Progression of left ventricular hypertrophy and the angiotensin-converting enzyme gene polymorphism in hypertrophic cardiomyopathy

Int J Cardiol. 2004 Aug;96(2):157-63. doi: 10.1016/j.ijcard.2004.05.003.

Abstract

Background: Hypertrophic cardiomyopathy is an inherited primary disorder of the myocardium characterised by clinical heterogeneity. The severity and rate of progression of hypertrophy is an important factor in prognosis, and is likely to be dependent on factors including age, the disease-causing gene mutation, environmental influences and genetic modifiers.

Methods: To study the influence of age on progression of hypertrophy, 62 patients with hypertrophic cardiomyopathy followed up for a minimum of 2 years were studied to determine the changes in left ventricular hypertrophy based on transthoracic M-mode and 2D echocardiography. DNA studies were performed to determine the role of the angiotensin-converting enzyme (ACE) gene deletion polymorphism in modulating progression of left ventricular hypertrophy.

Results: Sixty-two patients were followed-up over a period of 6.0 +/- 3.2 years (range 2-16 years). Patient data were analysed in two age groups: group 1 (patients aged < or = 30 years at first echocardiogram) had an increase in left ventricular septal wall thickness from 23.8 +/- 8.9 to 28.8 +/- 8.7 mm (p < 0.001), while group 2 (patients aged > 30 years) had a smaller but significant increase from 17.8 +/- 4.2 to 19.5 +/- 6.2 mm (p < 0.05). DNA analysis of the ACE gene deletion polymorphism showed those with the deletion/deletion (D/D) genotype had a greater progression of left ventricular hypertrophy compared to those carrying the other ACE genotypes (increase in hypertrophy: 6.2 +/- 3.3 vs. 1.7 +/- 4.2 mm; p < 0.01, D/D vs. I/D genotype; 2.8 +/- 5.8 mm; p = ns, D/D vs. I/I genotype). This association was independent of age, body mass and resting blood pressure.

Conclusions: Progression of left ventricular hypertrophy is most evident in the first 3 decades of life, but is also observed in older age groups. Presence of the ACE gene D/D polymorphism may be an important marker to identify those individuals with hypertrophic cardiomyopathy who are likely to have more progressive disease, and therefore at higher risk of adverse clinical outcomes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Base Sequence
  • Cardiomyopathy, Hypertrophic / complications
  • Cardiomyopathy, Hypertrophic / genetics*
  • Cohort Studies
  • Disease Progression
  • Echocardiography, Doppler
  • Female
  • Humans
  • Hypertrophy, Left Ventricular / complications
  • Hypertrophy, Left Ventricular / diagnostic imaging
  • Hypertrophy, Left Ventricular / genetics*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Peptidyl-Dipeptidase A / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Probability
  • Prognosis
  • Risk Assessment
  • Sensitivity and Specificity
  • Severity of Illness Index

Substances

  • Peptidyl-Dipeptidase A