Efficacy and safety of bempedoic acid in patients not receiving statins in phase 3 clinical trials

BACKGROUND: Despite the high incidence of patients with statin tolerance problems, randomized evaluations of nonstatin oral treatment options for lowering of low-density lipoprotein cholesterol (LDL-C) in this population are sparse. OBJECTIVE: To assess the LDL-C lowering effect of bempedoic acid in patients not taking statins. METHODS: This was a pooled analysis of data from patients enrolled in four phase 3 bempedoic acid studies (12 to 52 weeks in duration) who were not taking concomitant statins (Phase 3 No Statin Cohort) and a phase 3 bempedoic acid plus ezetimibe fixed-dose combination study (BA+EZE FDC No Statin Cohort). The primary endpoint for all studies was the percent change from baseline to week 12 in LDL-C levels. Safety and tolerability were assessed by laboratory values and adverse events. RESULTS: In the Phase 3 No Statin Cohort, bempedoic acid (n = 394) lowered LDL-C levels at week 12 significantly more than placebo (n = 192; -26.5% [95% CI, -29.7%, -23.2%]; P\u3c0.001). The fixed-dose combination of bempedoic acid with ezetimibe lowered LDL-C by 39.2% (95% CI, -51.7% to -26.7%; P\u3c0.001). Muscle-related disorders occurred at a rate of 26.4 and 28.6 per 100 person-years with bempedoic acid and placebo, respectively. CONCLUSIONS: In patients with hypercholesterolemia unable to take statins, bempedoic acid lowered LDL-C levels by a mean of 26.5% vs placebo and bempedoic acid + ezetimibe fixed-dose combination lowered LDL-C by 39.2%. The treatments were generally well tolerated, suggesting that bempedoic acid may be efficacious and well tolerated in this challenging-to-treat patient population

Lack of effect of lowering LDL cholesterol on cancer: meta-analysis of individual data from 175,000 people in 27 randomised trials of statin therapy

<p>Background: Statin therapy reduces the risk of occlusive vascular events, but uncertainty remains about potential effects on cancer. We sought to provide a detailed assessment of any effects on cancer of lowering LDL cholesterol (LDL-C) with a statin using individual patient records from 175,000 patients in 27 large-scale statin trials.</p> <p>Methods and Findings: Individual records of 134,537 participants in 22 randomised trials of statin versus control (median duration 4.8 years) and 39,612 participants in 5 trials of more intensive versus less intensive statin therapy (median duration 5.1 years) were obtained. Reducing LDL-C with a statin for about 5 years had no effect on newly diagnosed cancer or on death from such cancers in either the trials of statin versus control (cancer incidence: 3755 [1.4% per year [py]] versus 3738 [1.4% py], RR 1.00 [95% CI 0.96-1.05]; cancer mortality: 1365 [0.5% py] versus 1358 [0.5% py], RR 1.00 [95% CI 0.93–1.08]) or in the trials of more versus less statin (cancer incidence: 1466 [1.6% py] vs 1472 [1.6% py], RR 1.00 [95% CI 0.93–1.07]; cancer mortality: 447 [0.5% py] versus 481 [0.5% py], RR 0.93 [95% CI 0.82–1.06]). Moreover, there was no evidence of any effect of reducing LDL-C with statin therapy on cancer incidence or mortality at any of 23 individual categories of sites, with increasing years of treatment, for any individual statin, or in any given subgroup. In particular, among individuals with low baseline LDL-C (<2 mmol/L), there was no evidence that further LDL-C reduction (from about 1.7 to 1.3 mmol/L) increased cancer risk (381 [1.6% py] versus 408 [1.7% py]; RR 0.92 [99% CI 0.76–1.10]).</p> <p>Conclusions: In 27 randomised trials, a median of five years of statin therapy had no effect on the incidence of, or mortality from, any type of cancer (or the aggregate of all cancer).</p&gt

