The spectrum of systemic sclerosis-associated pulmonary hypertension: Insights from the ASPIRE registry.

BACKGROUND: There are limited data assessing the spectrum of systemic sclerosis-associated pulmonary hypertension (PH). METHODS: Data for 912 systemic sclerosis patients assessed between 2000 and 2020 were retrieved from the Assessing the Spectrum of Pulmonary hypertension Identified at a REferral centre (ASPIRE) registry and classified based on 2022 European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines and multimodality investigations. RESULTS: Reduction in pulmonary vascular resistance (PVR) diagnostic threshold to >2WU resulted in a 19% increase in precapillary PH diagnoses. Patients with PVR ≤2WU had superior survival to PVR >2-3WU which was similar to PVR >3-4WU. Survival in pulmonary arterial hypertension (PAH) was superior to PH associated with lung disease. However, patients with mild parenchymal disease on CT had similar characteristics and outcomes to patients without lung disease. Combined pre- and postcapillary PH had significantly poorer survival than isolated postcapillary PH. Patients with mean pulmonary arterial wedge pressure (PAWP) 13-15 mm Hg had similar haemodynamics and left atrial volumes to those with PAWP >15 mm Hg. Unclassified-PH had more frequently dilated left atria and higher PAWP than PAH. Although Unclassified-PH had a similar survival to No-PH, 36% were subsequently diagnosed with PAH or PH associated with left heart disease. The presence of 2-3 radiological signs of pulmonary veno-occlusive disease was noted in 7% of PAH patients and was associated with worse survival. Improvement in incremental shuttle walking distance of ≥30 m following initiation of PAH therapy was associated with superior survival. PAH patients diagnosed after 2011 had greater use of combination therapy and superior survival. CONCLUSION: A number of systemic sclerosis PH phenotypes can be recognized and characterized using haemodynamics, lung function and multimodality imaging.

Rheumatoid arthritis-associated polymorphisms at 6q23 are associated with radiological damage in autoantibody-positive RA.

OBJECTIVE: Recent studies have identified 6q23 as an important susceptibility locus for rheumatoid arthritis (RA), with risk alleles at 3 single-nucleotide polymorphisms combining to give an effect size greater than that of these markers individually. We investigated whether these polymorphisms are also associated with disease severity measured by radiological damage. METHODS: We studied 927 patients from a cross-sectional RA cohort. Median Larsen scores (LS) read from radiographs taken at study entry were compared by genotype at rs6920220, rs13207033, and rs5029937 according to a dominant model using negative binomial regression with stratification for autoantibody status. RESULTS: Median LS was associated with genotype at rs6920220 [LS 31 GG vs 36 GA/AA (p=0.02) in cyclic citrullinated peptide+ (CCP) RA] and rs13020220 [LS 37 GG vs 29 GA/AA (p=0.02) in CCP+ RA] only in autoantibody-positive RA, with no association at rs5029937. Association was stronger for these markers in combination [LS 28 vs 42 for lowest vs highest risk genotype combination in rheumatoid factor positivity (p=0.007), LS 28 vs 37 for anti-CCP+ (p=0.01)]. CONCLUSION: Established RA risk markers at 6q23 are associated also with radiographic severity in autoantibody-positive RA; as for susceptibility, the association for these markers in combination is stronger than that for markers alone.