Discrimination and net reclassification of cardiovascular risk with lipoprotein(a): prospective 15-year outcomes in the Bruneck Study

J Am Coll Cardiol. 2014 Sep 2;64(9):851-60. doi: 10.1016/j.jacc.2014.03.061.

Abstract

Background: Recent studies showed that lipoprotein(a) [Lp(a)] is a causal risk factor for cardiovascular disease (CVD). However, whether Lp(a) modifies clinical risk assessment was not established.

Objectives: This study was conducted to determine whether Lp(a) improves CVD risk prediction.

Methods: In 1995, Lp(a) was measured in 826 men and women (age range, 45 to 84 years) from the general community. Incidence of CVD was recorded over 15 years of follow-up.

Results: In models adjusted for Framingham Risk Score (FRS) and Reynolds Risk Score (RRS) variables, the hazard ratio (HR) for incident CVD was 1.37 per 1-SD higher Lp(a) level (SD = 32 mg/dl) and 2.37 when comparing the top fifth quintile with other quintiles. The addition of Lp(a) to the RRS increased the C-index by 0.016. Of the 502 subjects who remained free of CVD, 82 were correctly reclassified to a lower risk category and 49 were reclassified to a higher risk category (predicted 15-year categories: <7.5%, 7.5% to <15%, 15% to <30%, ≥30%) (p < 0.001). Of the 148 subjects who developed CVD, 18 were correctly reclassified to a higher risk category and 17 were reclassified to a lower risk category. In subjects at intermediate risk (15% to <30%), the net reclassification improvement afforded by Lp(a) was 22.5% for noncases, 17.1% for cases, and 39.6% overall. Allele-specific Lp(a) levels did not add to the predictive ability of the FRS or RRS or to Lp(a).

Conclusions: Elevated Lp(a) predicts 15-year CVD outcomes and improves CVD risk prediction. These findings suggest that Lp(a) levels may be used in risk assessment of subjects in the general community, particularly in intermediate-risk groups.

Keywords: atherosclerosis; autoantibodies; lipoproteins; oxidation; oxidation-specific epitopes; oxidized phospholipids.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cardiovascular Diseases / diagnosis*
  • Female
  • Follow-Up Studies
  • Humans
  • Italy
  • Lipoprotein(a) / chemistry*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Predictive Value of Tests
  • Prospective Studies
  • Reproducibility of Results
  • Risk Assessment
  • Risk Factors

Substances

  • Lipoprotein(a)