on January 29, 2004
Published online before print January 29, 2004, doi: 10.1161/01.ATV.0000119354.41615.33
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Submitted on November 19, 2003
Accepted on January 16, 2004
Angiotensin-Converting Enzyme D/I Gene Polymorphism and Age-Related Changes in Pulse Pressure in Subjects with Hypertension
Michel E. Safar *;
From the Diagnosis Center (M.E.S., A.R.), Hôtel-Dieu Hospital, Paris, France; the Geriatric Center (M.L., A.B.), Brabois Hospital, Nancy, France; and the Institut Cardio-Vasculaire (R.A.), Paris, France.
* To whom correspondence should be addressed. E-mail: centre.diagnostic{at}htd.ap-hop-paris.fr.
Background--Few studies have examined the possible influence of gene polymorphisms on the increase of systolic blood pressure (SBP) and pulse pressure (PP) with age, although in older populations, SBP>160 mm Hg or PP>60 mm Hg are strong mechanical factors predicting cardiovascular mortality.
Methods and Results--This cross-sectional study involved 315 men and 154 women with either systolic-diastolic or isolated systolic hypertension. Using polymerase chain reaction, the angiotensin-converting enzyme (ACE) D/I gene polymorphism was investigated separately in men and women, enabling us to determine the relationships between age and PP, SBP, and diastolic blood pressure (DBP) for each genotype in each population. In men, most of which were under 50 years of age, the slope of the age-PP and age-SBP (but not age-DBP) relationships differed significantly between genotypes (P=0.0096 and 0.0175). The interslope difference was unmodified after adjustments involving all of the following factors together: plasma glucose, cholesterol, creatinine, potassium, body weight, tobacco consumption, mean blood pressure, and previous antihypertensive therapy. Adjustment of the two latter parameters alone significantly attenuated the interslope difference. Based on logistic regressions, the DD genotype was shown to independently predict a PP>60 mm Hg but not a SBP>160 mm Hg.
Conclusions--In men, the ACE D/I gene polymorphism independently modulates age-related increase of PP, and potentially modulates the resulting cardiovascular risk. This finding requires the development of long-term follow-up.
Key words: hypertension • gene polymorphism • angiotensin-converting enzyme • pulse pressure
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