Cardiovascular Disease in Patients with Hemophilia: Single Centre Experience.
Authors: Sharathkumar Anjali , Trawinski Brandy , Soucie J. Michael , Greist Anne , Haddix Craig , Shapiro Amy D. 
Published: April 2020

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

Variable Hemophilia A (N=81) Hemophilia B (N=76) P value Severity     Severe 21 (25.9%) 21 (27.63%) 0.001 Moderate 15 (18.5%) 32 (42.10%)     Mild 45 (55.6%) 23 (30.26%) Age (decade)     40–50 35 (43.2%) 28 (36.8%) 0.757     51–60 24 (29.6%) 20 (26.3%)     61–70 16 (19.8%) 19 (25%)     &gt;70 6 (7.4%) 9 (11.9%) Mean Age (yrs) 54±11.32 57.35±13 0.092 Hypertension     No 56 (69.1%) 42 (55.3%) 0.041     Yes 24 (29.6%) 34 (44.7%) Cholesterol (↑)     No 50 (61.7%) 34 (44.7%) 0.103     Yes 21 (25.9%) 27 (35.5%) Missing data 10 (12.3%) 15 (19.75) Diabetes     No 72 (88.9%) 63 (82.9%) 0.0359     Yes 9 (11.1%) 13 (17.1%) Obesity     No 64 (79.0%) 35 (46.1%) 0.001     Yes 16 (19.8%) 40 (52.6%) HIV     No 21 (25.9%) 73 (96.1%) 0.000     Yes 59 (72.8%) 3 (3.9%) HCV     No 21 (25.9%) 29 (38.2%) 0.125     Yes 59 (72.8%) 47 (61.8%) Inhibitor     No 75 (92.6%) 75 (98.7%) 0.059     Yes 5 (6.2%) 1 (2.3%) CVD events     No 66 (81.5%) 55 (72.4%) 0.189     Yes 15 (18.5%) 21 (27.6%) CVD event type     Cardiac 9/15 (60%) 18/21 (85.7%) 0.03 Stroke/TIA 8/15 (53.3%) 5/21 (23.8%) 0.563

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

95% Wald Confidence Limits Variable Odds ratio Lower limit Upper limit Hypertension 5.77 1.77 18.84 Smoking 5.99 1.92 18.72 Hemophilia B versus A 1.87 0.548 6.38 Age (51–60 years versus 40–50 years) 13.40 2.59 69.44 Age group (61–70 years versus 40–50 years) 4.14 0.78 21.871 Age group (&gt;70 years versus 40–50 years) 44.46 5.72 345.75 Disease severity (Moderate versus Mild) 2.22 0.57 8.70 Disease severity (Severe versus Mild) 4.04 0.77 21.23 Diabetes 2.90 0.84 10.10 Obesity 0.491 0.149 1.615