Background: The phase 3 A-LONG and Kids A-LONG studies demonstrated low annualized bleeding rates (ABRs) with reduced infusion frequency rFVIIIFc prophylaxis 1-2 times/week in adults, adolescents, ...and children with severe hemophilia A. Median prestudy and on-study total weekly prophylactic factor consumption was comparable for subjects previously receiving FVIII prophylaxis.
Aims: To evaluate the effect of rFVIIIFc on subjects' physical activity across age groups using a subject-reported assessment and examine ABRs according to change in physical activity and prestudy treatment regimen (prophylaxis or episodic) in A-LONG and Kids A-LONG.
Methods: Previously treated males with severe haemophilia A (<1 IU/dL endogenous FVIII activity) were eligible for A-LONG (≥ 12 years of age) and Kids A-LONG (<12 years of age). A-LONG enrolled subjects into 1 of 3 arms: Arm 1, individualized prophylaxis; Arm 2, weekly prophylaxis; or Arm 3, episodic treatment. All subjects in Kids A-LONG received rFVIIIFc prophylaxis. There were no restrictions on physical activity in either study. Physical activity assessments were conducted at Weeks 7, 14, 28, 38, and 52 (A-LONG) and Weeks 2, 7, 12, 17, 22, and 26 (Kids A-LONG). At each visit after their first rFVIIIFc dose, subjects were asked to report their activity levels relative to their prior study visit as: more (or more intensive), fewer (or less intensive), or about the same amount of activity. To summarize changes in physical activity throughout the study versus baseline, subjects were classified into 1 of 4 groups: more, same, less, or undetermined. Within treatment groups, prestudy and on-study ABRs were analyzed according to change in physical activity category and prestudy regimen. Analyses included all subjects who received ≥ 1 dose of rFVIIIFc during the efficacy period and who completed ≥ 1 physical activity assessment.
Results: This analysis included 163 subjects from A-LONG and 69 subjects from Kids A-LONG. The majority of subjects in both studies reported more or the same amount of physical activity; few subjects reported less physical activity (more, same, less, undetermined): A-LONG Arm 1 (n = 117), 51%, 36%, 8%, 5%; Arm 2 (n = 23), 39%, 48%, 9%, 4%; Arm 3 (n = 23), 26%, 52%, 9%, 13%; and Kids A-LONG (n = 69), 61%, 26%, 6%, 7%, respectively. Similar physical activity results were observed in subjects with target joints at baseline. Median ABRs were lower with rFVIIIFc prophylaxis in A-LONG for all categories of change in physical activity, regardless of prestudy regimen (Table). In Kids A-LONG subjects on prestudy prophylaxis who reported more or similar physical activity, median ABRs with rFVIIIFc were similar or lower than prestudy ABRs.
Summary/Conclusion: The majority of subjects in A-LONG (86%) and Kids A-LONG (87%) reported maintained or increased physical activity levels on-study, with low ABRs. These results suggest that people with severe hemophilia A across age groups may maintain or increase physical activity levels with rFVIIIFc while maintaining low bleeding rates with reduced infusion frequency.
