Association of Habitual Physical Activity With Cardiovascular Risk Factors and Target Organ Damage in Adolescents and Young Adults.

BACKGROUND: We aimed to (1) compare a subjective and objective measure of habitual physical activity (PA), (2) determine the association of PA and cardiovascular risk factors, and (3) test the hypothesis that PA is an independent determinant of target organ damage in youth. METHODS: Cross-sectional analysis of youth with and without type 2 diabetes [mean age = 22 (3.9) y]. PA was measured with International Physical Activity Questionnaire and Actical accelerometer. Target organ damage was assessed with echocardiography and peripheral arterial testing. Subjects were stratified into tertiles of total PA, and differences were tested by analysis of variance and χ2 tests. General linear models tested for independent associations. RESULTS: The correlation between International Physical Activity Questionnaire and accelerometry was weak (r = .23, P = .0003). Less active subjects had worse cardiovascular risk profiles and target organ damage, including stiffer arteries (P < .01). These outcome differences did not reach statistical significance when adjusted for covariates, such as lipid levels and glycemic control. CONCLUSION: Survey assessment of PA is complicated by inaccurate reporting. There is a strong association of habitual PA with cardiovascular risk factor clustering. PA may exert its beneficial effect on arterial stiffness in obese youth through improved glycemic control.

Lipoprotein particle number and size predict vascular structure and function better than traditional lipids in adolescents and young adults.

BACKGROUND: In adults, dyslipidemia is associated with higher carotid thickness and arterial stiffness, predictors of cardiovascular events. In young subjects, lipid concentrations have not been consistently associated with vascular measures. OBJECTIVE: The objective of the study was to compare nuclear magnetic resonance (NMR) measures of lipoprotein particle number (low-density lipoprotein [LDL] particle, low-density lipoprotein [HDL] particle, very low-density lipoprotein [VLDL] particle) and size (LDL size, HDL size, and VLDL size) to determine if they were associated with vascular measures more strongly than lipid concentrations (LDL cholesterol, HDL cholesterol, and triglyceride [TG]). METHODS: We evaluated 214 lean (L), 228 obese (O), and 214 diabetic (T2DM) subjects aged 10 to 24 years (33% male and 39% Caucasian). Cardiovascular risk factors, vascular structure, and arterial stiffness were measured. General linear models were constructed including demographics, risk factors, and traditional or NMR lipid parameters. A composite vascular function score was developed as the outcome in receiver operator characteristic scores for determining which lipid parameter was superior in predicting vascular damage. RESULTS: Risk factors worsened from L to O to T. However, LDL cholesterol was similar in O and T, whereas LDL size differentiated the 3 groups (T > O > L, P ≤ .0001). Models demonstrated the superiority of NMR values, which entered for all but 1 vascular outcome and explained more of the variance than traditional lipid concentrations. Receiver operator characteristic curves demonstrated that NMR values were superior in predicting vascular outcomes. Models stratified by race were similar but cutpoints predicting vascular outcomes differed by race for TG, TG/HDL, and VLDL. CONCLUSION: Lipoprotein particle number and size are more strongly related to vascular structure and function than traditional lipid values. NMR lipid measures may be a better indicator of risk for target organ damage than traditional lipid measures in adolescents and young adults.

Adiposity has no direct effect on carotid intima-media thickness in adolescents and young adults: Use of structural equation modeling to elucidate indirect & direct pathways.

