Objectives Calcium pyrophosphate deposition (CPPD) disease, broadly defined, has been associated with increased risk of cardiovascular (CV) events. We investigated risk of CV events in patients with acute CPP crystal arthritis, the acute manifestation of CPPD.
Methods Cohort study using Mass General Brigham electronic health record (EHR) data, 1991–2017. Patients with acute CPP crystal arthritis were identified using a published machine learning algorithm with positive predictive value 81%. Comparators were matched on year of EHR entry and index date of patients with acute CPP crystal arthritis (first positive synovial fluid CPP result or mention of ‘pseudogout’, or matched encounter). Major adverse cardiovascular event (MACE) was a composite of non-fatal CV event (myocardial infarction, acute coronary syndrome, coronary revascularisation, stroke) and death. We estimated incidence rates (IRs) and adjusted hazard ratios for MACE, non-fatal CV event and death, allowing for differential estimates during years 0–2 and 2–10. Sensitivity analyses included: (1) patients with acute CPP crystal arthritis diagnosed during outpatient visits, (2) patients with linked Medicare data, 2007–2016 and (3)patients matched on number of CV risk factors.
Results We matched 1200 acute CPP crystal arthritis patients to 3810 comparators. IR for MACE in years 0–2 was 91/1000 person-years (p-y) in acute CPP crystal arthritis and 59/1000 p-y in comparators. In years 2–10, IR for MACE was 58/1000 p-y in acute CPP crystal arthritis and 53/1000 p-y in comparators. Acute CPP crystal arthritis was significantly associated with increased risk for MACE in years 0–2 (HR 1.32, 95% CI 1.01 to 1.73) and non-fatal CV event in years 0–2 (HR 1.92, 95% CI 1.12 to 3.28) and years 2–10 (HR 2.18, 95% CI 1.27 to 3.75), but not death. Results of sensitivity analyses were similar to the primary analysis; in the outpatient-only analysis, risk of non-fatal CVE was significantly elevated in years 2–10 but not in years 0–2.
Conclusions Acute CPP crystal arthritis was significantly associated with elevated short and long-term risk for non-fatal CV event.
- Crystal arthropathies
- Cardiovascular Diseases
Data availability statement
Data are available on reasonable request. Requests for access to unpublished de-identified data will be reviewed by the authors and subject to a data use agreement with Brigham and Women’s Hospital.
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Handling editor Josef S Smolen
Contributors SKT conceived the study, oversaw study design, results interpretation and drafted the first version of the manuscript. WH performed data analysis and provided comments on the manuscript. KY aided with biostatistical analysis, results interpretation and provided comments on the manuscript. DHS contributed to study design, results interpretation and provided comments on the manuscript. SKT takes full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish.
Funding This work was supported by the National Institutes of Health (K23 AR075070, L30 AR070514, P30 AR072577, K23 AR076453) and the Brigham and Women’s Hospital Department of Medicine Hearst Young Investigator Award (Tedeschi).
Disclaimer The funding sources had no role in study design, data analysis, results interpretation or manuscript preparation.
Competing interests SKT: Research support to Brigham and Women’s Hospital from NIH; consulting fees from NGM Biopharmaceuticals. KY: Research support to Brigham and Women’s Hospital from NIH; consulting fees from OM1. DHS: Research support to Brigham and Women’s Hospital from ModernaTx, Amgen, Abbvie, CorEvitas and NIH; royalties from UpToDate for a chapter related to NSAIDs.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
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