A Standardized Lindera obtusiloba Extract Improves Endothelial Dysfunction and Attenuates Plaque Development in Hyperlipidemic ApoE-Knockout Mice.

Lindera obtusiloba extract (LOE), a traditional herbal medicine used to enhance blood circulation and to reduce inflammation, induced NO-mediated endothelium-dependent relaxation, and reduced the formation of reactive oxygen species (ROS). The study investigated whether LOE improves endothelial dysfunction and reduces plaque inflammation and progression by inhibiting ROS generation in a mouse model of atherosclerosis. Eight-week-old apolipoprotein E-deficient (apoE-/-) mice fed with a western diet (WD) were randomized into different groups by administering vehicle (0.5% carboxymethylcellulose (CMC)), LOE (100 mg/kg/day), or losartan (30 mg/kg/day) by gavage until the age of 28 weeks. Fourteen male C57BL/6 mice that were fed normal chow and treated with CMC were used as negative controls. Similar to losartan treatment, LOE treatment induced the concentration-dependent relaxation of aorta rings in WD-fed apoE-/- mice. LOE treatment significantly reduced the vascular ROS formation and expression of NADPH oxidase subunits, including p22phox and p47phox. Compared with WD-fed apoE-/- mice, mice exposed to chronic LOE treatment exhibited reductions in plaque inflammation-related fluorescence signals and atherosclerotic lesions. These effects were greater than those of losartan treatment. In conclusion, LOE treatment improves endothelial dysfunction and reduces plaque inflammation as well as lesion areas by reducing vascular NADPH oxidase-induced ROS generation in a mouse model of atherosclerosis.

Comparison of the Efficacy and Safety of Atorvastatin 40 mg/ω-3 Fatty Acids 4 g Fixed-dose Combination and Atorvastatin 40 mg Monotherapy in Hypertriglyceridemic Patients who Poorly Respond to Atorvastatin 40 mg Monotherapy: An 8-week, Multicenter, Randomized, Double-blind Phase III Study.

PURPOSE: Residual cardiovascular risk in patients with hypertriglyceridemia, despite optimal low-density lipoprotein cholesterol levels being achieved with intensive statin treatment, is a global health issue. The purpose of this study was to investigate the efficacy and tolerability of treatment with a combination of high-dose atorvastatin/Ω-3 fatty acid compared to atorvastatin + placebo in patients with hypertriglyceridemia who did not respond to statin treatment. METHODS: In this multicenter, randomized, double-blind, placebo-controlled study, patients who had residual hypertriglyceridemia after a 4-week run-in period of atorvastatin treatment were randomly assigned to receive UI-018 (fixed-dose combination atorvastatin/Ω-3 fatty acid 40 mg/4 g) or atorvastatin 40 mg + placebo (control). The primary efficacy end points were the percentage change from baseline in non-high density lipoprotein cholesterol (non-HDL-C) level at the end of treatment and the adverse events recorded during treatment. A secondary end point was the percentage change from baseline in triglyceride level. FINDINGS: After 8 weeks of treatment, the percentage changes from baseline in non-HDL-C (-4.4% vs +0.6%; p = 0.02) and triglycerides (-18.5% vs +0.9%; p < 0.01) were significantly greater in the UI-018 group (n = 101) than in the control group (n = 99). These changes were present in subgroups of advanced age (≥65 years), status (body mass index ≥25 kg/m2), or without diabetes. The prevalences of adverse events did not differ between the 2 treatment groups. IMPLICATIONS: In patients with residual hypertriglyceridemia despite receiving statin treatment, a combination of high-dose atorvastatin/Ω-3 fatty acid was associated with a greater reduction of triglyceride and non-HDL-C compared with atorvastatin + placebo, without significant adverse events.

Coronary artery calcium score plays an important role for cardiovascular risk stratification in the statin benefit groups of asymptomatic individuals.