Love and limblessness: male heterosexuality, disability, and the Great War

Tens of thousands of British men were permanently wounded as a result of war service. Their return home sparked debates about the wounded male body, female accountability for war-injuries, and the ideology, performance, and practice of masculinity. Other historians have shown how ‘broken heroes’ from the First World War were constituted into ‘men’ in four contexts: physical appearance, occupation, sport, and Britishness. This article explores a fifth dimension: sexuality. It explores debates about the need for war-disabled men to establish stable marital relationships and investigates some attempts to encourage this, including encouraging women to take the initiative in proposing marriage and the establishment of The League for the Marrying of Broken Heroes

Epidemiology of cardiovascular risk factors in Greece: aims, design and baseline characteristics of the ATTICA study

BACKGROUND: In an attempt to evaluate the levels of several cardiovascular risk factors in Greece we conducted a population-based health and nutrition survey, the "ATTICA study". In this work we present the design and the methodology of the study, as well as the status of various baseline characteristics of the participants. METHODS: From May 2001 to December 2002 we randomly enrolled 1514 adult men and 1528 adult women, stratified by age – gender (census 2000), from the greater area of Athens. More than 300 demographic, lifestyle, behavioral, dietary, clinical and biochemical variables have been recorded. RESULTS: Regarding the frequency of the classical cardiovascular risk factors we observed that 51% of men and 39% of women reported smokers (p < 0.05), 37% of men and 25% of women were defined as hypertensives (p < 0.05), 46% of men and 40% of women had total serum cholesterol levels above 200 mg/dl (p < 0.05) and 8% of men and 6% of women had history of diabetes mellitus. Moreover, 20% of men and 15% of women were obese (p < 0.05), while men were more physically active as compared to women (42% vs. 39%, p < 0.05). 19% of men and 38% of women had mild to severe depressive symptoms (p < 0.01). Finally, 72 men (5%) and 45 (3%) women reported history of coronary heart disease at entry evaluation. CONCLUSIONS: The prevalence of the common cardiovascular risk factors in our population seems high. As a consequence a considerable proportion of Greek adults are at "high-risk" for future cardiovascular events

Metabolic Syndrome: a challenging health Issue in highly urbanized Union Territory of north India

<p>Abstract</p> <p>Objectives</p> <p>1. To determine the prevalence of Metabolic Syndrome in adults aged 18 years and above in Chandigarh, India. 2. To determine the socio-demographic factors associated with MS. 3. To determine the agreement between IDF (International Diabetes federation definition) and ATP-III (National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults criteria).</p> <p>Methods</p> <p>In a community based cross-sectional study, total 605 subjects aged 18 yrs and above were studied using multistage random sampling.</p> <p>Results</p> <p>Prevalence of Metabolic Syndrome was estimated by using IDF and ATP-III criteria. By IDF, Metabolic Syndrome was found in 287 (47.4%) subjects and it was more prevalent among females 171 (59.6%) as compared to males 116 (40.4%). By applying ATP-III overall prevalence was less i.e. 233 (38.5%) but again its prevalence was more among females 141 (44.8%) than males 116 (39.5%). Higher socioeconomic status, sedentary occupation and high body mass index were significantly associated with Metabolic Syndrome.</p> <p>Conclusions</p> <p>Metabolic Syndrome is a major health problem in the region and proper emphasis should be given on its prevention and control.</p

Epidemiology of acute coronary syndromes in a Mediterranean country; aims, design and baseline characteristics of the Greek study of acute coronary syndromes (GREECS)

BACKGROUND: The present study GREECS was conducted in order to evaluate the annual incidence of acute coronary syndromes (ACS) and to delineate the role of clinical, biochemical, lifestyle and behavioral characteristics on the severity of disease. In this work we present the design, methodology of the study and various baseline characteristics of people with ACS. METHODS/DESIGN: A sample of 6 hospitals located in Greek urban and rural regions was selected. In these hospitals we recorded almost all admissions due to ACS, from October 2003 to September 2004. Socio-demographic, clinical, dietary, psychological and other lifestyle characteristics were recorded. 2172 patients were included in the study (76% were men and 24% women). The crude annual incidence rate was 22.6 per 10,000 people and the highest frequency of events was observed in winter. The in-hospital mortality rate was 4.3%. The most common discharged diagnosis for men was Q-wave MI, while for women it was unstable angina. DISCUSSION: This study aims to demonstrate current information about the epidemiology of patients who suffer from ACS, in Greece

