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Title: Prevalence of sub clinical atherosclerosis among UK South Asians and Europeans
Author: Jain, Piyush
ISNI:       0000 0004 7232 9817
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2015
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Background: South Asians demonstrate high coronary heart disease mortality, largely unexplained by conventional risk factors and unidentified by risk stratification tools. Developments in technology allow us to visualize coronary atherosclerosis non-invasively, thus providing the potential to identify presence of coronary atherosclerosis before it manifests clinically. Coronary artery calcification is closely correlated with total plaque burden and provides an assessment of coronary plaque burden. Myocardial perfusion scintigraphy provides an estimate of myocardial blood flow and thus, severity of coronary artery disease. Increased coronary artery calcification and silent myocardial ischemia predict future risk of coronary heart disease mortality, independent of conventional factors. Inflammation is a key factor in initiation and progression of atherosclerosis. High sensitivity C-reactive protein (CRP) is an important marker of active inflammation and is considered an independent predictor of future cardiovascular events. Thus, markers of subclinical atherosclerosis and inflammation could provide us with a tool for early identification of South Asians at risk of coronary events, unidentified by traditional means. However, majority of the data for such markers is from North American and European populations, with no data evaluating the role of coronary artery calcification, myocardial perfusion scintigraphy and CRP in assessing the coronary heart disease risk in South Asians. Methods and Results: I carried out assessments including coronary artery calcium, myocardial perfusion imaging and assessment of high sensitivity C-reactive protein for a cohort of asymptomatic South Asians and Europeans men and women, aged 35 to 75 years, who were part of the London Life Sciences Population (LOLIPOP) study. I found that: 1) Coronary artery calcification scores were closely associated with age, male gender, cigarette smoking, hypertension, systolic blood pressure, diabetes and total cholesterol. 2) There were no differences in either coronary artery calcification prevalence or mean levels of coronary artery calcification between South Asians and Europeans, after adjustment for the measured cardiovascular risk factors. 3) Presence of diabetes and increasing coronary artery calcification were independent predictors for silent myocardial ischemia. 4) South Asian ethnicity did not influence the prevalence or the extent of silent myocardial ischemia, after adjustment for conventional risk factors. 5) C-reactive protein levels did not correlate with measures of plaque burden. 5) South Asian ethnicity was an independent predictor of inflammation as seen by levels of high sensitivity C-reactive protein. This effect was independent of, and remained significant after adjusting for conventional cardiovascular risk factors and novel factors linked to inflammation such as diabetes and indices of abdominal obesity. Conclusions: While traditional risk factor correlate well with markers of atherosclerosis, the higher coronary heart disease risk and mortality observed in South Asians is not identified by markers of atherosclerotic burden such as coronary artery calcification and myocardial perfusion scintigraphy. South Asians have elevated levels of inflammation as seen by high sensitivity C-reactive protein levels. C-reactive protein levels are not correlated with coronary artery calcium or myocardial ischemia measured by myocardial perfusion scintigraphy. These findings suggest a role of factors such as systemic and plaque inflammation, unrelated to and unmeasured by plaque burden assessment in the higher coronary heart disease mortality observed among South Asians. The study therefore suggests a role of potential risk stratification tools reflecting the multisystem nature of CHD. These could be a combination of clinical risk factors contributing towards CHD, imaging of atherosclerotic plaque and assessment of plaque or systemic inflammation.
Supervisor: Kooner, Jaspal ; De Silva, Ranil Sponsor: Biotechnology and Biological Sciences Research Council
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral