Determinants of Cardiovascular Disease, Kidney Disease and Diabetes

Overview

Cardiovascular disease (CVD), chronic kidney disease (CKD), diabetes mellitus (DM) and HIV infection are long-term conditions (LTC) with major health implications for people of African ancestry. These LTC often arise in the setting of an adverse demographic, social, biologic and genetic environment, although this remains poorly understood. The investigators plan to conduct a comprehensive syndemic evaluation in individuals with and without CVD, CKD and DM in people of African ancestry with HIV to obtain novel insights into the development of LTC in this population. In addition, the investigators will conduct focus groups to explore the role of syndemic factors in the development of LTC and develop and pilot an educational programme to improve knowledge about LTC in the African/Caribbean community.

Black African/Caribbean Communities in South London are disproportionally affected by long-term conditions (LTC), with a higher prevalence and an earlier onset (by about 13 years) (1). This population experiences high rates of hypertension, obesity, diabetes mellitus (DM), chronic kidney disease (CKD), cardiovascular disease (CVD) including stroke, social deprivation, poor housing, and mental health conditions such as anxiety and depression (1). HIV infection is also considerably more common in Black African/Caribbean Communities in South London than in the general UK population (2,3) and gives rise to stigma and discrimination, low self-esteem, dysfunctional relationships and loneliness (4). The relationship between hypertension, obesity, metabolic syndrome, diabetes mellitus and CKD is well recognised. In this population, 'hypertensive nephropathy' is about 10-fold more common than in Caucasians, with earlier onset of end stage kidney disease (ESKD) (5). Although hypertensive nephropathy in people of African ancestry was previously attributed to resistant hypertension, exacerbated by poor engagement with health care services and suboptimal adherence to antihypertensive therapy, there is emerging evidence of strong genetic susceptibility to CKD as a result of prevalent mutations in the apolipoprotein L1 (APOL1), glutathione-S-transferase-μ1 (GSTM1) genes or sickle cell trait (SCT) (6-12). However, despite their strong associations with CKD, many individuals with these genetic variants do not develop kidney disease, suggesting that additional (i) biologic (e.g. coinfections, inflammation), (ii) environmental factors (e.g. obesity, diabetes), and (iii) socio-economic aspects, (e.g. inadequate health care access, stigma) may contribute to the development or progression of CKD although this has not been well studied. There is growing recognition of the important role of social determinants of health (SDH) and its impact across a wide range of health indicators, settings, and populations (13,14). The World Health Organization (WHO) refers to SDH as conditions to which people are born, grow, work, live and age, linked to personal circumstances and systems (e.g. social, economic and political policies/heath care systems) that influences their daily lives (15-16). The new conceptual framework of syndemics provide an opportunity to study diseases and health conditions in populations that are deepened by the social, economic, environmental and political environment of a given population (17). The definition of a syndemic is 'the presence of two or more disease states (anchored around a core disease, in our case HIV) that adversely interact with each other, negatively affecting the mutual course of each disease trajectory, enhance vulnerability, and which are more harmful by experienced inequities' (18). This approach of a so-called 'syndemic lens' may be helpful in our study to identify the associations between genetic, biologic and social factors that contribute to the development of CKD and DM in people with hypertension, obesity, sub-clinical CKD and/or metabolic syndrome. This systemic approach can offer a new understanding of diseases that can improve public health and treat individual patients at the same time (19). South London has a large (\>200,000) population of African and Caribbean ancestry who are disproportionally affected by HIV and experience a higher burden of CKD, DM and other LTC, often with earlier onset compared to white populations. The investigators aim to study the demographic, clinical, social and genetic factors that associate with CKD, DM and multiple LTC in people with HIV. CKD and DM are key LTC that associate with hypertension, obesity and cardiovascular disease, resulting in or contribute to functional impairment, polypharmacy and impaired bio-psycho-social health outcomes. The HIV clinics in South London provide a unique opportunity to access a diverse African and Caribbean population of working age in whom LTC can be studied. People with HIV from black African/Caribbean communities experience a high degree of social and economic deprivation, stigma, anxiety and depression which are considered important syndemic factors in the development of LTC. CKD and DM are common LTC, highly relevant to the black population, and relatively early events in the development of multiple and disabling LTC, thus identifying a population for targeted interventions that may reduce the rate of progression from a single to multiple LTC. HIV infection, itself a LTC, can be effectively controlled with antiretroviral therapy, affording normal life expectancy and interrupting onward transmission. Routine care includes 6-12 monthly assessments for other LTCs, providing opportunities for recruitment of well characterised populations unselected for specific co-morbid conditions. No studies to date in the UK have examined the contribution of biologic, clinical, social and genetic factors to the development of LTC in African/Caribbean populations with HIV to date. The team will generate detailed information on factors that associate with CKD, DM, CVD and multiple LTC as well as hypertension, sub-clinical CKD, obesity and insulin resistance, which often precede the development of CKD, DM and other LTC in this population. This study is likely to identify novel associations which can be confirmed and further explored in subsequent studies of HIV positive and general African/Caribbean populations. Stored biological samples will allow us to explore pathogenetic mechanisms in subsequent studies. Key barriers to uptake of existing and novel interventions include low literacy levels, low perception of quality of life, lack of knowledge of LTCs, etc. The investigators will explore how best to overcome these barriers in focus groups and develop a culturally sensitive educational programme, aiming to reach individuals in communities that tend to poorly engage with health care and preventive programmes.