Achieved dose and treatment discontinuation of candesartan in men and women with chronic heart failure: data from CHARM.

AIMS: Angiotensin receptor blockers have been shown to reduce heart failure hospitalization and cardiovascular mortality in men and women with heart failure with reduced ejection fraction (HFrEF). It is unknown whether there are differences between men and women in achieved dose and treatment discontinuation due to adverse events of candesartan. METHODS AND RESULTS: We conducted a post hoc analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme. A total of 3172 men and 1106 women with HFrEF [left ventricular ejection fraction (LVEF) ≤ 40%] in New York Heart Association class II-IV were randomized to candesartan or placebo. Every 2 weeks, patients were up-titrated from 4 or 8, to16, to 32 mg once daily, unless a higher dose was contraindicated or not tolerated. Women were older (66 vs. 64 years), had a higher LVEF (29.9% vs. 28.6%), and had more hypertension (54% vs. 47%) than men. The mean achieved dose of candesartan was 21.5 ± 12.6 mg in men and 20.7 ± 12.9 mg in women (P = 0.19). In both the candesartan and placebo groups, cardiovascular death and heart failure hospitalizations were higher in men and women who achieved lower dose levels. Event rates for achieved dose levels of 0, 4 or 8, 16, and 32 mg candesartan were 20.8, 17.2, 14.0, and 10.1 per 100 person-years in men, respectively, and 23.6, 13.7, 14.0, and 9.1 per 100 person-years in women, respectively. In each of the achieved dose levels, there was no sex difference in the proportion of patients with an event, neither in the candesartan group nor in the placebo group (P-value for all > 0.05). There was no significant interaction between sex and treatment-related discontinuation for hypotension (P = 0.520), an increase in creatinine (P = 0.102), and hyperkalaemia (P = 0.905). CONCLUSIONS: In a randomized clinical trial in patients with HFrEF, men and women achieved similar doses of candesartan. Primary event rates and treatment-related discontinuation due to adverse events were also similar between men and women.

Sex-related similarities and differences in responses to heart failure therapies.

Although sex-related differences in the epidemiology, risk factors, clinical characteristics and outcomes of heart failure are well known, investigations in the past decade have shed light on an often overlooked aspect of heart failure: the influence of sex on treatment response. Sex-related differences in anatomy, physiology, pharmacokinetics, pharmacodynamics and psychosocial factors might influence the response to pharmacological agents, device therapy and cardiac rehabilitation in patients with heart failure. In this Review, we discuss the similarities between men and women in their response to heart failure therapies, as well as the sex-related differences in treatment benefits, dose-response relationships, and tolerability and safety of guideline-directed medical therapy, device therapy and cardiac rehabilitation. We provide insights into the unique challenges faced by men and women with heart failure, highlight potential avenues for tailored therapeutic approaches and call for sex-specific evaluation of treatment efficacy and safety in future research.

Higher triglyceride to high-density lipoprotein cholesterol ratio increases cardiovascular risk: 10-year prospective study in a cohort of Chinese adults.

AIMS/INTRODUCTION: A higher ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) is considered as the independent risk index of cardiovascular (CV) events. However, cohort studies regarding this correlation are rarely reported, especially in the Chinese population. The aim of present study was to explore the relationship of the TG/HDL-C ratio with CV risks among Chinese adults during 10-year follow-up period. MATERIALS AND METHODS: We carried out a prospective study using data obtained from 96,542 individuals in Kailuan, who were grouped through the median value (0.8533) of the TG/HDL-C ratio. Adverse outcomes mainly referred to major CV events. We used the person-years incidence and cumulative incidence to predict the morbidity. The risk of CV events was estimated through Cox proportional hazard models. RESULTS: The mean age of the cohort was 51.5 ± 12.6 years, and 79.6% of participants were men. During a median follow-up period of 9.75 years, 5,422 major CV events occurred, including 1,312 myocardial infarction cases and 4,228 stroke cases. The cumulative incidence of myocardial infarction, stroke and total CV events was 1.36% (range 1.29-1.43%), 4.38% (range 4.25-4.51%) and 5.62% (range 5.47-5.76%), respectively. Compared with low the TG/HDL-C ratio (≤0.8533) group, the high TG/HDL-C ratio (>0.8533) group had higher morbidity of CV events. The hazard ratio of total CV events, stroke and myocardial infarction was 1.19 (95% CI 1.12-1.26), 1.11 (95% CI 1.03-1.18) and 1.50 (95% CI 1.33-1.70), respectively. Furthermore, the TG/HDL-C ratio and major CV events had a line-shaped relationship with each other. CONCLUSIONS: Among the Chinese population, a higher TG/HDL-C ratio is correlated with an increased risk of major CV events.

