The Association between HDL-C and Subclinical Atherosclerosis Depends on CETP Plasma Concentration:Insights from the IMPROVE Study

The impact of cholesteryl ester transfer protein (CETP) on atherosclerosis is highly debated. This study aimed to investigate the associations between plasma CETP or CETP genotypes and carotid intima-media thickness (cIMT) and the influence of high-density lipoprotein cholesterol (HDL-C) on these associations. Plasma CETP and HDL-C concentrations were measured in 552 subjects free of any pharmacological treatment from the IMPROVE cohort, which includes 3711 European subjects at high cardiovascular risk. CETP single-nucleotide polymorphisms (SNPs) and cIMT measures (cIMT(max); cIMT(mean-max) of bifurcations, common and internal carotids; plaque-free common carotid [PF CC]-IMTmean) were available for the full cohort. In drug-free subjects, plasma CETP correlated with HDL-C levels (r = 0.19, p < 0.0001), but not with cIMT variables. When stratified according to HDL-C quartiles, CETP positively correlated with cIMT(max) and cIMT(mean-max), but not with PF CC-IMTmean, in the top HDL-C quartile only. Positive associations between the CETP concentration and cIMT(max) or cIMT(mean-max) were found in the top HDL-C quartile, whereas HDL-C levels were negatively correlated with cIMT(max) and cIMT(mean-max) when the CETP concentration was below the median (HDL-C x CETP interaction, p = 0.001 and p = 0.003 for cIMT(max) and cIMT(mean-max), respectively). In the full cohort, three CETP SNPs (rs34760410, rs12920974, rs12708968) were positively associated with cIMT(max). rs12444708 exhibited a significant interaction with HDL-C levels in the prediction of cIMT(max). In conclusion, a significant interplay was found between plasma CETP and/or CETP genotype and HDL-C in the prediction of carotid plaque thickness, as indexed by cIMT(max). This suggests that the association of HDL-C with carotid atherosclerosis is CETP-dependent

The overlap of genetic susceptibility to schizophrenia and cardiometabolic disease can be used to identify metabolically different groups of individuals

Understanding why individuals with severe mental illness (Schizophrenia, Bipolar Disorder and Major Depressive Disorder) have increased risk of cardiometabolic disease (including obesity, type 2 diabetes and cardiovascular disease), and identifying those at highest risk of cardiometabolic disease are important priority areas for researchers. For individuals with European ancestry we explored whether genetic variation could identify sub-groups with different metabolic profiles. Loci associated with schizophrenia, bipolar disorder and major depressive disorder from previous genome-wide association studies and loci that were also implicated in cardiometabolic processes and diseases were selected. In the IMPROVE study (a high cardiovascular risk sample) and UK Biobank (general population sample) multidimensional scaling was applied to genetic variants implicated in both psychiatric and cardiometabolic disorders. Visual inspection of the resulting plots used to identify distinct clusters. Differences between these clusters were assessed using chi-squared and Kruskall-Wallis tests. In IMPROVE, genetic loci associated with both schizophrenia and cardiometabolic disease (but not bipolar disorder or major depressive disorder) identified three groups of individuals with distinct metabolic profiles. This grouping was replicated within UK Biobank, with somewhat less distinction between metabolic profiles. This work focused on individuals of European ancestry and is unlikely</p

Genome-Wide Association Study and Functional Characterization Identifies Candidate Genes for Insulin-Stimulated Glucose Uptake

Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in \u3e55,000 participants from three ancestry groups. We identified ten new loci (P \u3c 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits

Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.Peer reviewe

Psychosocial and health behavioural characteristics of longitudinal physical activity patterns: a cohort study from adolescence to young adulthood

