Determinants of the severity of ischemic heart disease with the burden of multiple risk factors.

在工业发达国家，多危险因素的概念更有利于心脏病学家和流行病学家治疗和/或预防缺血性心脏病。近年来机动化的发展和摄入含动物脂肪和富含碳水化合物的高热量食物的增加，使缺血性心脏病的严重程度恶化。然而，动脉粥样硬化的发生和发展以及随后发生的缺血性心脏病的机制尚不清楚。本项目的目的是：1)对山形县急性心肌梗死的发生和预后进行血凝学调查，阐明危险因素及其临床意义；2)建立多危险因素的遗传动物模型，特别是与高脂血症相关的危险因素；3)阐明高甘油三酯血症在动脉粥样硬化和心肌缺血中的病理生理意义。山形县急性心肌梗死的区域流行病学研究表明：(1)早期再灌注将急性死亡率从18%降低到约5%；(2)急性心肌梗死的日发病高峰主要出现在老年患者中，而不是年轻患者。兔研究已经成功分离出高甘油三酯血症和餐后高甘油三酯血症的遗传模型。后一种模式目前正在国内和美国的患者中应用

In industrial countries, the concept of multiple risk factors has favored cardiologists and epidemiologists for treating and/or preventing the ischemic heart disease. Recent advances of motorization and increases of intaking a high caloric food containing animal fat and rich in carbohydrates have gotten worse in the severity of ischemic heart disease. However, the mechanisms not only in evolution and progression of atherosclerosis but also in ensuing ischemic heart disease have not been settled. The goals of this project were 1) epichemiological survey of occurrence and prognosis of acute myocardial infarction in Yamagata and to elucidate risk factors and their clinical significance, 2) development of genetic animal models with multiple risk factors, especially related to hyperlipidemia and 3) to elucidate pathophysiological significance of hypertriglyceridemia in atherogenosis and myocardial ischemia. Regional epidemiological studies of acute myoardial infarction in Yamagata showed that (1) early reperfusion reduced acute mortality from 18 % to about 5 % and (2) diurnal peaks of the onset of acute myocardial infarction were prodominantly seen in aged but not younger patients. Rabbit studies have succeeded in segregating heritable models of hypertriglyceridemia and post prandial hypertriglyceridemia. The latter model is now applying patients in domestic and in the U.S.A.