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BACKGROUND Lipid abnormalities are common in patients with renal disease. Such individuals might respond to lipid-lowering therapy in a manner different to patients with coronary artery disease. OBJECTIVES To analyze the safety of fluvastatin in patients with moderate to severe renal insufficiency, and to compare its effect on cardiovascular outcomes in this population with that in patients with normal or mildly impaired renal function. DESIGN AND INTERVENTION Double-blind trials that randomized patients to receive at least 6 weeks' treatment with fluvastatin 20 mg/day, 40 mg/day or 80 rag/day were included in this pooled analysis. The study population was divided into patients with baseline Cockcroft-Gault-estimated creatinine clearance <50ml/min (moderate to severe renal insufficiency) and those with baseline Cockcroft-Gault-estimated creatinine clearance ≥50ml/min (normal renal function or mild renal insufficiency). The pooled database only included patients who received &GE; 1 dose of study drug, and the analyses of clinical end points only included studies of >1 year in duration. OUTCOME MEASURES The clinical end points included a composite of cardiac death and nonfatal myocardial infarction, a composite of cardiac death, nonfatal myocardial infarction and cardiac revascularizations ('major cardiac events'), and all-cause mortality. Adverse events that occurred during treatment and up to 30 days after stopping treatment were also analyzed. RESULTS Of the 30 trials included in the pooled database (11,815 patients), 24 were placebo-controlled. In total, 1,569 patients had moderate to severe renal insufficiency (mean age 61 years; 55% female) and 9,914 had normal renal function or mild renal insufficiency (mean age 57 years; 37% female). The remaining 332 patients lacked sufficient data for calculation of creatinine clearance. Fluvastatin was associated with significant reductions in LDL-cholesterol, total cholesterol, triglycerides and apolipoprotein B compared with placebo (P<0.0001 for all), irrespective of renal function. Five studies (n =5,402) were included in the analyses of clinical end points. Compared with placebo, fluvastatin significantly reduced the combined incidence of cardiac death and nonfatal myocardial infarction in patients with moderate to severe renal insufficiency (-41%; P = 0.007) and in patients with normal or mildly impaired renal function (-30%; P=0.009). The reduction in the risk of major cardiac events associated with fluvastatin versus placebo was also significant in the normal or mildly impaired renal function group (-17%; P=0.01) but not in the moderate to severe renal insufficiency group (-17%; P=0.18). Fluvastatin had no significant effect on all-cause mortality or coronary interventions in either renal function group. The adverse event profile of fluvastatin was similar to that of placebo in both groups. CONCLUSION Fluvastatin safely and effectively reduces the combined risk of cardiac death and nonfatal myocardial infarction in patients with moderate to severe renal insufficiency. [ABSTRACT FROM AUTHOR]

Aims: To elucidate the effects of intensive LDL-C lowering treatment with a standard dose of statin and ezetimibe in patients with dyslipidaemia and high risk of coronary events, targeting LDL-C less than 70 mg/dL (1.8 mmol/L), compared with standard LDL-C lowering lipid monotherapy targeting less than 100 mg/dL (2.6 mmol/L)., Methods and Results: The HIJ-PROPER study is a prospective, randomized, open-label trial to assess whether intensive LDL-C lowering with standard-dose pitavastatin plus ezetimibe reduces cardiovascular events more than standard LDL-C lowering with pitavastatin monotherapy in patients with acute coronary syndrome (ACS) and dyslipidaemia. Patients were randomized to intensive lowering (target LDL-C < 70 mg/dL [1.8 mmol/L]; pitavastatin plus ezetimibe) or standard lowering (target LDL-C 90 mg/dL to 100 mg/dL [2.3-2.6 mmol/L]; pitavastatin monotherapy). The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, unstable angina, and ischaemia-driven revascularization. Between January 2010 and April 2013, 1734 patients were enroled at 19 hospitals in Japan. Patients were followed for at least 36 months. Median follow-up was 3.86 years. Mean follow-up LDL-C was 65.1 mg/dL (1.68 mmol/L) for pitavastatin plus ezetimibe and 84.6 mg/dL (2.19 mmol/L) for pitavastatin monotherapy. LDL-C lowering with statin plus ezetimibe did not reduce primary endpoint occurrence in comparison with standard statin monotherapy (283/864, 32.8% vs. 316/857, 36.9%; HR 0.89, 95% CI 0.76-1.04, P = 0.152). In, ACS patients with higher cholesterol absorption, represented by elevated pre-treatment sitosterol, was associated with significantly lower incidence of the primary endpoint in the statin plus ezetimibe group (HR 0.71, 95% CI 0.56-0.91)., Conclusion: Although intensive lowering with standard pitavastatin plus ezetimibe showed no more cardiovascular benefit than standard pitavastatin monotherapy in ACS patients with dyslipidaemia, statin plus ezetimibe may be more effective than statin monotherapy in patients with higher cholesterol absorption; further confirmation is needed., Trial No: UMIN000002742, registered as an International Standard Randomized Controlled Trial., (© The Author 2017. Published by Oxford University Press on behalf of the European Society of Cardiology)

