Cardiovascular Disease in Patients with Hemophilia: Single Centre Experience.

Background: Cardiovascular disease (CVD) is at epidemic levels (37%, Heart Disease and Stroke Statistics, 2008 Update) in the US and is also affecting hemophilia patients. Conflicting reports exist concerning the potential protective effect of hemophilia on the occurrence of CVD.

Objective: To evaluate the prevalence and risk factors of CVD events in patients with hemophilia ≥40 years old.

Methods: This cross sectional study included all patients with hemophilia followed at Indiana Hemophilia and Thrombosis Center (IHTC) from January 2004 to June 2008. The following data were obtained from patient medical records: demographics; hemophilia severity; inhibitor history; HIV/HCV infection; established CVD risk factors including body mass index (BMI), hypertension, diabetes, smoking, hypercholesterolemia, and lipid profiles; information on CVD events; and cause of death. CVD events were defined as documented ischemic heart disease, coronary artery disease, and stroke/transient ischemic attacks due to hypertension/atherosclerosis. Univariate and multivariate analyses were performed to identify risk factors for CVD in this population.

Results: A total of 174 patients were identified; 17 (9.7%) were excluded due to incomplete medical records. Population characteristics are described in Table I. Compared to hemophilia A, hemophilia B patients were more frequently obese, hypertensive and prone to cardiac events (Table I). The life-time prevalence of CVD events for the entire cohort was 22.9% (36/157; 95% CI 16.7 to 29.7%). Mortality rate for the entire cohort was 10.8% (17/157); CVD contributed to 64.7% (11/17) of deaths. For hemophilia A, hypertension, high cholesterol, smoking, obesity/elevated BMI were associated with risk of CVD events while HCV infection and low HDL showed a trend towards significance. For hemophilia B, age, hypertension and presence of diabetes were associated with CVD events while smoking showed a trend towards significance. In multivariate analysis, older age, presence of hypertension, and smoking were predictors of CVD. Type and severity of hemophilia, presence of HIV/HCV infection, lipid profile abnormalities, HCV infection and inhibitor history did not influence the CVD risk. The loss of a considerable number of severe hemophilics due to HIV related deaths over the last two decades may have influenced the demographics of the study cohort.

Conclusion: This single center study underscores the increasing burden of CVD in patients with hemophilia in the US, implying that the diagnosis of hemophilia regardless of severity does not confer a protective effect against CVD. Routine screening for CVD thus should be mandatory for hemophilia patients after the age of 40 years.

Table I: Patient characteristics of hemophilia A and B

Table II: Multivariate analysis showing association between variables and cardiovascular events for the entire cohort