmonary hypertension (PH) due to left heart disease (LHD) is a common condition associated with significant morbidity. It contributes to the elevation of pulmonary vascular resistance and mean pulmonary pressure, eventually leading to heart failure and even mortality. The present study aimed to explore the potential efficacy of late and long­term treatment with a Rho­kinase (ROCK) signaling inhibitor, namely fasudil, in a rat model of end­stage PH­LHD. The PH­LHD model was established by supracoronary aortic banding, and the effect of fasudil treatment on the progression of PH­LHD was monitored. After 9 weeks (63 days) of supracoronary aortic banding, a significant increase in mean pulmonary pressure and RV systolic pressure was observed in the rats, associated with increased RhoA/ROCK activity in the lungs. Therapy with fasudil (30 mg/kg/day, intraperitoneal) for 4 weeks from postoperative day 35 reversed the hemodynamic disorder and prevented pulmonary vascular remodeling in rats with PH­LHD. In addition, the blockade of ROCK signaling by fasudil decreased the protein levels of endothelin­1 (ET­1) and the mRNA expression levels of endothelin A receptor and promoted the production of nitric oxide (NO) in rats with PH­LHD. Furthermore, fasudil inhibited the migration of human pulmonary microvascular endothelial cells and the proliferation of pulmonary artery smooth muscle cells induced by ET­1. Therefore, this late, long­term blockade of the ROCK pathway by fasudil may be a promising strategy to reverse hemodynamic dysfunction and impede the development of end­stage PH­LHD in patients.