The prognosis of patients after acute coronary syndromes is still suboptimal, mainly due to the risk of recurrent adverse coronary events, which is greatest during the first year, but persists over one's lifetime. Meaningful progress in preventing cardiovascular events has been achieved. However, there remains much room for improvement by embracing innovative therapies and investing in multidisciplinary approaches. Pharmacological interventions focused on optimising antithrombotic and lipid-lowering therapies are both pillars of secondary prevention that have seen recent ground-breaking advances. Moreover, new approaches in diabetic patients with cardiovascular disease and new targets for anti-inflammatory treatment may significantly improve prevention strategies in the future. However, pharmacological treatments are expensive and can have significant side effects. Developing better tools in order to identify high-risk patients and promote more personalised strategies for each patient should be an absolute priority. Furthermore, adherence to medication is still low and represents a real challenge; several strategies to improve low adherence to treatment are currently under discussion. Non-pharmacological interventions are also essential. Improving communication with patients and advanced surveillance for those secondary risk factors that may negatively impact prognosis are crucial. Encouraging multidisciplinary teams that work effectively to optimise all aspects of secondary prevention, including a cardiac rehabilitation programme, is the optimal approach. Current secondary prevention strategies and suggestions for areas of improvement are discussed in this manuscript. However, the question remains: will research in secondary prevention continue to focus on stronger and more expensive drugs, or is it time for us to embrace a more patient-centred clinical and research model?

Polygonum multiflorum is widely used in the prevention and treatment of hyperlipidemia in traditional Chinese Medicine. In this study, the effects and relevant mechanisms of lipid-regulation by raw Polygonum multiflorum (RPM) were investigated. The results indicated that the basal plasma lipids, such as low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG), were significantly decreased in RPM treatment groups compared with the model group, especially in the RPM high dose group. The key enzymes involved in lipid metabolism, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) in plasma were generally reduced after oral administration, which was consistent with the transcription levels of their target genes. In addition, the hepatotoxicity of RPM was investigated, and RPM showed slightly less liver injury than that induced by simvastatin. Histological analysis indicated that the fat vacuoles and steatosis in hepatocytes were relieved after oral administration of RPM extract at a high dose of 16.2 g/kg, which was more obvious than that induced by simvastatin. These results revealed that RPM exerted its lipid-lowering effect by regulating the expression of related genes, and performed better than simvastatin in the treatment of hyperlipidemia.

The effects of cholesterol-lowering drugs, including those that reduce cholesterol synthesis (statins) and those that reduce cholesterol absorption (ezetimibe), on cholesterol absorption and synthesis are well understood. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a novel class of cholesterol-lowering drugs that robustly reduce LDL-cholesterol (LDL-C), but little is known about their effects on cholesterol absorption and synthesis. We evaluated how treatment with evolocumab, a fully human monoclonal IgG2 antibody to PCSK9, affects markers of cholesterol synthesis and absorption by measuring these markers in patients from an evolocumab clinical trial. At 2 weeks, changes in β-sitosterol/total cholesterol (TC) from baseline were 4% for placebo, 10% for evolocumab 140 mg (nonsignificant vs. placebo), and 26% for evolocumab 420 mg (P < 0.001 vs. placebo). Changes in campesterol/TC at week 2, relative to baseline between placebo and evolocumab, were all nonsignificant. Evolocumab had a modest effect on markers of cholesterol synthesis. At 2 weeks, changes in desmosterol/TC were 1% for placebo, 7% for evolocumab 140 mg (nonsignificant vs. placebo), and 15% for evolocumab 420 mg (P < 0.01 vs. placebo). Changes from baseline in lathosterol/TC at week 2 between placebo and evolocumab were nonsignificant. These results suggest that evolocumab has a modest effect on cholesterol synthesis and absorption despite significant LDL-C lowering., (Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.)

