Cardiovascular effects of I/D angiotensin-converting enzyme gene polymorphism in healthy subjects. Findings after follow-up of six years.
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.
Di Pasquale
Pietro
P
Division of Cardiology Paolo Borsellino, G.E Ingrassia Hospital, Palermo, Italy. LEHDi@Tin.It
Cannizzaro
Sergio
S
Scalzo
Sebastiano
S
Maringhini
Giorgio
G
Pipitone
Fernanda
F
Fasullo
Sergio
S
Giubilato
Alfonso
A
Ganci
Filippo
F
Vitale
Giuseppe
G
Sarullo
Filippo M
FM
Paterna
Salvatore
S
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
D007703:Peptidyl-Dipeptidase A