What Is PAH-CTD?

PAH Introduction

Pulmonary arterial hypertension (PAH, WHO Group I) is a progressive syndrome resulting from restricted blood flow through the pulmonary arterial circulation, which leads to reduced cardiac output, right heart failure, and ultimately, death.1 PAH subgroups include idiopathic PAH, heritable PAH, drug- or toxin-induced PAH, and associated PAH. Associated PAH may be linked with a number of diseases or conditions, including connective tissue disease (CTD).2

Prevalence of PAH-SSc

PAH associated with connective tissue disease (PAH-CTD) is the second most prevalent type of PAH (after idiopathic PAH) in the US and Europe,3 affecting 0.5% to 15% of patients with CTD.4 Although PAH-CTD can affect patients of all races, among people in the National Biological Sample and Data Repository for PAH (PAH Biobank), African American patients were 2.5 times more likely to have PAH-CTD than patients of other races.5* PAH may be a serious complication of CTD such as systemic sclerosis (SSc, or scleroderma), mixed CTD, and systemic lupus erythematosus (SLE).6,7

PAH-CTD associations6
PAH-CTD associations chart PAH-CTD associations chart

While SLE and rheumatoid arthritis are among the most common CTDs, PAH occurs most 
frequently in SSc, with 74% of PAH-CTD cases being diagnosed in patients with SSc.6

≈100,000 people living with SSc in the United States8
5% to 12% of patients with SSc will develop PAH3
44% of patients with PAH-SSc in the DETECT study with follow-up data (25/57) progressed during a short time (median observation time, 12.6 months)9†
You can help make the connection between CTD and the risk of PAH earlier using noninvasive tests—see how the DETECT algorithm can help identify patients with SSc in need of right heart catheterization.10 Learn More >

PAH-SSc and Racial Disparities

As mentioned above, PAH-CTD may disproportionately occur in African Americans compared with other races.5 That disparity may persist in PAH-SSc:

One study from 2003 found that 48% (n=130) OF AFRICAN AMERICANS IN A SCLERODERMA CENTER HAD PAH, compared with 39% OVERALL (n=709)11

Another study from 2014 reported that AFRICAN AMERICAN PATIENTS (n=29) HAD GREATER DISEASE SEVERITY AT PAH-SSc DIAGNOSIS, including worse Functional Class, right ventricular function, NT-proBNP and 6-minute walk distance THAN EUROPEAN AMERICAN PATIENTS (n=131)12‡

The PAH-SSc Link

SSc is a chronic, inflammatory, autoimmune disease characterized by endothelial dysfunction and microvascular disease.13-15 This baseline inflammation and endothelial dysfunction contributes to the development of associated PAH, followed by vasoconstriction and vascular remodeling and eventual right heart failure.6,13 While earlier-stage PAH is characterized by smooth muscle hypertrophy and vasoconstriction, proliferative features predominate in later stages.16 It is in this stage of progression that most patients with PAH-SSc are diagnosed, reducing effectiveness of vasodilator treatment and carrying a worse prognosis.16-18

Diagram showing pathoggenesis of PAH


Diagram showing vasoconstriction and advanced vascular lesion
Figure reproduced with permission from [JAMA. 2000;284(24):3160-3168.]. Copyright ©2000 American Medical Association. All rights reserved.

Delays in PAH-SSc Diagnosis

Patients with SSc can develop PAH at any time, but experience a median delay in diagnosis of 4 years.19 The following chart is an example for illustrative purposes only to portray the delay in diagnosis of PAH-SSc that a patient may experience. In some patients with SSc, median time to diagnosis of SSc after Raynaud’s phenomenon onset was 2.8 years.20 Additionally, median time to diagnosis of PAH in patients with SSc was 4 years.19

Delay in PAH-SSc diagnosis19,20

4-year chart showing PAH-CTD diagnosis to detection
Learn about annual screenings for PAH in patients with SSc.3 Find Out What the Guidelines Say >

Symptoms and Risk Factors

Awareness of symptoms and predictive risk factors can help identify PAH in patients with SSc. Misdiagnosis and delayed diagnosis may be attributed to the nonspecific nature of the presenting symptoms.21,22

Symptoms of PAH-SSc13

  • Dyspnea
  • Syncope
  • Orthostasis
  • Fatigue
  • Chest pain

Regular screening followed by diagnostic right heart catheterization is required to consistently detect PAH-SSc.23

Risk factors for PAH-SSc24,25

Time-Related Risk Factors

  • Older age at scleroderma onset
  • Long-standing disease

Co-Existing Conditions

  • Limited cutaneous scleroderma
  • Cutaneous telangiectasias
  • Severe digital ischemia
  • Severe Raynaud’s phenomenon

Diagnostic Results

  • Nucleolar pattern of antinuclear antibodies
  • Anticentromere antibodies
  • Declining or isolated low Dlco
*This 2017 study of racial and ethnic differences in PAH included 1837 White, African American, and Hispanic patients enrolled in the National Biological Sample and Data Repository for PAH (PAH Biobank).5
DETECT was a global cross-sectional study involving 62 experienced centers. DETECT was funded and supported by Actelion Pharmaceuticals Ltd. 488 patients with SSc enrolled between 2008 and 2011, and nearly 1 in 5 (18.7%, 87/466) were found to have PAH. Disease progression was defined as FC worsening, combination therapy for PAH, PAH-related hospitalization, or death.9,10
Racial classification was based on self-report. Hispanic patients (2% of 131) were considered together with White patients within the group of European Americans for simplicity.12
Dlco=diffusing capacity of the lungs for carbon monoxide; FC=Functional Class; NT-proBNP=N-terminal pro-brain natriuretic peptide; PAH-SSc=pulmonary arterial hypertension associated with systemic sclerosis; WHO=World Health Organization.
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