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 > 30 kg/m2). 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.

Variability of Thinness and its Relation to Cardio-metabolic Risk Factors using Four Body Mass Index References in School-children from Delhi, India.

Objectives: To compare: (i) prevalences of thinness in schoolchildren by four body mass index references in common use viz., Centre for Disease Control (CDC); Cole; Indian Academy of Pediatrics (IAP); World Health Organization (WHO); and (ii) relationship of thinness with absence of cardio-metabolic risk factors in these BMI references. Design: Cross-sectional. Setting: Schools in Delhi. Participants: Anthropometry and blood pressure were measured in 16,245 school children aged 5 to 18 years. Fasting lipids and blood sugar were estimated in 2796 subjects. Outcome measures: Age and sex-specific prevalences of thinness and predictive ability of reference cut-off for detecting any cardio-metabolic risk factor were compared. Results: Prevalence of thinness varied with the reference employed; more so for boys. Overall prevalence of thinness was least with IAP reference and highest with CDC cut-offs (6.6% to 16.9% in boys, 6.5% to 10.3% in girls). Children identified as thin by any reference had comparable, significantly lower risks (OR 0.59 to 0.73) of associated cardio-metabolic aberrations. In subjects with any cardio-metabolic or blood pressure aberration, the prevalence of thinness was highest with CDC and least with IAP definition. Conclusion: Prevalence of thinness varies considerably with the reference employed. Thin children, identified by any reference, have a lower risk of associated cardio-metabolic aberrations; however, thinness is a poor diagnostic test for this purpose. In populations undergoing nutrition transition, there is a need to link cardio-metabolic risk factors with recommended anthropometric criteria to define undernutrition.

Apo E genotyping from blood stored on filter paper.

Background & objectives: Dried blood spotted on to filter paper has been found suitable for a large number of studies. In tropical countries with varying temperature conditions the use of dried blood needs to be validated. We carried out this study to assess the use of blood spotted filter paper as a transport system to study genotyping of Apo E gene. Methods: Fifty five patients visiting Cardiothoracic Neuroscience Centre (CNC) OPD at the All India Institute of Medical Sciences (AIIMS), New Delhi, and referred for lipid investigations to Cardiac Biochemistry Laboratory were selected at random. Blood was spotted on to Whatman 3 MM filter paper, dried and stored at room temperature. Genomic DNA was extracted and genotyping was carried out at the end of 0, 3 and 12 months. The study was further validated using samples collected on to filter paper from four centres and stored for eight years at room temperature. The temperature and humidity conditions of the centre varied widely. Results: Fifty five samples collected on to filter paper showed exact match of the genotyping when compared to fresh blood. In dried blood samples collected and stored for 1 yr at room temperature DNA extraction and apo E genotyping was done successfully. Interpretation & conclusions: The present results showed the feasibility of using dried blood samples on filter paper for apo E genotyping in tropical temperature. The findings need to be validated on a large sample before being recommended for use.

Prevalence of metabolic syndrome in a north Indian hospital-based population with obstructive sleep apnoea.

Background & objectives: Obstructive sleep apnoea (OSA) is known to be associated with cardiovascular risk factors and metabolic syndrome (MS). The burden of MS in patients with OSA in India is unknown. We investigated the prevalence of MS and its components in a cross-sectional study in patients with and without OSA in a hospital-based population of a tertiary health care centre in New Delhi, India. Methods: Consecutive patients undergoing overnight polysomnography in the Sleep Laboratory of the Department of Internal Medicine of All India Institute of Medical Sciences (AIIMS) hospital, New Delhi, were studied. Anthropometry and body composition analysis, blood pressure (BP), fasting blood glucose, insulin resistance by homeostasis model assessment (HOMA-IR) and fasting blood lipid profile were measured. MS was defined using the National Cholesterol Education Program Adult treatment panel III criteria, with Asian cut-off values for abdominal obesity. Results: Of the 272 subjects recruited, 187 (82%) had OSA [apnoea-hypopnoea index (AHI)>5 events/h] while 40 (18%) had a normal sleep study. Prevalence of MS in OSA patients was 79 per cent compared to 48 per cent in non-OSA individuals [OR 4.15, (2.05-8.56), P<0.001]. Prevalence of OSA in mild, moderate and severe OSA was 66, 72 and 86 per cent, respectively (P<0.001). Patients with OSA were more likely to have higher BP [OR: 1.06 (1.02-1.11)], fasting insulin [OR: 1.18 (1.05-1.32)], HOMA-IR [OR: 1.61 (1.11-2.33)] and waist circumference [OR: 1.20 (1.13-1.27)]. Interpretation & conclusions: Our findings suggest that OSA is associated with a 4-fold higher occurrence of MS than patients without OSA. The prevalence of MS increases with increasing severity of OSA, therefore, early detection will be beneficial.

Paraoxonase gene Q192R & L55M polymorphisms in Indians with acute myocardial infarction & association with oxidized low density lipoprotein.

Background & objectives: Paraoxonase (PON) is an HDL associated ester hydrolase with an ability to retard LDL oxidation in vitro by preventing lipid peroxide generation. The population variability in enzyme activity is attributed to polymorphisms in paraoxonase gene. For example, polymorphism at codon 192 and 55 of the paraoxonase gene has been reported to be associated with coronary heart disease (CAD) and diabetes among different ethnic groups. The present study looks at PON192 and 55 polymorphism among hospitalized Asian Indian patients with myocardial infarction (MI) and their association with circulating oxidized LDL and antioxidant status. Methods: One hundred and twenty four consecutive patients of acute myocardial infarction and 221 age-matched controls were recruited for the study. Oxidized LDL was measured in serum by ELISA and total antioxidant levels by the 2,2’-azino-bis-(3 ethyl benzothiozoline-6-sulfonate) (ABTS) method. Other known cardiovascular risk factors, apolipoprotein B, apolipoproteinA1, lipoprotein(a), hsCRP and homocysteine were also measured. Paraoxonase gene polymorphism at codon 192 and 55 were analyzed by PCR-RFLP. Results: Patients with MI had significantly higher oxidized LDL (P<0.05) and lower total antioxidant capacity (P<0.001) as compared to controls. Oxidized LDL correlated with total cholesterol, LDL and Apo B in patients. B allele frequency of the codon 192 polymorphism in paraoxonase gene was higher in cases as compared to controls and odds ratio of developing the MI with BB genotype versus AA genotype was 2.37, (P=0.044). Codon 55 polymorphism in paraoxonase gene was not associated with CAD. There was no difference in oxidized LDL between the different genotypes of PON192 and PON55. Interpretation & conclusions: Although PON192 polymorphism was associated with CAD, no correlation of PON192 or 55 polymorphism was found with oxidized LDL suggesting that presence of other antioxidant factors may be of equal importance in preventing LDL oxidation.

Improved method of total antioxidant assay.

Commercially available analytical kits for the estimation of total antioxidant status are expensive and time-consuming. Most of the commercially available kits for total antioxidants estimation are based on the principle of suppression of ABTS radical cation formation by antioxidant in the serum sample. The method requires stringent assay conditions, like exact incubation time and the temperature (37 degrees C) of the reaction and on an average not more than 40 samples can be analyzed on a day. We have adapted the assay to a microplate, thereby allowing more number of samples to be analyzed per day. Further, the reagent volume required is one fourth than that for the original procedure thereby cutting cost. Thirty samples were analyzed by original method on spectrophotometer and our adapted microplate assay. The values of total antioxidant obtained by the two methods correlated well. Thus, total antioxidant can be estimated reliably using the microplate method.