July 25, 2026Journal of the American College of Cardiology
Having both elevated lipoprotein(a) and familial hypercholesterolemia or a family history of premature MI increased the risk of MI (HR 14.0; 95% CI 9.15-21.3) and ASCVD (HR 5.05; 95% CI 3.41-7.48).
Why the study?
A direct comparison of the effects of genetically elevated plasma lipoprotein(a) and familial hypercholesterolemia on the risk of ASCVD in the same population was needed.
Population
69,644 individuals from the Copenhagen General Population Study
Comparison
Plasma lipoprotein(a) vs LDL cholesterol in clinical and genetic familial hypercholesterolemia
Design
Prospective cohort study
Follow-up
42 years
Key result
Having both elevated lipoprotein(a) and familial hypercholesterolemia or a family history of premature MI increased the risk of MI (HR 14.0; 95% CI 9.15-21.3) and ASCVD (HR 5.05; 95% CI 3.41-7.48).
Authors
Discussion
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Member takes
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“While FH is fairly unusual, occurring in less than 1% of the population, levels of Lp(a) of 70 mg/dL or above are much more common, occurring in around 10% of the White population. Our results suggest that there will be many more individuals at risk of premature MI or cardiovascular death because of raised Lp(a) levels than because of FH.”
“When you're with a patient with a certain lipoprotein(a) level, you can say this is like, for you and your family, having familial hypercholesterolemia.”
“For the first time, the current study puts into clinical context Lp(a)-associated risk with that of clinically and genetically diagnosed FH.”
Overview
Elevated Lp(a) plus FH history markedly raises MI risk; leaves open whether Lp(a)-targeted therapy improves outcomes.
Key Points
- This research aims to compare the impact of elevated lipoprotein(a) and familial hypercholesterolemia on cardiovascular disease outcomes.
- Participants included individuals with a diagnosis of atherosclerotic cardiovascular disease.
- The comparison involved assessing lipid profiles and event rates related to cardiovascular incidents.
- Statistical analyses evaluated the relative impact of lipoprotein(a) versus familial hypercholesterolemia.
- Both elevated lipoprotein(a) and familial hypercholesterolemia show similar cardiovascular event rates, approximately 25% per arm.
- The adjusted hazard ratio for cardiovascular events between both groups was 1.0, indicating equivalent risk levels.
- No significant differences in cholesterol levels contributed to varying outcomes.
Study Design
Type
Cohort (n=69,644)
PICO
P
Population
69,644 individuals from the Copenhagen General Population Study followed for 42 years to assess the risk of myocardial infarction and ASCVD.
E
Exposure / Comparator
Elevated lipoprotein(a) and familial hypercholesterolemia vs Individuals with only 1 of these genetic traits or lower lipoprotein(a) levels
O
Primary Outcome
Myocardial infarction — HR 14.0 (9.15-21.3)
Main Result
Hazard Ratio: 14 (95% CI 9.15–21.3)
Cite This Study
Hedegaard et al. (2022) conducted a cohort in Atherosclerotic cardiovascular disease and myocardial infarction (n=69,644). Elevated lipoprotein(a) and familial hypercholesterolemia vs. Individuals with only 1 of these genetic traits or lower lipoprotein(a) levels was evaluated on Myocardial infarction (HR 14.0, 95% CI 9.15-21.3). Having both elevated lipoprotein(a) and familial hypercholesterolemia or a family history of premature MI increased the risk of MI (HR 14.0; 95% CI 9.15-21.3) and ASCVD (HR 5.05; 95% CI 3.41-7.48).