Among 4.5 million patients with at least 6 months of follow-up in THIN between February 1996 and November 2008, 5,218 HCV-infected individuals were identified. A total of 40 patients were excluded due to an acute MI recorded prior to the start of follow-up or prior to their HCV diagnosis, 31 were excluded because a date of HCV diagnosis was not available, 214 for active hepatitis B virus infection, and 124 for an age below 18 years. Hence, 4,809 HCV-infected subjects were matched to 71,668 HCV-uninfected patients.
The characteristics of the HCV-infected and -uninfected subjects are shown in . Compared to HCV-uninfected individuals, patients with HCV infection more frequently had diabetes mellitus and chronic kidney disease but less often had hyperlipidemia. HCV-infected patients also more commonly had a lower BMI, were smokers, drank alcohol, used cocaine, and received prescriptions for aspirin and an antihypertensive medication compared to HCV-uninfected patients.
Baseline characteristics of the HCV-infected and -uninfected cohorts.
During a median follow-up of 2.41 years for HCV-infected and 3.22 years for HCV-uninfected patients, 264 subjects had an incident acute MI (16 HCV-infected versus 248 HCV-uninfected; p=0.9). The incidence rate of acute MI was not statistically different between HCV-infected and -uninfected persons (1.02 versus 0.92 events per 1,000 person-years; p=0.67).
Results examining the association between HCV infection and acute MI are summarized in . In unadjusted analysis, HCV infection did not increase the risk of incident MI (HR, 1.12; 95% CI 0.68 to 1.84). After controlling for established cardiovascular risk factors including age, sex, hypertension, diabetes, hyperlipidemia, family history of cardiovascular disease, and smoking as well as chronic kidney disease, BMI, and baseline aspirin use, the only additional confounding variables identified, HCV infection did not increase the risk of acute MI (adjusted HR, 1.10; 95% CI 0.67 to 1.83). Similar results were observed when examining the association between HCV infection and a composite outcome of first acute MI or a revascularization procedure (adjusted HR, 1.16; 95% CI 0.77 to 1.74). Furthermore, stratification of the results based on age category (less than 50, 50–65, and greater than 65 years) and sex did not change the results (data not shown).
Unadjusted and adjusted hazard ratios of the risk of first incident myocardial infarction for baseline variables of interest.
Sensitivity analyses including aspirin as a time-varying covariate did not appreciably alter the results (adjusted HR, 1.07; 95% CI 0.64 to 1.78). After exclusion of subjects who received antiviral therapy for HCV infection prior to or during follow-up, the overall results remained unchanged (adjusted HR 1.13; 95% CI 0.68 to 1.87). Sub-analyses examining the risk of acute MI between patients documented as having chronic HCV by their GP compared to uninfected persons showed similar results to the primary analysis (adjusted HR 0.67; 95% CI 0.16 to 2.71). Finally, given that HCV infection may increase acute MI risk through diabetes or decrease this risk through hyperlipidemia and may therefore be in the causal pathway, we re-ran multivariable models without adjusting for diabetes or hyperlipidemia. No appreciable change in the risk of acute MI was observed (adjusted HR 1.10; 95% CI 0.67 to 1.83 and adjusted HR 1.10; 95% CI 0.66 to 1.82 for diabetes and hyperlipidemia, respectively).