Abstract
Background: Heterozygous familial hypercholesterolemia (FH) is a common genetic disorder leading to premature cardiovascular disease and death as a result of lifelong high plasma low-density lipoprotein cholesterol levels, if not treated early in life. The prevalence of FH varies between countries because of founder effects, use of different diagnostic criteria, and screening strategies. However, little is known about differences in FH prevalence according to ethnicity. We aimed to investigate the ethnic distribution of FH in diverse populations and estimate the prevalence of FH according to ethnicity. Methods: We performed a systematic review and meta-analysis, searching PubMed and Web of Science for studies presenting data on the prevalence of heterozygous FH among different ethnicities in non-founder populations. Studies with more than 100 individuals, relevant data on prevalence, ethnicity, and using the Dutch Lipid Clinical Network Criteria, Simon Broome, Making Early Diagnosis Prevents Early Death, genetic screening, or comparable diagnostic criteria were considered eligible for inclusion. Results: Eleven general population studies and two patient studies were included in a systematic review and 11 general population studies in a random-effects meta-analysis. The overall pooled FH prevalence was 0.33% or 1:303 in 1,169,879 individuals (95% confidence interval: 0.26-0:40%; 1:385-1:250). Included studies presented data on six ethnicities: black, Latino, white, Asian, brown, and mixed/other. Pooled prevalence was estimated for each group. The highest prevalence observed was 0.52% or 1:192 among blacks (0.34-0.69%; 1:294-1:145) and 0.48% or 1:208 among browns (0.31-0.74%; 1:323-1:135) while the lowest pooled prevalence was 0.25% or 1:400 among Asians (0.15-0.35; 1:500-1:286). The prevalence was 0.37% or 1:270 among Latino (0.24-0.69%; 1:417-1:145), 0.31% or 1:323 among white (0.24-0.41%; 1:417-1:244), and 0.32% or 1:313 among mixed/other individuals (0.13-0.52%; 1:769-1:192). Conclusion: The estimated FH prevalence displays a variation across ethnicity, ranging from 0.25% (1:400) to 0.52% (1:192), with the highest prevalence seen among the black and brown and the lowest among the Asian individuals. The differences observed suggest that targeted screening among subpopulations may increase the identification of cases and thus the opportunity for prevention.