Background/Purpose

Limited literature is available on the incidence of myocardial infarction (MI) and cerebrovascular accidents (CVA) in patients with Granulomatosis with Polyangiitis (GPA).  We assessed the risk of MI and CVA in cases with GPA compared to controls from the general population using hospitalization databases and physician billings that encompasses the entire province of British Columbia, Canada. We further determined the time trend risks of MI and CVA since diagnosis of GPA.

Methods

Our data included all visits to health professionals and all hospital admissions from 1990 to 2010 as well as all dispensed medication from 1996 to 2010 for all individuals.

We conducted a retrospective matched cohort study among new cases with GPA meeting a pre-defined criteria as follows: a) diagnosis of GPA (ICD-9-CM 446.4) in adults on at least two visits within a two-year period between 1996 and 2010 by a non-rheumatologist physician; b) diagnosis of GPA on at least one visit by a rheumatologist or from hospitalization; c) absence of a prior GPA diagnosis between January 1990 and December 1995 (to ensure incident GPA cases). Ten controls matched by birth year, sex and calendar year of follow-up were selected from the general population. Incident MI and CVA events based on hospitalization or death certificate were recorded as an outcome. We estimated relative risks (RRs) comparing GPA with age-, sex- and entry time-matched comparison cohorts, adjusting for potential cardiovascular risk factors. Sensitivity analyses were conducted to assess for unmeasured confounders (e.g. smoking).

Results

Among 640 incident cases of GPA (54.2% female, mean age 58.6), 28 developed a first time MI and 25 CVA events with an incident rate (IR) of 13.9 and 12.3 per 1000 person-years, respectively. Compared with the age, sex, and entry-matched controls, the incidence rate ratio (IRR) were 3.3 (95% CI 2.1-5.0) and 3.2 (95% CI 2.0-5.1) for MI and CVA respectively. The risk of developing MI and CVA was highest within the first year following diagnosis of GPA, decreasing over time and persisting after 5 years (see table).  After adjusting for covariates, the results remained significant for both MI and CVA. The results also remained statistically significant after adjusting for the potential impact of unmeasured confounders (adjusted RRs ranging between 2.57 and 3.84 in all sensitivity analyses).

Conclusion

This large general population-based study found an increased an increased risk of MI and CVA in patients with GPA. Furthermore, the risk is highest in the first year of disease and decreases subsequently persisting at 5 years of follow up.  Our results support increased monitoring for cardiovascular disease in patients with GPA, including management of traditional risk factors to reduce this risk.

Table: Risk of Incident MI and CVA according to GPA Status