Sjögren's disease may impose a substantial cardiovascular burden, with higher event rates and mortality than the general population.
"Integrating cardiovascular assessment and prevention into routine Sjögren's management is essential to improve long-term outcomes," observed Olga Rusinovich, MD, PhD, of Puerta de Hierro University Hospital in Madrid, who presented findings from a prospective study at the American College of Rheumatology (ACR) annual meeting.
Rusinovich and colleagues reported data from Sjögren SER, a multicenter registry coordinated by the Spanish Society of Rheumatology. They followed 314 patients with primary Sjögren's disease for almost 10 years.
"We found that cardiovascular and cerebrovascular events were more frequent than expected in Sjögren's disease: 29 events occurred during follow-up, including 17 major adverse cardiovascular events [MACE] such as nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death," Rusinovich told MedPage Today.
"Cardiovascular mortality was five times higher than in the general population," she added.
Sjögren's and Cardiovascular Risks
Sjögren's disease is an autoimmune disorder that affects exocrine glands and results in sicca syndrome, but extraglandular involvement can occur. When it does, it is often associated with additional dysfunction including renal, lung, neurologic, and lymphoma disorders.
Chronic inflammation, immune dysregulation, and atherosclerotic vascular pathology may link Sjögren's and other autoimmune diseases to risks for additional manifestations, including cardiovascular disease.
In 2019, a meta-analysis suggested that the risk of coronary morbidity was 30% higher among Sjögren's patients than it was among the general population. The risk for cerebrovascular morbidity was even higher, but cardiovascular mortality risk was not elevated.
Recent research has helped clarify links between Sjögren's and cardiovascular disease. In 2023, a retrospective study examined 102 patients at a single center in Spain who had primary Sjögren's disease for an average of 12.5 years and found that those with extraglandular involvement were more likely have hypertension, dyslipidemia, hyperuricemia, and coronary artery disease than those without such involvement.
The retrospective study also showed that patients with Ro/SSA and La/SSB autoantibodies had a higher frequency of hyperuricemia, arrhythmia, coronary artery disease, cerebrovascular disease, and venous thrombosis. Hypergammaglobulinemia, elevated erythrocyte sedimentation rates, and low C3 complement levels were tied to a higher prevalence of cardiovascular comorbidities.
In 2025, researchers published data from a nationwide population-based cohort study that evaluated all patients in Denmark with a primary Sjögren's disease diagnosis from 1996 to 2017, matching them with a comparison group on age, gender, and calendar year.
The analysis included 4,697 Sjögren's patients with a median age of 57 and 46,970 persons in the comparison group. Participants were followed for a median of 7.6 years and most (87%) were women.
Sjögren's disease was linked with higher adjusted rates of myocardial infarction (HR 1.23) ischemic stroke (HR 1.31), hemorrhagic stroke (HR 1.51), peripheral artery disease (HR 1.44), and venous thromboembolism (HR 1.57).
The highest risk during the first year of follow-up was for venous thromboembolism. Ischemic stroke risk rose during the follow-up period, while increased risks for myocardial infarction and peripheral artery disease were stable.
The association between Sjögren's and cardiovascular death was not significant, with similar results for heart failure.
Analysis of Spanish Registry Data
At the ACR meeting, Rusinovich presented data from 314 patients with Sjögren's disease who were followed for a median of 9.5 years. Mean age was 59 years, 95% were women, and mean disease duration was 6.8 years.
The study assessed cardiovascular mortality in this group relative to the general population, using standardized mortality rates from the Spanish National Institute of Statistics.
A total of 29 cardiovascular events (9.2%) occurred in the Sjögren's cohort during follow-up. These included pericarditis (1.27%), conduction abnormalities (1.27%), ischemic heart disease (1.59%), heart failure (1.59%), peripheral artery disease (0.95%), and cerebrovascular events (2.55%).
MACE occurred in 5.41% of Sjögren's patients: 2.23% had stroke, 1.59% had myocardial infarction, and 1.59% had cardiovascular death. Predictors of MACE included cryoglobulinemia (OR 10.41), glucocorticoid use (OR 3.53), and age (OR 1.07).
Cardiovascular mortality accounted for 11.9% of all deaths among Sjögren's patients. Compared with the general population, cardiovascular mortality was 5.09 times higher. Sjögren's patients who had prior cardiovascular events had more than a threefold higher risk of death (RR 3.27).
Rusinovich and colleagues calculated a SCORE2 value -- an estimate of 10-year risk for myocardial infarction and stroke -- for a subset of 130 Sjögren's patients with complete data. The expected SCORE2 risk among Sjögren's patients was 4.41%.
"The predicted 10-year MACE risk of 4.41% closely matched the observed incidence of 4.62%," Rusinovich noted. "In other words, SCORE2 accurately estimated major cardiovascular events in this cohort, although it did not capture the broader spectrum of cardiovascular and cerebrovascular complications observed."
Independent predictors of a cardiovascular event were age (OR 1.06), cryoglobulinemia (OR 10.13), glucocorticoid use (OR 3.44), and antiphospholipid antibodies (OR 5.33).
"Age, cryoglobulinemia, and glucocorticoid use were independent predictors of both cardiovascular events and MACE, while antiphospholipid antibodies were specifically associated with cardiovascular events," Rusinovich pointed out.
"These results highlight that cardiovascular risk in Sjögren's extends beyond traditional mechanisms and involves immune-mediated pathways and treatment-related exposures," she said.