Impact of genetic defects on coronary atherosclerosis in patients suspected of having familial hypercholesterolaemia

Eur J Clin Invest. 2003 Jan;33(1):1-9. doi: 10.1046/j.1365-2362.2003.01094.x.

Abstract

Background: In the present study we assessed whether the presence of genetic mutations typical of familial hypercholesterolaemia (FH) was associated with greater atherosclerosis in the coronary vessels in patients with severe hypercholesterolaemia and a family history of early cardiovascular disease.

Materials and methods: Two hundred and thirty-five patients selected for having severe hypercholesterolaemia and a family history of cardiovascular disease were classified as FH (57 men and 38 women) or non-FH (84 men and 56 women) according to a genetic analysis of the LDL-R or ApoB genes. Coronary atherosclerosis was evaluated by performing a thoracic CT scan and exercise stress testing.

Results: Familial hypercholesterolaemia individuals had a significantly higher prevalence of coronary calcification than the non-FH patients from among both the men (OR = 3.90; 95% CI 1.86-8.19; P < 0.001) and the women (OR = 2.34; 95% CI 1.01-5.48; P = 0.05). In exercise stress testing, ECG abnormalities suggestive of cardiac ischaemia were found with a higher prevalence in the FH patients than the non-FH patients from among both the men (OR 6.15; 95% CI 2.16-17.5; P < 0.001) and the women (OR 4.76; 95% CI 0.91-24.6; P = 0.06). All differences were statistically significant after adjusting for age and cholesterol and for most classical risk factors that differed between the FH and non-FH groups.

Conclusion: Among patients with severe hypercholesterolaemia and a family history of early cardiovascular disease, the presence of a genetically ascertained FH is associated with a higher prevalence of coronary artery calcifications and a positive exercise stress test. These results suggest that despite a similar phenotype, patients carrying mutations suggestive of FH may have a greater cardiovascular risk than patients without these mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Apolipoproteins B / genetics
  • Calcinosis / genetics
  • Coronary Artery Disease / etiology
  • Coronary Artery Disease / genetics*
  • Exercise Test
  • Female
  • Heterozygote
  • Humans
  • Hyperlipoproteinemia Type II / complications
  • Hyperlipoproteinemia Type II / genetics*
  • Lipoprotein(a) / genetics
  • Male
  • Middle Aged
  • Mutation*
  • Odds Ratio
  • Receptors, LDL / genetics
  • Risk Factors

Substances

  • Apolipoproteins B
  • Lipoprotein(a)
  • Receptors, LDL