The Angiotensin Converting Enzyme DD Genotype is Associated with Preserved Right Ventricular Function in Patients with Severe Primary Pulmonary Hypertension

polymorphic marker within the ACE gene has been found to correlate with circulating and tissue ACE activities and with the incidence of severe pulmonary hypertension (Abraham et al, JACC 1994; 23: 177A). While the association of the ACE DD genotype and pulmonary hypertension suggests role for angiotensin II (Ang II) in the pulmonary vasoconstriction and pulmonary vascular smooth muscle proliferation characteristic of this disorder, we hypothesize compensatory role for Ang II in the maintenance of right ventricular (RV) function in such patients. We evaluated the frequency of the ACE DD genotype in 55 patients with severe primary pulmonary hypertension (PPH) and compared clinical severity and right heart hemodynamics at the time of presentation in 20 of these patients stratified on the basiw of their ACE genotype (DD vs non-DD, N = 10 in each group). The incidence of the ACE DD genotype was 49% in the PPH patients compared to 23% in control population (n = 89, P = 0.0009). Mean ± SEM right heart hemodynamics, echocardiographic RV internal dimensions (RVID) and NYH classifications for the 2 groups are shown below: Significantly, the duration of symptoms attributable to PPH was not different between the DD and non-DD groups (35 ± 19 vs 22 ± 6 months, P = 0.58). Conclusion: The ACE DD genotype is associated with preserved RV function in PPH patients, supporting compensatory myocardial or inotropic role for Ang II in PPH.