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Document Details :

Title: Cardiovascular effects of I/D angiotensin-converting enzyme gene polymorphism in healthy subjects
Subtitle: Findings after follow-up of six years
Author(s): DI PASQUALE, Pietro , CANNIZZARO, Sergio , SCALZO, Sebastiano , MARINGHINI, Giorgio , PIPITONE, Fernanda , FASULLO, Sergio , GIUBILTO, Alfonso , GANCI, Filippo , VITALE, Giuseppe , SARULLO, Filippo M. , PATERNA, Salvatore
Journal: Acta Cardiologica
Volume: 60    Issue: 4   Date: August 2005   
Pages: 427-435
DOI: 10.2143/AC.60.4.2004993

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 — Population: 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: 1) 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/219 M, mean age 43.6 ± 7 years) with16 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 1 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.

Conclusion — 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.