Background-Biological mechanisms underlying statin and angiotensin II type 1 receptor blocker therapies differ.Therefore, we compared vascular and metabolic responses to these therapies either alone or in combination in hypercholesterolemic, hypertensive patients. Methods and Results-This was a randomized, double-blind, placebo-controlled crossover trial with 3 treatment arms (each 2 months) and 2 washout periods (each 2 months). Forty-seven hypertensive, hypercholesterolemic patients were given simvastatin 20 mg and placebo, simvastatin 20 mg and losartan 100 mg, or losartan 100 mg and placebo daily during each 2-month treatment period. Losartan alone or combined therapy significantly reduced blood pressure compared with simvastatin alone. Compared with losartan alone, simvastatin alone or combined therapy significantly changed lipoproteins. All 3 treatment arms significantly improved flow-mediated dilator response to hyperemia and decreased plasma malondialdehyde and monocyte chemoattractant protein-1 levels relative to baseline measurements. However, these parameters were changed to a greater extent with combined therapy compared with simvastatin or losartan alone (both PϽ0.001 and Pϭ0.030 for monocyte chemoattractant protein-1 by ANOVA). Combined therapy or losartan alone significantly increased plasma adiponectin levels and insulin sensitivity (determined by QUICKI) relative to baseline measurements. These changes were significantly greater than in the group treated with simvastatin alone (PϽ0.001 for adiponectin, Pϭ0.029 for QUICKI by ANOVA). Conclusions-Simvastatin combined with losartan improves endothelial function and reduces inflammatory markers to a greater extent than monotherapy with either drug in hypercholesterolemic, hypertensive patients.

Combination therapy is safe and has beneficial additive effects on endothelial function in patients with combined hyperlipidemia.

Despite recent advances in understanding of the pathobiology and targeted treatments of pulmonary arterial hypertension (PAH), epidemiologic data from large populations have been limited to western countries. The aim of the Korean Registry of Pulmonary Arterial Hypertension (KORPAH) was to examine the epidemiology and prognosis of Korean patients with PAH. KORPAH was designed as a nationwide, multicenter, prospective data collection using an internet webserver from September 2008 to December 2011. A total of 625 patients were enrolled. The patients' mean age was 47.6 ± 15.7 yr, and 503 (80.5%) were women. The diagnostic methods included right heart catheterization (n = 249, 39.8%) and Doppler echocardiography (n = 376, 60.2%). The etiologies, in order of frequency, were connective tissue disease (CTD), congenital heart disease, and idiopathic PAH (IPAH) (49.8%, 25.4%, and 23.2%, respectively). Patients with WHO functional class III or IV at diagnosis were 43.4%. In total, 380 (60.8%) patients received a single PAH-specific treatment at the time of enrollment, but only 72 (18.9%) patients received combination therapy. Incident cases during the registry represented 297 patients; therefore, the incidence rate of PAH was 1.9 patients/yr/million people. The 1st-, 2nd-, and 3rd-yr estimated survival rates were 90.8%, 87.8%, and 84.4%, respectively. Although Korean PAH patients exhibited similar age, gender, and survival rate compared with western registries, they showed relatively more CTD-PAH in the etiology and also systemic lupus erythematosus among CTD-PAH. The data suggest that earlier diagnosis and more specialized therapies should be needed to improve the survival of PAH patients.Graphical Abstract

Author's summary The Korean Society of Cardiology has recently published the Korea Heart Disease Fact Sheet 2020 to provide overview of the cardiovascular disease (CVD) burden and its temporal changes. CVD mortality, hospitalization, and risk factor distributions were analyzed from nationwide databases. Over the last decade, CVD mortality and hospitalization have increased, while their age-standardized rates have declined. In addition, a considerable proportion of adults had multiple risk factors, which markedly increased with older age. Thus, concerted efforts should be continued to address the rising burden of CVD in Korea.

