Does angiotensin-converting enzyme gene polymorphism affect blood pressure? Findings after 6 years of follow-up in healthy subjects.
BACKGROUND
There has been an increase in research into the association between angiotensin-converting enzyme (ACE) gene deletion polymorphism and cardiovascular disease, with conflicting results. 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.


METHODS



METHODS
684 healthy volunteers (aged, 25-55 years): normotensive and free of cardiovascular diseases, with acceptable echocardiographic window. All subjects had to have a normal electrocardiogram (ECG) and echocardiogram (ECHO) at entry.


METHODS
All subjects underwent a complete physical examination, 12-lead ECG and ECHO, and venous blood samples were drawn for DNA analysis and cholesterol. All subjects had a clinical evaluation each year for the 6 year duration of the study.


RESULTS
All 684 subjects completed 6 years of follow-up. We identified three genetically distinct groups. The 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 no association between family history, smoking habit, hypercholesterolemia and events. The ACE-ID group (n=335, 116F/219M, mean age 43.6+/-7 years) had 16 hypertensive subjects (4.7%) and 3 subjects with ACS. The ACE-II group (n=124, 45F/79M, mean age 42.5+/-6.9 years) had 2 hypertensive subjects (1.6%) and 1 HF subject. The incidence of hypertension and cardiovascular events was significantly higher in the ACE-DD group (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.


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. The higher incidence of hypertension was apparent predominantly in the older age groups.
Di Pasquale
Pietro
P
Division of Cardiology, Paolo Borsellino, G.F. Ingrassia Hospital, Via Val Platani 3, 90144 Palermo, Italy. lehdi@tin.it
Cannizzaro
Sergio
S
Paterna
Salvatore
S
D000328:Adult; D001794:Blood Pressure / Q000235:genetics; 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; D016254:Mutagenesis, Insertional; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies; D012016:Reference Values; D013997:Time Factors
D007703:Peptidyl-Dipeptidase A