Increased Risk of Valvular Heart Disease in Systemic Sclerosis: An Underrecognized Cardiac Complication.

OBJECTIVE: Cardiac involvement is a poor prognostic marker in systemic sclerosis (SSc). While diastolic dysfunction, myocardial fibrosis, and arrhythmias are traditionally considered features of primary cardiac involvement in SSc, the incidence of valvular heart disease (VHD) is not well reported. Our objective was to examine the prevalence of VHD at the time of SSc diagnosis and incidence of VHD during follow-up compared to non-SSc subjects. METHODS: Medical records of patients with suspicion of SSc were reviewed to identify incident cases. SSc subjects were matched 1:2 by age and sex to non-SSc subjects. RESULTS: The study included 78 incident SSc cases and 156 non-SSc comparators (56 yrs [± 15.7], 91% female). A nearly 4-fold increase in the prevalence of moderate/severe VHD prior to SSc diagnosis compared to non-SSc subjects (6% vs 0%; P = 0.004) was identified. During follow-up, 18 SSc and 12 non-SSc patients developed moderate/severe VHD. The cumulative incidence of VHD at 10 years after SSc incidence/index was 17.9% (95% CI 10.7-29.9) in patients with SSc compared with 2.3% (95% CI 0.7-7.0) in non-SSc subjects (HR 4.23, 95% CI 2.03-8.83). Coronary artery disease was the only significant risk factor for VHD. CONCLUSION: Patients with SSc have a 4-fold increase in the prevalence of moderate/severe VHD at diagnosis compared to non-SSc patients. They also have a 4-fold increased risk of developing moderate/severe VHD after diagnosis of SSc. Aortic stenosis and mitral regurgitation have a much higher prevalence in patients with SSc, besides secondary tricuspid regurgitation. Underlying mechanisms for this association require further elucidation.

Epidemiology and Trends in Survival of Systemic Sclerosis in Olmsted County (1980-2018): A Population-based Study.

Background/Purpose: To update the epidemiology of systemic sclerosis (SSc) and evaluate the performance of the ACR/EULAR 2013 vs. 1980 ARA classification criteria in a U.S. population-based cohort. Methods: An inception cohort of patients with incident SSc from January 1, 1980, through December 31, 2018, in Olmsted County, Minnesota, was identified based on comprehensive individual medical record review. Incidence and prevalence rates were age- and sex-adjusted to the 2010 US white population. Survival rates were compared with expected rates in the general population. Fulfillment of 1980 and 2013 classification criteria was ascertained. Results: A total of 85 incident cases of SSc (91% female, mean age 55.4 ± 16 y) and 49 prevalent cases on Jan 1, 2015 were identified. The overall age- and sex-adjusted annual incidence was 25 (95% CI 20-31) per million population, with no change in incidence over time. The age- and sex-adjusted prevalence was 436 (95% CI: 313-558) per 1,000,000 population. 77 (91%) patients fulfilled the 2013 classification criteria, and 38 (45%) fulfilled the 1980 criteria. Mortality among patients with SSc was significantly higher in comparison to the general population, with a standardized mortality ratio of 2.48 (95% CI:1.76-3.39) and no evidence of improvement over time. Conclusions: SSc developed in 25 persons/million/year with no change over the 39-year study period. The 2013 classification criteria perform significantly better than the 1980 criteria but failed to classify 9% of patients. SSc portends a 2.5-fold higher risk of mortality than the general population, with no evidence of improved survival over time.

Systemic Sclerosis Portends Increased Risk of Conduction and Rhythm Abnormalities at Diagnosis and During Disease Course: A US Population-Based Cohort.

