Calcium Pyrophosphate Crystal Arthritis Associated With Higher Risk for Cardiovascular Events

heart attack
Researchers investigated the risk for cardiovascular events in patients with acute calcium pyrophosphate (CPP) crystal arthritis.

The presence of acute calcium pyrophosphate (CPP) crystal arthritis is associated with higher risk for cardiovascular (CV) events in both the short and long term, according to study results published in Annals of the Rheumatic Diseases.

This cohort study included 1200 individuals with acute CPP crystal arthritis (mean age 72.9 years; 44.8% men) and 3810 control participants (mean age 72.7 years; 40.6% men) matched on index date of CPP crystal arthritis and year of database entry. All electronic health record (EHR) data were sourced from Mass General Brigham between 1991 and 2017.

The primary outcome was a major adverse cardiovascular event (MACE), which was defined as a composite of death and nonfatal CV events, including stroke, myocardial infarction, coronary revascularisation, and acute coronary syndrome. Incidence rates and adjusted hazard ratios (HR) were estimated for MACE and stratified by time period (years 0 to 2 and years 2 to 10). Sensitivity analyses were conducted that included individuals diagnosed with acute CPP crystal arthritis during outpatient visits, individuals with linked Medicare data between 2007 and 2016, and individuals matched on CV risk factor count.

In years 0 to 2, MACE incidence for acute CPP crystal arthritis was 90.57/1000 person-years (py) (95% CI, 78.20-104.90) vs 59.06/1000 py (95% CI, 53.28-65.47) in control participants. In years 2 to 10, MACE incidence was 58.30/1000 py (95% CI, 50.69-67.07) vs 53.15/1000 py (95% CI, 48.43-58.32), respectively. Acute CPP crystal arthritis showed a significant association with increased risk for a nonfatal CV event (HR 1.92; 95% CI, 1.12-3.28) and MACE (HR 1.32; 95% CI, 1.01-1.73) in years 0 to 2, as well as with a nonfatal CV event in years 2 to 10 (HR 2.18; 95% CI, 1.27-3.75). No significant association was identified between acute CPP crystal arthritis and death. Sensitivity analyses yielded similar results to primary analysis, though in the analysis of outpatients, nonfatal CV event risk was significantly higher in years 2 to 10.

Limitations to the study included use of EHR data from a single health care system, limited detection power in the outpatient-only sensitivity analysis, potential unmeasured confounding, an inability to assess recurrent episodes, an inability to assess the contribution of multiple manifestations of CPP disease, limited generalizability, and potential reverse causation.

The study authors concluded, “[W]ell-characterized acute CPP crystal arthritis [may be] an independent risk factor for non-fatal CV event and replicate the prior report of increased CV risk in a nationwide study of Veterans.” They indicated that further research is needed to understand “the mechanisms linking this common crystalline arthritis to CV risk.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Tedeschi SK, Huang W, Yoshida K, Solomon DH. Risk of cardiovascular events in patients having had acute calcium pyrophosphate crystal arthritis. Ann Rheum Dis. Published online May 25, 2022. doi:10.1136/annrheumdis-2022-222387