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Aim To evaluate the effectiveness of empagliflozin in clinical practice in East Asia in the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) East Asia study. Materials and methods Data were obtained from the Medical Data Vision database (Japan), National Health Insurance Service database (South Korea) and National Health Insurance database (Taiwan). Patients aged ≥ 18 years with type 2 diabetes initiating empagliflozin or a dipeptidyl peptidase‐4 (DPP‐4) inhibitor were 1:1 propensity score (PS) matched into sequentially built cohorts of new users naïve to both drug classes. This design reduces confounding due to switching treatments, time lag and immortal time biases. Outcomes included hospitalization for heart failure (HHF), end‐stage renal disease (ESRD) and all‐cause mortality. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional models, controlling for > 130 baseline characteristics in each data source and pooled by random‐effects meta‐analysis. Results Overall, 28 712 pairs of PS‐matched patients were identified with mean follow‐up of 5.7‐6.8 months. Compared with DPP‐4 inhibitors, the risk of HHF was reduced by 18% and all‐cause mortality was reduced by 36% with empagliflozin (HR 0.82; 95% CI 0.71‐0.94, and HR 0.64; 95% CI 0.50‐0.81, respectively). Reductions were consistent across countries, and in patients with and without baseline cardiovascular disease. ESRD was also significantly reduced with empagliflozin versus DPP‐4 inhibitors (HR 0.37; 95% CI 0.24‐0.58). Conclusions Empagliflozin treatment was associated with reduced risk for HHF, all‐cause mortality and ESRD compared with DPP‐4 inhibitors in routine clinical practice in Japan, South Korea and Taiwan.

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Objective-The effects of hormone replacement therapy (HRT) can affect many aspects relevant to cardiovascular disease, including vasomotor function, inflammation, and hemostasis. Recent studies have demonstrated that current doses of HRT exert a mixture of both protective and adverse effects. In the current study, we compared the effects of lower doses of HRT (L-HRT) and conventional doses of HRT (C-HRT) on a variety of relevant cardiovascular parameters. Methods and Results-This randomized, double-blind, crossover study included 57 women who received micronized progesterone 100 mg with either conjugated equine estrogen 0.625 mg (C-HRT) or 0.3 mg (L-HRT) daily for 2 months. L-HRT showed comparable effects to C-HRT on high-density lipoprotein cholesterol and triglyceride levels, but not on low-density lipoprotein cholesterol levels. C-HRT and L-HRT significantly improved the percent flow-mediated dilator response to hyperemia from baseline values (both PϽ0.001) by a similar degree (Pϭ0.719). C-HRT significantly increased high-sensitivity C-reactive protein ( Key Words: hormone replacement therapy Ⅲ lower doses Ⅲ endothelial function Ⅲ inflammation Ⅲ hemostasis Ⅲ menopause P rospective cohort surveys suggest that hormone replacement therapy (HRT) decreases the risk of coronary artery disease in relatively young and healthy postmenopausal women. 1,2 In contrast, 2 recent randomized studies, the Heart and Estrogen/progestin Replacement Study (HERS) 3 and the Women's Health Initiative (WHI), 4 reported that HRT did not reduce the risk of cardiovascular events and further demonstrated some trends toward an increased risk of cardiovascular events. The increased risk of coronary heart disease was surprising given that low-density lipoprotein (LDL) cholesterol levels decreased and that high-density lipoprotein (HDL) cholesterol levels increased. The reasons may result from the effects of HRT on C-reactive protein (CRP) levels and thromboembolism risk through activating coagulation pathways evidenced by decreased antithrombin III and increased prothrombin fragment 1ϩ2 (F1ϩ2). 5,6 Activation of coagulation pathways has been detected dose-dependently in postmenopausal women treated with conjugated equine estrogen (CEE) 0.625 and 1.25 mg. 7 In this regard, we reported that conventional dosages of CEE 0.625 mg increased tissue factor activity and F1ϩ2, indicator of coagulation activation, 8,9 and observational studies demonstrated that the risk for thromboembolism increases dosedependently in postmenopausal women. 2,10,11 The apparent protective effect of CEE in the Nurses' Health Study was noted only at the 0.3 mg and 0.625 mg doses; 1.25 mg and higher doses were not cardioprotective. 11 It has been reported that Ϸ59% of women discontinue HRT within 2 years, and the use of lower doses of HRT has been proposed to improve long-term compliance with HRT. 12 Recently, lower doses (CEE 0.3 mg) of HRT (L-HRT) demonstrated comparable effects to conventional doses (CEE 0.625 mg) of HRT (C-HRT) on menopausal symptoms, 13,14 endometria...