Plasma insulin as coronary heart disease risk factor: relationship to other risk factors and predictive value during 9 1/2-year follow-up of the Helsinki Policemen Study population.

In the Helsinki Policemen Study based on a cohort of 982 men aged 35-64 years and free of coronary heart disease (CHD) at entry plasma insulin level (fasting, 1-hour and 2-hour plasma insulin after oral glucose load) showed during a 9 1/2-year follow-up a non-linear association to the incidence of "hard criteria" CHD events (CHD death or non-fatal myocardial infarction) with highest incidence in the top decile of plasma insulin. Plasma insulin levels showed positive correlations, besides to blood glucose levels, to body mass index, plasma triglyceride level and blood pressure and inverse correlations to leisure time physical activity and objectively measured physical fitness. In multivariate analyses the predictive value of high plasma insulin with respect to CHD risk was found to be independent of other risk factors, including blood glucose levels.

Plasma prekallikrein, kallikrein inhibitors, kininogen and lipids during gemfibrozil treatment in type II dyslipidaemia.

The effects of gemfibrozil on plasma prekallikrein, kallikrein inhibitors, kininogen and plasma lipids were investigated in 31 male subjects having either type IIA or IIB dyslipidaemia. During gemfibrozil use, plasma prekallikrein and kininogen were increased significantly while kallikrein inhibitors increased only slightly. Total cholesterol and triglycerides decreased while HDL cholesterol was increased. Changes in prekallikrein and HDL cholesterol were correlated, whereas no other significant correlations between changes in lipid and kinin parameters were seen. The observed changes in prekallikrein and kininogen possibly indicate a shift in the thrombo-haemorrhagic balance in favour for increased fibrinolysis. If so, the effects of gemfibrozil in prevention and management of atherosclerosis would not be solely due to correlation of the dyslipidaemia but also to protection against the accelerated coagulation tendency seen in type II dyslipidaemia.

Gemfibrozil in the treatment of dyslipidaemias in middle-aged male survivors of myocardial infarction.

The effects of gemfibrozil on serum lipids and apolipoproteins were investigated in 60 male survivors of myocardial infarction (MI) (age range 29-48 years, mean 44). Fifteen had normal serum cholesterol (less than or equal to 7.0 mmol/l) and triglyceride (less than or equal to 1.7 mmol/l) levels, but most had low levels of high density lipoprotein (HDL) cholesterol (less than 1.00 mmol/l). Ten had type II A, 27 type II B and 8 type IV hyperlipidaemia. A double-blind placebo-controlled cross-over design was used with 3-month treatment periods. Gemfibrozil was given in daily doses of 1200 mg. The drug was well tolerated and there were no drop-outs attributable to its use. In all subjects, gemfibrozil reduced the mean serum total cholesterol by 17% and triglycerides by 54% and increased HDL cholesterol by 16%. The percentage HDL cholesterol of total cholesterol increased from 14 to 19%. The changes were similar in patients with normal serum cholesterol and triglyceride values and in those with classical hyperlipidaemias. In contrast, the changes during placebo treatment corresponded to those in healthy male untreated controls who were followed simultaneously. Apoprotein A-I remained unchanged, but A-II increased by 20% during gemfibrozil treatment. It is concluded that gemfibrozil corrects effectively dyslipidaemias in male MI patients but further long-term studies are warranted.

Effect of phenytoin on serum lipoproteins in middle-aged men.

We assessed the effect of phenytoin on serum lipids and lipoproteins in a group of 20 male volunteers. Nine of the subjects were healthy, and 11 had coronary heart disease. Their mean age was 44 +/- 7 years. Phenytoin was given at daily doses of 200-350 mg for a period of 4-9 months. Serum total cholesterol increased from 6.9 to 8.1 mmoles/liter (p < 0.001), high-density lipoprotein (HDL) cholesterol from 1.02 to 1.14 mmoles/liter (p < 0.05), low-density lipoprotein cholesterol from 5.0 to 5.9 mmoles/liter (p < 0.05), and total triglycerides from 1.9 to 2.4 mmoles/liter (p < 0.05). The ratio of HDL cholesterol to total cholesterol remained unchanged (14.8 vs. 14.1%). The level of apoprotein A-I increased from 145 to 164 mg/dl (p < 0.001), while A-II remained unchanged. Besides drowsiness, for which 1 patient dropped out, no side effects attributable to phenytoin were seen. As an indication of liver microsomal enzyme induction, serum gamma-glutamyltransferase activity was increased in all subjects during phenytoin treatment. These results cast doubt on the clinical usefulness of phenytoin in treating dyslipidemias.

Serum lipids with special reference to HDL cholesterol and triglycerides in young male survivors of acute myocardial infarction.

Serum cholesterol, triglycerides and high-density lipoprotein (HDL) cholesterol were determined in 56 male survivors of myocardial infarction (MI), suffered 6--20 months earlier, and in 82 healthy age- and sex-matched controls. The mean age of both groups was 39 years. Total serum cholesterol was within normal limits in both groups, whereas HDL cholesterol was considerably lower and triglycerides remarkably elevated in MI patients compared with the controls. Judging from previous and present data, low HDL cholesterol seems to be a coronary risk factor as such. This study indicates that low HDL cholesterol, and especially a low HDL cholesterol/total cholesterol ratio, may be stronger coronary risk factors than total serum cholesterol alone. Because HDL cholesterol and triglycerides were inversely correlated, these results also emphasize the importance of serum triglycerides as a risk factor for coronary heart disease.