BACKGROUND: Carotid intima-media thickness (cIMT) is associated with CV events in adults. Thicker cIMT is found in youth with CV risk factors including obesity. Which risk factors have the most effect upon cIMT in youth and whether obesity has direct or indirect effects is not known. We used structural equation modeling to elucidate direct and indirect pathways through which obesity and other risk factors were associated with cIMT. METHODS: We collected demographics, anthropometrics and laboratory data on 784 subjects age 10-24 years (mean 18.0 ± 3.3 years). Common, bulb and internal carotid cIMT were measured by ultrasound. Multivariable regression analysis was performed to assess independent determinants of cIMT. Analyses were repeated with structural equation modeling to determine direct and indirect effects. RESULTS: Multivariable regression models explained 11%-22% of variation of cIMT. Age, sex and systolic blood pressure (BP) z-score were significant determinants of all cIMT segments. Body mass index (BMI) z-score, race, presence of type 2 diabetes mellitus (T2DM), hemoglobin A1c (HbA1c) and non-HDL were significant for some segments (all p = 0.05). The largest direct effect on cIMT was age (0.312) followed by BP (0.228), Blood glucose control (0.108) and non-HDL (0.134). BMI only had a significant indirect effect through blood glucose control, BP & non-HDL. High sensitivity C-reactive protein (CRP) had a small indirect effect through blood glucose control (all p = 0.05). CONCLUSIONS: Age and BP are the major factors with direct effect on cIMT. Glucose and non-HDL were also important in this cohort with a high prevalence of T2DM. BMI only has indirect effects, through other risk factors. Traditional CV risk factors have important direct effects on cIMT in the young, but adiposity exerts its influence only through other CV risk factors.

Comparison of mercury sphygmomanometry blood pressure readings with oscillometric and central blood pressure in predicting target organ damage in youth.

OBJECTIVE: Hypertension (HT) is an important risk factor for target organ damage (TOD). New methods for measuring BP are replacing mercury sphygmomanometry in many clinics. We examined the utility of different BP measurement techniques in predicting subclinical TOD in adolescents and young adults. METHODS: Participants in a study of the cardiovascular effects of obesity and type 2 diabetes were evaluated (N=677, 18±3.3 years, 35% male, 60% non-White, 30% with type 2 diabetes). We measured adiposity, laboratory data, left ventricular mass, carotid intima-media thickness, and pulse wave velocity. BP was measured three times by mercury sphygmomanometry (BPm), using an oscillometric device (BPo), and by arterial tonometry to measure central aortic BP (BPc). Participants were stratified as normotensive, prehypertensive, or hypertensive. RESULTS: The prevalence of HT in this cohort with a mean BMI of 31 was the highest on BPo measurement (16%), followed by BPm (11%) and BPc (9%; P≤0.001) measurements. BPm was the most consistent in differentiating left ventricular mass and pulse wave velocity among participants in the prehypertensive group as compared with the normotensive and hypertensive groups. Mercury BP measurement was also more sensitive and specific at predicting greater left ventricular mass, pulse wave velocity, and carotid thickness compared with other BP measurement techniques in logistic regression. CONCLUSION: We conclude that mercury sphygmomanometry should remain the gold standard for evaluation of HT and the risk for TOD in adolescents and young adults.

Triglyceride to HDL-C ratio and increased arterial stiffness in children, adolescents, and young adults.

BACKGROUND AND OBJECTIVE: Lipid levels are linked to early atherosclerosis. Risk stratification may be improved by using triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C), which relates to arterial stiffness in adults. We tested whether TG/HDL-C was an independent predictor of arterial stiffness in youth. METHODS: Subjects 10 to 26 years old (mean 18.9 years, 39% male, 56% non-Caucasian, n = 893) had laboratory, anthropometric, blood pressure, and arterial stiffness data collected (brachial distensibility, augmentation index, carotid-femoral pulse-wave velocity). Subjects were stratified into tertiles of TG/HDL-C (low, n = 227; mid, n = 288; high, n = 379). RESULTS: There was a progressive rise in cardiovascular (CV) risk factors and arterial stiffness across TG/HDL-C ratio. The high TG/HDL-C ratio group had the stiffest vessels (all P < .03 by analysis of variance). TG/HDL-C as a continuous variable was an independent determinant of brachial distensibility in CV risk factor adjusted model and for carotid-femoral pulse-wave velocity in obese subjects, with trend for higher augmentation index. CONCLUSIONS: TG/HDL-C, an estimate of small, dense low-density lipoprotein cholesterol, is an independent determinant of arterial stiffness in adolescents and young adults, especially in obese youth. These data suggest that use of TG/HDL-C may be helpful in identifying young adults requiring aggressive intervention to prevent atherosclerotic CV diseases.