Table 1Prestudy and On-study Median (IQR) ABR by Physical Activity Level in A-LONG and Kids A-LONGParent study:A-LONGKids A-LONGOn-study rFVIIIFc prophylaxis:Arm 1 (Individualized)Arm 2 (Weekly)Twice-weeklyPrestudy FVIII regimen:Prophylaxis (n = 85)aEpisodic (n = 31)Episodic (n = 23)bProphylaxis (n = 62)Episodic (n = 7)Median (IQR) ABR by physical activity categoryMoren = 38n = 21n = 9n = 35n = 7Prestudy6.0 (3.0, 15.0)24.0 (17.0, 40.0)25.0 (20.0, 30.0)2.0 (1.0, 7.0)12.0 (10.0, 16.0)On-study2.15 (0, 5.42)0 (0, 1.81)1.93 (0, 3.59)2.01 (0, 4.04)2.05 (0, 3.96)Samen = 36n = 6n = 11n = 18n = 0Prestudy6.0 (1.0, 16.5)33.0 (23.0, 42.0)33.0 (16.0, 43.0)2.0 (1.0, 3.0)On-study2.76 (0, 6.06)0.86 (0, 2.03)4.34 (1.86, 7.62)0 (0,0)Lessn = 7n = 2n = 2n = 4n = 0Prestudy2.0 (1.0, 9.0)66.5 (13.0, 120.0)37.5 (23.0, 52.0)1.5 (0.5, 3.5)On-study0 (0, 3.78)0.72 (0, 1.44)15.04 (8.36, 21.71)4.07 (1.01, 8.31)Undeterminedn = 4n = 2n = 1n = 5n = 0Prestudy21.5 (6.0, 40.5)25.5 (14.0, 37.0)29.03.0 (2.0, 4.0)On-study2.80 (1.50, 7.55)0 (0,0)4.024.18 (2.01, 6.41)ABR, annualized bleeding rate; IQR, interquartile range.aOne subject did not have prestudy ABR data available and was excluded from the analysis.bAll subjects in Arm 2 received prior episodic treatment.
Quon:Baxter, Biogen, and Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Grifols: Speakers Bureau. Klamroth:Biogen and SOBI: Honoraria, Speakers Bureau; Bayer, Baxter, CSL Behring, Pfizer, Novo Nordisk, and Octapharma: Honoraria, Research Funding, Speakers Bureau. Kulkarni:BPL: Membership on an entity's Board of Directors or advisory committees; Kedrion: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Baxter: Membership on an entity's Board of Directors or advisory committees, Research Funding; Biogen: Research Funding, Speakers Bureau. Shapiro:Baxalta, Novo Nordisk, Biogen,: Membership on an entity's Board of Directors or advisory committees; Baxalta, Novo Nordisk, Biogen, ProMetic Life Sciences, and Kedrion Biopharma: Consultancy; Biogen: Speakers Bureau; Bayer Healthcare, Baxalta, Biogen, CSL Behring, Daiichi Sankyo, Kedrion Biopharma, Octapharma, OPKO, ProMetic Life Sciences, PTC Therapeutics, and Selexys: Research Funding. Baker:Novo Nordisk: Other: conference travel support; Bristol- Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Biogen Idec: Membership on an entity's Board of Directors or advisory committees, Research Funding; Boehringer Ingelheim: conference travel support, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Baxter Healthcare: Membership on an entity's Board of Directors or advisory committees, Other: conference travel support , Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Daiichi Sankyo: Research Funding; Portola Pharmaceuticals: Research Funding; Astellas: Research Funding; CSL Behring: Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: conference travel support; Alexion Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Other: conference travel support. Castaman:Bayer, Baxalta, CSL Behring, Kedrion, Novo Nordisk, and Pfizer: Membership on an entity's Board of Directors or advisory committees. Kerlin:Bayer Healthcare US and Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Research Funding. Tsao:Biogen: Employment, Equity Ownership. Allen:Biogen: Employment, Equity Ownership.
Introduction: Over a 3 year period, U.S. men with hemophilia were found to be 50 times more likely to die from renal disease than the general population (SMR 50; 95% CI 26.8-92.8) (Soucie et al., ...Blood 2000). Despite this finding, data regarding chronic kidney disease (CKD) and its risk factors in patients with hemophilia remain limited. The objective of this study is to determine the prevalence of CKD and CKD risk factors among older men with moderate and severe hemophilia.
