Prevalence, Incidence and Associates of Pulmonary Hypertension Complicating Type 2 Diabetes: Insights from the Fremantle Diabetes Study Phase 2 and National Echocardiographic Database of Australia

Abstract

There is a paucity of epidemiologic data examining the relationship between pulmonary hypertension (PH) and diabetes. The aim of this study was to determine prevalence, incidence and associates of PH complicating type 2 diabetes. Data from 1430 participants (mean age 65.5 years, 51.5% males) in the Fremantle Diabetes Study Phase 2 (FDS2) were linked with the National Echocardiographic Database of Australia (NEDA) to ascertain the prevalence and incidence of PH (estimated right ventricular systolic pressure (eRVSP) >30 mmHg as a new suggested threshold or the conventional >40 mmHg) over a 12-year period. PH prevalence in FDS2 was compared with that in NEDA overall and a geographically close sub-population. Multivariable analyses identified associates of prevalent/incident PH in the FDS2 cohort. Of 275 FDS2 patients (19.2%) with pre-entry echocardiography, 90 had eRVSP >30 mmHg and 35 had eRVSP >40 mmHg (prevalences 32.7% (95% CI 27.3–38.7%) and 12.7% (9.1–17.4%), respectively), rates that are 35–50% greater than national/local NEDA general population estimates. Moreover, 70 (5.0%) and 123 (9.2%) FDS2 participants were identified with incident PH at the respective eRVSP thresholds (incidence (95% CI) 7.6 (6.0–9.7) and 14.2 (11.8–17.0)/1000 person-years), paralleling data from recognised high-risk conditions such as systemic sclerosis. The baseline plasma N-terminal pro-brain natriuretic peptide concentration was the strongest independent associate of prevalent/incident PH. Approximately 1 in 8 people with type 2 diabetes have PH using the eRVSP >40 mmHg threshold. Its presence should be considered as part of regular clinical assessment of individuals with type 2 diabetes.

Polychlorinated Biphenyls and Pulmonary Hypertension

“…Li et al (2007) reported that the risk of PAH was two times higher in individuals with thyroid disease (OR, 2.53; 95% confidence interval, 1.55 to 4.08; p < 0.001) [30]. The prevalence of PAH was shown to be increased by up to 50% in type 2 diabetes [31]. Based on these studies, we identified a population with a combination of risk factors for PAH (hypertension, diabetes, thyroid problems, abnormal uric acid level, and insulin resistance) in the National Health and Nutrition Examination Survey (NHANES) to determine whether or not they had a higher level of exposure to PCBs.…”

The Relationship between Pulmonary Artery Pressure and Mortality in Type 2 Diabetes: A Fremantle Diabetes Study Phase II and National Echocardiographic Database of Australia Data Linkage Study

“…In people with diabetes, the risk of PH is increased [17,18] and the available evidence suggests that it carries a particularly poor prognosis [19,20]. Whether the presence of an eRVSP >30 mmHg, which was present in approximately one-third of community-based individuals with type 2 diabetes who had undergone echocardiography as part of routine clinical care [21], has the same prognostic significance as in the general population is unknown. The aims of the present study were, therefore, to determine the eRVSP threshold associated with increased mortality in well-characterised type 2 diabetes and to explore its demographic and clinical predictors.…”

Pulmonary disease in diabetes

“…13 In the Fremantle Diabetes Study, analysis of the subset of persons with T2D who had echocardiograms obtained for clinical reasons showed 6.4% and 2.6% prevalence of estimated right ventricular systolic pressure >30 and >40, respectively, and over 6.6-year follow-up an additional 9.2% and 5.0% developed this degree of PH, suggesting that the risk of PH is approximately 40% greater among persons with diabetes. 14 A study of patients with PH having versus not having diabetes showed that the former had higher BNP, shorter 6-min walking distance, more dyspnea, higher pulmonary artery pressure, and shorter survival, 15 and a study of 110 563 persons with newly diagnosed PH in the US national Veterans Health Affairs database showed that more than one third had diabetes, which was associated with a 1.21-fold greater mortality risk. 16 Genetic association studies in a population of 14 861 persons with echocardiogram-measured pulmonary pressure and right ventricular function suggest both T2D and obesity to be associated with greater levels of tricuspid regurgitation and right ventricular systolic pressure, suggesting both to play roles in the development of PH.…”

“…Insulin resistance has been proposed as underlying the relationship between diabetes and PH, with consequent inflammation, dyslipidemia, and endothelial dysfunction leading to adverse pulmonary vascular remodeling and to right ventricular dysfunction 13 . In the Fremantle Diabetes Study, analysis of the subset of persons with T2D who had echocardiograms obtained for clinical reasons showed 6.4% and 2.6% prevalence of estimated right ventricular systolic pressure >30 and >40, respectively, and over 6.6‐year follow‐up an additional 9.2% and 5.0% developed this degree of PH, suggesting that the risk of PH is approximately 40% greater among persons with diabetes 14 . A study of patients with PH having versus not having diabetes showed that the former had higher BNP, shorter 6‐min walking distance, more dyspnea, higher pulmonary artery pressure, and shorter survival, 15 and a study of 110 563 persons with newly diagnosed PH in the US national Veterans Health Affairs database showed that more than one third had diabetes, which was associated with a 1.21‐fold greater mortality risk 16 .…”