Risk factors for cardiovascular disease in primary Sjögren's syndrome (pSS): a 20-year follow-up study

Abstract

Introduction: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterized by a chronic grade of inflammation. Cardiovascular events represent the major causes of morbidity and mortality in patients with inflammatory rheumatic diseases; however, the significance and prevalence of cardiovascular disease in patients with pSS remain unclear.

Objective: To determine the clinical significance of cardiovascular disease in pSS and analyze the risk of cardiovascular disease according to glandular/extraglandular involvement and positivity to anti-Ro/SSA and/or anti-La/SSB autoantibodies.

Methods: A retrospective study including patients diagnosed with pSS fulfilling the 2016 ACR/EULAR classification criteria was followed and evaluated in our outpatient clinic between 2000 and 2022. The prevalence of cardiovascular risk factors with pSS was evaluated, and a possible association with clinical and immunological characteristics, the treatments received, and the impact on cardiovascular disease were determined. Univariate and multivariate regression analyses were performed in an attempt to determine potential risk factors associated with cardiovascular involvement.

Results: A total of 102 pSS patients were included. Eighty-two percent were female, with a mean age of 65±24 years and a disease duration of 12.5 ±6 years. Thirty-six patients (36%) had at least one cardiovascular risk factor. Arterial hypertension was diagnosed in 60 (59%) patients, dyslipidemia in 28 (27%), diabetes in 15 (15%), obesity in 22 (22%), and hyperuricemia in 19 (18%). History of arrhythmia was found in 25 (25%), conduction defects in 10 (10%), arterial peripheral vascular disease in 7 (7%), venous thrombosis in 10 (10%), coronary artery disease in 24 (24%), and cerebrovascular disease in 22 (22%) of patients. Patients with extraglandular involvement had a higher prevalence of arterial hypertension (p=0.04), dyslipidemia (p=0.003), LDL mean values (p=0.038), hyperuricemia (p=0.03), and coronary artery disease (p=0.01) after adjusting for age, sex, disease duration, and the significant variables in the univariate analysis. Patients with Ro/SSA and La/SSB autoantibodies had a substantially higher risk of hyperuricemia (p=0.01), arrhythmia (p=0.01), coronary artery disease (p=0.02), cerebrovascular disease (p=0.02), and venous thrombosis (p =0.03). In the multivariate logistic regression analysis, higher odds of cardiovascular risk factors were associated with extraglandular involvement (p=0.02), treatment with corticosteroids (p=0.02), ESSDAI>13 (p=0.02), inflammatory markers including ESR levels (p 0.007), and serologic markers such as low C3 levels (p=0.03) and hypergammaglobulinemia (p=0.02).

Conclusions: Extraglandular involvement was associated with a higher prevalence of arterial hypertension, dyslipidemia, hyperuricemia, and coronary artery disease. Anti-Ro/SSA and anti-La/SSB seropositivity was associated with a higher prevalence of cardiac rhythm abnormalities, hyperuricemia, venous thrombosis, coronary artery disease, and cerebrovascular disease. Raised inflammatory markers, disease activity measured by ESSDAI, extraglandular involvement, serologic markers including hypergammaglobulinemia and low C3, and treatment with corticosteroids were associated with a higher risk for cardiovascular comorbidities. Key Points • Patients with pSS are vulnerable to cardiovascular risk factors. There is an interconnection between extraglandular involvement, disease activity, inflammatory markers, and cardiovascular risk comorbidities. • Anti-Ro/SSA and anti-La/SSB seropositivity was associated with a higher frequency of cardiac conduction abnormalities, coronary artery disease, venous thrombosis, and stroke. • Hypergammaglobulinemia, elevated ESR, and low C3 are associated with a higher prevalence of cardiovascular comorbidities. • Valid risk stratification tools to help with prevention and consensus on the management of CVDs in pSS patients are warranted.

Keywords: Autoantibodies; Cardiovascular disease; Sjogren.