Hitoshi Kukita

Serum apolipoprotein A-I, A-II and B levels and their discriminative values in relatives of patients with coronary artery disease.

Serum cholesterol, triglyceride, high density lipoprotein cholesterol (HDL-C) and apolipoprotein (apo) A-I, A-II and B concentrations were measured in 109 first-degree relatives of patients with angiographically defined coronary artery disease (CAD). Age- and sex-matched healthy factory employees were chosen as a control group. Male relatives of the CAD patients had significantly higher serum triglyceride and apoB levels, and significantly lower serum HDL-C and apoA-I levels than the controls. Female relatives of the CAD patients also showed similar differences in serum HDL-C, apoA-I and apoB levels. Discriminant analysis indicated that apolipoproteins were better discriminators than lipids in both patients with CAD and their relatives. In univariate analysis, the best discriminator was apoB between male relatives and the controls, and apoA-I between female relatives and the controls. The percentage of exact classification achieved using three variables (serum cholesterol, triglyceride and HDL-C) was 74% in male relatives and 70% in female relatives. By adding variables of apoA-I and apoB, the percentage of correctly classified subjects was increased to 82% and 80%, respectively. These results indicate that serum apolipoprotein abnormalities are prevalent in relatives of the CAD patients. These abnormalities may explain the familial aggregation of CAD.

Clinical significance of measurements of serum apolipoprotein A-I, A-II and B in hypertriglyceridemic male patients with and without coronary artery disease

To examine the relationship of hypertriglyceridemia to coronary artery disease (CAD), we measured serum cholesterol, triglyceride, high density lipoprotein cholesterol (HDL-C) and apolipoproteins (apo) A-I, A-II and B in 82 male patients with angiographically defined CAD and 140 age-matched healthy controls. The CAD patients had significantly lower apo A-I and A-II and HDL-C levels, but had higher apo B and triglyceride levels than the controls. After adjustments of apolipoproteins for serum triglyceride, CAD patients had significantly higher apo B and lower apo A-I and A-II levels than the controls. Discriminant analysis showed that apo B was the best discriminator and that apo A-I was next. In the normotriglyceridemic subgroup HDL-C also had a sufficient power for discrimination between CAD patients and the controls, but in the hypertriglyceridemic subgroup HDL-C had no discriminative power. Both apo A-I and B had significant discriminative power between CAD patients and the controls, independently of the serum triglyceride level. These results indicate that measurements of serum apo A-I and apo B are useful for the study of coronary risk factor in hypertriglyceridemic subjects. Finally, it is necessary to sub-classify dyslipoproteinemia by serum apolipoprotein levels for predicting the future occurrence of CAD in the general population.

Plasma lipids and lipoproteins in Japanese male patients with coronary artery disease and in their relatives

Plasma cholesterol (CH), triglyceride (TG) and high density lipoprotein cholesterol (HDL-C) were measured in 92 consecutive Japanese male subjects undergoing diagnostic coronary cineangiography. Sixty-nine of them were classified as having coronary artery disease (CAD), the remaining 23 subjects were classified as having normal coronary arteries (NCA). The CAD group had significantly lower HDL-C and higher TG levels than the NCA group. However, there was no significant difference in plasma CH between the two groups. First-degree relatives of the CAD patients were also investigated. The male blood relatives of the CAD patients also had significantly lower HDL-C and higher TG levels than the non-blood male relatives and healthy control males. The female blood relatives, however, showed no significant differences from the non-blood female relatives and the healthy control females in plasma CH, TG and HDL-C levels. These results suggest that low HDL-C and hypertriglyceridemia are the prevalent coronary risk factors, rather than hypercholesterolemia, in a population with a low fat intake such as the Japanese, and that these lipid abnormalities are related to sex and genetic factors.

Clinical Characteristics of Female Patients With Coronary Spastic Angina

There are many patients with vasospastic angina who have minor atherosclerosis, and in Japan the majority of them are male. No data exist concerning sex differences in patients with coronary spastic angina, so the present study sought to clarify the clinical characteristics between male and female patients with vasospastic angina. Between April 1991 and June 1998, 204 consecutive patients were diagnosed with vasospastic angina and of these, 26 (12.7%) were female. An acetylcholine test was performed with incremental doses of 20, 50, and 80 microg injected into the right coronary artery and 20, 50, and 100 microg into the left coronary artery. Ergonovine was injected in a total dose of 40 microg into the right coronary artery and 64 microg into the left coronary artery. Coronary spasm was defined as 99% or more luminal narrowing accompanied by ischemic changes on ECG. Compared with male patients, female patients had less organic stenosis (12 vs 33%, p<0.05), less history of smoking (15 vs 85%, p<0.01), and fewer focal spasms (31 vs 64%, p<0.01). There were no other differences between the 2 groups. In conclusion, Japanese female patients with vasospastic angina had the characteristics of diffuse provoked spasm, less organic stenosis, and less history of smoking, but only 1 in 10 of all patients with vasospastic angina are female.

Effect of clinofibrate, a new hypelipidemic agent, on biliary and serum lipids in patients with hyperlipidemia

Clinofibrate was given to 15 patients with hyperlipidemia, for 6-8 weeks at the daily dose of 600 mg, and its effect on 3 biliary lipid components (cholesterol, bile acids and phospholipids) and on the lithogenic index was investigated. After clinofibrate treatment, 6 of the patients were given 1.5 g/day clofibrate for 6-8 weeks to compare the effect of clofibrate with that of clinofibrate. The molar percentages of biliary cholesterol and phospholipids to the total mol number of the 3 biliary lipid components decreased, and that of bile acids increased during clinofibrate administration. In this way, the molar ratio of bile acids to cholesterol increased during the treatment. Neither the lithogenic index calculated by the formula of Admirand and Small nor that of Hegardt, Dam and Holzbach was altered significantly by the treatment. There was no apparent relationship between the effect of the drug on the lithogenic index and any of the factors initial lithogenic index, rate of decrease of serum lipids, or type of hyperlipidemia. Although clofibrate had no significant effect on the maximum solubility of cholesterol in the bile, the molar percentage of biliary cholesterol was elevated and the lithogenic index increased as compared with the control and clinofibrate period. No significant influence on bile acid composition in the bile was observed, with either clinofibrate or clofibrate.