ORLANDO – Conventional wisdom holds that persons with hemophilia are at lower risk for death from cardiovascular events than the general population, but there are conflicting data from studies attempting to confirm or refute this notion.
In a prospective, multicenter European study of more than 500 patients with hemophilia, the predicted cardiovascular disease (CVD) event rate was less than half of what was expected, reported Paul R. van der Valk, MD, from University Medical Center in Utrecht, the Netherlands, and colleagues.
In patients with hemophilia, “the leading cause of death seems to be malignancy related and intracranial hemorrhage. Atrial fibrillation is quite common,” they wrote in a scientific poster presented at the World Federation of Hemophilia World Congress.
But a second study of 100 patients with hemophilia showed that the bleeding disorder did not appear to offer protection against cardiovascular or thrombotic adverse events, Beatriz Delgado, MD, and colleagues at the Centro Hospitalar São João in Porto, Portugal, also presented in a poster session.
Risk scores considered
The prospective study by Dr. van der Valk and colleagues was designed to assess the incidence of CVD in patients with hemophilia in the Netherlands and the United Kingdom, compared with the general population. They used the QRISK2 cardiovascular risk score (2011 version). This instrument is used to calculate risk of CVD events in adults from 30 to 84 with no history of CVD or statin use.
Among 557 patients with a calculable QRISK2 score at 2 years of follow-up, there were four CVD events, including two cases of ischemic heart disease, one ischemic stroke, and one intracranial hemorrhage. The median 2-year QRISK2 score was 1.7%, and the 10-year risk was 9.0%, which translated in to an expected 9.5 CVD events during 2 years of follow-up.
Among the additional 104 patients who could not have a QRISK2 score calculated because of age over 84, statin use, or history of CVD, there were four CVD events: ischemic heart disease, transient ischemic attack/carotid artery stenosis, myocardial infarction, and intracranial hemorrhage.
Other CVD events occurring in both groups included atrial fibrillation in eight patients, other arrhythmia in three, and, in one patient each, aortic valve pathology, pericarditis, and carotid artery plaque.
Portuguese experience
Dr, Delgado and colleagues noted that although hemophilia has traditionally been regarded as protective against ischemic heart disease or thrombotic events, modern management “has prolonged life expectancy of people with hemophilia and consequently, an associated increase in incidence and prevalence of conditions that affect the general older population, such as cardiovascular disease and hypertension, are expected.”
They conducted a retrospective analysis of 100 adults (69 with hemophilia A, and 31 with hemophilia B) treated at their center. Overall, 29 patients had severe hemophilia A, 20 moderate hemophilia A, and 20 mild hemophilia A. Among patients with hemophilia B, 11 had severe, 15 moderate, and 5 mild disease.
Two patients (one with moderate and one with severe hemophilia) had angina episodes with coronary artery disease and underwent multiple coronary bypass grafts. The patient with severe disease had a disabling ischemic stroke during recovery from bypass surgery, and the patient with moderate hemophilia had an acute myocardial infarction prior to bypass surgery.
Two other patients had transient ischemic strokes from which they recovered without disability.
The main cardiovascular risk factors identified in this population were hypertension, diabetes mellitus, heavy smoking, obesity, and dyslipidemia. All patients were screened for prothrombotic risk, and all patients had negative test results.
“Hemophilia does not seem to have a protective effect against thrombotic/cardiovascular events, mainly in [patients with] coronary artery disease,” the investigators wrote.
Endothelial function
Dr. Shannon Jackson
In a study presented in an oral abstract session, Shannon Jackson, MD, of the University of British Columbia in Vancouver found that men with hemophilia appear to have better macrovascular endothelial function but worse microvascular endothelial function than did men with normal clotting parameters.
“Based on endothelial function, contemporary hemophilia cohorts may have a different profile of cardiovascular risk than healthy controls,” she said.
Although they do not have an obvious mechanistic explanation for the differences in microvascular function among patients with hemophilia vs. healthy controls, there is evidence to show that microvascular function is predictive of cardiovascular events independent of other risk factors in otherwise healthy people. Their findings indicate that further study of the association between endothelial function, cardiovascular risk factors, and atherosclerosis among patients with hemophilia is warranted, she said.
Dr. van der Valk and colleagues and Dr. Delgado and colleagues did not disclose funding or conflicts of interest. The study by Dr. Jackson and colleagues was supported by the Canadian Hemophilia Society and Pfizer. She disclosed honoraria for speaking engagements for Biogen, Baxalta, and Pfizer and for participating in scientific advisory boards for Bayer, Pfizer, Baxalta, CLS Behring, and Novo Nordisk.