Cardiometabolic Health Among Adult Offspring of Hypertensive Pregnancies: The Cardiovascular Risk in Young Finns Study.

BACKGROUND: Cardiometabolic health among adult offspring of hypertensive disorders of pregnancy (HDP) is relatively unknown. We hypothesized that offspring of HDP would have abnormalities in the retinal microvasculature and cardiac structure by midadulthood. METHODS AND RESULTS: The Cardiovascular Risk in Young Finns Study included randomly selected children from 5 Finnish university cities. The mean age of participants was 40 years (range 34-49 years) at the time of retinal photography and cardiac assessment. Offspring born ≥37 weeks of gestation and appropriate for gestational age (n=1006) were included. Offspring of HDP had higher systolic blood pressure (β=4.68, P<0.001), body mass index (β=1.25, P=0.009), and waist circumference (β=0.25, P=0.042), compared with offspring of normotensive pregnancies. However, no differences in fasting glucose, insulin, lipid profile, carotid intima media thickness, or brachial artery flow-mediated dilatation were shown. Retinal arteriolar diameters were narrower (β=-0.43, P=0.009) and longer (β=32.5, P=0.023) and the arteriolar length-to-diameter ratio was higher (β=2.32, P=0.006) among offspring of HDP, after adjustment for age and sex. Left atrial volume indexed to body surface area (β=1.34, P=0.040) was increased. Adjustment for the confounding effects of birth weight, body mass index, smoking and socioeconomic status, and the mediating effect of hypertension had little impact on the associations. CONCLUSIONS: Abnormalities of the retinal microvasculature and cardiac structure are seen in offspring of HDP in midadulthood. These findings may need to be considered in future primary prevention strategies of cardiovascular disease among offspring of HDP

Early work-related physical exposures and low back pain in midlife: the Cardiovascular Risk in Young Finns Study

Objective To examine whether heavy physical workload in young adulthood increases the risk of local and radiating low back pain (LBP) in midlife.Methods Longitudinal nationally representative Young Finns Study data among women (n=414) and men (n=324), aged 18–24 years in 1986 (baseline), were used. Physical heaviness of work was reported at baseline and follow-up (2007), and local and radiating LBP at follow-up. Covariates were age, smoking and body mass index. Logistic regression was used to examine the associations between physical heaviness of work and LBP. Additionally, the mediating effect of back pain at baseline was examined (the Sobel test).Results After adjustment for the covariates, and as compared with sedentary/light physical workload, heavy physical workload was associated with radiating LBP among women (OR 4.09, 95% CI 1.62 to 10.31) and men (OR 2.01, 95% CI 1.06 to 3.82). Among men, early back pain mediated the association (p value from the Sobel test=0.006). Among women, early exposure to physically heavy work showed the most consistent associations, while early and late exposures were associated with radiating and local LBP among men. Persistently heavy physical work was associated with radiating LBP among women and men.Conclusions Physically heavy work at a young age can have a long-lasting effect on the risk of LBP, radiating LBP in particular. These results highlight the need to consider early and persistent exposures to prevent the adverse consequences of physical workload for the low back.</p

Cardiovascular Risk Factor Trajectories Since Childhood and Cognitive Performance in Midlife The Cardiovascular Risk in Young Finns Study

Background: Cardiovascular risk factors, such as high blood pressure, adverse serum lipids, and elevated body mass index in midlife, may harm cognitive performance. It is important to note that longitudinal accumulation of cardiovascular risk factors since childhood may be associated with cognitive performance already since childhood, but the previous evidence is scarce. We studied the associations of cardiovascular risk factors from childhood to midlife, their accumulation, and midlife cognitive performance. Methods: From 1980, a population-based cohort of 3596 children (3-18 years of age) have been repeatedly followed up for 31 years. Blood pressure, serum lipids, and body mass index were assessed in all follow-ups. Cardiovascular risk factor trajectories from childhood to midlife were identified using latent class growth mixture modeling. Cognitive testing was performed in 2026 participants 34 to 49 years of age using a computerized test. The associations of the cardiovascular risk factor trajectories and cognitive performance were studied for individual cardiovascular risk factors and cardiovascular risk factor accumulation. Results: Consistently high systolic blood pressure (beta=-0.262 SD [95% CI, -0.520 to -0.005]) and serum total cholesterol (beta=-0.214 SD [95% CI, -0.365 to -0.064]) were associated with worse midlife episodic memory and associative learning compared with consistently low values. Obesity since childhood was associated with worse visual processing and sustained attention (beta=-0.407 SD [95% CI, -0.708 to -0.105]) compared with normal weight. An inverse association was observed for the cardiovascular risk factor accumulation with episodic memory and associative learning (P for trend=0.008; 3 cardiovascular risk factors: beta=-0.390 SD [95% CI, -0.691 to -0.088]), with visual processing and sustained attention (P for trend Conclusions: Longitudinal elevated systolic blood pressure, high serum total cholesterol, and obesity from childhood to midlife were inversely associated with midlife cognitive performance. It is important to note that the higher the number of cardiovascular risk factors, the worse was the observed cognitive performance. Therefore, launching preventive strategies against cardiovascular risk factors beginning from childhood might benefit primordial promotion of cognitive health in adulthood.Peer reviewe

A Longitudinal Multilevel Study of the "Social" Genotype and Diversity of the Phenotype

Sociability and social domain-related behaviors have been associated with better well-being and endogenous oxytocin levels. Inspection of the literature, however, reveals that the effects between sociability and health outcomes, or between sociability and genotype, are often weak or inconsistent. In the field of personality psychology, the social phenotype is often measured by error-prone assessments based on different theoretical frameworks, which can partly explain the inconsistency of the previous findings. In this study, we evaluated the generalizability of "sociability" measures by partitioning the population variance in adulthood sociability using five indicators from three personality inventories and assessed in two to four follow-ups over a 15-year period (n = 1,573 participants, 28,323 person-observations; age range 20-50 years). Furthermore, we tested whether this variance partition would shed more light to the inconsistencies surrounding the "social" genotype, by using four genetic variants (rs1042778, rs2254298, rs53576, rs3796863) previously associated with a wide range of human social functions. Based on our results, trait (between-individual) variance explained 23% of the variance in overall sociability, differences between sociability indicators explained 41%, state (within-individual) variance explained 5% and measurement errors explained 32%. The genotype was associated only with the sociability indicator variance, suggesting it has specific effects on sentimentality and emotional sharing instead of reflecting general sociability

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