Imaging Biomarkers of Subclinical Cardiovascular Disease in Asymptomatic European Whites and Indian Asians: A Population Study

Abstract

Background: Subclinical biomarkers of cardiovascular disease (CVD) are being increasingly applied in clinical settings to refine cardiovascular risk stratification and also as an epidemiological tool to enhance the understanding of disease mechanisms. Indian Asians living in the United Kingdom have at least a 50% higher risk of CVD mortality compared to European whites. The excess mortality risk cannot be explained by the pattern of classical risk factors which are generally lower in Indian Asians, and there are no tools that identify their elevated CVD risk. Objectives: To explore potential CVD mechanisms using established and novel imaging biomarkers of subclinical atherosclerosis and left ventricular (LV) function, in a large bi-ethnic cohort of asymptomatic European white and Indian Asian subjects. Mechanisms potentially responsible for the excess CVD mortality observed in UK Indian Asians will also be examined. Methods: A total of 2,439 subjects were recruited from the LOLIPOP study, of which 2,288 were free from clinical CVD. All subjects underwent carotid ultrasonography and echocardiography with tissue Doppler imaging for estimation of LV filling pressure (E/Ea). Results: In hypertensives, increased LV mass is independently associated with impaired LV function and increased LV filling pressure, whereas increasing degrees of concentric remodeling are associated with attenuated diastolic function but augmented systolic function, possibly representing an adaptive response to pressure overload physiology. Subclinical carotid plaque disease, rather than IMT, is more closely related to LV systolic dysfunction and increased LV filling pressure. Compared to European whites, Indian Asians intrinsically have attenuated longitudinal LV function, higher E/Ea and demonstrate a greater degree of concentric remodeling independent of other demographic and clinical parameters. Despite their lower LV mass, an increased prevalence of LVH amongst Indian Asian men compared to European white men was observed. Conclusions: Novel relationships between biomarkers of subclinical LV geometry, LV function and carotid atherosclerosis have been presented. Given that the burden of carotid atherosclerosis was similar amongst both ethnic groups, this thesis suggests that further research is required into blood pressure aetiology, pro-hypertrophic mediators, end-organ damage and factors involved in acute arterial plaque destabilisation, to further understand the excess risk of CVD in Indian Asians