Triglyceride to high-density lipoprotein cholesterol ratio is associated with incident diabetes in men: A retrospective study of Chinese individuals.

AIMS/INTRODUCTION: Dyslipidemia is commonly present in type 2 diabetes mellitus patients. Recently, the triglyceride : high-density lipoprotein cholesterol (TG/HDL-C) ratio, a novel parameter of lipid abnormality, has been seen as an independent predictor for incident diabetes. However, the correlation of the TG/HDL-C ratio with incident diabetes in the Chinese population and how this relationship is impacted by sex have been rarely studied. In the present study, the correlation of the TG/HDL-C ratio with incident diabetes is investigated between different sexes of the Chinese population. MATERIALS AND METHODS: A total of 116,855 participants who were free of diabetes at baseline were enrolled in the study. The participants were grouped by the median value (0.82) of the TG/HDL-C ratio. Then, participants were further analyzed according to their sex. Cumulative incidence and person-years incidence were used to express the incidence rate. The predictive value of the TG/HDL-C ratio for incident diabetes was probed by the Cox regression proportional hazards model. RESULTS: The mean age of the participants was 44.1 ± 12.9 years, and 53% of participants (n = 62,868) were the men. A total of 2,685 incident diabetes cases occurred during the 3.1 years of the median follow-up period. The cumulative incidence in total incident diabetes patients, men and women was 2.30% (2.21-2.38%), 3.01% (2.87-3.14%) and 1.47% (1.37-1.57%), respectively. After the adjustment of multivariate factors, the multivariate Cox regression analysis results showed that a higher TG/HDL-C ratio was the independent predictive factor of incident diabetes in men (hazard ratio 1.30, 95% confidence interval 1.03-1.64), compared with women (hazard ratio 0.85, 95% confidence interval 0.53-1.38). CONCLUSIONS: Among the Chinese population, the TG/HDL-C ratio is an independent predictor for incident diabetes in male patients.

Correlation of triglyceride to high-density lipoprotein cholesterol ratio with nonalcoholic fatty liver disease among the non-obese Chinese population with normal blood lipid levels: a retrospective cohort research.

BACKGROUND: Although nonalcoholic fatty liver disease (NAFLD) is commonly seen in metabolic abnormalities patients, NAFLD is also occurred in the non-obese individuals. The ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) is considered as a predictive factor of NAFLD. However, it is still difficult to confirm the correlation of TG/HDL-C ratio with NAFLD among non-obese Chinese people with normal blood lipid levels. In our study, it is aimed to analyze the correlation of TG/HDL-C ratio with NAFLD among non-obese Chinese population without dyslipidemia. METHODS: In the retrospective cohort study, 9838 non-obese subjects who were free of NAFLD were enrolled. NAFLD was diagnosed by ultrasonography. RESULTS: During the median follow-up period of 2.9 years, cumulative incidence of NAFLD in non-obesity individuals was 8.69% among the overall population; meanwhile, its incidence was gradually enhanced across the quartiles of TG/HDL-C ratio (0.61, 1.28, 2.55 and 4.25% respectively). Then the multivariate factors were adjusted. The multivariate cox regression analysis results showed that the hazard ratio of NAFLD in higher quartiles (Q2-Q4) was 2.10 (1.33-3.32), 3.11 (2.03-4.75) and 3.40 (2.24-5.17), respectively. Besides, the area under receiver operator characteristic curve (AUC) of TG/HDL-C ratio in the male was 0.70 (0.68-0.72) and 0.72 (0.70-0.75) in the female. The final values were dramatically larger than the other lipid index. CONCLUSION: There is an independent relationship between TG/HDL-C and NAFLD among non-obese Chinese population without dyslipidemia, and TG/HDL-C may be used as a better predictor for NAFLD.

