Prevention & lipidsCohort study
Familial Hypercholesterolemia Variant and Cardiovascular Risk in Individuals With Elevated Cholesterol
- Pooled cohort study
- 6 US cohort studies
Authors' conclusion
In this pooled cohort study, the presence of FH variants was associated with a 2-fold higher CHD risk, even when LDL-C was only moderately elevated. The increased CHD risk appeared to be largely explained by the higher cumulative LDL-C exposure in individuals with an FH variant compared to those without.
Study context
- Population
- Individuals without preexisting coronary heart disease (CHD) from 6 US cohort studies, with moderately (130–189 mg/dL) or severely (≥190 mg/dL) elevated low-density lipoprotein cholesterol (LDL-C)
- Participants
- 21,426 individuals · 6 US cohorts
- Exposure
- Familial hypercholesterolemia (FH) variant vs no FH variant
- FH variantn = 63
- Outcome
- Incident CHD
- Follow-up
- Median (IQR) 18 (13-28) years
Main finding
As reported in the abstract
Incident CHD, by LDL-C level
FH variant vs No FH variantAdjusted hazard ratio (95% CI)
moderately elevated LDL-C
2.9(1.4–6.0)
severely elevated LDL-C
2.6(1.4–4.9)
Observational data: associations, not effects.
Further findings
Prevalence of FH variant, by LDL-C level
FH variant–CHD association, further adjusted
- Slightly attenuated after adjusting for baseline LDL-C
- No longer statistically significant after adjusting for cumulative past LDL-C exposure
Projected excess CHD deaths in US adults ≥20 y, no CHD, LDL-C ≥130 mg/dL (CVD Policy Model)
- US adults carrying an FH variant
- more than 417 000
- Excess CHD deaths, moderately elevated LDL-C
- more than 12 000
- Excess CHD deaths, severely elevated LDL-C
- 15 000
Original publication
Familial Hypercholesterolemia Variant and Cardiovascular Risk in Individuals With Elevated Cholesterol. JAMA Cardiol. Published 1 March 2024. doi:10.1001/jamacardio.2023.5366
Summarised from the published abstract; every number is checked against it