Association between anthropometry, cardiometabolic risk factors, & early life factors & adult measures of endothelial function: Results from the New Delhi Birth Cohort.

BACKGROUND & OBJECTIVES: Abnormal endothelial function represents a preclinical marker of atherosclerosis. This study was conducted to evaluate associations between anthropometry, cardiometabolic risk factors, and early life factors and adult measures of endothelial function in a young urban Indian cohort free of clinical cardiovascular disease. METHODS: Absolute changes in brachial artery diameter following cuff inflation and sublingual nitroglycerin (400 µg) were recorded to evaluate endothelium-dependent and -independent measures of endothelial function in 600 participants (362 men; 238 women) from the New Delhi Birth Cohort (2006-2009). Data on anthropometry, cardiometabolic risk factors, medical history, socio-economic position, and lifestyle habits were collected. Height and weight were recorded at birth, two and 11 yr of age. Age- and sex-adjusted linear regression models were developed to evaluate these associations. RESULTS: The mean age of participants was 36±1 yr. Twenty two per cent men and 29 per cent women were obese (BMI th > 30 kg/m [2] ). Mean systolic blood pressure (SBP) was 131±14 and 119±13 mmHg, and diabetes prevalence was 12 and 8 per cent for men and women, respectively. Brachial artery diameter was higher for men compared with women both before (3.48±0.37 and 2.95±0.35 cm) and after hyperaemia (3.87±0.37 vs. 3.37±0.35 cm). A similar difference was seen before and after nitroglycerin. Markers of increased adiposity, smoking, SBP, and metabolic syndrome, but not early life anthropometry, were inversely associated with endothelial function after adjustment for age and sex. INTERPRETATION & CONCLUSIONS: The analysis of the current prospective data from a young urban Indian cohort showed that cardiometabolic risk factors, but not early life anthropometry, were associated with worse endothelial function.

Lipoprotein (a)--lipid profile and apolipoprotein B in children of young parents with coronary artery disease.

OBJECTIVE: To evaluate lipoprotein(a), apolipoprotein B and lipid profile in children of young parents with coronary artery disease. DESIGN: Analytical observational study. SETTING: Tertiary care hospital. MATERIAL: The study included 80 children (9-18 years) out of which 40 were children of young parents (one or both) with established coronary artery disease (CAD), while the other 40 were children of parents with no evidence of CAD (controls). All were evaluated for fasting blood glucose, lipid profile, apolipoprotein B and lipoprotein (a) - Lp(a). Two sample 't' test was applied for analysis of continuous variables between study & control group. RESULTS: The study group children had significantly higher levels of total serum cholesterol (p = 0.004), LDL cholesterol (p = 0.002), lipoprotein a (p = 0.001) as compared to children of the control group. A significant difference in apolipoprotein B levels (p = 0.044) was observed in children in the adolescent age group (14-18 years). Both systolic and diastolic blood pressures were significantly higher without any significant difference being observed for weight and body mass index between the two groups. CONCLUSION: Higher levels of pro-atherogenic factors in children with family history of premature CAD indicate that the combined effects of "nature and nurture" are responsible for development of accelerated atherosclerosis especially in Indians. Tracking of Lp(a) levels from childhood may be a better option than detecting other elements of dyslipidemia which are not fully expressed until middle age.

Non-invasive evaluation of endothelial function, arterial mechanics and nitric oxide levels in children of hypertensive parents.

OBJECTIVE: To evaluate endothelial function, arterial mechanics and nitric oxide levels in apparently healthy children of hypertensive parents. DESIGN: Analytical observational study. SETTING: Tertiary Care hospital. MATERIAL: The group comprised 40 non-obese normotensives (11-18 years). Out of these, 20 were children of parents (one or both) with hypertension (systolic >140 mm Hg, diastolic > 90 mm Hg) while the rest were children of normotensive parents (controls). High resolution ultrasonography was performed to measure flow mediated and glyceryltrinitrate induced dilatation in the brachial artery and arterial mechanics in the common carotid artery. Fasting blood was assayed for nitric oxide by the Griess method. RESULTS: Flow mediated dilatation (FMD) was decreased in children of hypertensive parents as compared to controls (0.016 + 0.007 cm vs 0.075 vs 0.075 7plus; 0.130 cm, p < 0.05) the difference being statistically significant. But subsequently, the post glyceryl-trinitrate (GTN) dilation was comparable in both with no statistical significant difference being noted. Arterial mechanics (carotid intima-media thickness-C-IMT) were comparable in both the groups. Similarly nitric oxide levels estimated in platelet rich and platelet poor plasma were comparable in both the groups, with no statistical significance. CONCLUSIONS: Flow mediated vasodilatation (FMD) in the brachial artery was decreased in children of hypertensive parents as compared to controls. Subsequent post GTN vasodilatation was comparable in both the groups because, GTN acts directly on vascular muscle and not on endothelium. Similarly, arterial mechanics (C-IMT) and nitric oxide estimation in platelet rich and platelet poor plasma were comparable in both the groups. It is, therefore, concluded that children of hypertensive parents have evidence of endothelial dysfunction, as shown by the decrease in flow mediated dilatation, which could be an early marker for the development of coronary artery disease.

