Exploring Sirtuins: New Frontiers in Managing Heart Failure with Preserved Ejection Fraction.

With increasing research, the sirtuin (SIRT) protein family has become increasingly understood. Studies have demonstrated that SIRTs can aid in metabolism and affect various physiological processes, such as atherosclerosis, heart failure (HF), hypertension, type 2 diabetes, and other related disorders. Although the pathogenesis of HF with preserved ejection fraction (HFpEF) has not yet been clarified, SIRTs have a role in its development. Therefore, SIRTs may offer a fresh approach to the diagnosis, treatment, and prevention of HFpEF as a novel therapeutic intervention target.

Establishment of an Individual-Specific Nomogram for Predicting the Risk of Left Ventricular Hypertrophy in Chinese Postmenopausal Hypertensive Women.

Background and Objectives: The physiological phenomenon peculiar to women, namely menopause, makes the occurrence of left ventricular hypertrophy (LVH) in postmenopausal hypertensive women more characteristic. Less is known about the risk of developing LVH in Chinese postmenopausal hypertensive women. Thus, the present study was intended to design a nomogram for predicting the risk of developing LVH in Chinese postmenopausal hypertensive women. Materials and Methods: Postmenopausal hypertensive women aged between 49 and 68 years were divided into either the training set (n = 550) or the validation set (n = 284) in a 2:1 ratio. Patients in the validation set were followed up for one year. A stepwise multivariable logistic regression model was used to assess the predictors of LVH in postmenopausal women with hypertension. The best-fit nomogram was executed using R software. The calibration and decision curve were employed to verify the predictive accuracy of the nomogram. The results were evaluated in the validation set. Results: Menopause age (OR = 0.929, 95% CI 0.866-0.998, p = 0.044), BMI (OR = 1.067, 95% CI 1.019-1.116, p = 0.005), morning systolic blood pressure (SBP: OR = 1.050, 95% CI 1.032-1.069, p = 0.000), morning diastolic BP (DBP OR = 1.055, 95% CI 1.028-1.083, p = 0.003), angiotensin II receptor blocker (ARB) utilization rate (OR = 0.219, 95% CI 0.131-0.365, p = 0.000), LDL-C (OR = 1.460, 95% CI 1.090-1.954, p = 0.011) and cardio-ankle vascular index (CAVI) (OR = 1.415, 95% CI 1.139-1.757, p = 0.028) were associated with LVH in postmenopausal hypertension patients. The nomogram model was then developed using these variables. The internal validation trial showed that the nomogram model described herein had good performance in discriminating a C-index of 0.881 (95% CI: 0.837-0.924) and high quality of calibration plots. External validation of LVH-predictive nomogram results showed that the area under the ROC curve was 0.903 (95%CI 0.900-0.907). Conclusions: Our results indicate that the risk prediction nomogram model based on menopausal age, BMI, morning SBP, morning DBP, ARB utilization rate, LDL-C and CAVI has good accuracy and may provide useful references for the medical staff in the intuitive and individualized risk assessment in clinical practice.

mTOR inhibitor improves testosterone-induced myocardial hypertrophy in hypertensive rats.

Compelling evidence has described that the incidence of hypertension and left ventricular hypertrophy (LVH) in postmenopausal women is significantly increased worldwide. Our team's previous research identified that androgen was an underlying factor contributing to increased blood pressure and LVH in postmenopausal women. However, little is known about how androgens affect LVH in postmenopausal hypertensive women. The purpose of this study was to evaluate the role of mammalian rapamycin receptor (mTOR) signaling pathway in myocardial hypertrophy in androgen-induced postmenopausal hypertension and whether mTOR inhibitors can protect the myocardium from androgen-induced interference to prevent and treat cardiac hypertrophy. For that, ovariectomized (OVX) spontaneously hypertensive rats (SHR) aged 12 weeks were used to study the effects of testosterone (T 2.85 mg/kg/weekly i.m.) on blood pressure and myocardial tissue. On the basis of antihypertensive therapy (chlorthalidone 8 mg/kg/day ig), the improvement of blood pressure and myocardial hypertrophy in rats treated with different dose gradients of rapamycin (0.8 mg/kg/day vs 1.5 mg/kg/day vs 2 mg/kg/day i.p.) in OVX + estrogen (E 9.6 mg/kg/day, ig) + testosterone group was further evaluated. After testosterone intervention, the OVX female rats exhibited significant increments in the heart weight/tibial length (TL), area of cardiomyocytes and the mRNA expressions of ANP, ß-myosin heavy chain and matrix metalloproteinase 9 accompanied by a significant reduction in the uterine weight/TL and tissue inhibitor of metalloproteinase 1. mTOR, ribosomal protein S6 kinase (S6K1), 4E-binding protein 1 (4EBP1) and eukaryotic translation initiation factor 4E in myocardial tissue of OVX + estrogen + testosterone group were expressed at higher levels than those of the other four groups. On the other hand, rapamycin abolished the effects of testosterone-induced cardiac hypertrophy, decreased the systolic and diastolic blood pressure of SHR, and inhibited the activation of mTOR/S6K1/4EBP1 signaling pathway in a concentration-dependent manner. Collectively, these data suggest that the mTOR/S6K1/4EBP1 pathway is an important therapeutic target for the prevention of LVH in postmenopausal hypertensive female rats with high testosterone levels. Our findings also support the standpoint that the mTOR inhibitor, rapamycin, can eliminate testosterone-induced cardiomyocyte hypertrophy.