Abstract Background The decline in physical activity (PA) during adolescence is well-established. However, while some subgroups of adolescents follow the general pattern of decreased activity, others increase or maintain high or low activity. The correlates and determinants of different PA patterns may vary, offering valuable information for targeted health promotion. This study aimed to examine how psychosocial factors, health behaviours, and PA domains are associated with longitudinal PA patterns from adolescence to young adulthood. Methods This prospective study encompassed 254 participants measured at mean ages 15 and 19. Device-measured moderate-to-vigorous PA was grouped into five patterns (activity maintainers, inactivity maintainers, decreasers from moderate to low PA, decreasers from high to moderate PA, increasers) via a data-driven method, K-Means for longitudinal data. Multinomial logistic regression was used to analyse the associations between health behaviours, psychosocial factors, PA domains, and different PA patterns. Results A lack of sports club participation characterised inactivity maintainers throughout adolescence. Difficulties in communicating with one’s father at age 15 were associated with higher odds of belonging to inactivity maintainers and to decreasers from moderate to low PA. Lower fruit and vegetable consumption at age 19 was also related to increased odds of belonging to the groups of inactivity maintainers and decreasers from moderate to low PA. Smoking at age 19 was associated with being a decreaser from moderate to low PA. Conclusions Diverse factors characterise longitudinal PA patterns over the transition to young adulthood. Sports club participation contributes to maintained PA. Moreover, a father-adolescent relationship that supports open communication may be one determinant for sustained PA during adolescence. A healthier diet and non-smoking as a young adult are associated with more favourable PA development

Musculoskeletal examination in young athletes and non-athletes:the Finnish Health Promoting Sports Club (FHPSC) study

Abstract Objectives: To determine the inter-rater repeatability of a musculoskeletal examination and to compare findings between adolescent athletes and non-athletes in Finland. Methods: In this cross-sectional study, a musculoskeletal examination assessing posture, mobility and movement control was carried out by a sports and exercise medicine physician on 399 athletes aged 14–17 years and 177 non-athletes. Within 2 weeks another sports and exercise medicine physician repeated the examination for 41 adolescents to test the inter-rater repeatability. Results: In total, 10 of the 11 tests performed had at least moderate inter-rater reliability (κ ≥0.4 or percentage agreement &gt;80%). Athletes more often than non-athletes had one shoulder protruded (8.0% vs 4.0%, OR 2.81, 95% CI 1.16 to 6.81). Forty-six per cent of athletes had good knee control in the two-legged vertical drop jump test compared with 32% of non-athletes (OR 1.99, 95% CI 1.29 to 3.06). Athletes had better core muscle control with 86.3% being able to remain in the correct plank position for 30 s compared with 68.6% of non-athletes (OR 2.70, 95% CI 1.67 to 4.36). In the deep squat test, good lumbar spine control was maintained only by 35.8% of athletes and 38.4% of non-athletes. Conclusions: A basic musculoskeletal examination is sufficiently reliable to be performed by trained physicians as a part of a periodic health evaluation. Shortfalls in mobility, posture and movement control are common in both athletes and non-athletes. These deficits could have been caused by sedentary behaviour, monotonous training, or both

Haemoglobin, iron status and lung function of adolescents participating in organised sports in the Finnish Health Promoting Sports Club Study

Abstract Objectives: To compare laboratory test results and lung function of adolescent organised sports participants (SP) with non-participants (NP). Methods: In this cross-sectional study, laboratory tests (haemoglobin, iron status), and flow-volume spirometry were performed on SP youths (199 boys, 203 girls) and their NP peers (62 boys, 114 girls) aged 14–17. Results: Haemoglobin concentration &lt;120/130 g/L was found in 5.8% of SP and 5.1% NP (OR 1.20, 95% CI 0.54 to 2.68). Ferritin concentration below 15 µg/L was found in 22.7% of both SP and NP girls. Among boys ferritin &lt;30 µg/L was found in 26.5% of SP and 30.2% of NP (OR 0.76, 95% CI 0.40 to 1.47). Among SP iron supplement use was reported by 3.5% of girls and 1.5% of boys. In flow-volume spirometry with bronchodilation test, 7.0% of SP and 6.4% of NP had asthma-like findings (OR 1.17, 95% CI 0.54 to 2.54); those using asthma medication, that is, 9.8% of SP and 5.2% of NP were excluded from the analysis. Conclusions: Screening for iron deficiency is recommended for symptomatic persons and persons engaging in sports. Lung function testing is recommended for symptomatic persons and persons participating in sports in which asthma is more prevalent