Two years after molecular diagnosis of familial hypercholesterolemia: Majority on cholesterol-lowering treatment but a minority reaches treatment goal

Background: The risk of premature cardiovascular disease in patients with familial hypercholesterolemia (FH) can be profoundly reduced by cholesterol-lowering therapy, and current guidelines for FH advocate ambitious low-density lipoprotein cholesterol (LDL-C) goals. In the present study, we determined whether these goals are reflected in current clinical practice once FH has been diagnosed. Methodology/Principal Findings: In 2008, we sent questionnaires to all subjects (aged 18-65 years) who were molecularly diagnosed with FH in the year 2006 through the screening program in the Netherlands. Of these 1062 subjects, 781 completed the questionnaire (46% males; mean age: 42±12 years; mean LDL-C at molecular diagnosis (baseline): 4.1±1.3 mmol/L). The number of persons that used cholesterol-lowering therapy increased from 397 (51%) at baseline to 636 (81%) after diagnosis. Mean treated LDL-C levels decreased significantly to 3.2±1.1 mmol/L two years after diagnosis. Only 22% achieved the LDL-C target level of ≤2.5 mmol/L. Conclusions/Significance: The proportion of patients using cholesterol-lowering medication was significantly increased after FH diagnosis through

Renoprotective effects of atorvastatin in diabetic mice: downregulation of RhoA and upregulation of Akt/GSK3

Potential benefits of statins in the treatment of chronic kidney disease beyond lipid-lowering effects have been described. However, molecular mechanisms involved in renoprotective actions of statins have not been fully elucidated. We questioned whether statins influence development of diabetic nephropathy through reactive oxygen species, RhoA and Akt/GSK3 pathway, known to be important in renal pathology. Diabetic mice (db/db) and their control counterparts (db/+) were treated with atorvastatin (10 mg/Kg/day, p.o., for 2 weeks). Diabetes-associated renal injury was characterized by albuminuria (albumin:creatinine ratio, db/+: 3.2 ± 0.6 vs. db/db: 12.5 ± 3.1*; *P&lt;0.05), increased glomerular/mesangial surface area, and kidney hypertrophy. Renal injury was attenuated in atorvastatin-treated db/db mice. Increased ROS generation in the renal cortex of db/db mice was also inhibited by atorvastatin. ERK1/2 phosphorylation was increased in the renal cortex of db/db mice. Increased renal expression of Nox4 and proliferating cell nuclear antigen, observed in db/db mice, were abrogated by statin treatment. Atorvastatin also upregulated Akt/GSK3β phosphorylation in the renal cortex of db/db mice. Our findings suggest that atorvastatin attenuates diabetes-associated renal injury by reducing ROS generation, RhoA activity and normalizing Akt/GSK3β signaling pathways. The present study provides some new insights into molecular mechanisms whereby statins may protect against renal injury in diabetes

Low HDL Cholesterol, Smoking and IL-13 R130Q Polymorphism are Associated with Myocardial Infarction in Greek Cypriot Males. A Pilot Study

This study was carried out in Greek Cypriot males to identify risk factors that predispose to myocardial infarction (MI). Genetic and lipid risk factors were investigated for the first time in a Greek Cypriot male case-control study.Contrary to other studies, mean low density lipoprotein cholesterol did not differ between cases and controls. High density lipoprotein cholesterol on the other hand, although within normal range in cases and controls, was significantly higher in the control population. In agreement with many other studies, smoking was significantly more prevalent in cases compared with controls. In pooled cases and controls, smokers had a significantly lower HDL-C level compared with non-smokers. The frequency of the IL-13 R130Q homozygotes for the mutation (QQ), as well as the mutant allele were significantly higher in cases compared with controls. The IL-13 R130Q variant, or another locus, linked to it, may increase the risk of MI