Insulin resistance and lipid profile in the children of young ischemic parents.

OBJECTIVE: To determine serum levels of insulin, glucose and lipid profile in children of young parents with CAD. DESIGN: Cohort study. SETTING: Tertiary care teaching hospital. METHODS: Fifty children in the 5-18 years age group of young parents (< 45 years) with CAD, evaluated for fasting blood glucose, insulin and lipid profile compared with children of normal parents in the same age group. RESULTS: Serum total and LDL-Cholesterol, blood sugar and B.P., both systolic and diastolic were significantly higher in test group as compared to controls though there was no significant difference observed for weight and body mass index (BMI) between the two groups. The insulin levels were also significantly high in the test cases.

Noninvasive evaluation of endothelial function and arterial mechanics in overweight adolescents.

OBJECTIVE: To evaluate endothelial function and arterial mechanics in apparently healthy overweight adolescents. DESIGN: Analytical observational study. SETTING: Tertiary hospital. METHODS: 40 asymptomatic, normotensive and non-smoking adolescents (11 to 18 years old) were evaluated. Of these 20 were overweight or obese as per International Obesity Task Force criteria while 20 were controls. High resolution ultrasonography was performed to measure flow mediated and Glyceryltrinitrate induced dilation in brachial artery, and arterial mechanics in common carotid artery. RESULTS: Overweight adolescents had significantly lower ratio of flow mediated dilation to Glyceryltrinitrate mediated dilation (0.40 plusminus 0.41 versus 0.61 plusminus 0.17; P = 0.039). On age and sex adjusted multiple regression analysis, the ratio of flow mediated to Glyceryltrinitrate mediated dilation had a significant negative association with body mass index (P = 0.012) and mean skin fold thickness (P = 0.011). However, for mean skin fold thickness, flow mediated dilation also had a significant negative association (P = 0.027). None of the measures of arterial mechanics were significantly different amongst overweights and controls, or significantly associated with either body mass index or mean skin fold thickness. CONCLUSION: Endothelial function can be mildly impaired in apparently healthy adolescents who are overweight (assessed by body mass index) or adipose (assessed by skin fold thickness). The use of overweight for screening adolescents likely to develop coronary artery disease is therefore justified. Skin fold thickness is a better indicator than Body Mass Index for predicting endothelial function.

Predictors of carotid intima-media thickness and carotid plaque in young Indian adults: the New Delhi birth cohort.

BACKGROUND: Carotid intima-media thickness (CIMT) and carotid plaques represent preclinical markers of atherosclerosis. We sought to describe predictors of CIMT and carotid plaques, including early life growth, in a young urban Indian cohort free of clinical cardiovascular disease (CVD). METHODS: In 2006-2009, we performed B-mode carotid ultrasound on 600 participants (mean [SD] age 36 [1.1] years; 45% women) from the New Delhi Birth Cohort to evaluate CIMT and carotid plaques (>1mm). Height and weight were recorded at birth, 2 and 11 years of age. Data on CVD risk factors, anthropometry, medical history, socio-economic position, and lifestyle habits were collected in 1998-2002. RESULTS: Mean (SD) CIMT for men and women was 0.91 (0.12) and 0.86 (0.13) mm, respectively. Carotid plaque was present in 33% of men and 26% of women. Waist circumference in 1998-2002 was positively associated with CIMT (ß coefficient 0.26 mm [0.17, 0.36] per SD) and carotid plaque (OR 1.27 [1.06,1.52] per SD) in 2006-2009. Higher triglycerides, PAI-1, insulin resistance, and diastolic blood pressure, metabolic syndrome, and lower HDL-cholesterol and physical activity predicted higher CIMT and/or plaque (p<0.05). Longer length at 2 years was associated with higher CIMT (p<0.05). These associations were attenuated after adjusting for adult waist circumference. CONCLUSIONS: These are the first prospective data from India showing that early life growth, adult socio-demographics, and CVD risk factors predict future CIMT and/or carotid plaque. These relationships appear primarily mediated through central adiposity, highlighting the importance of maintaining a healthy weight in early adulthood to prevent CVD.

Homocysteine, fibrinogen and lipid profile in children of young adults with coronary artery disease.

Plasma homocysteine (9.05 ± 4.78 vs 5.93 ± 1.46 umol/L, P<0.01), plasma fibrinogen (313.76 ± 80.02 vs 275.47 ± 53.77 mg/dL, P<0.01), serum total cholesterol (171.64 ± 35.48 vs 152.62 ± 25.40 mg/dL, P<0.01), serum LDL cholesterol (109.51 ± 36.93 vs 87.6 ± 21.6 mg/dL, P<0.01) and fasting blood sugar (99.89 ± 7.46 vs 90.29 ± 9.85 mg/dL, ;were significantly higher in children (n=45) of young adults (<45 y) with coronary artery disease as compared to control group (n=45). No significant correlation was found for plasma homocysteine level of children with that of their parents in either group, whereas significant correlation was found for plasma fibrinogen of children with their parents in both the groups.