Insulin resistance in pulmonary arterial hypertension

¹ Division of Pulmonary and Critical Care Medicine, Dept. of Medicine, Stanford University School of Medicine; and Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford University
² Dept of Cardiology, Harvard Medical School; and Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford University
³ Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford University
⁴ Palo Alto Medical Foundation Research Institute
⁵ Division of Endocrinology, Metabolism and Gerontology, Dept. of Medicine, Stanford University
⁶ Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford University; and Division of paediatric Cardiology, Dept. of paediatrics, Stanford University

^* To whom correspondence should be addressed. E-mail: zamanian{at}stanford.edu.

	Abstract

Although obesity, dyslipidemia, and insulin resistance (IR) are well known risk factors for systemic cardiovascular disease, their impact on pulmonary arterial hypertension (PAH) is unknown. Our previous studies indicate that IR may be a risk factor for PAH. We now investigate the prevalence of IR in PAH and explore its relationship to disease severity.

Clinical data and fasting blood samples were evaluated in 81 non-diabetic PAH females. National Health and Nutrition Examination Surveys (NHANES) females (n=967) served as controls. Fasting triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) was used as a surrogate of insulin sensitivity.

While BMI was similar in NHANES vs PAH females (28.6 vs. 28.7 kg·m^-2), PAH females were more likely to be IR (45.7% vs. 21.5%) and less likely to be IS (43.2% vs. 57.8%, p<0.0001). PAH females mostly had NYHA class II and III symptoms (82.7%). Etiology, NYHA class, 6-minute-walk-distance, and hemodynamics did not differ between IR and IS PAH groups. However, the presence of IR and a higher NYHA class were associated with poorer 6-months event-free survival (58% vs. 79%, p<0.05).

Insulin Resistance appears to be more common in PAH females than in the general population, and may be a novel risk factor or disease modifier which might impact survival.