Gender- and Age-Specific Rates of Heart Failure and Other Adverse Cardiovascular Outcomes in Systemic Sclerosis

Guoli Sun; Adelina Yafasova; Charlotte Andersson; John J.V. McMurray; Pardeep S. Jhund; Kieran F. Docherty; Mikkel Faurschou; Christoffer T. Nielsen; Morten Schou; Gunnar H. Gislason; Christian Torp-Pedersen; Emil L. Fosbøl; Lars Køber; Jawad H. Butt


Rheumatology. 2022;61(11):4374-4383. 

In This Article

Abstract and Introduction


Objective: To investigate the long-term rates of heart failure (HF) and other adverse cardiovascular outcomes, including arrhythmias, myocardial infarction, ischaemic stroke, venous thromboembolism, pulmonary hypertension and pericarditis, in SSc patients according to gender and age.

Methods: Using Danish nationwide registries, SSc patients (diagnosed from 1996 to 2018) were matched with four controls from the background population by gender, age and comorbidities. Cox regression was used to compare the rates of cardiovascular outcomes between SSc patients and controls and the rate of mortality between SSc patients developing HF and HF patients without SSc, according to gender and age (above/below median).

Results: In total, 1569 SSc patients were matched with 6276 non-SSc controls (median age 55 years, 80.4% women, median follow-up 7.3 years). SSc had a higher rate of HF in both women [HR 2.99 (95% CI 2.18, 4.09)] and men [HR 3.01 (1.83, 4.95)] (P interaction = 0.88), with similar trends for other cardiovascular outcomes. SSc had a higher rate of HF in patients <55 years of age [HR 4.14 (95% CI 2.54, 6.74)] and ≥55 years [HR 2.74 (1.98, 3.78)] (P interaction = 0.22), with similar trends for other cardiovascular outcomes. SSc patients with new-onset HF had a higher rate of mortality than HF patients without a history of SSc, irrespective of gender (P interaction = 0.53) and age (P interaction = 0.43).

Conclusions: SSc was associated with higher rates of HF and other cardiovascular outcomes than matched controls, irrespective of gender and age. Among patients with new-onset HF, a history of SSc was associated with higher mortality.


SSc is a chronic inflammatory disease characterized by fibrosis of the skin and internal organs and vasculopathy.[1] Accumulating evidence suggests that cardiovascular manifestations such as heart failure (HF), conduction disturbances, atherosclerosis and cardiovascular death are common in patients with chronic inflammatory diseases, including SSc.[2–6] Imaging studies of SSc patients have demonstrated the presence of myocardial inflammation and fibrosis [even in those without any symptoms of cardiovascular disease (CVD)], both of which are associated with a higher risk of developing HF and arrhythmia.[7–10]

The incidence of CVD in general is higher in men than in women, and men also have a higher cardiovascular mortality.[11,12] In contrast, SSc is more common in women, but men may have a more severe disease course and worse prognosis than women.[13,14] However, data on the association between gender and cardiovascular outcomes in SSc are conflicting or limited by studies with small, selected populations or a lack of long-term follow-up.[13–18] Moreover, in several autoimmune diseases, such as SLE and type 1 diabetes, age at diagnosis appears to modify the disease course and diagnosis at a younger age is associated with a worse prognosis.[19,20] A better understanding of the association between SSc and cardiovascular outcomes according to gender and age is important to identify patients at particularly high risk of adverse cardiovascular outcomes, including HF, a condition associated with substantial morbidity and mortality.[21,22] CVDs may also portend a worse prognosis in patients with inflammatory diseases than the same events in those without inflammatory diseases.[23–25] It is of interest to investigate whether HF patients with SSc have a worse prognosis than those with HF without SSc.

Therefore we examined the long-term rates of HF and other adverse cardiovascular outcomes in a nationwide cohort of patients with SSc compared with matched controls from the Danish background population according to gender and age. We also compared the long-term prognosis of patients with new-onset HF with and without a history of SSc, overall and according to age at the time of HF and gender.