Relationship between elevated arterial stiffness and increased left ventricular mass in adolescents and young adults.

OBJECTIVE: To determine whether arterial stiffness relates to left ventricular mass (LVM) in adolescents and young adults. STUDY DESIGN: Demographic, anthropometric, laboratory, echo, carotid ultrasound and arterial stiffness data were obtained in 670 subjects 10 to 24 years of age (35% male, 62% non-Caucasian). Global stiffness index (GSI) was calculated from five measures of carotid artery stiffness, augmentation index, brachial distensibility, and pulse wave velocity (1 point if ≥95th% for subjects with body mass index <85th%). Stiff arteries (S = 73) were defined as GSI ≥95th%. Differences between flexible (F = 597) and S groups were evaluated by t tests. Models were constructed to determine whether GSI was an independent determinant of LVM index or relative wall thickness (RWT). RESULTS: The S group had more adverse cardiovascular risk factors, higher LVM index and RWT (P ≤ .05) with a trend for abnormal cardiac geometry. Independent determinants of LVM index were higher GSI, age, body mass index, systolic blood pressure, heart rate, glycated hemoglobin A1c, male sex, and sex-by-heart rate interaction (r(2) = 0.52; P ≤ .05). GSI was also an independent determinant of RWT. CONCLUSIONS: Increased arterial stiffness in adolescents and young adults is associated with LVM index independently of traditional cardiovascular risk factors. Screening for arterial stiffness may be useful to identify high risk adolescents and young adults.

Youth with obesity and obesity-related type 2 diabetes mellitus demonstrate abnormalities in carotid structure and function.

BACKGROUND: Adults with obesity or type 2 diabetes mellitus (T2DM) are at higher risk for stroke and myocardial infarction. Increased carotid intima-media thickness (cIMT) and stiffness are associated with these adverse outcomes. We compared carotid arteries in youth who were lean, were obese, or had T2DM. METHODS AND RESULTS: Carotid ultrasound for cIMT measurement was performed, the Young elastic modulus and beta stiffness index were calculated, and anthropometric and laboratory values and blood pressure were measured in 182 lean, 136 obese, and 128 T2DM youth (aged 10 to 24 years). Mean differences were evaluated by ANOVA. Independent determinants of cIMT, Young elastic modulus, and beta stiffness index were determined with general linear models. Cardiovascular risk factors worsened from lean to obese to T2DM groups. T2DM subjects had greater cIMT than that in lean and obese subjects for the common carotid artery and bulb. For the internal carotid artery, cIMT measurements in both obese and T2DM groups were thicker than in the lean group. The carotid arteries were stiffer in obese and T2DM groups than in the lean group. Determinants of cIMT were group, group x age interaction, sex, and systolic blood pressure for the common carotid artery (r2=0.17); age, race, and systolic blood pressure for the bulb (r2=0.16); and age, race, sex, systolic blood pressure, and total cholesterol for the internal carotid artery (r2=0.21). Age, systolic blood pressure, and diastolic blood pressure were determinants of all measures of carotid stiffness, with sex adding to the Young elastic modulus (r2=0.23), and body mass index Z score, group, and group x age interaction contributing to the beta stiffness index (r2=0.31; all P<0.0001). CONCLUSIONS: Youth with obesity and T2DM have abnormalities in carotid thickness and stiffness that are only partially explained by traditional cardiovascular risk factors. These vascular changes should alert healthcare practitioners to address cardiovascular risk factors early to prevent an increase in the incidence of stroke and myocardial infarction.