BACKGROUND: The purpose of this study was to describe and analyze the relationship between statin benefit groups based on statin-intensity class of drugs and coronary artery calcium score (CACS) using multidetector computed tomography (MDCT) in an asymptomatic Korean population. METHODS: A total of 3914 asymptomatic individuals (mean age: 55 ± 10 years; male: female = 2649: 1265) who underwent MDCT for health examination between January 2009 and December 2012 were retrospectively enrolled. They were categorized into three groups based on statin-intensity class of drugs (high-intensity (n = 1284, 32.8%); moderate-intensity (n = 1602, 40.9%) and low-intensity (n = 931, 23.8%) statin therapy groups) according to the American College of Cardiology (ACC)/American heart Association (AHA) 2013 guideline and the relationship between CACS and statin benefit group was analyzed. The statin benefit group was defined as individuals who should be considered moderate- and high-intensity statin therapy. RESULTS: Ten-year atherosclerotic cardiovascular disease (ASCVD; 12.6 ± 5.3% vs. 2.9 ± 1.9%, p < 0.001) and CACS (98 ± 270 vs. 3 ± 2, p < 0.001) were significantly higher in the high-intensity group compared to the moderate-intensity statin therapy group. In the high-intensity statin therapy group, age [odds ratio: 1.299 (1.137-1.483), p < 0.001], male gender [odds ratio: 44.252 (1.959-999.784), p = 0.001], and fasting blood glucose [odds ratio: 1.046 (1.007-1.087), p = 0.021] were independent risk factors associated with CACS ≥300 on multivariate logistic regression analysis. CONCLUSIONS: CACS on MDCT might be an important complementary tool for cardiovascular disease risk stratification. This study indicates that individualization of statin therapy as well as lifestyle modification will be useful in asymptomatic individuals, especially those in whom high-intensity statin therapy is required.

Safety of the Up-titration of Nifedipine GITS and Valsartan or Low-dose Combination in Uncontrolled Hypertension: the FOCUS Study.

PURPOSE: Doubling the dose of antihypertensive drugs is necessary to manage hypertension in patients whose disease is uncontrolled. However, this strategy can result in safety issues. This study compared the safety and efficacy of up-titration of the nifedipine gastrointestinal therapeutic system (GITS) with up-titration of valsartan monotherapy; these were also compared with low-dose combinations of the two therapies. METHODS: This prospective, open-label, randomized, active-controlled, multicenter study lasted 8 weeks. If patients did not meet the target blood pressure (BP) after 4 weeks of treatment with low-dose monotherapy, they were randomized to up-titration of the nifedipine GITS dose from 30 mg (N30) to 60 mg or valsartan from 80 mg to 160 mg or they were randomized to receive a low-dose combination of N30 and valsartan 80 mg for another 4 weeks. BP variability was assessed by using the SD or the %CV of the short-term BP measured at clinic. FINDINGS: Of the 391 patients (20~70 years with stage II or higher hypertension) screened for study inclusion, 362 patients who had 3 BP measurements were enrolled. The reduction in the mean systolic/diastolic BP from baseline to week 4 was similar in both low-dose monotherapy groups with either N30 or valsartan 80 mg. BP variability (SD) was unchanged with either therapy, but the %CV was slightly increased in the N30 group. There was no significant difference in BP variability either in SD or %CV between responders and nonresponders to each monotherapy despite the significant difference in the mean BP changes. The up-titration effect of nifedipine GTS from 30 to 60 mg exhibited an additional BP reduction, but this effect was not shown in the up-titration of valsartan from 80 to 160 mg. Although the difference in BP was obvious between high-dose nifedipine GTS and valsartan, the BP variability was unchanged between the 2 drugs and was similar to the low-dose combinations. There was a low rate of adverse events in all treatment groups. In addition, escalating the dose of either nifedipine GITS or valsartan revealed a similar occurrence of adverse effects with low-dose monotherapy or the low-dose combination. IMPLICATIONS: Compared with up-titration of the angiotensin receptor blocker valsartan, up-titration of the calcium channel blocker nifedipine GITS provided no additional increased safety concerns and revealed better mean reductions in BP without affecting short-term BP variability. ClinicalTrials.gov identifier: NCT01071122.

Calcium-phosphorus product concentration is a risk factor of coronary artery disease in metabolic syndrome.