Methods: A U.S. national study (ATHN-1) began enrollment in 10/2012. Inclusion criteria are men with moderate or severe congenital hemophilia A or B (FVIII or IX level ≤ 5%), age 54-73. Men with an additional bleeding disorder (besides liver dysfunction) were excluded. In this extension study, CKD risk factors, historical creatinine levels, and history of renal events were obtained from patient interview and chart review after obtaining informed consent. Glomerular filtration rate (GFR) values were calculated using the CKD-EPI equation and compared to values in the general population using the NHANES dataset (Coresh et al., JAMA 2007). CKD is defined as the presence of either kidney damage or decreased kidney function with GFR < 60 ml/min/1.73 m2 for ≥ 3 months, irrespective of cause.
Results: As of 6/30/2017, data from 98/200 subjects from 18 U.S. Hemophilia Treatment Centers have been collected, and interim analysis is presented here. The majority were white (88; 89.8%) or African American (9; 9.2%). Mean current age was 64 years (SD: 5; range: 57-77). 37.8% (37/98) were on prophylaxis, defined as ≥2 doses of FVIII or ≥ 1 dose FIX/week. Two (2.0%) had a current inhibitor. Viral infection was common: 35.7% currently had hepatitis C (HCV), and 17.4% HIV. Hypertension (HTN) was reported in 52.0% of subjects, 13.3% diabetes (DM), and average BMI was 28.1 kg/m2 (35.7% obese). 6.1% (6/98) were found to have CVD (defined as angina, MI, TIA, or ischemic or embolic stroke).
Fasting blood work showed an abnormally elevated creatinine in 30.9% subjects (mean 1.1 mg/dl, SD 0.4). Mean historical maximum creatinine was 1.0 (range 0.6-4.8), with mean GFR 68 (range 12-126). 11.3% (8/71) met the definition of CKD. Stages of CKD by GFR in the hemophilia cohort were similar to the NHANES general population (p=0.60).
A history of hematuria was reported in 45.1% (41/91) of subjects, mostly at age under 20. 26.4% (24/91) of subjects had a history of nephrolithiasis, 57.1% (52/91) past use of NSAIDs, and 45.1% (41/91) antifibrinolytic agents. 15.4% (14/91) of subjects reported obstructive symptoms with urination; 14.3% (13/91) had benign prostate disease. 7.7% (7/91) of subjects had a history of intrinsic kidney disease. Of these, 28.6% (2/7) had a renal biopsy, 71.4% (5/7) had seen a nephrologist, and 14.3% (1/7) were on dialysis. The renal disease in these 7 subjects was related to: DM (3), HCV (2), HTN (1), and glomerulonephritis (1).
In our cohort, hemophilia subjects with CKD non-significantly trended to have increased DM (20% vs 8.2%), age ≥65 years (15.6% vs 7.7%), and HTN (14.6% vs 6.7%) compared to subjects without CKD. No other significant trends were identified, including no association with CVD, HCV, HIV, BMI or hematuria.
Conclusions: In this interim analysis of an ongoing national prospective cohort study, older men with moderate to severe hemophilia commonly report risk factors for CKD, including HTN (52.0%), DM (13.3%), viral infection (35.7% HCV, 17.4% HIV), and potential renal damaging medication use (57.1% past use of NSAIDs, 45.1% antifibrinolytic agents). Only 6.1% had CVD. Urological symptoms were also common, including hematuria (45.1%, with 26.4% reporting a history of nephrolithiasis); 15.4% of subjects reported obstructive symptoms with urination, and 14.3% had benign prostate disease.
In our cohort, 11.3% (8/71) subjects met the definition of CKD, defined as the presence of either kidney damage or GFR < 60 ml/min/1.73 m2 for ≥ 3 months. The distribution of GFR values appeared similar to the general population. As in the general population, hemophilia subjects with CKD non-significantly trended to have more DM, older age, and HTN compared to subjects without CKD. We plan to formally compare the prevalence of CKD and CKD risk factors with similarly aged men in the ARIC database once enrollment is complete, as understanding the risk factors that contribute to CKD is essential to halt its progression.
