Age and Risk of Pulmonary Arterial Hypertension in Scleroderma*

doi:10.1378/chest.124.6.2098

Chest

Volume 124, Issue 6, December 2003, Pages 2098-2104

https://doi.org/10.1378/chest.124.6.2098 Get rights and content

Study objectives

To investigate whether age at disease onset is a risk factor for pulmonary arterial hypertension (PAH) in scleroderma.

Setting

Scleroderma center.

Patients

Seven hundred nine consecutive scleroderma patients who underwent echocardiography.

Measurements

The risk of PAH associated with age at disease onset was modeled as both a continuous and categorical variable. Risk estimates were adjusted for sex, race, scleroderma subtype, disease duration, smoking status, FVC, anticentromere and antitopoisomerase I antibody status.

Results

Overall, 274 patients (38.6%), 272 patients by Doppler echocardiography and 2 patients by M-mode echocardiography, had PAH at baseline or during follow-up. There were 114 patients with mild PAH (right ventricular systolic pressure [RVSP], 36 to 45 mm Hg), 66 patients with moderate PAH (RVSP, 46 to 55 mm Hg), and 92 patients with severe PAH (RVSP ≥ 56 mm Hg). A 52% increase in risk of PAH was demonstrated for every 10 years of age at disease onset (odds ratio [OR], 1.52; 95% confidence interval [CI], 1.31 to 1.76). In addition, there was a twofold greater risk of PAH (OR, 2.30; 95% CI, 1.32 to 3.99) for late-onset (age ≥ 60 years) vs earlier-onset (< 60 years) disease. These associations remained evident and were somewhat strengthened when the analyses were restricted to patients with moderate and severe PAH.

Conclusions

We identified increasing age at scleroderma onset as a risk factor for PAH. Vigilance among these high-risk patients may provide an opportunity to intervene prior to development of irreversible pulmonary vascular disease.

Section snippets

Study Sample and Measurements

A total of 899 patients with scleroderma attended The Johns Hopkins and University of Maryland Scleroderma Center over a 4.5-year period between January 1997 and June 2001 (Fig 1). Within this cohort, 849 patients (94.4%) satisfied the American College of Rheumatology (ACR) criteria for scleroderma,³⁰ or had at least three features of the CREST syndrome; 50 patients (5.6%) had systemic sclerosis sine scleroderma. The diagnosis of scleroderma was established by two of the authors (Dr. Wigley or

Results

Table 1 summarizes the demographic, clinical, and serologic features of the study population: 592 women (83.5%), 130 African Americans (18.3%), and 354 former or current smokers (49.9%). In terms of scleroderma subtype, 405 patient had limited (57.1%), 271 patients had diffuse (38.2%), and 33 patients had systemic sclerosis sine scleroderma (4.7%). ACA was identified in 130 patients (19.0%), whereas 89 patients had antitopoisomerase I antibody (13.0%). Mean age at disease onset was 41.8 ± 14.6

Discussion

In this large scleroderma cohort, we identified increasing age at disease onset as a risk factor for PAH. There was an approximately 50% increase in risk of PAH for every 10 years of age at onset of scleroderma after adjustment for demographic and clinical parameters. The oldest patients (≥ 60 years) had substantially higher risk of PAH, twice as high as those with earlier-onset disease. Furthermore, the association between increasing age and PAH remained evident when the outcome was restricted

ACKNOWLEDGMENT

We thank Christy Boling, Arash Banuwal, and Maria Fiesta for managing The Johns Hopkins and University of Maryland Scleroderma Center Database; and Gwen Leatherman, RN, and Jane Hofherr, RN, for their dedication to our Scleroderma Center and patients.

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This study was supported by a Maryland Chapter Arthritis Foundation Institutional Grant, the Scleroderma Research Foundation, and the Jack Alfano, Joachim & Nancy Bechtle and Don & Nancy Powell Research Funds.

Dr. Schachna was supported by an Arthritis Foundation Postdoctoral Fellowship Award.

Dr. Gelber was supported by an Arthritis Foundation Arthritis Investigator Award and Maryland Chapter Grant.

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Chest

Clinical InvestigationsPULMONARY HYPERTENSIONAge and Risk of Pulmonary Arterial Hypertension in Scleroderma*

Study objectives

Setting

Patients

Measurements

Results

Conclusions

Section snippets

Study Sample and Measurements

Results

Discussion

ACKNOWLEDGMENT

Rev Med Interne

Am J Med

Chest

Adv Immunol

Clin Immunol Immunopathol

Chest

Am J Med

Exp Gerontol

Rheum Dis Clin North Am

Mortality in systemic sclerosis (scleroderma)

Q J Med

Pulmonary hypertension in systemic sclerosis: an analysis of 17 patients

Br J Rheumatol

Pulmonary hypertension in systemic sclerosis: risk factors for progression and consequences for survival

Rheumatology

Pulmonary hypertension in the CREST syndrome variant of progressive systemic sclerosis (scleroderma)

Ann Intern Med

Pulmonary hypertension in the CREST syndrome variant of systemic sclerosis

Arthritis Rheum

Anti-endothelial cell antibodies in systemic sclerosis: significant association with vascular involvement and alveolo-capillary impairment

Clin Exp Rheumatol

Antiendothelial cell antibodies in scleroderma correlate with severe digital ischemia and pulmonary arterial hypertension

J Rheumatol

Measurement of anticardiolipin antibodies by ELISA using β2-glycoprotein I (β2-GPI) in systemic sclerosis

Clin Exp Immunol

Autoantibody to U3 nucleolar ribonucleoprotein (fibrillarin) in patients with systemic sclerosis

Arthritis Rheum

Isolated pulmonary hypertension in systemic sclerosis with diffuse cutaneous involvement: association with serum anti-U3RNP antibody

J Rheumatol

The effect of age on clinical and serological manifestations in unselected patients with systemic lupus erythematosus

J Rheumatol

Systemic lupus erythematosus: clinical and laboratory aspects related to age at disease onset

Clin Exp Rheumatol

The clinical features and prognosis of lupus with disease onset at age 65 and older

Lupus

Outcome of rheumatoid arthritis in relation to age and rheumatoid factor at diagnosis

J Rheumatol

Rheumatoid arthritis in a population of persons aged 85 years and over

Br J Rheumatol

Does the age of onset of rheumatoid arthritis influence phenotype? A prospective study of outcome and prognostic factors

Rheumatology

Effect of age on 3 year outcome in early rheumatoid arthritis

J Rheumatol

Clinical Investigations
PULMONARY HYPERTENSION
Age and Risk of Pulmonary Arterial Hypertension in Scleroderma*

Measurement of anticardiolipin antibodies by ELISA using β₂-glycoprotein I (β₂-GPI) in systemic sclerosis