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Cardiac markers of pre-clinical disease in adolescents with the metabolic syndrome: the strong heart study.

ABSTRACT: Our aim was to evaluate the impact of metabolic syndrome (MetS) on cardiac phenotype in adolescents.A high prevalence of MetS has been reported in adolescents.Four hundred forty-six nondiabetic American Indian adolescents (age 14 to 20 years, 238 girls) underwent clinical evaluation, laboratory testing, and Doppler echocardiography. Age- and gender-specific partition values were used to define obesity and hypertension. Metabolic syndrome was defined according to Adult Treatment Panel III criteria, modified for adolescents. Left ventricular (LV) hypertrophy and left atrial (LA) dilation were identified using age- and gender-specific partition values.One hundred eleven participants met criteria for MetS. They had a similar age and gender distribution as non-MetS participants. Analysis of covariance, controlling for relevant confounders, demonstrated that participants with MetS had higher LV, LA, and aortic root diameters, higher LV relative wall thickness, and greater LV mass index. Accordingly, MetS participants showed higher prevalences of LV hypertrophy (43.2% vs. 11.7%) and LA dilation (63.1% vs. 21.9%, both p < 0.001) compared with non-MetS participants. In addition, MetS was associated with a reduction in midwall shortening, lower transmitral mitral early to atrial peak velocity ratio, and mildly prolonged mitral early deceleration time (all p < 0.05). In multiple regression analysis, independently of demographics, obesity, blood pressure, and single metabolic components of MetS, clustered MetS was associated with a 2.6-fold higher likelihood of LV hypertrophy and a 2.3-fold higher likelihood of LA dilation (both p < or = 0.02).In a population sample of adolescents, MetS is associated with higher prevalences of LV hypertrophy and LA dilation and with reduced LV systolic and diastolic function, independently of individual MetS components.

SUBMITTER: Chinali M

PROVIDER: S-EPMC2703730 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Cardiac markers of pre-clinical disease in adolescents with the metabolic syndrome: the strong heart study.

Chinali Marcello M de Simone Giovanni G Roman Mary J MJ Best Lyle G LG Lee Elisa T ET Russell Marie M Howard Barbara V BV Devereux Richard B RB

Journal of the American College of Cardiology 20080901 11

<h4>Objectives</h4>Our aim was to evaluate the impact of metabolic syndrome (MetS) on cardiac phenotype in adolescents.<h4>Background</h4>A high prevalence of MetS has been reported in adolescents.<h4>Methods</h4>Four hundred forty-six nondiabetic American Indian adolescents (age 14 to 20 years, 238 girls) underwent clinical evaluation, laboratory testing, and Doppler echocardiography. Age- and gender-specific partition values were used to define obesity and hypertension. Metabolic syndrome was ...[more]

PMID: 18772065

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Project description:The world population is genetically predisposed to metabolic syndrome (MetS) and its components, also known as cardiometabolic risk phenotypes, which can cause severe health complications including coronary heart disease (CHD). Genetic variants in the 9p21 locus have been associated with CHD in a number of populations including Pakistan. However, the role of the 9p21 locus in MetS and cardiometabolic risk phenotypes (such as obesity, hypertension, hyperglycemia, and dyslipidemia) in populations with CHD or no established CHD has not been explored. Therefore, the present study was designed to explore the association of the minor/risk allele (C) of 9p21 locus SNP rs1333049 with MetS or its risk phenotypes regardless of an established CHD, in Pakistani subjects. Genotyping of rs1333049 (G/C) was performed on subjects under a case-control study design; healthy controls and cases, MetS with CHD (MetS-CHD+) and MetS with no CHD (MetS-CHD-), respectively. Genotype and allele frequencies were calculated in all study groups. Anthropometric and clinical variables (Means ± SD) were compared among study groups (i.e., controls, MetS + CHD and MetS-CHD) and minor/risk C allele carriers (GC + CC) vs. non-carriers (Normal GG genotype). Associations of the risk allele of rs1333049 SNP with disease and individual metabolic risk components were explored using adjusted multivariate logistic regression models (OR at 95% CI) with a threshold p-value of ≤0.05. Our results have shown that the minor allele frequency (MAF) was significantly high in the MAF cases (combined = 0.63, MetS-CHD+ = 0.57 and MetS-CHD- = 0.57) compared with controls (MAF = 0.39). The rs1333049 SNP significantly increased the risk of MetS, irrespective of CHD (MetS-CHD+ OR = 2.36, p < 0.05 and MetS-CHD- OR = 4.04, p < 0.05), and cardiometabolic risk phenotypes; general obesity, central obesity, hypertension, and dyslipidemia (OR = 1.56-3.25, p < 0.05) except hyperglycemia, which lacked any significant association (OR = 0.19, p = 0.29) in the present study group. The 9p21 genetic locus/rs1333049 SNP is strongly associated with, and can be a genetic predictor of, MetS and cardiometabolic risks, irrespective of cardiovascular diseases in the Pakistani population.

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Project description:TGF-? involvement in Chagas disease cardiomyopathy has been clearly demonstrated. The TGF-? signaling pathway is activated in the cardiac tissue of chronic phase patients and is associated with an increase in extracellular matrix protein expression. The aim of this study was to investigate the effect of GW788388, a selective inhibitor of T?R1/ALK5, on cardiac function in an experimental model of chronic Chagas' heart disease. To this end, C57BL/6 mice were infected with Trypanosoma cruzi (102 parasites from the Colombian strain) and treated orally with 3mg/kg GW788388 starting at 120 days post-infection (dpi), when 100% of the infected mice show cardiac damage, and following three distinct treatment schedules: i) single dose; ii) one dose per week; or iii) three doses per week during 30 days. The treatment with GW788388 improved several cardiac parameters: reduced the prolonged PR and QTc intervals, increased heart rate, and reversed sinus arrhythmia, and atrial and atrioventricular conduction disorders. At 180 dpi, 30 days after treatment interruption, the GW3x-treated group remained in a better cardiac functional condition. Further, GW788388 treatment reversed the loss of connexin-43 enriched intercellular plaques and reduced fibrosis of the cardiac tissue. Inhibition of the TGF-? signaling pathway reduced TGF-?/pSmad2/3, increased MMP-9 and Sca-1, reduced TIMP-1/TIMP-2/TIMP-4, and partially restored GATA-6 and Tbox-5 transcription, supporting cardiac recovery. Moreover, GW788388 administration did not modify cardiac parasite load during the infection but reduced the migration of CD3+ cells to the heart tissue. Altogether, our data suggested that the single dose schedule was not as effective as the others and treatment three times per week during 30 days seems to be the most effective strategy. The therapeutic effects of GW788388 are promising and suggest a new possibility to treat cardiac fibrosis in the chronic phase of Chagas' heart disease by TGF-? inhibitors.

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Cardiac markers of pre-clinical disease in adolescents with the metabolic syndrome: the strong heart study.

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Cardiac markers of pre-clinical disease in adolescents with the metabolic syndrome: the strong heart study.

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