Metabolomic Profiling of Statin Use and Genetic Inhibition of HMG-CoA Reductase

Background Statins are first-line therapy for cardiovascular disease prevention, but their systemic effects across lipoprotein subclasses, fatty acids, and circulating metabolites remain incompletely characterized. Objectives This study sought to determine the molecular effects of statin therapy on multiple metabolic pathways. Methods Metabolic profiles based on serum nuclear magnetic resonance metabolomics were quantified at 2 time points in 4 population-based cohorts from the United Kingdom and Finland (N = 5,590; 2.5 to 23.0 years of follow-up). Concentration changes in 80 lipid and metabolite measures during follow-up were compared between 716 individuals who started statin therapy and 4,874 persistent nonusers. To further understand the pharmacological effects of statins, we used Mendelian randomization to assess associations of a genetic variant known to mimic inhibition of HMG-CoA reductase (the intended drug target) with the same lipids and metabolites for 27,914 individuals from 8 population-based cohorts. Results Starting statin therapy was associated with numerous lipoprotein and fatty acid changes, including substantial lowering of remnant cholesterol (80% relative to low-density lipoprotein cholesterol [LDL-C]), but only modest lowering of triglycerides (25% relative to LDL-C). Among fatty acids, omega-6 levels decreased the most (68% relative to LDL-C); other fatty acids were only modestly affected. No robust changes were observed for circulating amino acids, ketones, or glycolysis-related metabolites. The intricate metabolic changes associated with statin use closely matched the association pattern with rs12916 in the HMGCR gene (R2 = 0.94, slope 1.00 ± 0.03). Conclusions Statin use leads to extensive lipid changes beyond LDL-C and appears efficacious for lowering remnant cholesterol. Metabolomic profiling, however, suggested minimal effects on amino acids. The results exemplify how detailed metabolic characterization of genetic proxies for drug targets can inform indications, pleiotropic effects, and pharmacological mechanisms

Football in the community schemes: Exploring the effectiveness of an intervention in promoting healthful behaviour change

This study aims to examine the effectiveness of a Premier League football club’s Football in the Community (FitC) schemes intervention in promoting positive healthful behaviour change in children. Specifically, exploring the effectiveness of this intervention from the perspectives of the participants involved (i.e. the researcher, teachers, children and coaches). A range of data collection techniques were utilized including the principles of ethnography (i.e. immersion, engagement and observations), alongside conducting focus groups with the children. The results allude to the intervention merely ‘keeping active children active’ via (mostly) fun, football sessions. Results highlight the important contribution the ‘coach’ plays in the effectiveness of the intervention. Results relating to working practice (i.e. coaching practice and coach recruitment) are discussed and highlighted as areas to be addressed. FitC schemes appear to require a process of positive organizational change to increase their effectiveness in strategically attending to the health agenda

Does neuregulin-1 play a role in Type A behavior? The cardiovascular risk in young Finns study

BACKGROUND: Neuregulin-1 proteins are related to physiological correlates of Type A in terms of cardiac reactivity. Furthermore, neuregulin-1 gene (NRG1) may play a role in cardiovascular disease such as atherosclerosis and coronary heart disease i.e. the suggested "outcomes" of Type A behavior. Therefore, NRG1 is hypothesized to be associated with Type A behavior. METHODS: The study examined whether Type A behavior pattern is associated with the single nucleotide polymorphism (SNP) SNP8NRG221533 of the NRG1. The subjects were 631 men and women participating in the population-based Cardiovascular Risk in Young Finns study in 1992 and 2001. Type A was self-assessed with the Framingham Type A Scale and reassessed nine years later. RESULTS: Type A was associated with NRG1 genotype. Carriers of genotype CC scored lower on Type A compared to the others. CONCLUSION: Our study has pinpointed a SNP in NRG1 that predicts Type A behavior. As previous evidence suggests an association for NRG1 with beta-adrenergic stimulation, its role underlying Type A is discussed

Childhood Infections, Socioeconomic Status, and Adult Cardiometabolic Risk

BACKGROUND AND OBJECTIVES: Socioeconomic disadvantage throughout the life course is associated with increased risk of cardiometabolic diseases, but traditional risk factors do not fully account for the social gradient. We investigated the interactions between low socioeconomic status (SES) and infection in childhood and adverse cardiometabolic parameters in adulthood. METHODS: Participants from the Cardiovascular Risk in Young Finns Study, a cohort well phenotyped for childhood and adulthood cardiometabolic risk factors and socioeconomic parameters, were linked to lifetime hospitalization data from birth onward available from the Finnish National Hospital Registry. In those with complete data, we investigated relationships between infection-related hospitalization in childhood, SES, and childhood and adult cardiometabolic parameters. RESULTS: The study cohort consisted of 1015 participants (age range 3–18 years at baseline and 30–45 years at follow-up). In adults who were raised in below-median income families, childhood infection-related hospitalizations (at age 0–5 years) were significantly associated with higher adult BMI (β ± SE comparing those with 0 vs ≥1 hospitalizations 2.4 ± 0.8 kg/m2, P = .008), waist circumference (7.4 ± 2.3 cm, P = .004), and reduced brachial flow–mediated dilatation (−2.7 ± 0.9%, P = .002). No equivalent associations were observed in participants from higher-SES families. CONCLUSIONS: Infection was associated with worse cardiovascular risk factor profiles only in those from lower-SES families. Childhood infection may contribute to social gradients observed in adult cardiometabolic disease risk factors. These findings suggest reducing childhood infections, especially in socioeconomic disadvantaged children, may reduce the cardiometabolic disease burden in adults