Complex trait susceptibilities and population diversity in a sample of 4,145 Russians.

The population of Russia consists of more than 150 local ethnicities. The ethnic diversity and geographic origins, which extend from eastern Europe to Asia, make the population uniquely positioned to investigate the shared properties of inherited disease risks between European and Asian ancestries. We present the analysis of genetic and phenotypic data from a cohort of 4,145 individuals collected in three metro areas in western Russia. We show the presence of multiple admixed genetic ancestry clusters spanning from primarily European to Asian and high identity-by-descent sharing with the Finnish population. As a result, there was notable enrichment of Finnish-specific variants in Russia. We illustrate the utility of Russian-descent cohorts for discovery of novel population-specific genetic associations, as well as replication of previously identified associations that were thought to be population-specific in other cohorts. Finally, we provide access to a database of allele frequencies and GWAS results for 464 phenotypes.

Efficacy and Safety of K-877 (Pemafibrate), a Selective PPARα Modulator, in European Patients on Statin Therapy.

OBJECTIVE: High plasma triglyceride (TG) is an independent risk factor for cardiovascular disease. Fibrates lower TG levels through peroxisome proliferator-activated receptor α (PPARα) agonism. Currently available fibrates, however, have relatively low selectivity for PPARα. The aim of this trial was to assess the safety, tolerability, and efficacy of K-877 (pemafibrate), a selective PPARα modulator, in statin-treated European patients with hypertriglyceridemia. RESEARCH DESIGN AND METHODS: A total of 408 statin-treated adults were recruited from 68 European sites for this phase 2, randomized, double-blind, placebo-controlled trial. They had fasting TG between 175 and 500 mg/dL and HDL-cholesterol (HDL-C) ≤50 mg/dL for men and ≤55 mg/dL for women. Participants were randomly assigned to receive placebo or one of six pemafibrate regimens: 0.05 mg twice a day, 0.1 mg twice a day, 0.2 mg twice a day, 0.1 mg once daily, 0.2 mg once daily, or 0.4 mg once daily. The primary end points were TG and non-HDL-C level lowering at week 12. RESULTS: Pemafibrate reduced TG at all doses (adjusted P value <0.001), with the greatest placebo-corrected reduction from baseline to week 12 observed in the 0.2-mg twice a day treatment group (54.4%). Reductions in non-HDL-C did not reach statistical significance. Reductions in TG were associated with improvements in other markers for TG-rich lipoprotein metabolism, including reductions in apoB48, apoCIII, and remnant cholesterol and an increase in HDL-C levels. Pemafibrate increased LDL-cholesterol levels, whereas apoB100 was unchanged. Pemafibrate was safe and well-tolerated, with only minor increases in serum creatinine and homocysteine concentrations. CONCLUSIONS: Pemafibrate is effective, safe, and well-tolerated for the reduction of TG in European populations with hypertriglyceridemia despite statin treatment.

Physical Activity Is Associated With Sleep Quality: Results of the ESSE-RF Epidemiological Study.

BACKGROUND AND HYPOTHESIS: Physical activity (PA) is an important behavioral factor associated with the quality of life and healthy longevity. We hypothesize that extremely low and extremely high levels of daily PA (including occupational PA) may have a negative impact on sleep quality and psychological well-being. OBJECTIVE: The aim of the study is to investigate the association between the level and type of PA and sleep problems in adult population. MATERIALS AND METHODS: The sample of the study consisted of the participants from the population-based cohort of The Epidemiology of Cardiovascular Risk Factors and Diseases in Regions of the Russian Federation Study (ESSE-RF). The data of three regions (Saint Petersburg, Samara, Orenburg), varying in geographic, climatic, socioeconomic characteristics, was included into analysis. The total sample consisted of 4,800 participants (1,600 from each region; 1,926 males, 2,874 females), aged 25-64. The level of PA was evaluated using three parameters: the type of PA at work, the frequency of an intensive/high PA including sport (times a week), the mean duration of leisure-time walking (minutes a day). The measures of sleep quality were sleep duration and the frequency of difficulty falling asleep, difficulty maintaining sleep, daytime sleepiness, and sleep medication use. PA and sleep characteristics were assessed by interview carried by the trained medical staff. RESULTS: When controlling for gender, age and socioeconomic status (SES) extremely high occupational PA was a significant risk factor for difficulty falling asleep three or more times a week [OR(CI95%) = 1.9(1.2-3.0), p = 0.003] while working in a sitting position or having moderate physical load at work were not associated with sleep characteristics. Having a high physical load six or more times a week was a risk factor for difficulty falling asleep controlling for gender, age and SES [OR(CI95%) = 1.9(1.4-3.4), p = 0.001]. The association between leisure-time walking and sleep characteristics was insignificant. Walking less than an hour a day was associated with increased depression scores (46.5 vs. 41.9%, p = 0.006). CONCLUSION: High physical load at work and excessively frequent intensive PA are associated with difficulties initiating sleep and may represent a risk factor for insomnia.