Sex and racial differences in prevalence and clinical characteristics of people living with LDLR and PCSK9 familial hypercholesterolemia genetic variants: Data from the All of Us Research program.

BACKGROUND

Data on the prevalence and clinical characteristics of people with Familial hypercholesterolemia (FH) genetic variants across sex and diverse racial and ethnic groups in the United States are limited.

METHODS

Using data from the All of Us research program, we examined the prevalence and clinical characteristics of FH variant carriers in a diverse U.S. population. LDLR and PCSK9 FH genetic variants were identified using the ClinVar database. Atherosclerotic cardiovascular disease (ASCVD) and lipid-lowering therapy (LLT) use were ascertained from electronic health records. Prevalence, ASCVD burden, and LLT use among FH variant carriers were estimated and stratified by sex, race, and ethnicity.

RESULTS

Among 245,388 participants (mean age 51.8 years, 59.3 % women, 51.3 % non-Hispanic White, 20.4 % non-Hispanic Black, 3 % non-Hispanic Asian, 19.3 % Hispanic), 448 were identified as FH genetic variant carriers, yielding a prevalence of 1 in 546 (95 % CI: 1/602- 1/500). Prevalence was highest among Asian non-Hispanics (1 in 286) and lowest in Hispanics (1 in 694); p-value = 0.003. Males had a higher prevalence of FH variants than females (1 in 485 vs. 1 in 602, p-value = 0.03). Regardless of LDL-C levels, FH variant carriers had a higher prevalence of ASCVD history than those without FH variants (p-value = 0.04). Black non-Hispanics, Asian non-Hispanics, and Hispanics had lower ASCVD prevalence and LLT use than White non-Hispanics. ASCVD prevalence was higher in males with FH variants than females (25 % vs. 18 %, p-value = 0.04).

CONCLUSION

Significant racial, ethnic, and sex disparities exist in the prevalence, ASCVD burden, and LLT use among FH variant carriers. Further targeted efforts, including increased genetic testing, are needed to improve FH detection and optimize treatment, particularly in racial and ethnic minority groups where LLT use remains inadequate.