Patient demographics
A total of 408 patients with SSc were included, 55% had the diffuse subtype, 89% were women, mean age at inclusion was 58.4 ± 14.5 years and patients were matched 1:1 for age and gender to 408 patients with RA. As shown in Table
1, disease duration was comparable between patients with SSc and patients with RA (10.1 ± 7.7 years vs 9.2 ± 7.8 years, respectively,
p not significant (NS)), while no significant differences were observed in smoking or current treatment with corticosteroids (treatment duration and mean dose). On the other hand, body mass index (BMI) was significant higher in patients with RA (26.5 ± 4.86 vs 24.2 ± 3.61,
p = 0.001). In Table
1, the characteristics of the limited and diffuse SSc subgroups and those of their matched patients with RA are also shown.
Table 1
Demographic characteristics of systemic sclerosis (SSc) and rheumatoid arthritis (RA) matched cohorts
Number of patients | 408 | 408 | 182 | 182 | 226 | 226 |
Female, n (%) | 364 (89%) | 364 (89%) | 169 (93) | 169 (93) | 195 (86) | 195 (86) |
Age at inclusion (years) | 58.4 ± 13.5 | 57.5 ± 13.4 | 58.3 ± 12.6 | 57.4 ± 12.5 | 58.7 ± 14.2 | 57.9 ± 13.9 |
Disease duration (years) | 10.1 ± 7.8 | 9.2 ± 7.7 | 8.85 ± 8.79 | 8.3 ± 7.39 | 10.7 ± 8.4 | 10.2 ± 7.9 |
Smoking, n (%) | 104 (25.4%) | 128 (31.3%) | 54 (29.7) | 59 (32.4) | 50 (22.1) | 69 (30.6) |
Body mass index | 24.2 ± 3.6 | 26.5 ± 4.9 * | 24.4 ± 4.0 | 26.8 ± 4.8 * | 24.1 ± 3.4 | 26.1 ± 4.7 * |
Current corticosteroid treatment | 196 (48%) | 185 (45%) | 78 (43.1) | 84 (46.7) | 118 (48.7) | 101 (44.7) |
Duration (months) | 14.6 ± 21.6 | 15.5 ± 26 | 14.1 ± 20.8 | 13.8 ± 36.5 | 15.2 ± 21.7 | 15.9 ± 36.9 |
Μean daily dose (mg) | 2.8 ± 1.3 | 3.2 ± 1.5 | 2.3 ± 2.1 | 2.9 ± 3.2 | 3.1 ± 2.4 | 3.3 ± 2.6 |
Comorbidities
A comparative analysis of the prevalence of comorbidities between the two cohorts is shown in Table
2. Dyslipidemia (17.7% vs 30.2%,
p = 0.001), and DM (5.6% vs 11.8%,
p = 0.007) were less prevalent in SSc and RA, respectively, and the respective ORs were 0.5 (95% CI 0.36–0.69) and 0.45 (95% CI 0.27–0.75). On the contrary no differences were noted for the prevalence of arterial hypertension (31.8% vs 30.6%, respectively,
p = 0.742). Despite the higher BMI and almost double the prevalence of dyslipidemia and DM in RA, no remarkable differences in coronary events (2.7% vs. 3.7%,
p = 0.445; OR 0.73 (95% CI 0.33–1.60)) or stroke (1.9% vs 3.4%,
p = 0.195; OR 0.56 (95% CI 0.23–1.35)) were noted between the two groups, although a trend for lower prevalence of ischemic stroke in patients with SSc than in patients with RA was observed (1.2% vs 2.9%,
p = 0.085; OR 0.40 (95% CI 0.14–1.17)). Additionally, when we adjusted the analysis for corticosteroid treatment, hypertension and dyslipidemia, no relevant changes in the ORs were observed (Table
2).
