Associations Between Low HDL, Sex and Cardiovascular Risk Markers are Markedly Different in Sub-Saharan Africa and the UK: Analysis of Four Population Studies

Background: Low high-density lipoprotein (HDL) is widely used as a marker of cardiovascular disease risk, despite lack of evidence of a casual role. It is extremely common in sub-Saharan African populations, where reported cardiovascular risk is low. We aimed to determine whether the association between HDL and other cardiovascular risk factors differed between populations in sub-Saharan Africa and the UK. Methods: We compared data from adults living in Uganda and Malawi (n=26,216) and the UK (n=8,747). We examined unadjusted and adjusted levels of HDL, and applied WHO recommended cut-offs for prevalence estimates. We used spline and linear regression to assess the relationship between HDL and other cardiovascular risk factors. Findings: Geometric-mean HDL was substantially lower in the African than European studies (0.9-1.2mmol/l vs 1.3-1.8mmol/l), with African prevalence of low-HDL as high as 77%. In comparison to European studies the relationship between HDL and adiposity (BMI, waist-hip ratio) was greatly attenuated in African studies, and the relationship with non-HDL cholesterol reversed: low HDL was associated with lower non-HDL. The association between sex and HDL was also markedly different; using WHO sex-specific definitions low-HDL was substantially more common among women (69-77%) than men (41-59%) in Uganda/Malawi. Interpretation: The relationship between HDL and sex, adiposity and Non-HDL cholesterol in sub-Saharan Africa is markedly different from European populations. Low HDL is a marker of low overall cholesterol, and sex differences are markedly attenuated. Therefore low HDL may not be a reliable marker of cardiovascular risk in Sub-Saharan Africa, and WHO sex based cut-offs are inappropriate. Funding Statement: This work is funded by the National Institute of Health and Social Care (UK), NIHR Global Health Group 17/63/131. Declaration of Interests: All authors report no conflicts of interest in relation to this work. Ethics Approval Statement: The Ugandan cohort was approved by the Uganda Virus Research Institute Science and Ethics Committee and the Uganda National Council of Science and Technology. The Malawian study was approved by the National Health Sciences Research Committee of Malawi nd London School of Hygiene and Tropical Medicine Ethics Committee, UK.The Exeter 10,000 study was approved by the UK NHS Health Research Authority South West Ethics Committee. The Exeter Family Study was approved by the University of Exeter Research Ethics Committee, UK.