Objective: Evidence suggests prolonged exposure to lower levels of low-density lipoprotein cholesterol (LDL-C), starting at a younger age, substantially lowers cardiovascular (CV) risk. Accordingly, the CV pandemic affecting younger population in low- to low-middle-income countries, where statin usage is poor even in secondary prevention, may benefit from lipid-lowering nutritional products, as nutritional intervention is generally preferred in these cultures. However, the safety and efficacy of such preparations have not been systematically tested., Methods: In this multicenter, double-blind study, 191 statin-free subjects with newly-diagnosed hyperlipidemia (LDL-C >120 mg/dL, 3.11 mmol/L) and no evidence of CV disease were randomized to one capsule of a proprietary bioactive phytonutrient formulation containing red yeast rice, grape-seed, niacinamide, and folic acid (RYR-NS) or matched placebo twice daily, along with lifestyle modification, for 12 wk., Results: Mean baseline LDL-C levels were 148.5 ± 24.0 mg/dL (3.85 ± 0.62 mmol/L) and 148.6 ± 21.9 mg/dL (3.85 ± 0.57 mmol/L) in the RYR-NS and placebo groups respectively. Compared with placebo, RYR-NS resulted in a significant reduction in LDL-C (-29.4% versus -3.5%, P < 0.0001) and non-high-density lipoprotein cholesterol (non-HDL-C; -29.8% versus -10.3%, P < 0.0001) at 12 wk. With RYR-NS, 43.4% individuals attained desirable LDL-C levels and 55.4% desirable non-HDL-C levels by week 12, compared to only 0% and 1.1%, respectively, at baseline. No safety issues were observed., Conclusion: This study demonstrates the efficacy and safety of RYR-NS in lowering LDL-C and non-HDL-C after 12 wk, with magnitude of LDL-C reduction being comparable to that seen with moderate-intensity statin therapy. Further long-term studies are required to determine the impact of RYR-NS on treatment adherence and clinical outcomes., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Tomato is a globally famous food and contains several phytonutrients including lycopene, β-carotene, anthocyanin, and flavonoids. The increased temperature used to produce tomato juice, ketchup, tomato paste and canned tomato enhances the bioactive composition. We aimed to verify the beneficial effects of processed tomato juice from Kagome Ltd. (KOT) on hypolipidemic action in hamsters with hyperlipidemia induced by a 0.2% cholesterol and 10% lard diet (i.e., high-cholesterol diet (HCD)). Male Golden Syrian hamsters were randomly divided into two groups for treatment: normal (n = 8), standard diet (control); and experimental (n = 32), HCD. The 32 hamsters were further divided into four groups (n = 8 per group) to receive vehicle or KOT by oral gavage at 2787, 5573, or 13,934 mg/kg/day for six weeks, designated the HCD-1X, -2X and -5X groups, respectively. The efficacy and safety of KOT supplementation was evaluated by lipid profiles of serum, liver and feces and by clinical biochemistry and histopathology. HCD significantly increased serum levels of total cholesterol (TC), triacylglycerol (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), LDL-C/HDL-C ratio, hepatic and fetal TC and TG levels, and degree of fatty liver as compared with controls. KOT supplementation dose-dependently decreased serum TC, TG, LDL-C levels, LDL-C/HDL-C ratio, hepatic TC and TG levels, and fecal TG level. Our study provides experiment-based evidence to support that KOT may be useful in treating or preventing the onset of hyperlipidemia.

We aimed to verify the beneficial effects of probiotic strain Lactobacillus reuteri 263 (Lr263) on hypolipidemic action in hamsters with hyperlipidemia induced by a 0.2% cholesterol and 10% lard diet (i.e., high-cholesterol diet (HCD)). Male Golden Syrian hamsters were randomly divided into two groups: normal (n = 8), standard diet (control), and experimental (n = 32), a HCD. After a two-week induction followed by a six-week supplementation with Lr263, the 32 hyperlipidemic hamsters were divided into four groups (n = 8 per group) to receive vehicle or Lr263 by oral gavage at 2.1, 4.2, or 10.5 × 10(9) cells/kg/day for 6 weeks, designated the HCD, 1X, 2X and 5X groups, respectively. The efficacy and safety of Lr263 supplementation were evaluated by lipid profiles of serum, liver and feces and by clinical biochemistry and histopathology. HCD significantly increased serum levels of total cholesterol (TC), triacylglycerol (TG) cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), LDL-C/HDL-C ratio, hepatic and fetal TC and TG levels, and degree of fatty liver as compared with controls. Lr263 supplementation dose dependently increased serum HDL-C level and decreased serum TC, TG, LDL-C levels, LDL-C/HDL-C ratio, hepatic TC and TG levels, and fecal TG level. In addition, Lr263 supplementation had few subchronic toxic effects. Lr263 could be a potential agent with a hypolipidemic pharmacological effect.

Background: This study examined the distribution of the 10-year risk for development of atherosclerotic cardiovascular disease (ASCVD) and coronary heart disease (CHD), and the proportion of participants eligible for lipid management, in the Korean population., Methods: The risk was estimated using the Pooled Cohort Equations for non-Hispanic Whites and the Adult Treatment Panel (ATP) III equations. Eligibility for lipid-lowering treatment was assessed using the American College of Cardiology/American Heart Association Blood Cholesterol Guideline and the ATP III recommendation. Complex sampling design and area under the receiver operator characteristic curve (AUC) were used., Results: Among 7594 ASCVD-free Korean adults, aged 40-79 years, 31.3% (men, 44.1%; women, 19%) had a 10-year risk for an ASCVD event of ≥ 7.5%, and 27.1% (men, 39.4%; women, 15.2%) had a 10-year risk for a CHD event of ≥ 10%. These proportions differed according to age groups, ranging from 6.1 to 91.9% and 8.7 to 58.7% for patients in their 40s-70s, using the ASCVD and CHD risk estimations, respectively. Overall, 78.7% of individuals remain in the same risk stratum. Those eligible for lipid management included 32.8% of the participants using the ACC/AHA Guideline and 11.9% of those using the ATP III recommendation. In discriminating ASCVD, AUCs for the ASCVD risk assessment method and the CHD risk assessment method were 0.70 and 0.64, respectively (P<0.001)., Conclusions: The distribution of 10-year ASCVD and CHD risk was different according to the risk assessment methods., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)