901-94 The Angiotensin Converting Enzyme DD Genotype is Associated with Preserved Right Ventricular Function in Patients with Severe Primary Pulmonary Hypertension

A 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 a role for angiotensin II (Ang II) in the pulmonary vasoconstriction and pulmonary vascular smooth muscle proliferation characteristic of this disorder, we hypothesize a 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 a control population (n=89, p=0.0009). Mean±SEM right heart hemodynamics, echocardiographic RV internal dimensions (RVID) and NYHA classifications for the 2 groups are shown below: DDNon-DDp valueMean PA Pressure (mmHg)52±453±30.84PCWP (mmHg)5±16±10.59Cardiac Output (L/min)5.12±0.432.65±0.210.00007PVR (Wood Units)10.0±1.319.3 ±2.40.004RA Pressure (mmHg)5±110±20.08RVID(cm)3.1±0.33.7±0.20.08NYHA Class2.2±0.33.3±0.20.02Significantly, 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 a compensatory myocardial or inotropic role for Ang II in PP

Rationale, design, and baseline characteristics in Evaluation of LIXisenatide in Acute Coronary Syndrome, a long-term cardiovascular end point trial of lixisenatide versus placebo

BACKGROUND: Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Furthermore, patients with T2DM and acute coronary syndrome (ACS) have a particularly high risk of CV events. The glucagon-like peptide 1 receptor agonist, lixisenatide, improves glycemia, but its effects on CV events have not been thoroughly evaluated. METHODS: ELIXA (www.clinicaltrials.gov no. NCT01147250) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study of lixisenatide in patients with T2DM and a recent ACS event. The primary aim is to evaluate the effects of lixisenatide on CV morbidity and mortality in a population at high CV risk. The primary efficacy end point is a composite of time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. Data are systematically collected for safety outcomes, including hypoglycemia, pancreatitis, and malignancy. RESULTS: Enrollment began in July 2010 and ended in August 2013; 6,068 patients from 49 countries were randomized. Of these, 69% are men and 75% are white; at baseline, the mean ± SD age was 60.3 ± 9.7 years, body mass index was 30.2 ± 5.7 kg/m(2), and duration of T2DM was 9.3 ± 8.2 years. The qualifying ACS was a myocardial infarction in 83% and unstable angina in 17%. The study will continue until the positive adjudication of the protocol-specified number of primary CV events. CONCLUSION: ELIXA will be the first trial to report the safety and efficacy of a glucagon-like peptide 1 receptor agonist in people with T2DM and high CV event risk