Baseline Characteristics and Risk Factors of Pulmonary Arterial Hypertension in Systemic Lupus Erythematosus Patients

Abstract

Peking Union Medical College Hospital (PUMCH) has started a single-center right heart catheterization (RHC)-based pulmonary arterial hypertension (PAH) study in systemic lupus erythematosus (SLE) since 2006. The baseline characteristics of these patients were described and the risk factor for PAH in lupus was identified.The demographic, clinical, laboratory, and treatment characteristics of SLE patients with PAH when they were registered were collected as the baseline data. A case-control study was conducted by taking the admitted SLE-non-PAH patients adjusted for age and gender in a 4:1 ratio during the same period as the controls. The associated variables were examined by binary multivariate logistic regression analysis to identify possible risk factors. A total of 111 RHC-confirmed SLE-PAH patients were enrolled, with the onset age of 34.6 ± 8.6 years old and the average SLE duration of 5 years. RHC revealed mPAP as 46.4 ± 11.4 mm Hg, CI as 2.7 ± 0.8 L/min × m2, and PVR as 10.5 ± 4.8 WU. 46% of patients were WHO Fc I–II. All patients were treated with immunosuppressive agents and 65% patients had PAH-targeted therapy. The case-control study had confirmed 2 independent risk factors previously published: pericardial effusion (OR = 21.290, P < 0.001) and anti-RNP antibody (OR = 12.399, P < 0.001). Meanwhile, 6 independent variables were discovered: baseline SLE duration (OR = 1.118, P = 0.007), interstitial lung disease (OR = 17.027, P < 0.001=, without acute rash (OR = 3.258, P = 0.019), anti-SSA antibody (OR = 4.836, P = 0.004), SLEDAI≤9 (OR = 26.426, P < 0.001), ESR≤20 mm/h (OR = 12.068, P < 0.001), and uric acid > 357 μmol/L (OR = 9.666, P < 0.001) to be associated with PAH in SLE patients.The PUMCH study has shown that SLE patients complicated with PAH are usually earlier diagnosed and have less disease severity than patients without PAH. The immunosuppressive therapy rate and the PAH target therapy rate were high, which is consistent with reports from Western countries. This study has confirmed that pericardial effusion and positive anti-RNP antibody are risk factors for SLE-associated PAH. Long SLE disease duration, the presence of interstitial lung disease, without acute skin rash, positive anti-SSA antibody, low SLEDAI and ESR, and high uric acid levels are also associated with PAH in SLE patients.

Systemic lupus erythematosus and pulmonary arterial hypertension: links, risks, and management strategies

“…In rare cases, PAH is the first manifestation leading to SLE diagnosis 12. Concerning severity, this is usually moderate with pulmonary artery systolic pressure (PASP) ranging between 40 and 60 mmHg and PVR between 5 and 15 Wood units 11,13…”

“…In a recent analysis of a large Chinese cohort (n=1,934, 74 patients with PAH), pleuritis was an independent predictor of PAH in lupus and showed an odds ratio (OR) =3.06 (95% confidence interval [CI] =1.6–5.85) 18. Additional clinical manifestations with an independent predictive ability for PAH were interstitial lung disease (OR =17, 95% CI =3.6–80) and pericardial effusion (OR =21.3, 95% CI =4.1–110.6) 13. In the same study, it was shown that, paradoxically, lupus patients with PAH had less severe disease, as assessed by the SLE Disease Activity Index (SLEDAI); actually, a SLEDAI ≤9 was strongly predictive of PAH with an OR =26.4 (95% CI =6.6–105.5) 13.…”

“…Additional clinical manifestations with an independent predictive ability for PAH were interstitial lung disease (OR =17, 95% CI =3.6–80) and pericardial effusion (OR =21.3, 95% CI =4.1–110.6) 13. In the same study, it was shown that, paradoxically, lupus patients with PAH had less severe disease, as assessed by the SLE Disease Activity Index (SLEDAI); actually, a SLEDAI ≤9 was strongly predictive of PAH with an OR =26.4 (95% CI =6.6–105.5) 13. Moreover, the lack of acute rash and low erythrocyte sedimentation rate (≤20 mm/h) were also independent predictors.…”

“…Immunological variables associated with PAH in lupus patients include positive anti-U1-RNP (ribonuclear protein) and antiphospholipid antibodies 13. Anti-U1-RNP antibodies, in particular, were strong predictors for PAH in several studies with a hazard ratio ranging from 2.6 to 12.4 (95% CI =3.6–42.9) 12,13,18.…”

Pulmonary hypertension associated with antiphospholipid antibody: Call for a screening tool?

“…Mejia M et al (37) in 2017 have found several autoantibodies associated with ILD. Many studies have shown association of ILD with SLE, but there is a paucity of literature showing a specific relationship of aPL antibodies with PH in this group (38). Similarly the association of other CTD's with ILD is well established (39).…”