Table 2
Prevalence of comorbidities in systemic sclerosis (SSc) and rheumatoid arthritis (RA) matched cohorts
Diabetes mellitus | 23 (5.6) | 48 (11.8) | 0.45 (0.27–0.75) | – |
Dyslipidemia | 72 (17.7) | 123 (30.2) | 0.50 (0.36–0.69) | – |
Arterial hypertension | 131 (32.1) | 125 (30.6) | 1.07 (0.80–1.44) | – |
Coronary event | 11 (2.7) | 15 (3.7) | 0.73 (0.33–1.60) | 0.74 (0.34–1.62)* |
Stroke | 8 (1.9) | 14 (3.4) | 0.56 (0.23–1.35) | 0.55 (0.21–1.32)* |
Ischemic stroke | 5 (1.2) | 12 (2.9) | 0.40 (0.14–1.17) | 0.39 (0.14–1.15) |
Hemorrhagic stroke | 3 (0.7) | 2 (0.5) | 1.5 (0.25–9.04) | 1.48 (0.23–8.96) |
Neoplasia | 17 (4.2) | 19 (4.7) | 0.89 (0.46–1.74) | – |
Chronic obstructive pulmonary disease | 21 (5.2) | 15 (3.7) | 1.42 (0.72–2.80) | 1.46 (0.74–2.90)** |
Osteoporosis | 98 (24.0) | 92 (22.6) | 1.09 (0.79–1.50) | 1.08 (0.78–1.49)*** |
Depression | 90 (22.1) | 49 (12) | 2.07 (1.42–3.03) | – |
The overall prevalence of malignancies did not differ between SSc and RA (4.2% vs 4.7%, p = 0.733; OR 0.89 (95% CI 0.46–1.74)). However, there were differences in the type of neoplasms observed in the two cohorts. In particular, in the SSc cohort the most frequent type was lung cancer (7/17, 41%), while patients with RA developed mainly hematologic malignancies (7/19, 36%) and breast cancer (7/19, 36%).
Among the other comorbidities analyzed, the prevalence of chronic obstructive pulmonary disease (5.2% vs 3.7%, respectively, p = 0.326), osteoporosis or osteoporotic fractures was similar between the two groups (24% vs 22%, p = 0.619; OR 1.08 ([95% CI 0.78–1.49) and 6.1% vs 6.7%, p = 0.665; OR 1.13 (95% CI 0.64–2.0), respectively). However, depression (defined by the use of antidepressants) was almost twice as frequent in SSc compared to patients with RA (22% vs 12%, p = 0.001; OR 2.07 (95% CI 1.42–3.03), respectively).
In addition, sub-analysis between patients with limited (
n = 182) or diffuse SSc (
n = 226) and matched patients with RA was performed in order to examine the impact of SSc subtype on the prevalence of comorbidities. As shown in Table
3, with the exception of depression, no other differences were noted compared to the primary analysis. Dyslipidemia and DM were confirmed to be significantly less prevalent both in limited or diffuse SSc compared to RA, while no differences were noted in the prevalence of arterial hypertension, coronary events, stroke, malignancies, chronic obstructive pulmonary disease or osteoporosis. On the contrary, the sub-analysis revealed that depression was significantly more frequent in the diffuse SSc subgroup compared to matched patients with RA (27.2% vs 11.9%,
p = 0.001; OR 2.753 (95% CI 1.675–4.523)), while it was comparable between patients with limited SSc and patients with RA (14.8% vs 12.1%,
p = 0,455; OR 1.259 (CI 95% 0.688–2.304)).
Table 3
Prevalence of comorbidities in limited or diffuse systemic sclerosis (SSc) and rheumatoid arthritis (RA) matched controls
Diabetes mellitus | 12 (6.6) | 23 (12.6) | 0.485 (0.234–1.007) | 11 (4.8) | 25 (11.1) | 0.408 (0.195–0850) |
Dyslipidemia | 34 (18.7) | 56 (30.8) | 0.513 (0.315–0.836) | 38 (16.7) | 67 (29.6) | 0.475 (0.303–0.745) |
Arterial hypertension | 56 (30.8) | 54 (29.7) | 1.04 (0.668–1.635) | 75 (33.2) | 71 (31.4) | 1.084 (0.731–1.609) |
Coronary event | 4 (2.2) | 6 (3.3) | 0.655 (0.182–2.363) | 7 (3.1) | 9 (4.0) | 0.764 (0.279–2.087) |
Stroke | 5 (2.7) | 6 (3.3) | 0.824 (0.247–2.749) | 3 (1.3) | 8 (3.5) | 0.363 (0.095–1.387) |
Ischemic | 3 (1.6) | 5 (2.7) | 0.590 (0.139–2.506) | 2 (0.9) | 7 (3.1) | 0.277 (0.057–1.347) |
Hemorrhagic | 2 (1.1) | 1 (0.5) | 2.00 (0.18–22.252) | 1 (0.4) | 1 (0.4) | 0.991 (0.062–15.944) |
Neoplasia | 7 (3.8) | 8 (4.4) | 0.865 (0.307–2.437) | 10 (4.4) | 11 (4.9) | 0.897 (0.373–2.155) |
Chronic obstructive pulmonary disease | 8 (4.4) | 6 (3.3) | 1.341 (0.456–3.945) | 13 (5.7) | 9 (4.0) | 1.758 (0.610–3.482) |
Osteoporosis | 41 (22.4) | 39 (21.4) | 1.09 (0.79–1.50) | 57 (25) | 52 (23) | 1.115 (0.725–1.716) |
Depression | 27 (14.8) | 22 (12.1) | 1.259 (0.688–2.304) | 63 (27.6) | 27 (11.9) | 2.814 (1.714–4.620) |