MiR-15b-5p is Involved in Doxorubicin-Induced Cardiotoxicity via Inhibiting Bmpr1a Signal in H9c2 Cardiomyocyte.

The wide use of anthracyclines represented by doxorubicin (DOX) has benefited cancer patients, yet the clinical application is limited due to its cardiotoxicity. Although numerous evidences have supported a role of microRNAs (miRNAs) in DOX-induced myocardial damage, the exact etiology and pathogenesis remain largely obscure. In this study, we focused on the role of miR-15b-5p in DOX-induced cardiotoxicity. We employed a public miRNA and gene microarray to screen differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs) in rat cardiomyocytes, and 33 DEMs including miR-15b-5p and 237 DEGs including Bmpr1a and Gata4 were identified. The Gene ontology (GO) and pathway enrichment analysis of 237 DEGs indicated that the DEGs were mainly enriched in heart development and ALK pathway in cardiomyocyte which included the main receptor Bmpr1a and transcription factor Gata4. The up-regulated miR-15b-5p and down-regulated Bmpr1a and Gata4 mRNA expressions were further validated in H9c2 cardiomyocytes exposed to DOX. Moreover, the results showed overexpression of miR-15b-5p or inhibition of Bmpr1a may enhance the DOX-induced apoptosis, oxidative stress and mitochondria damage in H9c2 cardiomyocytes. The Bmpr1a was suggested as a potential target of miR-15b-5p by bioinformatics prediction. We further verified the negatively regulatory effect of miR-15b-5p on Bmpr1a signaling. Moreover, we also confirmed that overexpression of miR-15b-5p may exacerbate the DOX-induced apoptosis of H9c2 cardiomyocytes by affecting the protein expression ratio of Bcl-2/Bax and Akt activation, while this pro-apoptotic effect was able to be suppressed by Bmpr1a agonist. Collectively, the results suggest that miR-15b-5p is likely involved in doxorubicin-induced cardiotoxicity via inhibiting Bmpr1a signaling in H9c2 cardiomyocytes. Our study provides a novel insight for investigating DOX-induced cardiotoxicity.

Triglyceride to high density lipoprotein cholesterol ratio may serve as a useful predictor of major adverse coronary event in female revascularized ST-elevation myocardial infarction.

BACKGROUND: Elevated triglyceride to high density lipoprotein cholesterol (TG/HDL-C) ratio has been identified as a surrogate marker of insulin resistance and an independent predictor for cardiovascular events in the general population. However, the prognostic value of TG/HDL-C ratio in revascularized ST-elevation myocardial infarction(STEMI) patients remains unclear. We examined the association between TG/HDL-C ratio and clinical outcome of revascularized STEMI patients in the Chinese population. METHODS: 464 STEMI patients who underwent successful revascularization were enrolled to determine the relationship between TG/HDL-C ratio and major adverse coronary events(MACEs) with a 30-month follow-up. The Kaplan-Meier analysis and Cox regression proportional hazard model were applied to assess the prognostic value of TG/HDL-C ratio. RESULTS: TG/HDL-C ratio was found to be significantly associated with age (p = 0.017), history of diabetes(p = 0.017), heart rate(p = 0.011), TG(p < 0.001), HDL-C(p < 0.001) and Gensini score(p = 0.034). The multivariate Cox regression analysis revealed that elevated TG/HDL-C ratio was an independent prognostic factor for MACE in female patients (HR = 2.624,95%CI = 1.211-5.687,p = 0.014) but not in male patients(HR = 0.756, 95%CI = 0.484-1.179,p = NS) after adjustment with other MACE-related prognostic factors. CONCLUSION: The TG/HDL-C ratio may be independently associated with MACEs in female revascularized STEMI patients in the Chinese population.