title: Cardiovascular effects of I/D angiotensin-converting enzyme gene polymorphism in healthy subjects. Findings after follow-up of six years.
abstract: BACKGROUND
  An increasing number of studies with conflicting results regarding the association between angiotensin-converting enzyme (ACE) gene deletion polymorphism and cardiovascular disease has recently been published. The present prospective long-term study was conducted to evaluate whether the DD genotype could also be associated with a higher prevalence of hypertension in healthy subjects over 6 years of follow-up. We also investigated the effects of the ACE-I/D genotypes on diastolic function by echocardiography in healthy subjects without any risk factors and any events after 6 years of follow-up.
  
  
  METHODS
  
  
  
  METHODS
  684 healthy volunteers (aged 25-55 years) normotensive and free of cardiovascular diseases, with acceptable echocardiographic window were enrolled. All subjects had to have a normal electrocardiogram (ECG) and echocardiogram (ECHO) at entry. All subjects have undergone a complete physical examination, 12-lead ECG and ECHO; DNA analysis and serum cholesterol have been performed on venous blood samples. All subjects underwent a clinical evaluation each year for the 6-year duration of the study. In addition, 275 subjects without any risk factors underwent an ECHO every year of the follow-up, to check the influence of genotypes on myocardial diastolic performances.
  
  
  RESULTS
  All 684 subjects completed 6 years of follow-up. We obtained 3 genetically distinct groups: I) the ACE-DD group (n = 225, 80 F/ 145 M, mean age 43.4 +/- 7.6 years) with 42 hypertensive subjects (18.3%), 5 heart failure (HF) subjects and 6 subjects with acute coronary syndromes (ACS). There was no association between family history, smoking habit, hypercholesterolaemia and events. 2) the ACE-ID group (n = 335, 116 F/2 19 M, mean age 43.6 +/- 7 years) with 16 hypertensive subjects (4.7%) and 3 subjects with ACS. 3) the ACE-II group (n = 124, 45 F/79 M, mean age 42.5 +/- 6.9 years) with 2 hypertensive subjects (1.6%) and I HF subject. The incidence of hypertension and cardiovascular events, was significantly higher in the ACE-DD (53 cases, 23%) than in the ACE-ID and ACE-II groups (20 and 3 cases, 5.9% and 2.4%, respectively), p = 0.0001. The higher incidence of hypertension was observed in the older age groups (36-45 and 46-55 years) with ACE-DD and ACE-ID genotypes. Moreover, ACE-DD significantly and early affected myocardial diastolic properties in the total group examined, also when stratified for age. There was a reduction of E/A ratio and it was more evident in subjects aged 36-45 and 46-55 years, p = 0.0001.
  
  
  CONCLUSIONS
  Our data suggest that ACE-DD polymorphism is associated with a higher incidence of hypertension in baseline healthy subjects, irrespective of other risk factors, and appears to affect the diastolic function. These effects were apparent predominantly in the older age groups.
authors.affiliation: Division of Cardiology Paolo Borsellino, G.E Ingrassia Hospital, Palermo, Italy. LEHDi@Tin.It
authors.forename: Pietro
authors.initials: P
authors.lastname: Di Pasquale
authors.forename: Sergio
authors.initials: S
authors.lastname: Cannizzaro
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Scalzo
authors.forename: Giorgio
authors.initials: G
authors.lastname: Maringhini
authors.forename: Fernanda
authors.initials: F
authors.lastname: Pipitone
authors.forename: Sergio
authors.initials: S
authors.lastname: Fasullo
authors.forename: Alfonso
authors.initials: A
authors.lastname: Giubilato
authors.forename: Filippo
authors.initials: F
authors.lastname: Ganci
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Vitale
authors.forename: Filippo M
authors.initials: FM
authors.lastname: Sarullo
authors.forename: Salvatore
authors.initials: S
authors.lastname: Paterna
mesh_terms: D000328:Adult; D000367:Age Factors; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics; D003971:Diastole / Q000502:physiology; D004452:Echocardiography; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D015995:Prevalence; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D007703:Peptidyl-Dipeptidase A