Abstract
Mortality in individuals with hemophilia is 2.7-fold higher than the general population. By contrast, ischemic heart disease mortality in this group is 60% lower than in the general population. The reason for these differences is not known. While high VIII:C is associated with thrombotic risk, and low VIII:C is associated with bleeding risk, it remains unproven whether low VIII:C is protective against atherosclerosis or cardiovascular morbidity or mortality. We, therefore, conducted a case-control study to compare coronary atherosclerosis at autopsy in 14 hemophilic men who died between 1983 and 1992, on whom autopsies were available, and 42 HIV-negative age-, gender-, and race-matched non-hemophilic controls. The mean age at death in hemophilic cases was 40 ± 4 yr (19–74), as compared with 41 ± 2 yr (18 to 75) in the controls, p > 0.25. The cause of death in cases was AIDS in 7 (50.0%), hepatitis C liver disease in 4 (28.6%), CNS bleeding in 2 (14.3%), and cancer in 1 (7.1%). The cause of death in controls was cardiopulmonary disease in 14 (33.3%), infection in 13 (30.9%), cancer in 4 (9.5%), organ failure in 4 (9.5%), and other in 7 (16.7%). None (0%) of the hemophilia cases had coronary disease symptoms vs. 2 (4.8%) of the controls, p = 0.559. Ten (71.4%) of the cases were HIV-infected, but none had received HAART therapy. Twelve cases had severe hemophilia (VIII < 0.01 U/ml), one moderate disease (VIII = 0.01–0.04 U/ml), and one mild disease (VIII ≥ 0.05 U/ml). None of the cases had diabetes or hypercholesterolemia (> 220 mg/dl); five (35.7%) were smokers, five (35.7%) were hypertensive (systolic > 140 and/or diastolic > 80 mm Hg), and three (21.4%) were obese (body mass index > 25 kg/m2). Body mass index, mean 23.84 ± 0.84 kg/m2, and blood pressure, mean systolic, 129 ± 6 mm Hg, and mean diastolic, 82 ± 3 mm Hg, increased with age, r = 0.439, r = 0.488, r = 0.209, respectively, but not significantly so, p > 0.05. Intraluminal coronary stenosis was assessed by a semi-quantitative scoring system, with 0 = minimal (< 25%), 1= mild (≥ 25%), 2 = moderate (≥ 50%), and 3 = severe (≥ 75%). Coronary stenosis was detected in 11 of 14 (78.6%) hemophilic cases and in 25 of 42 (59.5%) controls, p = 0.118. There was no difference in the proportion with > 75% narrowing, 2 of 14 (14.3%) cases vs. 9 of 42 (21.4%) controls, respectively, p = 0.272. The overall mean stenosis score in hemophilic cases was 1.1 ± 0.2, not different from that in non-hemophilic controls, 1.2 ± 0.2, p > 0.25. The degree of intraluminal narrowing increased with age in cases, r = 0.773, p < 0.01, and in controls, r = 0.694, p < 0.01. There was no difference between age and coronary narrowing between groups, p = 0.928. In conclusion, the prevalence of coronary atherosclerosis in hemophilic men is comparable to that in age-, gender-, and race-matched non-hemophilic controls. Although factor VIII:C does not appear to promote atherogenesis, it is possible, although not proven, that low or missing VIII:C in hemphilia may be protective against thrombotic occlusion of atherosclerotic vessels by interfering with fibrin formation, thereby affording protection from ischemic heart disease mortality.
Recent decline in life expectancy at birth in Slovenia
