Cardiovascular effects of I/D angiotensin-converting enzyme gene polymorphism in healthy subjects. Findings after six years follow up

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 echocardiographic method in healthy subjects without any risk factors and without any events after 6 years of follow-up. 684 healthy volunteers (aged 25–55 years) with acceptable echocardio-graphic window were enrolled. Physical examination,12-lead ECG, echocardiograms and venous blood samples for DNA analysis were performed. All subjects had a clinical evaluation each year for the 6 year. 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. All 684 subjects completed 6 years of follow up. We obtained 3 genetically distinct groups. ACE-DD group,(n=225,80F/145M,mean age 43.4±7.6 years),had 42 hypertensive subjects (18.3%), 5 heart failure (HF) subjects and 6 subjects with acute coronary syndromes (ACS).There was not association between family history,smoking habit,hypercholesterolemia and events.ACE-ID group: (n=335, 116F/219M, mean age 43.6±7 years),had 16 hypertensive subjects (4.7%),and 3 subjects with ACS. ACE-II group:(n=124,45/79 F/M, mean age 42.5±6.9 years),had 2 hypertensive subjects (1.6%), and 1 HF subject. The incidence of hypertension and cardiovascular events, were significantly higher in ACE-DD (53 cases, 23%) than 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 whole examined group, also when stratified for the 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.Our data suggest that ACE-DD polymorphism is associated to a higher incidence of hypertension and appears to affect the diastolic function.