HbA1c in pulmonary arterial hypertension: a marker of prognostic relevance?

Background: Patients with pulmonary arterial hypertension (PAH) exhibit impaired glucose metabolism and increased insulin resistance. The clinical consequences of these metabolic changes are not known.

Methods: We assessed HbA1c levels in 115 patients newly diagnosed with PAH (79 females and 36 males; mean age 49.2 years; idiopathic n = 67, collagen vascular disease n = 16, congenital heart defect n = 19, pulmonary veno-occlusive disease n = 8, portopulmonary n = 5). No patients had diabetes or were receiving anti-diabetic medication or systemic steroids. After initiation of pulmonary vasoactive treatment, patients remained in long-term follow-up.

Results: Initially, patients were in an advanced stage of disease (mean pulmonary arterial pressure 53 ± 18 mm Hg, cardiac index 2.3 ± 0.8 liters/min/m2) with a 6-minute-walk distance of 337 ± 123 meters, and in NYHA Functional Class 3.0 ± 0.7. The HbA1c was 5.73 ± 0.75%. A moderate but statistically significant positive correlation was observed between HbA1c levels and BNP (r(p) = 0.41, p = 0.014), but no correlation was found with hemodynamics or 6-minute-walk distance. The 5-year survival rate for the entire group was 68%. Kaplan-Meier analysis and multivariate Cox proportional hazard models correcting for demographic and clinical covariates revealed that patients with HbA1c < 5.7% had a significantly better 5-year survival compared with those having higher initial values (85.1% vs. 55.9%; log rank p = 0.002). HbA1c was a predictor of all-cause mortality with a hazard ratio of 2.23 (95% CI 1.06 to 4.70; p = 0.034) per 1-unit increase of HbA1c.

Conclusions: In patients with pulmonary arterial hypertension, the HbA1c level at time of diagnosis is an independent predictor of long-term prognosis.