Sood:Bayer: Research Funding. Kempton:Genentech: Membership on an entity's Board of Directors or advisory committees. Cuker:T2 Biosystems: Research Funding; Spark Therapeutics: Research Funding. Ragni:Alnylam, CSL Behring, BAYER, Biomarin, Biomarin, Bioverativ, Genetech/Roche, Pfizer, Shire, SPARK: Research Funding; A Anylam, Biomarin, Bioverativ, Shire: Honoraria. Gill:Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; CSL Behring: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Von Drygalski:Baxalta/Shire: Honoraria; Bayer: Honoraria; Biogen: Honoraria; CSL Behring: Honoraria; Novo Nordisk: Honoraria; Pfizer: Honoraria; Hematherix LLC: Membership on an entity's Board of Directors or advisory committees. Escobar:Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees; CSL Behring: Honoraria, Membership on an entity's Board of Directors or advisory committees; NovoNordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees. Wheeler:NovoNordisk: Membership on an entity's Board of Directors or advisory committees; Octapharma: Membership on an entity's Board of Directors or advisory committees; Shire: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees.
Introduction: P-FiQ enrolled US adults with hemophilia and included administration of patient-reported outcome (PRO) instruments to assess pain, functional impairment, and quality of life (QoL). ...Regression methods were used to determine associations between patient characteristics and responses to PRO instruments.
Methods: Adults with mild to severe hemophilia and a history of joint pain or bleeding were enrolled from 15 sites. During routine visits, participants completed a pain history and 5 PROs: EQ-5D-5L with visual analog scale (VAS), Brief Pain Inventory v2 Short Form (BPI), International Physical Activity Questionnaire (IPAQ), SF-36v2, and Hemophilia Activities List (HAL). To evaluate subject characteristics associated with the 5 PRO instruments, simple linear regression (outcomes: EQ-5D-5L VAS, BPI pain severity, SF-36v2 overall health, and HAL overall score) and logistic regression (outcome: IPAQ total activity, high vs moderate/low) were used. Subject characteristics shown here either had statistically significant associations or were considered directional (p≤0.15).
Results: The study enrolled 381 patients; median age was 34 years. Most participants were employed (68%) and 61% had attended college. A majority had severe hemophilia (71%), and half (50%) reported a history of joint procedures; over the previous 6 months, 85% experienced pain and 67% had restrictions in school/work or recreational activities. Comorbidities and viral diseases included diabetes (6%), cardiovascular disease (19%), depression (19%), anxiety (14%), HIV infection (16%), and HCV infection (32%). Functional impairment as measured by HAL overall score was associated with a lack of college education, unemployment, older age, history of joint procedures, viral disease (HIV, hepatitis C), comorbidities (diabetes, cardiovascular disease, depression, anxiety), and severe hemophilia (Table). Reduced physical activity as measured by IPAQ total activity was associated with a history of joint procedures, viral disease, and comorbidities, and being younger was associated with 4-fold greater physical activity. BPI pain severity was associated with a lack of college education, unemployment, older age, history of joint procedures, viral disease, comorbidities, severe hemophilia, and not having a current or past history of inhibitors. Reduced EQ-5D-5L VAS was associated with a lack of college education, unemployment, older age, history of joint procedures, viral disease, comorbidities, and no current or past history of inhibitors. Reduced SF-36v2 overall health was associated with employment, a history of routine factor infusions, younger age, a lack of comorbidities, and severe hemophilia.
Conclusions: This analysis identified sociodemographic characteristics and comorbidities potentially associated with PRO measurements. Some of the factors most consistently associated with pain, functional impairment, and reduced QoL were a lack of college education, unemployment, older age, a history of joint procedures, viral disease, and comorbidities. Measuring PROs during clinical encounters may facilitate monitoring the impact of patient characteristics on important health outcomes.
