[Searching for a new risk factor of sudden cardiac death]

Sudden death of cardiovascular origin has been recognized as a major cause of sudden natural death. Advanced coronary atherosclerosis often co-existent, despite this, little or no coronary atherosclerosis was seen in approximately half of the sudden coronary death cases. Some components in the blood seem to induce not only the coronary atherosclerosis but also coronary spasm and/or thrombogenesis under certain conditions, which does not necessarily relate to the severity of atherosclerosis. Postmortem plasma lipids and lipoprotein levels, especially triglyceride-rich lipoprotein remnants (abbreviated as remnants) were measured as remnant-like particles-cholesterol (RLP-C) and triglyceride (RLP-TG) in two groups of Japanese subjects who died suddenly and unexpectedly due to coronary or non-coronary causes. Our study on the postmortem plasma analysis of lipids and lipoproteins indicated that RLP-C was most strongly correlated with the severity of the coronary atherosclerosis and to be the best predictor among various parameters. Furthermore, RLP-TG appeared to be highly associated with the risk of sudden coronary event or death, especially in cases without advanced coronary atherosclerosis, which might be associated with clinical events as coronary spasm or thrombosis. Biological activities of RLP from postmortem plasmas of sudden coronary death cases showed strong effects on platelet aggregation and impaired vasorelaxation in vitro. RLP determined as RLP-TG might affect on the process of spasm or on the formation of thrombus in the coronary artery at the time of sudden coronary death, independent of the severity of coronary atherosclerosis. These data might be clinically important to predict or to prevent sudden coronary death. The studies were conducted as followed: 1) Separation, purification and quantitative analysis of remnants from postmortem plasma. 2) Isolation and characterization of remnants from postmortem plasma. 2-1) Assessment of the methods of TG measurement. 2-2) Characterization of remnants by HPLC methods. 2-3) Characterization of remnants by electrophoresis. 2-4) Electron microscopical observation of remnants. 3) Lipid and lipoprotein analysis of sudden coronary death and control cases. 3-1) Lipid and lipoprotein levels of sudden coronary death and control cases. 3-2) Plasma remnant levels in the postprandial state. 3-3) Severity of coronary atherosclerosis and plasma lipid and lipoprotein levels, especially remnant levels. 3-4) Sudden coronary death cases without advanced coronary atherosclerosis and their plasma lipid, lipoprotein levels, especially remnant levels. 4) Biological activities of the remnants. 4-1) Endothelium-dependent vasodilator function in the coronary artery. 4-2) Aggregation of human blood platelets by remnants. 5) Fatty acids analysis of remnants from sudden coronary death cases. 6) Immuno-histochemical examination of various apo-lipoproteins on the coronary artery. 7) Gene analysis of plasma lipid metabolites.