title: Discrimination and net reclassification of cardiovascular risk with lipoprotein(a): prospective 15-year outcomes in the Bruneck Study.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Neurology, Innsbruck Medical University, Innsbruck, Austria; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Willeit
authors.affiliation: Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. Electronic address: Stefan.Kiechl@i-med.ac.at.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kiechl
authors.affiliation: Department of Medical Genetics, Molecular and Clinical Pharmacology, Division of Genetic Epidemiology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Florian
authors.initials: F
authors.lastname: Kronenberg
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Witztum
authors.affiliation: Department of Laboratory Medicine, Bruneck Hospital, Bruneck, Italy.
authors.forename: Peter
authors.initials: P
authors.lastname: Santer
authors.affiliation: King's British Heart Foundation Centre, King's College London, London, United Kingdom.
authors.forename: Manuel
authors.initials: M
authors.lastname: Mayr
authors.affiliation: King's British Heart Foundation Centre, King's College London, London, United Kingdom.
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Laboratory Medicine, Bruneck Hospital, Bruneck, Italy.
authors.forename: Agnes
authors.initials: A
authors.lastname: Mayr
authors.affiliation: Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Johann
authors.initials: J
authors.lastname: Willeit
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California. Electronic address: stsimikas@ucsd.edu.
authors.forename: Sotirios
authors.initials: S
authors.lastname: Tsimikas
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000175:diagnosis*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007558:Italy; D017270:Lipoprotein(a) / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011446:Prospective Studies; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D017270:Lipoprotein(a)
keywords: atherosclerosis; autoantibodies; lipoproteins; oxidation; oxidation-specific epitopes; oxidized phospholipids