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PH, ILD Contribute to Higher Mortality Risks Among Patients With Systemic Sclerosis


This investigation involved analyses of the potential for pulmonary hypertension (PH) and interstitial lung disease (ILD) to have an impact on patients living with systemic sclerosis.

For patients already living with systemic sclerosis, also having both pulmonary hypertension (SSc-PH) and interstitial lung disease (SSc-ILD) exacerbates their risk of all-cause mortality, and this risk only goes up with increasing severity of both comorbidities, reports a recent published study in Pulmonary Circulation.

The PH or ILD diagnosis had to be delivered between January 1, 1999, and January 1, 2021, and each was classified as mild, moderate, or severe:

  • PH: mild, mean pulmonary artery pressure (mPAP) > 20 and < 25 mmHg; moderate, mPAP ≥25 and < 35mmHg; severe, mPAP ≥35 mm Hg
  • ILD: mild, forced vital capacity (FVC) on pulmonary function ≥ 85% predicted; moderate, FVC ≥ 45% predicted and < 85% predicted); severe, FVC < 45% predicted

“Little is known of how ILD severity affects outcomes in those with SSc‐PH or how PH severity affects outcomes in those with SSc‐ILD,” the study authors wrote. “We aimed to delineate clinical features of patients with SSc‐PH and SSc‐ILD and determine to what degree PH and ILD severity contribute to mortality in patients with SSc.”

They used pulmonary function testing to determine ILD severity, and they used cardiopulmonary hemodynamics to determine PH severity. The primary outcome of their retrospective single-center study was all-cause mortality from time of diagnosis of PH or ILD in the patients who had SSc-PH (n = 88) and SSc-ILD (n = 195), respectively, for which the study authors “adjusted risks of time to all‐cause mortality using Cox proportional hazards models.”

Comorbid PH was seen among 26.2% of the SSc-ILD patient cohort, with most having severe or moderate PH, at 39.2% and 51.0%, respectively. More male patients were seen in this group vs patients with SSC-ILD who did not have PH. Chest CT findings—the most common find was round‐glass and/or reticular opacities—were similar with or without PH, and cyclophosphamide was the most prescribed first-line treatment (40.5%).

All-cause mortality in those with SSc-ILD and PH was elevated at moderate and severe disease stages vs the mild stage. In patients with moderate disease, the risk of death was elevated 1.65 times (HR, 2.65; 95% CI, 1.12-6.31), and in severe disease, 5.6 times (HR, 6.60; 95% CI, 2.98-14.61), when adjusting for diagnosis age, male sex, and pulmonary function testing.

Comorbid ILD was seen in 58.0% of the SSc-PH cohort, and moderate ILD was the most common subtype (68.6%), followed by 17.6% with mild ILD. Male patients were again more common among those with SSc-PH and ILD compared with the patients who had only SSc-PH. Also, the more severe the ILD, the younger the patient age at PH diagnosis. The overwhelming most common first-line treatment was that specific to pulmonary arterial hypertension.

All-cause mortality in those with SSc-PH and ILD was elevated only in the presence of severe ILD. The unadjusted analysis produced an 0.81-times elevated risk of death (HR, 1.81; 95% CI, 0.67-4.89), and adjusting for PH diagnosis age, male sex, diffuse cutaneous SSc, and cardiopulmonary hemodynamics elevated the risk to 2.54 times greater (HR, 3.54; 95% CI, 1.05-11.99).

The authors emphasized that knowing the severity of PH or ILD among patients who have SSc can help to risk stratify patients and that in turn can help to guide treatment decisions that include intensifying treatment referral for lung transplantation.

“Among patients with SSc‐ILD or SSc‐PH, concomitant PH or ILD disease, respectively, may increase risk of all‐cause mortality in a severity‐response relationship,” the study investigators concluded. “These findings emphasize the importance of therapies to target slowing of disease progression earlier in the disease course.”

Future randomized controlled trials should evaluate ILD- and PAH-specific therapies in patients with SSc-PH and SSc-ILD, the investigators recommended, and they said their findings should be confirmed in a larger patient cohort.


Sangani RA, Lui JK, Gillmeyer KR, et al. Clinical characteristics and outcomes in pulmonary manifestations of systemic sclerosis: Contribution from pulmonary hypertension and interstitial lung disease severity. Pulm Circ. Published online October 1, 2022.doi:10.1002/pul2.12117

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