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Batt:Merck: Equity Ownership; Sanofi: Equity Ownership; Novo Nordisk: Research Funding. Recht:Kedrion: Consultancy; Novo Nordisk: Consultancy, Research Funding; Baxalta: Research Funding; Biogen Idec: Research Funding. Wang:Baxalta: Membership on an entity's Board of Directors or advisory committees; HEMA Biologics: Membership on an entity's Board of Directors or advisory committees; LFB: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees; Biogen: Membership on an entity's Board of Directors or advisory committees. Quon:Novo Nordisk: Consultancy, Speakers Bureau; Biogen: Consultancy, Speakers Bureau; Grifols: Speakers Bureau; Bayer: Consultancy. Boggio:Bayer: Consultancy, Research Funding; Novo Nordisk: Consultancy, Research Funding; Baxter: Consultancy, Research Funding; CSL Behring: Consultancy, Research Funding; OctaPharma: Consultancy, Research Funding; Selexys: Research Funding; OPKO: Research Funding. Kessler:LFB: Other: Member of DSMB; Biogen: Consultancy; Pfizer: Consultancy; Grifols: Consultancy; Genentech: Consultancy, Research Funding; Bayer: Consultancy, Research Funding; Baxalta: Consultancy, Research Funding; Octapharma: Consultancy, Research Funding; Novo Nordisk: Consultancy, Research Funding. Buckner:Genentech: Consultancy; Novo Nordisk: Consultancy; Baxalta: Consultancy. Neff:Shire: Membership on an entity's Board of Directors or advisory committees; Pfizer: Other: DSMB Chair for research study; ABIM: Other: Hematology Exam committee; CSL Behring: Membership on an entity's Board of Directors or advisory committees; HEMA Biologics: Membership on an entity's Board of Directors or advisory committees. Iyer:Novo Nordisk: Employment. Cooper:Novo Nordisk: Employment. Kempton:Baxalta: Consultancy; Novo Nordisk: Consultancy, Research Funding; Genentech: Consultancy.
Metronidazole 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole is used to treat infections caused by Trichomonas vaginalis, a sexually transmitted human parasite. This drug is administered in an inactive ...form and is reduced to its cytotoxic form within the hydrogenosome, an unusual organelle found in trichomonads. Metronidazole reduction occurs via ferredoxin-mediated electron transport. We have investigated the role of ferredoxin in metronidazole resistance. Immunoblot analysis of drug-resistant and -sensitive T. vaginalis strains shows that intracellular levels of ferredoxin are invariably reduced in the resistant strains relative to a sensitive strain. Similarly, Northern blot analysis shows that ferredoxin mRNA levels are reduced 50-65% in resistant strains. Using nuclear run-on assays, we show that ferredoxin gene transcription is reduced 40-65% in resistant strains. Sequence comparison of the region 5' of the ferredoxin gene among drug-sensitive and -resistant strains reveals two point mutations, at -178 and -239 nucleotides relative to the start of transcription, in a resistant strain. Interestingly, a protein of ≈23 kDa binds to a 28-base-pair region that encompasses the mutation at -239 nucleotides. The binding affinity of this protein appears to be reduced in the mutant. These data strongly correlate drug resistance with altered regulation of ferredoxin gene transcription. A reduction in gene transcription results in decreased intracellular levels of ferredoxin. This, in turn, may play a role in metronidazole resistance by decreasing the ability of the cell to activate the drug.
To identify regulatory elements that play a role in transcription initiation in ancient eukaryotes, we have analyzed the upstream regions of protein-coding genes from Trichomonas vaginalis, one of ...the most ancient eukaryotes studied to date. Characterization of seven protein-coding genes from this protist invariably revealed the presence of a highly conserved DNA sequence motif immediately upstream of the coding region. This 13-nt motif was shown to surround and contain precise sites for transcription initiation. No typical TATA boxes, positioned at 25-30 nt upstream of the transcription start sites of these genes, were found. The start-site regions from all seven T. vaginalis genes impart strong specific initiation of transcription in a mammalian in vitro transcription assay. This consensus promoter element in an ancient eukaryote is similar, both structurally and functionally, to initiator elements found in promoters of higher eukaryotes.
