Lp(a) Discrimination and Risk Reclassification: Prospective 15-Year Outcomes in the Bruneck Study

The Bruneck Study is a prospective community-based cohort in northern Italy that followed 826 participants over 15 years, measuring incident cardiovascular disease events and examining whether Lp(a) concentration at baseline improved cardiovascular risk discrimination and reclassification beyond established risk scores.

Over 15 years, 148 incident CVD events occurred. The hazard ratio for CVD was 1.37 per 1-SD increase in Lp(a) and 2.37 comparing the top quintile (>45 mg/dL) to lower quintiles, after adjustment for Reynolds Risk Score. Adding Lp(a) to the Reynolds Risk Score increased the C-index by 0.016, with significant net reclassification improvement concentrated in the intermediate-risk group — where clinical decision-making about treatment initiation is most uncertain.

The reclassification benefit is clinically meaningful. Intermediate-risk patients (10-year cardiovascular risk 7.5–20%) are exactly the population where Lp(a) measurement adds the most value: those who are already clearly high-risk don’t need Lp(a) to decide on treatment, and those clearly low-risk don’t either. Lp(a) measurement in intermediate-risk patients reclassifies a meaningful proportion to higher risk warranting treatment, and a smaller proportion to genuinely lower risk where treatment can be appropriately deferred.

The Bruneck Study’s 15-year follow-up provides unusually long-horizon prospective validation of Lp(a) as a risk predictor — most epidemiological Lp(a) studies have shorter follow-up. The consistency of the Lp(a) risk association over 15 years is consistent with Lp(a)‘s genetically fixed, lifelong exposure pattern.

We rate the evidence moderate. A 15-year prospective Bruneck Study analysis demonstrating that Lp(a) significantly improves CVD risk reclassification over established risk scores, particularly in intermediate-risk patients — supporting Lp(a) measurement as a risk discriminator for clinical decision-making.