Longitudinal physical activity patterns and the development of cardiometabolic risk factors during adolescence

Abstract Purpose: To examine the associations between longitudinal physical activity (PA) patterns and the development of cardiometabolic risk factors from adolescence to young adulthood. Methods: This cohort study encompassed 250 participants recruited from sports clubs and schools, and examined at mean age 15 and 19. Device-measured moderate-to-vigorous PA was grouped into five patterns (via a data-driven method, using inactivity maintainers as a reference). The outcomes were: glucose, insulin, homeostasis model assessment for insulin resistance (HOMA-IR), total cholesterol, HDL and LDL cholesterol, triglycerides, blood pressure, and body mass index (BMI). Linear growth curve models were applied with adjustment for sex, age, fruit/vegetable consumption, cigarette/snuff use, and change in the device wear-time. Results: Insulin and BMI increased among decreasers from moderate to low PA (β for insulin 0.23, 95% CI 0.03–0.46; β for BMI 0.90; CI 0.02–1.78). The concentration of HDL cholesterol decreased (β −0.18, CI −0.31 to −0.05) and that of glucose increased (β 0.18, CI 0.02–0.35) among decreasers from high to moderate PA. By contrast, among increasers, blood pressure declined (systolic β −6.43, CI −12.16 to −0.70; diastolic β −6.72, CI −11.03 to −2.41). Conclusions: Already during the transition to young adulthood, changes in PA are associated with changes in cardiometabolic risk factors. Favorable blood pressure changes were found among PA increasers. Unfavorable changes in BMI, insulin, glucose, and HDL cholesterol were found in groups with decreasing PA. The changes were dependent on the baseline PA and the magnitude of the PA decline

The Association between HDL-C and Subclinical Atherosclerosis Depends on CETP Plasma Concentration:Insights from the IMPROVE Study

The impact of cholesteryl ester transfer protein (CETP) on atherosclerosis is highly debated. This study aimed to investigate the associations between plasma CETP or CETP genotypes and carotid intima-media thickness (cIMT) and the influence of high-density lipoprotein cholesterol (HDL-C) on these associations. Plasma CETP and HDL-C concentrations were measured in 552 subjects free of any pharmacological treatment from the IMPROVE cohort, which includes 3711 European subjects at high cardiovascular risk. CETP single-nucleotide polymorphisms (SNPs) and cIMT measures (cIMT(max); cIMT(mean-max) of bifurcations, common and internal carotids; plaque-free common carotid [PF CC]-IMTmean) were available for the full cohort. In drug-free subjects, plasma CETP correlated with HDL-C levels (r = 0.19, p &lt; 0.0001), but not with cIMT variables. When stratified according to HDL-C quartiles, CETP positively correlated with cIMT(max) and cIMT(mean-max), but not with PF CC-IMTmean, in the top HDL-C quartile only. Positive associations between the CETP concentration and cIMT(max) or cIMT(mean-max) were found in the top HDL-C quartile, whereas HDL-C levels were negatively correlated with cIMT(max) and cIMT(mean-max) when the CETP concentration was below the median (HDL-C x CETP interaction, p = 0.001 and p = 0.003 for cIMT(max) and cIMT(mean-max), respectively). In the full cohort, three CETP SNPs (rs34760410, rs12920974, rs12708968) were positively associated with cIMT(max). rs12444708 exhibited a significant interaction with HDL-C levels in the prediction of cIMT(max). In conclusion, a significant interplay was found between plasma CETP and/or CETP genotype and HDL-C in the prediction of carotid plaque thickness, as indexed by cIMT(max). This suggests that the association of HDL-C with carotid atherosclerosis is CETP-dependent.</p