Associations between TG and cardiometabolic risk factors influenced by ancestral and environmental differences
Ancestral and environmental patterns in the association between triglycerides and other cardiometabolic risk factorsLiterature - Meeks KAC, Bentley AR, Agyemang C, et al. - EBioMedicine. 2023;91:104548. doi: 10.1016/j.ebiom.2023.104548
Introduction and methods
Circulating triglyceride (TG) levels differ by ancestry and environment. For example, West Africans and African Americans of West African ancestry have lower TG levels compared with European ancestry populations in Europe and the US [1-3]. East Africans, on the other hand, show disproportionately high TG levels [4-8]. The relationship between TG levels and other cardiometabolic risk factors may differ between ethnic groups and within the same ethnic group living in distinct geographic environments due to genetic and environmental factors.
Aim of the study
The study aim was to compare the association between TG levels and known cardiometabolic risk factors and disorders (i.e., hypertension, systolic blood pressure (SBP), BMI, waist circumference, T2DM, and fasting glucose levels) across West African, East African, and European ancestry populations residing in 3 vastly different environmental settings (i.e., sub-Saharan Africa, the US, and Europe).
Data were used from the following 4 cross-sectional studies: (1) AADM (Africa America Diabetes Mellitus) study, which included West Africans (Ghana and Nigeria) and East Africans (Kenya); (2) RODAM (Research on Obesity and Diabetes among African Migrant) study, which included West Africans (Ghanaians) living in Ghana and Europe; (3) HELIUS (Healthy Life in an Urban Setting) study, which included Europeans, and 2 groups of West African ancestry (Ghanaians and African Surinamese) living in the Netherlands; and (4) NHANES (National Health and Nutrition Examination Survey) study, which included African Americans (West African ancestry) and European Americans in the US.
In total, 32,019 adults were included: people of West Africans ancestry living in sub-Saharan Africa (n=7201), the US (n=4390), or Europe (n=6436), those of East African ancestry living in sub-Saharan Africa (urban East Africans; n=781), and those of European ancestry living in the US (n=8670) or Europe (n=4541).
- Of all populations, median TG level was highest in urban East Africans (1.61 mmol/L; IQR: 1.12–2.39) and lowest among West African migrants in Europe (0.62 mmol/L; IQR: 0.46–0.89). Levels of total cholesterol, HDL-c, and LDL-c were similar across ancestries.
- Hypertension was more strongly associated with TG levels in people of European ancestry (β: 0.179; 95%CI: 0.156–0.203) compared with individuals of West African ancestry (β: 0.102; 95%CI: 0.086–0.118; P for interaction=0.00093). In urban East Africans, the β was 0.138 (95%CI: 0.057–0.218).
- TG levels were associated with SBP in individuals of West African ancestry (β: 0.0027; 95%CI: 0.0022–0.0031) or European ancestry (β: 0.0065; 95%CI: 0.0058–0.0072; P for interaction<0.0001) but not in urban East Africans (β: 0.0004; 95%CI: –0.0021 to 0.0029). After adjustment for potential confounders including BMI, the associations between TG levels and hypertension or SBP, as well as variations in ancestry groups, were attenuated.
- In individuals of European ancestry, TG levels were more strongly associated with BMI compared with West African ancestry populations (β: 0.028; 95%CI: 0.027–0.030 vs. β: 0.015; 95%CI: 0.014–0.016; P for interaction<0.0001). Urban East Africans showed a similar association with BMI (β: 0.017; 95%CI: 0.010–0.024) as West African ancestry individuals (P for interaction=0.28).
- TG levels also showed a stronger association with waist circumference in European ancestry individuals (β: 0.013; 95%CI: 0.013–0.014) compared with West African ancestry individuals (β: 0.009; 95%CI: 0.008–0.009; P for interaction<0.0001), while urban East Africans showed a similar association with waist circumference (β: 0.013; 95%CI: 0.011–0.016) as European ancestry individuals (P for interaction=0.75). The associations between TG levels and BMI or waist circumference were not influenced by environmental differences within ancestry groups.
T2DM and fasting glucose levels
- TG levels were more strongly associated with T2DM in European ancestry individuals (β: 0.193; 95%CI: 0.162–0.225) and urban East Africans (β: 0.274; 95%CI: 0.199–0.349) compared with West African ancestry individuals (β: 0.136; 95%CI: 0.117–0.155) (P for interaction=0.0085 and 0.0034, respectively). The association between TG levels and T2DM showed environmental variation, with the strongest association observed in rural West Africans (β: 0.322; 95%CI: 0.207–0.437) and the weakest in urban West Africans (β: 0.090; 95%CI: 0.064–0.115).
- Among individuals without T2DM, TG levels were more strongly associated with fasting glucose levels in European ancestry populations compared with West African ancestry populations (β: 0.184; 95%CI: 0.164–0.205 vs. β: 0.118; 95%CI: 0.104–0.132; P for interaction=0.00018). In urban East Africans, the β was 0.148 (95%CI: 0.083–0.212). The association between TG and fasting glucose levels was similar for individuals residing in sub-Saharan Africa and those in the US, irrespective of ancestry, while it was much stronger among Europeans compared with European Americans (P for interaction<0.0001).
In this analysis comparing African and European ancestry populations who resided on one of 3 different continents, the associations between TG levels and hypertension, SBP, BMI, or waist circumference were stronger in European ancestry individuals compared with West African ancestry individuals with minimal or no influence by environmental context. In contrast, the associations of TG levels with T2DM or fasting glucose levels showed considerable variability by environmental context. The associations between TG levels and SBP, waist circumference, or T2DM differed between West African ancestry individuals and urban East Africans.
According to the authors, “[the a]ncestry differences [observed] could partially be attributed to variation in genetic factors underlying TG biology, while environmental differences likely reflect differences in health-related behaviors such as diet.” Moreover, their “findings imply that neither ‘African ancestry’ nor ‘European ancestry’ can be viewed as a single entity when discussing cardiometabolic risk.”