BACKGROUND: High serum phosphorus and the calcium-phosphorus product concentration has been associated with increased mortality and cardiovascular events in patients with chronic kidney disease. OBJECTIVE: This study was designed to determine the relationship between calcium-phosphorus product concentration and the presence of coronary artery calcification in subjects with metabolic syndrome (MetS). METHODS: We reviewed the medical records of 2056 general subjects with a mean age of 55.1 ± 9.9 years and a glomerular filtration rate of 88.9 ± 16.2 mL/min/1.73 m(2). The enrolled subjects consisted of 384 (18.7%) subjects with MetS and 1672 (81.3%) subjects without MetS. The severity of coronary artery calcification was assessed by the coronary artery calcification score (CACS) using multi-detector computed tomography (MDCT). RESULTS: The CACS correlated with calcium-phosphorus product concentration in subjects with MetS (r = 0.184, P < 0.01). The odds ratio of calcium-phosphorus product concentration having CACS >50 was 1.053 in subjects with MetS (P < 0.05). After adjustment for age, sex, diabetes, and dyslipidemia, calcium-phosphorus product concentrations had a positive correlation with CACS in subjects with MetS. In single regression analysis, calcium-phosphorus product concentration as independent variable was the significant predictor of CACS in subjects with MetS. Using a multivariate analysis, calcium-phosphorus product concentration remained a significant factor associated with CACS in subjects with MetS. CONCLUSIONS: Calcium-phosphorus product concentration was weakly associated with CACS and an independent factor predicting for CACS by MDCT in subjects with MetS. These results suggest that calcium-phosphorus product concentration might be considered as a risk factor of coronary artery disease in subjects with MetS.

Effects of Ecklonia cava polyphenol in individuals with hypercholesterolemia: a pilot study.

We evaluated the efficacy and safety of Ecklonia cava polyphenol (Seapolynol™, a polyphenol antioxidant and anti-inflammatory agent purified from E. cava) during a 12-week treatment period (400 mg orally once daily) in individuals with hypercholesterolemia and performed subgroup analysis for metabolic syndrome (MetS). As a noncomparative study, forty-six individuals (M:F=22:24, mean age=54±11 years) with fasting total cholesterol concentration >240 mg/dL or low-density lipoprotein cholesterol (LDL-C) concentration >130 mg/dL were enrolled. Hip circumference (100±7 cm vs. 98±7 cm, P<.01), total cholesterol (244±25 mg/dL vs. 225±37 mg/dL, P<.01), LDL-C (161±24 mg/dL vs. 146±34 mg/dL, P<.01), and C-reactive protein (2.51±3.55 mg/L vs. 1.37±1.32 mg/L, P<.05) were significantly decreased without significant adverse effect. A differential assessment according to the presence [MetS(+) group, n=18] and absence [MetS(-) group, n=28] of MetS showed that Hb(A1c) decreased significantly following 12-week Seapolynol treatment in the MetS(+) compared with the MetS(-) group (-0.3%±0.5% vs. 0.1%±0.3%, P<.01). In conclusion, although our results showed that Seapolynol treatment is effective and safe without significant adverse events or abnormal laboratory findings during a 12-week period in individuals with hypercholesterolemia, more research in a larger population with a longer-term follow-up period in a randomized placebo-controlled study is needed to confirm the results.

A warm footbath improves coronary flow reserve in patients with mild-to-moderate coronary artery disease.

BACKGROUNDS: Recent studies have shown that thermal therapy by means of warm waterbaths and sauna has beneficial effects in chronic heart failure. However, a comprehensive investigation of the hemodynamic effects of thermal vasodilation on coronary arteries has not been previously undertaken. In this study, we studied the effect of a warm footbath (WFB) on coronary arteries in patients with coronary artery disease (CAD), as well as any adverse effect. METHODS: We studied 21 patients (33.3% men, mean age 60.8 ± 13.5 years) with CAD. Coronary flow Doppler examination of the left anterior descending coronary artery and coronary flow reserve (CFR) were performed and measured using adenosine before and after a WFB. RESULTS: Systolic and diastolic blood pressure and heart rate did not change with the WFB. Mean velocity of diastolic coronary flow significantly increased (diastolic mean flow velocity: 18.3 ± 7.1 cm/sec initial, 21.5 ± 8.0 cm/sec follow-up, P = 0.002) and CFR significantly improved (1.6 ± 0.4 vs. 2.2 ± 0.5, P < 0.001) after WFB. The WFB was well accepted and no relevant adverse effects were observed. The change of CFR after WFB correlated well with diastolic function (E', r = 0.51, P = 0.031; E/E', r =-0.675, P = 0.002). CONCLUSIONS: A WFB significantly improved CFR without any adverse effects in patients with mild-to-moderate CAD and can be applied with little risk of a coronary artery event if appropriately performed.