Population Analysis of a Hemophilia Treatment (HTC) for Prevalence and Outcome of Cardiovascular Disease (CVD) in Patients with Congenital Bleeding Disorders (PWBD).
Authors: Parameswaran Rekha , Greist A. , Lynn H. S. , Roberson C. P. , Kirk J. , Shapiro A. D. 
Published: October 2019

Abstract
CVD, acute coronary syndrome (ACS)/cerebrovascular accident (CVA), is a leading cause of morbidity and mortality in the US. Risk factors are hypertension, hypercholesterolemia (HC), smoking and diabetes. Therapeutic advances allow PWBD to live longer; CVD may emerge as in the general population. No data address prevalence and treatment of CVD in PWBD. Previous data suggest that hemophilia may protect against CVD. A single HTC analysis of PWBD for CVD prevalence and outcome was performed. Query of HTC database identified patients with hemophilia/ von Willebrand disease(vWD) with CVD and retrospective chart analysis performed for risk factors. Coronary risk assessment score, expressed as a percentage(Framingham model), was calculated; unknown HC values assigned level 1 (scale maximum level 3) to avoid bias. Age at CVD event was used for risk comparison to age/ sex matched general population. HTC population was analyzed for bleeding disorder, severity, age ≥ 40 yrs, sex and utilized as the denominator for population event analysis. PWBD demographics ≥ 40 yrs revealed 146 with FVIII deficiency (60 severe, 18 moderate, 68 mild); 99 with FIX deficiency (20 severe, 52 moderate, 27 mild); 164 vWD (106 Type 1, 48 Type 2, 10 Type 3). Twenty-four PWBD, all ≥ 40 yrs of age, had experienced 26 CVD events. These PWBD included 8 FVIII (0 severe, 1 moderate, 7 mild), 6 FIX (2 severe, 4 moderate, 0 mild), and 10 vWD (5 Type 1, 4 Type 2, 1 Type 3). Events included 20 ACS; 6 were CVA; two patients each had both ACS and CVA. Six were deceased at time of analysis; five deaths due to CVD; one death (type III vWD) due to lung cancer. Framingham risk scores were comparable to expected general population scores. Eight patients received anti-platelet therapy. Of these, two had major bleeds (CNS and GI bleed); one had a minor bleed (epistaxis).
Approximately one in 20 US population over age 40 yrs has CVD. Given this prevalence, we would expect 20 patients with CVD in our patient population. If bleeding disorders, specifically hemophilia and vWD, conferred protection against CVD, then we would expect decreased prevalence of CVD in our patient population. This putative protective effect would likely manifest in PWBD with severe deficiencies than in PWBD with mild deficiencies. Interestingly, we identified three patients with severe deficiency (two severe FIX; one type III vWD) with CVD; one of whom (type III vWD) had a higher calculated CVD risk score that age matched general population. CVD patients with mild/moderate deficiencies appear more similar to the general population for CVD risk than their severely affected counterparts. CVD prevalence in the former group could approach expected general population prevalence given Framingham scores equal to or higher than expected compared to the general population. In fact, Framingham score for identified CVD patients revealed 10 year comparative risk of CVD similar to general population risk. Accurate prevalence rates will be determined through prospective risk factor screening/CVD evaluation in PWBD over 40 yrs. Further study is warranted as prophylaxis becomes more widely utilized converting patients with severe disease to a more moderate disease state and possibly altering CVD prevalence. Invasive procedure outcome and optimal CVD therapy in PWBD require prospective investigation. This single center analysis represents the largest reported registry of PWBD analyzed for CVD to date.