African Americans generally have a healthier lipid profile (lower triglycerides and higher high-density lipoprotein cholesterol concentration) compared with those of other ethnicities. Paradoxically, African Americans do not experience a decreased risk of the cardiometabolic diseases that serum lipids are expected to predict. This review explores this mismatch between biomarker and disease among African ancestry individuals by investigating the presence of interethnic differences in the biological relationships underlying the serum lipids–disease association. This review also discusses the physiologic and genomic factors underlying these interethnic differences. Additionally, because of the importance of serum lipids in assessing disease risk, interethnic differences in serum lipids have implications for identifying African ancestry individuals at risk of cardiometabolic disease. Where possible, data from Africa is included, to further elucidate these ancestral differences in the context of a different environmental background.

Highlights

• African ancestry is associated with a healthier serum lipid profile.
• African Americans do not have lower cardiometabolic risk despite lower lipids.
• Interethnic differences in underlying physiology may explain the metabolic paradox.