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


METHODS
PAH 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.


RESULTS
Among 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.


CONCLUSIONS
The 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.
Department of Medicine, The University of Melbourne at St Vincent's Hospital (Melbourne), 41 Victoria Parade, Fitzroy, 3065, VIC, Australia.|Department of Rheumatology St Vincent's Hospital (Melbourne), 41 Victoria Parade, Fitzroy, 3065, VIC, Australia.
Kathleen
K
Morrisroe
Department of Medicine, The University of Melbourne at St Vincent's Hospital (Melbourne), 41 Victoria Parade, Fitzroy, 3065, VIC, Australia.|Department of Rheumatology St Vincent's Hospital (Melbourne), 41 Victoria Parade, Fitzroy, 3065, VIC, Australia.
Molla
M
Huq
Department of Rheumatology St Vincent's Hospital (Melbourne), 41 Victoria Parade, Fitzroy, 3065, VIC, Australia.
Wendy
W
Stevens
Department of Rheumatology St Vincent's Hospital (Melbourne), 41 Victoria Parade, Fitzroy, 3065, VIC, Australia.
Candice
C
Rabusa
Department of Rheumatology, Royal Adelaide Hospital, North Terrace, Adelaide, SA, 5000, Australia.|Discipline of Medicine, University of Adelaide, Adelaide, SA, 5000, Australia.
Susanna M
SM
Proudman
Department of Medicine, The University of Melbourne at St Vincent's Hospital (Melbourne), 41 Victoria Parade, Fitzroy, 3065, VIC, Australia. m.nikpour@unimelb.edu.au.|Department of Rheumatology St Vincent's Hospital (Melbourne), 41 Victoria Parade, Fitzroy, 3065, VIC, Australia. m.nikpour@unimelb.edu.au.
Mandana
M
Nikpour
Incidence; Prevalence; Pulmonary arterial hypertension; Risk factors; Systemic sclerosis
Int J Rheum Dis. 2013 Feb;16(1):88-92
23441777
Chest. 2003 Dec;124(6):2098-104
14665486
Curr Opin Rheumatol. 2015 Nov;27(6):542-8
26352733
Chest. 2009 Nov;136(5):1211-9
19429720
Autoimmun Rev. 2011 Mar;10 (5):248-55
20863911
Curr Rheumatol Rep. 2013 Jan;15(1):302
23292818
Intern Med J. 2005 Jan;35(1):28-33
15667465
Dig Dis Sci. 1997 Jan;42(1):113-8
9009125
Arthritis Rheum. 1980 May;23(5):581-90
7378088
Scand J Rheumatol. 2008 Jul-Aug;37(4):278-83
18612928
Am Heart J. 2010 Feb;159(2):245-57
20152223
J Rheumatol. 1998 Mar;25(3):462-6
9517764
Arthritis Care Res (Hoboken). 2014 Mar;66(3):489-95
23983198
Arthritis Rheum. 2009 Jun;60(6):1831-9
19479881
Intern Med J. 2015 Nov;45(11):1134-40
26337683
J Cardiovasc Nurs. 2014 Mar-Apr;29(2):178-84
23151837
J Rheumatol. 2006 Jun;33(6):1117-22
16622903
J Heart Lung Transplant. 2007 Feb;26(2):181-7
17258153
Arthritis Res Ther. 2015 Jan 18;17:7
25596924
Semin Arthritis Rheum. 2014 Aug;44(1):55-62
24709277
Kardiol Pol. 2015 ;73(12 ):1127-206
26727670
Int J Rheum Dis. 2012 Feb;15(1):102-9
22324953
Arthritis Rheum. 2003 Feb;48(2):516-22
12571862
Rheum Dis Clin North Am. 2015 Aug;41(3):489-506
26210131
Ann Rheum Dis. 2011 Dec;70(12):2218-24
21873333
Thorax. 2009 Feb;64(2):167-73
19176842
Am J Med. 2010 Apr;123(4):304-11
20362747
Clin Exp Rheumatol. 2014 Nov-Dec;32(6 Suppl 86):S-133-7
24564981
Ann N Y Acad Sci. 2002 Jun;966:238-46
12114278
J Am Coll Cardiol. 2013 Dec 24;62(25 Suppl):D34-41
24355639
Rheumatology (Oxford). 2008 Aug;47(8):1185-92
18515867
Ann Surg. 2006 Oct;244(4):491-7
16998357
J Rheumatol. 2001 Jul;28(7):1573-6
11469464
Scand J Rheumatol. 2006 Nov-Dec;35(6):468-71
17343256
Rheumatology (Oxford). 2007 Feb;46(2):321-6
16877466
J Rheumatol. 1998 Jan;25(1):84-8
9458208
J Rheumatol. 2010 Jan;37(1):98-104
19955048
Chest. 2010 Aug;138(2):461-2; author reply 462-3
20682545