September 7, 2026Journal of the American College of Cardiology
Discrimination and Net Reclassification of Cardiovascular Risk With Lipoprotein(a)
Key result
Higher Lp(a) linked to ~37% greater incident CVD risk per SD.
- HR 1.37
- n=826
Why the study?
Does Lipoprotein(a) measurement improve cardiovascular disease risk prediction in adults from the general community?
Population
826 men and women (age range, 45 to 84 years) from the general community
Comparison
Lipoprotein [Lp] measurement added to Framingham… vs Framingham Risk Score and Reynolds Risk Score…
Design
Cohort
Follow-up
15 years
Authors
Discussion
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Implication
Elevated Lipoprotein(a) predicts 15-year cardiovascular outcomes and significantly improves risk reclassification, particularly in intermediate-risk individuals.
Key Points
- To determine whether measuring lipoprotein(a) improves clinical cardiovascular disease risk prediction and discrimination beyond established risk scores.
- Prospective cohort study in 826 community men and women aged 45 to 84 years, with baseline lipoprotein(a) measured in 1995.
- Tracked incident cardiovascular disease over a 15-year follow-up period.
- Evaluated discrimination and net reclassification improvement after adding lipoprotein(a) to the Framingham Risk Score and Reynolds Risk Score.
- Adjusting for Framingham and Reynolds Risk Score variables, the hazard ratio for incident cardiovascular disease was 1.37 per 1-SD higher lipoprotein(a) level (SD = 32 mg/dl) and 2.37 comparing the top quintile to lower quintiles.
- Adding lipoprotein(a) to the Reynolds Risk Score increased the C-index by 0.016 and significantly reclassified risk across 15-year categories (p < 0.001).
- Among participants at intermediate risk (15% to <30%), lipoprotein(a) yielded a net reclassification improvement of 22.5% for noncases, 17.1% for cases, and 39.6% overall, whereas allele-specific levels added no predictive gain.
Study Design
Type
Cohort (n=826)
Structured PICO
Does Lipoprotein(a) measurement improve cardiovascular disease risk prediction in adults from the general community?
P
Population
826 men and women aged 45 to 84 years from the general community, followed for 15 years to assess incident cardiovascular disease.
E
Exposure
Lipoprotein(a) [Lp(a)] measurement added to Framingham Risk Score (FRS) and Reynolds Risk Score (RRS)
C
Comparator
Framingham Risk Score (FRS) and Reynolds Risk Score (RRS) alone
O
Outcome
Incidence of cardiovascular disease (CVD)hard clinical
Main Result
Hazard Ratio: 1.37
Elevated Lipoprotein(a) predicts 15-year cardiovascular outcomes and significantly improves risk reclassification, particularly in intermediate-risk individuals.
Cite This Study
Willeit et al. (2014) conducted a cohort in Cardiovascular disease (n=826). Elevated Lipoprotein(a) vs. Lower Lipoprotein(a) levels was evaluated on Incident cardiovascular disease (HR 1.37). Elevated lipoprotein(a) was associated with increased incident cardiovascular disease (HR 1.37 per 1-SD increase) and improved 15-year risk reclassification.