Trajectory patterns for continuous metabolic syndrome score in childhood and the cardiovascular risk in adolescence
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ABSTRACT:
SUBMITTER: Choi E
PROVIDER: S-EPMC8604916 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Platelets are key mediators of atherothrombosis; yet, limited tools exist to identify individuals with a hyperreactive platelet phenotype. Here we derive and validate a Platelet Reactivity ExpreSsion Score (PRESS) integrating platelet aggregation responses and RNA sequencing in multiple cohorts. PRESS performs well in identifying a hyperreactive phenotype in patients with cardiovascular disease (AUC [cross-validation] 0.81, 95% CI 0.68 to 0.94), with similar discrimination in an independent cohort of healthy participants (AUC [validation] 0.77, 95% CI 0.75 to 0.79); accuracy 80%, sensitivity 71%, and specificity 86%. Next, we validate PRESS in multiple cohorts of patients with platelet RNASeq available. Following multivariable adjustment, PRESS was significantly higher in MI (β=1.8, p=0.02), and individuals with a score above the median more frequently develop a future cardiovascular event (adjusted HR 1.90, CI 1.07 to 3.36), p=0.027). Altogether, we provide strong evidence that PRESS is a robust prognostic marker, which could have an essential role in facilitating a personalized approach to cardiovascular risk management.
2024-06-30 | GSE232027 | GEO
Project description:Importance:The American Heart Association 2020 Strategic Impact Goals target an improvement in overall cardiovascular health, as assessed by 7 health metrics (smoking, body weight, physical activity, diet, plasma glucose level, plasma cholesterol level, and blood pressure). Objective:To examine whether trajectories of overall cardiovascular health over time, as assessed by the cardiovascular health score (CHS) in 2006, 2008, and 2010, are associated with subsequent risk of CVD. Design, Setting, and Participants:The Kailuan study is a prospective, population-based study that began in 2006. The cohort included 74?701 Chinese adults free of myocardial infarction, stroke, and cancer in or before 2010. In the present study, CHS trajectories were developed from 2006 to 2010 to predict CVD risk from 2010 to 2015. Data analysis was performed from January 1, 2006, to December 31, 2015. Exposures:The CHS trajectories during 2006-2010 were identified using latent mixture models. Main Outcomes and Measures:Incident CVD events (myocardial infarction and stroke) during 2010-2015 were confirmed by review of medical records. The CHS trajectories were determined using 7 cardiovascular health metrics scored as poor (0 points), intermediate (1 point), and ideal (2 points); total score ranges from 0 (worst) to 14 (best). Based on the baseline CHS and patterns over time, 5 trajectories were categorized (low-stable, moderate-increasing, moderate-decreasing, high-stable I, and high-stable II). Results:Of the 74?701 adults included in the study (mean [SD] age at baseline, 49.6 [11.8] years), 58?216 (77.9%) were men and 16?485 (22.1%) were women. Five CHS trajectories were identified from 2006 to 2010: low-stable (n?=?4393; range, 4.6-5.2), moderate-increasing (n?=?4643; mean increase from 5.4 to 7.8), moderate-decreasing (n?=?14?853; mean decrease from 7.4 to 6.3), high-stable I (n?=?36?352; range, 8.8-9.0), and high-stable II (n?=?14?461; range, 10.9-11.0). During 5 years of follow-up, 1852 incident CVD cases were identified. Relative to the low-stable trajectory, the high-stable II trajectory was associated with a lower subsequent risk of CVD (adjusted hazard ratio, 0.21; 95% CI, 0.16-0.26, after adjusting for age, sex, educational level, income, occupation, alcohol intake, and serum high-sensitivity C-reactive protein concentration at baseline). Conclusions and Relevance:Cardiovascular health trajectories may be associated with subsequent CVD risk.
