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Polymorphism and peripheral levels of apolipoprotein(a) in polygenic hypercholesterolemia and combined hyperlipidemia

G X Shen1, D Mymin, T Dembinski

  • 1Department of Internal Medicine, University of Manitoba, Winnipeg.

Clinical and Investigative Medicine. Medecine Clinique Et Experimentale
|February 1, 1995
PubMed

Insights

Peripheral apolipoprotein(a) [apo(a)] levels are elevated in patients with polygenic hypercholesterolemia and combined hyperlipidemia. Smaller apo(a) isoforms are more frequent in these patients, correlating with increased cardiovascular disease risk.

Area of Science:

  • Cardiovascular Medicine
  • Lipid Metabolism
  • Genetics

Background:

  • Apolipoprotein(a) [apo(a)] is a key component of lipoprotein(a) [Lp(a)], a lipoprotein linked to cardiovascular disease risk.
  • Polygenic hypercholesterolemia (PH) and combined hyperlipidemia (CH) are common dyslipidemias associated with increased cardiovascular risk.
  • The relationship between apo(a) levels, apo(a) isoform size, and specific dyslipidemias like PH and CH requires further elucidation.

Purpose of the Study:

  • To investigate peripheral apolipoprotein(a) [apo(a)] levels and apo(a) isoform size distribution in patients with polygenic hypercholesterolemia (PH) and combined hyperlipidemia (CH) compared to controls.
  • To determine the correlation between apo(a) levels, apo(a) isoform size, and the presence of coronary artery disease (CAD) or a family history of premature cardiovascular diseases.

Main Methods:

  • Quantification of peripheral apolipoprotein(a) [apo(a)] levels in patient cohorts.
  • Analysis of apolipoprotein(a) [apo(a)] isoform size distribution using established methods.
  • Comparison of apo(a) levels and isoform frequencies between patient groups (PH, CH, controls) and clinical subgroups (CAD, family history).

Main Results:

  • Peripheral apo(a) levels were significantly higher in patients with PH and CH compared to control subjects.
  • Apo(a) levels showed an inverse correlation with apo(a) isoform size, meaning smaller isoforms were associated with higher apo(a) levels.
  • Smaller apo(a) isoforms were found more frequently in PH and CH patients than in controls.
  • Increased frequency of smaller apo(a) isoforms was also observed in patients with existing coronary artery disease (CAD) or a family history of premature cardiovascular diseases.

Conclusions:

  • Elevated peripheral apo(a) levels and a higher prevalence of smaller apo(a) isoforms are characteristic features of polygenic hypercholesterolemia (PH) and combined hyperlipidemia (CH).
  • These findings suggest that apo(a) isoform size and concentration may contribute to the pathophysiology of dyslipidemias and associated cardiovascular risk.
  • Further research into the role of apo(a) in lipid metabolism and cardiovascular disease development is warranted.

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