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.

Statin use and asthma control in patients with severe asthma.

OBJECTIVES: We hypothesised that severe asthmatics taking a statin drug, in addition to inhaled corticosteroids/long-acting ß-agonist inhaler therapy, would have better asthma symptom control and improved lung function compared to their controls. STUDY DESIGN: A retrospective, cross-sectional study of 165 patients with severe asthma seen from 2001-2008. Hierarchical linear and logistic regression models were used for modelling fitting. SETTING: University of California, Davis Medical Center (Sacramento, California, USA). Academic, single-centre, severe asthma subspecialty clinic. PARTICIPANTS: 612 screened, 223 eligible and 165 adult patients were included in the final study (N=165; 31 statin users and 134 non-users). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was asthma control as measured by the Asthma Control Test (ACT). The secondary endpoints included lung function, symptoms and the need for corticosteroid burst and peripheral eosinophil count. RESULTS: At baseline, statin users compared to non-users were older, had lower lung function (FEV1% predicted, FEV1, forced vital capacity and FEF25-75%) and had a higher prevalence of comorbid conditions. Statin use was associated with more aspirin and ipratropium inhaler use than in non-users. Patients in both groups were obese (body mass index ≥ 30). Statin users had better asthma symptom control compared to non-users (higher adjusted mean ACT score by 2.2±0.94 points, p<0.02). Median statin use was for 1 year. There were no statistically significant differences in lung function, corticosteroid or rescue bronchodilator use or peripheral eosinophilia between the two groups. CONCLUSIONS: In our severe asthma referral population, statin users already taking inhaled controller therapy achieved better asthma control compared to non-users. The implications of this study is that patients with severe asthma could potentially benefit from added statin treatment. Because our study population was on average obese, the obese severe asthmatic may be a viable asthma subphenotype for further studies. Prospective randomised clinical trials evaluating the safety and efficacy of statins in severe asthma are warranted.