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Apolipoprotein(a) size polymorphism is associated with coronary heart disease in polygenic hypercholesterolemia

E Emanuele1, E Peros, P Minoretti

  • 1Molecular Medicine Laboratory, IRCCS San Matteo Hospital, University of Pavia, Pavia, Italy.

Nutrition, Metabolism, and Cardiovascular Diseases : NMCD
|November 24, 2004
PubMed

Insights

High lipoprotein(a) levels did not independently predict coronary heart disease (CHD) in polygenic hypercholesterolemia. However, low molecular weight apolipoprotein(a) isoforms are a significant genetic predictor of CHD in these patients.

Area of Science:

  • Cardiology
  • Genetics
  • Biochemistry

Background:

  • Polygenic hypercholesterolemia (PH) is associated with increased cardiovascular risk.
  • Lipoprotein(a) [Lp(a)] is an independent cardiovascular risk factor often elevated in PH.
  • The role of Lp(a) and its phenotypes in CHD development within PH requires further investigation.

Purpose of the Study:

  • To investigate plasma Lp(a) levels and apolipoprotein(a) [apo(a)] phenotypes in relation to coronary heart disease (CHD) events in PH patients.
  • To determine if Lp(a) levels and apo(a) phenotypes are independent predictors of CHD in hypercholesterolemic subjects.

Main Methods:

  • Determined Lp(a) levels and apo(a) phenotypes in 191 PH patients, 83 normocholesterolemic subjects with CHD, and 94 normocholesterolemic controls.
  • Utilized stepwise multiple-discriminant analysis to assess the independence of various cardiovascular risk factors, Lp(a) levels, and apo(a) isoforms in predicting CHD.

Main Results:

  • Lp(a) levels were similar between hypercholesterolemic subjects with and without CHD.
  • Low molecular weight apo(a) isoforms were more prevalent in PH patients with CHD (55%) compared to those without (p<0.05).
  • Family history of CHD, smoking, age, and low molecular weight apo(a) isoforms were independently associated with CHD.

Conclusions:

  • Lp(a) levels do not appear to play an independent role in determining clinical CHD in PH subjects.
  • The presence of at least one low molecular weight apo(a) isoform is an independent genetic predictor of CHD in hypercholesterolemic individuals.
  • Apo(a) phenotypes, alongside other risk factors, should be assessed for comprehensive CHD risk evaluation in subjects with high cholesterol.
Abstract

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