Abstract Background Patients with haemophilia have a higher prevalence of hypertension than the general population that cannot be explained by traditional cardiovascular risk factors such as age, ...race, diabetes or obesity. Patients with severe haemophilia, who are on clotting factor prophylaxis, have a higher prevalence of hypertension compared to patients with milder forms of haemophilia, who infuse clotting factor less frequently. This raises the question of whether there is a link between clotting factor usage and blood pressure in haemophilia patients. Methods Data was collected from 193 patients with severe haemophilia presenting to three haemophilia treatment centres in the United States and Canada, including age, body mass index (BMI), blood pressure (BP), Hepatitis C (HCV) and Human Immunodeficiency Virus (HIV) infection status, and clotting factor usage from pharmacy prescriptions (units/kg/year). The correlation between BP and factor usage was examined using quantile regression models. Results Systolic and diastolic BP plotted against factor use showed a cone-shaped scatter of points. There was no association between clotting factor usage and higher systolic or diastolic BP. Conclusion Our observations provide no evidence for an association between increased clotting factor usage and high BP.
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Introduction: Cardiovascular disease (CVD) is a disease of aging. While men with hemophilia were initially thought to be protected from CVD, it is now clear that atherothrombotic events do occur. ...The objective of this study is to determine the prevalence of CVD and CV risk factors among older men with moderate and severe hemophilia.
Methods: A U.S. national cross-sectional study began enrollment in 10/2012. Inclusion criteria are men with moderate or severe congenital hemophilia A or B (FVIII or IX level ≤ 5%), age 54-73. Men with an additional bleeding disorder (besides liver dysfunction) were excluded. After obtaining informed consent, CV risk factors, medications, and history of thrombotic events were obtained from patient interview and chart review. A fasting blood sample was assayed centrally.
Results: As of 8/1/2014, 160/200 planned subjects were recruited and interim analysis on 126 subjects from 18 U.S. Hemophilia Treatment Centers is presented here. The majority were white (109; 86.9%) or African American (15; 11.5%). Mean age was 62 years (SD: 5; range: 54-74). Most used factor on demand, with only 34.1% (43/126) on prophylaxis, defined as ≥2 doses of FVIII or ≥ 1 dose FIX/week. Five (4.0%) had a current inhibitor. Viral infection was common; 68.3% currently had hepatitis C, and 25% HIV.
Hypertension (HTN) was reported in 65.6% of subjects, 37.3% dyslipidemia and 24.6% diabetes (DM); 44.5% had ever smoked, 56.3% denied engaging in at least moderate physical activity and 43.7% had a family history of CVD. Average BMI was 28 kg/m2 (29.4% obese) and waist circumference 97 cm. Fasting blood work showed an abnormally elevated: creatinine in 27.6% subjects (mean 1.09 mg/dl, SD 0.5), CRP in 6.3% (4.15 mg/L, 10.6), total cholesterol in 18.1% (169.49 mg/dl, 35.8), triglycerides in 25.2% (122.10 mg/dl, 58.2), LDL in 19.7% (102.27 mg/dl, 32.3); and low HDL in 45.7% (42.80 mg/dl, 12.2).
Ten subjects (7.9%) reported prior angina; 7 (5.6%) atrial fibrillation/flutter; 3 (2.4%) leg deep venous thrombosis; 2 (1.6%) myocardial infarction (MI), transient ischemic event (TIA), or pulmonary emboli; and 1 (0.8%) coronary artery angioplasty, stent placement, CABG, or peripheral arterial angioplasty.
