Validation of clinically applicable biomarkers of insulin resistance to explain increased CVD in UK Indian Asians

Lead Research Organisation: Imperial College London
Department Name: National Heart and Lung Institute

Abstract

Heart disease and strokes are more common amongst Indian Asians living in the UK than in European whites. The traditional risk factors such as smoking and high cholesterol do not account for the difference. Insulin resistance, a defect of sugar metabolism, and related metabolic problems are more common in Indians, and have been proposed to account for their increased risk of heart disease. This needs to be tested and confirmed in a large-scale study. We have completed the initial, baseline assessment of 24,000 Indian Asian and Northern European men and women, living in West London. This is the London Life Sciences Prospective Population Study (LOLIPOP) study. We will follow up these LOLIPOP participants for heart attack and stroke. We expect to find that ~1500 people had heart / brain events. Most of these events will be captured through links to electronic databases. We will relate markers of insulin resistance to risk of heart attack and stroke to quantify the contribution of insulin resistance to increased cardiovascular risk in Asians. Our results will substantially improve our understanding of the causes of heart attack and stroke in Indian Asians, and will allow us to develop the first tool for identifying risk of heart attack and stroke specifically applicable to UK Indian Asians. We will ensure that the results of our work are immediately available for use in clinical practice. The work will be performed in collaboration with the pharmaceutical company GSK, who will also use the results to help develop new treatments to prevent heart attacks and strokes in the population.

Technical Summary

Cardiovascular disease (CVD) mortality rate are almost two-fold higher in UK Indian Asians than Northern Europeans. Traditional risk factors do not account for the difference, and existing risk prediction methods underestimate CVD risk in Asians. Insulin resistance and associated metabolic disturbances are more common in Indian Asians than Northern Europeans. Cross-sectional data suggest insulin resistance may account for increased CVD in Indian Asians, but this needs to be validated in a large-scale prospective study. We hypothesise that biomarkers of insulin resistance, and related metabolic disturbances, explain increased CVD risk in Indian Asians. We have assembled the London Life Sciences Prospective Population Study (LOLIPOP) cohort of 24,000 Indian Asian and Northern European men and women, aged 35-75 years, recruited from the lists of 58 GPs in West London. We will follow up the LOLIPOP participants for fatal and non-fatal CVD events, via flagging of mortality with the Office for National Statistics; electronic primary care data captured through the MRC funded VOTES project; hospital admissions data from national Hospital Episode Statistics; local hospital cardiac clinical databases. Average follow-up of the cohort will be 5.5 years, with an expected 1480 CVD events and 95% power to detect odds ratios for CVD as low as 1.3 at p=0.01. Biomarkers selected for validation against incident CVD are i. Homeostasis Model Assessment of insulin sensitivity, ii. Waist-hip ratio (abdominal obesity), iii. fasting HDL cholesterol and triglycerides (dyslipidaemia), and iv. high sensitivity CRP (inflammation). Cox regression will be used to quantify the contribution of these insulin resistance biomarkers to the increased CVD among Indian Asians compared with Northern Europeans. Based on these findings, we will develop the first CVD risk prediction function directly applicable to UK Indian Asians, which will be immediately available for use in clinical practice. Results of this research will aid the Industrial partner, GSK, in developing new therapeutic treatments for insulin resistance among non-Caucasian groups.

Publications

10 25 50

publication icon
C Reactive Protein Coronary Heart Disease Genetics Collaboration (CCGC) (2011) Association between C reactive protein and coronary heart disease: mendelian randomisation analysis based on individual participant data. in BMJ (Clinical research ed.)

 
Description Health
Amount € 2,999,000 (EUR)
Funding ID 279143 
Organisation European Commission 
Department Seventh Framework Programme (FP7)
Sector Public
Country European Union (EU)
Start 01/2012 
End 12/2014
 
Description Program Grant
Amount £1,800,000 (GBP)
Funding ID RP-PG-0407-10371 
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 06/2007 
End 06/2013