Impact of insulin resistance on ventricular function in pulmonary arterial hypertension.

BACKGROUND

Insulin resistance (IR) is an independent prognostic marker in pulmonary arterial hypertension (PAH), although the mechanism by which it engenders risk is unknown. We prospectively investigated the clinical, laboratory, hemodynamic, and echocardiographic characteristics of insulin-sensitive (IS) and IR patients with PAH.

METHODS

This was a prospective cohort study including well-phenotyped patients with PAH proven at cardiac catheterization. Patients were classified as IS or IR on the basis of the well-validated triglyceride/high-density lipoprotein-cholesterol ratio. Clinical, laboratory, and hemodynamic characteristics were compared between cohorts. Distance walked on the 6-minute walk test (6MWT) and echocardiograms were compared between IS and IR for the sub-set of patients that had these tests within 1 month of cardiac catheterization.

RESULTS

Of the 111 PAH patients enrolled, 59 were IS, 25 were IR, and 27 were classified as indeterminate. Mean age was 45.8 ± 15.0 years. IR was associated with worse New York Heart Association class (p = 0.02). There were no differences in hemodynamics, biomarkers, 6MWT distance, or parameters of right ventricular function (i.e., tricuspid annular plane systolic excursion, myocardial performance index, and fractional area change) between groups. Despite similar systemic vascular resistance, parameters of left ventricular diastolic function were more favorable for IS vs IR, including mitral inflow E wave velocity (82 ± 17 vs. 64 ± 19 msec, p = 0.02), E/A ratio (1.2 ± 0.4 vs. 0.8 ± 0.2, p = 0.01), and lateral mitral valve E' velocity (13.9 ± 3.5 vs. 10.4 ± 2.2 msec, p = 0.01).

CONCLUSIONS

IR is associated with worse functional class and diastology compared with IS in PAH, although other prognostic parameters are similar.