Analysis of 45 episodes of arterial occlusive disease in Japanese patients with congenital protein C deficiency

Hereditary protein C deficiency is associated with a predisposition to venous thrombosis. It is not clear whether the deficiency is involved in arterial occlusion. In the present study, we screened for protein C amidolytic activity in patients admitted to the National Cardiovascular Center Hospital, and we identified among them 43 probands and 51 relatives with heterozygous protein C deficiency. Among them, 34 patients with heterozygous protein C deficiency had manifested 45 episodes of arterial occlusive disease. Venous thrombotic diseases were less common. In the examination of whether protein C deficiency hastens arterial occlusion, we found a significant difference (p=0.02) in the age at onset of acute myocardial infarction between the patients with protein C deficiency (n=10; 49.4±14.8 years) and a group of patients with normal protein C levels (n=42; 60.5±10.6 years). Acute myocardial infarction occurred before 40 years of age in a significantly greater proportion of the patients with protein C deficiency (3:10, 30%) as compared with the controls (2:42, 5%) (χ²=5.9, p=0.015). At the onset of atherothrombotic cerebral infarction the patients with protein C deficiency were significantly (p=0.022) younger (n=11; 57.4±12.8 years) than those with normal protein C levels (n=48; 64.6±10.1 years). Venous thrombosis was the most frequent clinical manifestation (21 of 31 episodes) in the patients with antithrombin III deficiency (n=26; 68% of the total), who were admitted to our hospital. Thus, our study suggests that congenital protein C deficiency contributes to earlier onset of arterial occlusive diseases, especially acute myocardial infarction, in Japanese subjects.