| S-EPMC6547110 | biostudies-literature
Project description:OBJECTIVE:Poor behavioral self-regulation in the first 2 decades of life has been identified as an important precursor of disease risk in adulthood. However, physiological regulation has not been well studied as a disease risk factor before adulthood. We tested whether physiological regulation at the age of 2 years, in the form of vagal regulation of cardiac function (indexed by respiratory sinus arrhythmia [RSA] change), would predict three indicators of cardiovascular risk at the age of 16 years (diastolic and systolic blood pressure and body mass index). METHODS:Data came from 229 children who participated in a community-based longitudinal study. At the age of 2 years, children were assessed for RSA baseline and RSA change (ln(ms)) in response to a series of challenge tasks. These same children were assessed again at the age of 16 years for diastolic and systolic blood pressure (millimeters of mercury), height (meters), and weight (kilogram). RESULTS:Regression analyses revealed that less RSA withdrawal at the age of 2 years predicted higher diastolic blood pressure at the age of 16 years, adjusting for demographic characteristics (B = -3.07, M [S E] = 1.12, p = .006). Follow-up analyses demonstrated that these predictions extended to clinically significant levels of diastolic prehypertension (odds ratio = 0.43, 95% confidence interval = 0.22-0.89). RSA withdrawal did not significantly predict adolescent body mass index or systolic blood pressure. CONCLUSIONS:Vagal regulation of cardiac function in early childhood predicts select indicators of cardiovascular risk 14 years later. Early signs of attenuated vagal regulation could indicate an increased risk for elevated blood pressure before adulthood. Future research should test biological, behavioral, and psychological mechanisms underlying these long-term predictions.
| S-EPMC5489373 | biostudies-literature
Project description:The dichotomous nature of the current definition of metabolic syndrome (MS) in youth results in loss of information. On the other hand, the calculation of continuous MS scores using standardized residuals in linear regression (Z scores) or factor scores of principal component analysis (PCA) is highly impractical for clinical use. Recently, a novel, easily calculated continuous MS score called siMS score was developed based on the IDF MS criteria for the adult population.To develop a Pediatric siMS score (PsiMS), a modified continuous MS score for use in the obese youth, based on the original siMS score, while keeping the score as simple as possible and retaining high correlation with more complex scores.The database consisted of clinical data on 153 obese (BMI ?95th percentile) children and adolescents. Continuous MS scores were calculated using Z scores and PCA, as well as the original siMS score. Four variants of PsiMS score were developed in accordance with IDF criteria for MS in youth and correlation of these scores with PCA and Z score derived MS continuous scores was assessed.PsiMS score calculated using formula: (2xWaist/Height) + (Glucose(mmol/l)/5.6) + (triglycerides(mmol/l)/1.7) + (Systolic BP/130)-(HDL(mmol/l)/1.02) showed the highest correlation with most of the complex continuous scores (0.792-0.901). The original siMS score also showed high correlation with continuous MS scores.PsiMS score represents a practical and accurate score for the evaluation of MS in the obese youth. The original siMS score should be used when evaluating large cohorts consisting of both adults and children.
| S-EPMC5718410 | biostudies-literature
Project description:BackgroundWhile the number of established genetic variants associated with adult body mass index (BMI) is growing, the relationships between these variants and growth during childhood are yet to be fully characterised. We examined the association between validated adult BMI associated single nucleotide polymorphisms (SNPs) and growth trajectories across childhood. We investigated the timing of onset of the genetic effect and whether it was sex specific.MethodsChildren from the ALSPAC and Raine birth cohorts were used for analysis (n?=?9,328). Genotype data from 32 adult BMI associated SNPs were investigated individually and as an allelic score. Linear mixed effects models with smoothing splines were used for longitudinal modelling of the growth parameters and measures of adiposity peak and rebound were derived.ResultsThe allelic score was associated with BMI growth throughout childhood, explaining 0.58% of the total variance in BMI in females and 0.44% in males. The allelic score was associated with higher BMI at the adiposity peak (females ?=? 0.0163 kg/m(2) per allele, males ?=? 0.0123 kg/m(2) per allele) and earlier age (-0.0362 years per allele in males and females) and higher BMI (0.0332 kg/m(2) per allele in females and 0.0364 kg/m(2) per allele in males) at the adiposity rebound. No gene:sex interactions were detected for BMI growth.ConclusionsThis study suggests that known adult genetic determinants of BMI have observable effects on growth from early childhood, and is consistent with the hypothesis that genetic determinants of adult susceptibility to obesity act from early childhood and develop over the life course.
