Risk factors for development of pulmonary arterial hypertension in Australian systemic sclerosis patients: results from a large multicenter cohort study

Abstract

BackgroundPulmonary arterial hypertension (PAH) is the leading cause of mortality in patients with systemic sclerosis (SSc). We sought to determine the incidence, prevalence and risk factors for PAH development in a large Australian SSc cohort.MethodsPAH was diagnosed on right heart catheterisation (mPAP >25 and PAWP <15 mmHg at rest). Patients with PH secondary to interstitial lung disease (ILD; defined as abnormal HRCT scan and FVC < 60 %) were excluded. Summary statistics, chi-square tests, univariate and multivariable logistic regression along with post-estimation diagnostics were used to determine the associations of different combinations of risk factors with PAH.ResultsAmong 1579 SSc patients, 8.4 % (132 patients) were diagnosed with PAH over a mean (±SD) follow-up of 3.2 (±2.5) years. The incidence of PAH in this cohort was 0.7 % per annum. Of these, 68.9 % had limited disease subtype (lcSSc). In multivariable regression analysis, the presence of anti-centromere antibody (ACA) (OR 1.6, 95 % CI 1.1–2.5, p = 0.03), oesphageal stricture (OR 2.0, 95 % CI 1.2–3.3, p = 0.006), calcinosis (OR 1.9, 95 % CI 1.2–2.9, p = 0.003), sicca symptoms (OR 1.6, 95 % CI 1.1–2.5, p = 0.03), mild ILD (OR 2.3, 95 % CI 1.5–3.7, p < 0.001) and digital ulcers (OR 1.6, 95 % CI 1.0–2.4, p = 0.03) were predictive of PAH. This model had an area under the curve of 0.7 and concordance of 91.8 %. When analysed by disease subtype, the presence of calcinosis (OR 2.2, 95 % CI 1.4–3.7, p = 0.01), sicca symptoms (OR 2.6, 95 % CI 1.5–4.6, p = 0.001), mild ILD (OR 2.3, 95 % CI 1.4–3.8, p = 0.001) and digital ulcers (OR 1.9, 95 % CI 1.2–3.7, p = 0.01) were predictive of PAH in lcSSc; and oesophageal stricture (OR 4.4, 95 % CI 1.9–10.5, p = 0.001), mild ILD (OR 2.8, 95 % CI 1.2–6.8, p = 0.02) and ACA (OR 5.2, 95 % CI 1.8–14.8, p = 0.002) were predictive of PAH in dcSSc.ConclusionsThe incidence and prevalence of PAH in this cohort are 0.7 % per annum and 8.4 %, respectively. The clinical-serologic risk factors for PAH differ based on disease subtype. In both subtypes, mild ILD is associated with PAH, suggesting the possibility of common pathogenic mechanisms underlying both of these disease manifestations. This model identifies a subset of patients at an appreciably higher risk of developing PAH, who should be screened and would in future, benefit from preventative therapies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12890-016-0296-z) contains supplementary material, which is available to authorized users.

Combined measurement of carbon monoxide and nitric oxide lung transfer does not improve the identification of pulmonary hypertension in systemic sclerosis

“…common among patients with diffuse cutaneous subtype than among those with limited subtype. The prevalence of pulmonary hypertension (10.1%) found here is also close to that reported in previous series [3,11,39,40].…”

Clinical Characteristics of Systemic Sclerosis With Interstitial Lung Disease

“…As predictive factors for PAH, its incidence was higher in SSc patients with ILD. 27 Conversely, another study reported no association between the severity of ILD and the right atrial pressure measured via right catheterization in SSc patients, suggesting that the pulmonary fibrotic changes in the ILD of SSc differ from those of the pulmonary vascular pathophysiology in PAH. 28 Clinically, combined PAH in SSc patients with ILD leads to a large difference in the prognosis compared to that in SSc patients with ILD only.…”

Pulmonary Arterial Hypertension in Systemic Connective Tissue Diseases: The Current State of the Problem

“…Изменения кожи по типу отека или атрофии в большей степени ассоциируются с ЛАГ, чем диффузное поражение. Тем не менее в части работ среди пациентов с ЛАГ имеется весомая доля больных с диффузной клинической формой [20]. Вероятно, причиной подобного несоответствия является включение в исследование пациентов с интерстициальным поражением легких (ИПЛ), так как известно, что это висцеральное проявление ССД более характерно для диффузной клинической формы [21].…”

“…Это утверждение, помимо классификационной путаницы, приводит к курьезным результатам, взаимоисключающим друг друга. Так, в двух работах [20,22] Другое клиническое проявление ССД, очень часто выявляемое у больных ЛАГ, -телеангиэктазии [24]. Клинический симптом, которому ранее уделялось достаточно мало внимания, в последние годы показал свою значимость в диагностике и оценке прогноза.…”