Adiposity Phenotypes and Subclinical Atherosclerosis in Adults from Sub–Saharan Africa: An H3Africa AWI–Gen Study

Abstract

Background: Obesity and adipose tissue distribution contribute to an increased risk of cardiovascular disease (CVD) by promoting atherosclerosis. This association has been poorly studied in sub–Saharan Africa (SSA) despite the rising prevalence of cardiovascular disease. Objectives: We determined the association between various adiposity phenotypes and carotid intima–media thickness (CIMT), a proxy of subclinical atherosclerosis, in a large SSA population. Methods: A population–based cross–sectional study was performed from 2013–2016 in Burkina Faso, Ghana, Kenya and South Africa. Body mass index (BMI), waist (WC), hip circumferences (HC), visceral (VAT) and subcutaneous adipose tissue (SCAT) using B-mode ultrasound were measured. Ultrasonography of left and right far wall CIMT of the common carotid artery was used as an indicator of subclinical atherosclerosis. Individual participant data meta–analyses were used to determine the associations between adiposity phenotypes and CIMT in the pooled sample while adjusted multivariable linear regression analyses were used for site specific analyses. Results: Data were obtained from 9,010 adults (50.3% women and a mean age of 50± 6years). Men had higher levels of visceral fat than women while women had higher BMI, waist and hip circumference and subcutaneous fat than men at all sites except Burkina Faso. In the pooled analyses, BMI (β–value [95% CIs]: 19.5 [16.8, 22.3] μm) showed the strongest relationship with CIMT followed by VAT (5.86 [4.65, 7.07] μm), SCAT (5.00 [2.85, 7.15] μm), WC (1.27 [1.09, 1.44] μm) and HC (1.23 [1.04, 1.42] μm). Stronger associations were observed in men than in women. Conclusion: Obesity within SSA will likely result in higher levels of atherosclerosis and promote the occurrence of cardio- and cerebrovascular events, especially in males, unless addressed through primary prevention of obesity in both rural and urban communities across Africa. The inverse association of VAT with CIMT in Burkina Faso and Ghana requires further investigation. Highlights All adiposity phenotypes were positively associated with common carotid intima–media thickness (CIMT) in the entire cohort (pooled analyses). BMI had the strongest association with CIMT compared to other phenotypes. The magnitude of association between adiposity phenotypes and CIMT was higher in men than in women. Subcutaneous adipose tissue was inversely associated with CIMT only in women. An unexpected finding was the inverse association of visceral adipose tissue with CIMT in Burkina Faso and Ghana.

Meta-analysis of sub-Saharan African studies provides insights into genetic architecture of lipid traits

“…For example, a recent study reported that fine-scale population structure was strong enough to influence association signals among the South African participants from our cohort 51 . This, added to environmental and lifestyle differences within and between geographic regions, as observed in several phenotype studies based on the AWI-Gen cohort 34 , 35 , 52 , 53 , could limit the ability of modest sample size GWAS based on pan-African datasets to identify associations accurately. We have employed a LMM based approach to conduct association testing on the full dataset with principal components as covariates for the Stage 1 GWAS.…”

Genetic associations with carotid intima-media thickness link to atherosclerosis with sex-specific effects in sub-Saharan Africans

“…The mean-max cIMT was generated as the average of the maximum cIMT from the left and right carotid arteries, and this value was used for the GWAS analyses. The association of cIMT with non-genetic risk factors in our cohort have been documented 26,61 .…”

“…The Africa Wits-INDEPTH Partnership for Genomic Studies cohort (AWI-Gen) was developed to examine genetic and environmental contributions to cardiometabolic diseases in Africans. It has over 12,000 participants from four sub-Saharan African countries, Burkina Faso, Ghana, Kenya and South Africa, and the distributions and associated risk factors for cIMT have been described [23][24][25][26] . This study aimed to investigate genetic susceptibility to atherosclerosis in sub-Saharan Africans in the AWI-Gen cohort.…”