| S-EPMC3823612 | biostudies-literature
Project description:BackgroundEvidence on the causal link between plasma triglyceride (TG) levels and risk for cardiovascular disease (CVD) has recently emerged. Individuals with the metabolic syndrome have an increased risk for acquiring elevated TG levels later in life. Moreover, common DNA sequence variations in genes affecting TG levels identify individuals at risk for elevated plasma TG levels.ObjectiveWe evaluated whether a 3-single nucleotide polymorphism (SNP) TG gene risk score (GRS) and a metabolic risk score (MetRS) both improved CVD risk prediction.MethodsA 3-SNP GRS and MetRS were generated in the EPIC-Norfolk cohort (n = 20,074) based on 3 SNPs in LPL and APOA5 or the number of Metabolic Syndrome criteria present (maximum 5), respectively. The associations between the 3-SNP GRS, MetRS, TG levels, and CVD risk were evaluated.ResultsThe 3-SNP GRS and MetRS were both linearly associated with plasma TG levels, that is, +0.25 mmol/L [95% CI 0.22-0.27] per allele change (P < .001) and +0.72 mmol/L [95% CI 0.70-0.73] per increase of number of metabolic syndrome risk score points (P < .001), respectively. We observed a positive association between the 3-SNP GRS and the risk of CVD with an adjusted hazard ratio (HR) of 1.35 [95% CI 1.04-1.74] for the highest versus the lowest GRS, which was independent of the MetRS. For the MetRS, the adjusted HR was 2.03 [95% CI 1.73-2.40] for the highest versus the lowest MetRS.ConclusionBoth the 3-SNP GRS and the MetRS are associated with increased plasma TG levels and increased risk for CVD.
| S-EPMC7340536 | biostudies-literature
Project description:BackgroundAssociations have been observed among genetic variants, dietary patterns, and metabolic syndrome (MetS). A gap in knowledge is whether a genetic risk score (GRS) and dietary patterns interact to increase MetS risk among African Americans. We investigated whether MetS risk was influenced by interaction between a GRS and dietary patterns among Whites and African Americans. A secondary aim examined if molecular genetic clusterings differed by racial ancestry.MethodsWe used longitudinal data over 4-visits (1987-1998) that included 10,681 participants aged 45-64y at baseline from the Atherosclerosis Risk in Communities study (8451 Whites and 2230 African Americans). We constructed a simple-count GRS as the linear weighted sum of high-risk alleles (0, 1, 2) from cardiovascular disease polymorphisms from the genome-wide association studies catalog associated with MetS risk. Three dietary patterns were determined by factor analysis of food frequency questionnaire data: Western, healthy, and high-fat dairy. MetS was defined according to the 2016 National Cholesterol Education Program Adult Treatment Panel III criteria but used 2017 American Heart Association/American College of Cardiology criteria for elevated blood pressure. Analyses included generalized linear model risk ratios (RR), 95% confidence intervals (CI), and Bonferroni correction for multiple testing.ResultsThe Western dietary pattern was associated with higher risk for MetS across increasing GRS tertiles among Whites (p < 0.017). The high-fat dairy pattern was protective against MetS, but its impact was most effective in the lowest GRS tertile in Whites (RR = 0.62; CI: 0.52-0.74) and African Americans (RR = 0.67; CI: 0.49-0.91). Among each racial group within GRS tertiles, the Western dietary pattern was associated with development and cycling of MetS status between visits, and the high-fat dairy pattern with being free from MetS (p < 0.017). The healthy dietary pattern was associated with higher risk of MetS among African Americans which may be explained by higher sucrose intake (p < 0.0001). Fewer genes, but more metabolic pathways for obesity, body fat distribution, and lipid and carbohydrate metabolism were identified in African Americans than Whites. Some polymorphisms were linked to the Western and high-fat dairy patterns.ConclusionThe influence of dietary patterns on MetS risk appears to differ by genetic predisposition and racial ancestry.