Objectives: To study the incidence, risk factors and outcomes of conduction and rhythm disorders in a population-based cohort of patients with systemic sclerosis (SSc) vs. non-SSc comparators. Methods: An incident cohort of patients with SSc (1980-2016) from Olmsted County, MN was compared to age- and sex-matched non-SSc subjects (1:2). Electrocardiograms (ECGs), Holter ECGs, and need for cardiac interventions were reviewed to determine the occurrence of any conduction or rhythm abnormalities. Results: 78 incident SSc cases and 156 comparators were identified (mean age 56 y, 91% female). The prevalence of any conduction disorder prior to SSc diagnosis compared to non-SSc subjects was 15% vs. 7% (p=0.06), and any rhythm disorder was 18% vs. 13% (p=0.33). During a median follow-up of 10.5 years in patients with SSc and 13.0 years in non-SSc comparators, conduction disorders developed in 25 patients with SSc with cumulative incidence of 20.5% (95% CI: 12.4-34.1%) vs. 28 non-SSc patients with cumulative incidence of 10.4% (95% CI: 6.2-17.4%) (HR: 2.57; 95% CI: 1.48-4.45), while rhythm disorders developed in 27 patients with SSc with cumulative incidence of 27.3% (95% CI: 17.9-41.6%) vs. 43 non-SSc patients with cumulative incidence of 18.0% (95% CI: 12.3-26.4%) (HR: 1.62; 95% CI: 1.00-2.64). Age, pulmonary hypertension and smoking were identified as risk factors. Conclusion: Patients with SSc have an increased risk of conduction and rhythm disorders both at disease onset and over time, compared to non-SSc patients. These findings warrant increased vigilance and screening for ECG abnormalities in SSc patients with pulmonary hypertension.

Hospitalization Rates Are Highest in the First 5 Years of Systemic Sclerosis: Results From a Population-based Cohort (1980-2016).

OBJECTIVE: Few studies have estimated the healthcare resource usage of patients with systemic sclerosis (SSc). The purpose of this study was to compare hospitalization among incident cases of SSc vs age- and sex-matched comparators. METHODS: A retrospective, population-based cohort of patients with SSc in Olmsted County, Minnesota, from January 1, 1980, to December 31, 2016, was assembled. A 2:1 cohort of age- and sex-matched patients without SSc from the same population was randomly selected for comparison. All hospitalizations in the geographic area from January 1, 1987, to September 30, 2018, were obtained. Rates of hospitalization, lengths of stay, and readmissions were compared between groups. RESULTS: There were 76 incident SSc cases and 155 non-SSc comparators (mean age 56 ± 16 yrs at diagnosis/index, 91% female) included. Rates of hospitalization among cases and comparators were 31.9 and 17.9 per 100 person-years, respectively (rate ratio [RR] 1.78, 95% CI 1.52-2.08). Hospitalization rates were higher in patients with SSc than comparators during the first 5 years after SSc diagnosis (RR 2.16, 95% CI 1.70-2.74). This difference decreased over time and was no longer significant at ≥ 15 years after SSc incidence/index. Lengths of stay (median [IQR] 4 [2-6] vs 3 [2-6], P = 0.52) and readmission rates (25% vs 23%, P = 0.51) were similar between groups. CONCLUSION: Patients with SSc were hospitalized more frequently than comparators, indicating high inpatient care needs in this population. Hospitalization rates were highest during the first 5 years following SSc diagnosis.

Cardiovascular Risk Factors and Atherosclerotic Cardiovascular Events Among Incident Cases of Systemic Sclerosis: Results From a Population-Based Cohort (1980-2016).

OBJECTIVE: To characterize cardiovascular (CV) risk factors and outcomes among incident cases of systemic sclerosis (SSc) in a population-based cohort. METHODS: Medical records of patients with SSc diagnosed in Olmsted County, Minnesota, between January 1, 1980, and December 31, 2016, were reviewed to identify 78 incident SSc cases. The comparators were 156 sex- and age-matched individuals from the same population. Data for SSc characteristics, traditional CV risk factors, and CV events were collected. Cumulative incidence was adjusted for the competing risk for death. RESULTS: During a median follow-up of 9.8 (SSc) and 9.2 years (non-SSc), 21 patients with SSc and 17 patients without SSc developed CV events, corresponding to 10-year cumulative incidence of 24.4% and 15.2%, respectively. The risk for incident CV disease was increased by 2-fold (hazard ratio, 2.38; 95% CI, 1.28-4.43) in patients with SSc vs comparators, predominately due to coronary artery disease (hazard ratio, 2.35; 95% CI, 1.17-4.71). Mean body mass index and prevalence of diabetes mellitus were lower in SSc vs non-SSc. There was no significant difference in smoking, hypertension, or hyperlipidemia. Observed CV events were increased compared with CV events predicted by the Framingham Risk Score and American College of Cardiology/American Heart Association score with standardized incident ratios of 4.16 (95% CI, 2.16-7.99) and 5.69 (95% CI, 2.71-11.94), respectively. CONCLUSION: Patients with SSc are at >2-fold increased risk for experiencing a CV event compared with persons without SSc. Framingham Risk Score and American College of Cardiology/American Heart Association score dramatically underestimate CV risk in SSc.