In total, 11 subjects had CVD (defined as angina, MI, TIA, or ischemic or embolic stroke), a prevalence rate of 8.7%. This is significantly lower than the reported prevalence of 23% CVD in similar aged men without hemophilia in the longitudinal ARIC cohort (p-value <0.001). The qualifying diagnoses in our cohort included angina, MI and TIA. None of the men with CVD were on antiplatelet or anticoagulant medications.
Due to the small number of events, individual CV risk factors thus far did not achieve statistical significance in predicting CVD. Compared to never smokers, ever smokers had an odds ratio (OR) of 3.7 (95% CI: 0.9-14.8) of CVD. For HTN, dyslipidemia, and DM, the OR (95% CI) of CVD were 2.5 (0.5-12.1), 2.2 (0.6-7.5), and 1.9 (0.5-6.8), respectively. Positive family history (OR 2.4 (0.7-8.8)) and low-level of physical activity (1.4 (0.4-5.0)) also suggested some association with increased CVD risk. Obese BMI and large waist circumference were not significant.
Men using prophylaxis appeared less likely to have CVD (1/43, 2.3%) than men not on prophylaxis (10/83, 12.1%), OR 0.2 (0.02-1.4), although the difference was not statistically significant. HIV+ men (1/32, 3.1%) were also less likely to have CVD compared to non-HIV+ men (10/92, 10.9%), OR 0.3 (0.2-10.9), but not significantly so.
Lastly we investigated the role of anti-HTN (used in 36.5% of all subjects), cholesterol lowering (16.7%), and DM medications (10.3%) in reducing CVD. Not taking anti-HTN, cholesterol or DM medications non-significantly increased CVD risk with an OR in all subjects of 1.5, 3.3, or 3.9 respectively.
Conclusions: In this interim analysis of an ongoing national cross-sectional study, older men with moderate to severe hemophilia commonly report risk factors for CVD, including HTN (65.6%), dyslipidemia (37.3%) and renal insufficiency (27.6%). Despite this, the prevalence of reported CVD is low at 8.7%, suggesting that men with hemophilia may be protected from forming pathogenic thrombi. More data is needed to determine if the approach to prophylaxis or other therapies should be altered in this population. We plan to formally compare the prevalence of CVD and CV risk factors with similarly aged men in the ARIC database once enrollment is complete.
Sood:Bayer: Research Funding. Shapiro:Baxter: Consultancy, Global Steering Committee Other, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bayer: Consultancy, Global Steering Committee, Global Steering Committee Other, Research Funding; CSL Behring: Research Funding; Biogen Idec: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Kedrion: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Kempton:Baxter Healthcare, Inc: Membership on an entity’s Board of Directors or advisory committees; CSL Behring: Membership on an entity’s Board of Directors or advisory committees; Kedrion Biopharma: Membership on an entity’s Board of Directors or advisory committees; NovoNordisk, Inc: Research Funding. Fogarty:Amgen Inc: Consultancy; Bayer HealthCare Pharmaceuticals: Consultancy; Baxter: Consultancy; Biogen Idec Inc.: Consultancy; Chugai Pharma USA: Consultancy; Pfizer Inc: Consultancy; Baxter: Research Funding; Biogen Idec Inc.: Research Funding; CSL Behring: Research Funding; Pfizer Inc: Research Funding; Medscape LLC: Honoraria; VindicoMed: Honoraria. Ragni:Biogen Idec: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; GlaxoSmithKline: Consultancy, Research Funding; Tacere Benitec: Consultancy, Drug Safety Monitoring Board, Drug Safety Monitoring Board Other; Baxter: Research Funding; Bayer: Research Funding; CSL Behring: Research Funding; Merck: Research Funding; Novartis: Research Funding; Novo Nordisk: Research Funding; Pfizer: Research Funding; Spark Therapeutics: Research Funding; Vascular Medicine Institute, PIttsburgh, PA: Research Funding. Neff:Baxter: Membership on an entity’s Board of Directors or advisory committees. Konkle:CDC: Research Funding, This work was supported by CDC grant 1U01DD000761-01 Other.
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