| S-EPMC8088631 | biostudies-literature
Project description:OBJECTIVE:To evaluate the impact of infant growth on childhood health by examining the associations of detailed longitudinal infant weight velocity patterns with childhood cardiovascular and metabolic outcomes. STUDY DESIGN:In a population-based prospective cohort study of 4649 children, we used repeated growth measurements at age 0-3 years to derive peak weight velocity (PWV), age at adiposity peak (AGEAP), and body mass index at adiposity peak (BMIAP). At age 6 years, we measured blood pressure, left ventricular mass, and cholesterol, triglyceride, and insulin concentrations and defined children with clusters of risk factors. We assessed associations using 2 multivariable linear regression models. RESULTS:A 1-SDS-higher infant PWV was associated with higher diastolic blood pressure (0.05 SDS; 95% CI, 0.02-0.09) and lower left ventricular mass (-0.05 SDS; 95% CI, -0.09 to -0.01), independent of body size. A 1-SDS-higher BMIAP was associated with higher systolic (0.12; 95% CI, 0.09-0.16) and diastolic (0.05; 95% CI, 0.01-0.08) blood pressure, but these associations were explained by childhood BMI. We did not observe any associations of PWV, BMIAP, and AGEAP with cholesterol and insulin concentrations. Higher PWV and AGEAP were associated with elevated risk of clustering of cardiovascular risk factors in childhood (P?<?.05). CONCLUSION:Infant weight velocity patterns are associated with cardiovascular outcomes. Further studies are needed to explore the associations with metabolic outcomes and long-term consequences.
| S-EPMC5489080 | biostudies-literature
Project description:Metabolic syndrome (MS) and Framingham risk score (FRS) can be used for predicting the risk of developing cardiovascular diseases (CVD). Previous studies that compared FRS and MS have focused on high-income urban areas. This study focused on the comparison between FRS and MS when used in nomadic minorities in mountain areas. Moreover, an applicable tool for predicting the risk of developing CVD was identified. 2,286 participants who were recruited from the far west of China were followed-up for a median of 5.49 years. MS and FRS were compared in terms of their ability in predicting development of CVD using Cox regression and receiver operating characteristic curve. After each component of MS was appraised, its area under the curve (AUC) was 0.647. When age was included, the AUC of MS risk score increased from 0.647 to 0.758 (P?<?0.001). After adjusting for age, the AUC of FRS decreased from 0.732 to 0.582 (P?<?0.001). The association between CVD and each quintile of MS risk score that included age was more significant than that between FRS and CVD under the same exposed condition. In conclusion, MS risk score that included age may be a better predictor of CVD among Kazakhs.
| S-EPMC6220288 | biostudies-literature
Project description:Obesity is associated with higher cardio-metabolic risk even in childhood and adolescence; whether this association is mediated by epigenetic mechanisms remains unclear. We examined the extent to which mid-childhood body mass index (BMI) z-score (median age 7.7 years) was associated with cardio-metabolic risk score in early adolescence (median age 12.9 years) via mid-childhood DNA methylation among 265 children in the Project Viva. We measured DNA methylation in leukocytes using the Infinium Human Methylation450K BeadChip. We assessed mediation CpG-by-CpG using epigenome-wide association analyses, high-dimensional mediation analysis, and natural effect models. We observed mediation by mid-childhood DNA methylation at 6 CpGs for the association between mid-childhood BMI z-score and cardio-metabolic risk score in early adolescence in the high-dimensional mediation analysis (accounting for 10% of the total effect) and in the natural effect model (? = 0.04, P = 3.2e-2, accounting for 13% of the total effect). The natural direct effect of BMI z-score on cardio-metabolic risk score was still evident (? = 0.27, P = 1.1e-25). We also observed mediation by mid-childhood DNA methylation at 5 CpGs that was in the opposite direction from the total effect (natural effect model: ? = -0.04, P = 2.0e-2). Mediation in different directions implies a complex role of DNA methylation in the association between BMI and cardio-metabolic risk and needs further investigation. Future studies with larger sample size and greater variability in cardio-metabolic risk will further help elucidate the role of DNA methylation for cardio-metabolic risk.
| S-EPMC6342073 | biostudies-literature