CRF is accompanied by characteristic alterations of lipoprotein metabolism with a retarded catabolism of triglyceride-rich lipoproteins as a prominent feature. Further investigation of the lipoprotein profile of CRF could provide information on the fundamental pathophysiological processes responsible for these disturbances and their possible clinical significance.

In a group of normocholesterolemic, non-diabetic middle-aged males surviving an acute myocardial infarction for 4 +/- 2 years (mean +/- SD), we have previously described a low apolipoprotein A-I and a deficient fibrinolytic activity as two major characteristics. In the present study we have followed morbidity and mortality risk factors for five years in these males. Mortality was 40% in a hypertensive group and 16% in a normotensive group. In the normotensive group mortality was related to reinfarction. Furthermore, patients with a poor prognosis in the normotensive group had lower high density lipoprotein (HDL) cholesterol and lower apolipoprotein A-I concentration in plasma than patients with a good prognosis. Unexpectedly, in the hypertensive group death was related to a low (p less than 0.05) cortisol concentration in urine. It is concluded that a low HDL level may be a bad prognostic sign in males who have sustained an acute myocardial infarction and show no evidence of other risk factors, such as diabetes, hypercholesterolemia or hypertension.

The effect of a diet rich in marine fatty acids, especially eicosapentaenoic acid, on plasma lipids (total plasma cholesterol, HDL cholesterol, total triglycerides and apolipoproteins A and B) and fatty acid composition in plasma phosphatidylcholine (PC) was studied in 10 healthy men. They were maintained for 11 weeks on their normal diet which was partly replaced by 150-200 g of fatty fish per day. In the same individuals this diet had previously caused a delay in primary haemostasis and a decrease in platelet aggregability similar to that caused by acetylsalicylic acid, a known inhibitor of thromboxane A2 formation. Apart from its effect on haemostasis, the fish diet substantially reduced serum triglycerides (by 43%, p less than 0.01) but caused no changes in total plasma or HDL cholesterol or apolipoproteins A and B. After three weeks on the diet the proportion of plasma PC omega-3 polyunsaturated fatty acids increased (C20:5 and C22:6) and omega-6 fatty acids decreased (C18:2 and C20:3). The relative plasma PC content of arachidonic acid was unaffected throughout. These alterations in plasma PC fatty acid composition were principally in accordance with those seen in platelet membrane PC. There was a linear correlation between the content of omega-3 and of omega-6 fatty acids in plasma PC with that of platelet PC as well as in predominate individual fatty acids of the two series. Six weeks after the volunteers had resumed their usual diet, total triglycerides and the fatty acid composition of plasma PC had returned to the original state.

The effect of treatment with protein-reduced diet on plasma lipids, apolipoproteins and lipolytic activities was studied in 15 patients with chronic renal failure. Mean treatment time was 7.4 months. Before treatment serum triglycerides were elevated as were the levels of apolipoprotein C-I and especially C-III. Postheparin plasma lipolytic activities were reduced. The treatment was effective in reducing the serum urea levels but had no significant influence on either plasma lipids, apolipoprotein levels or lipolytic activities. The abnormalities of lipid transport in chronic renal failure thus seem to be more dependent on loss of renal function than the degree of uremic intoxication.

The effect of acetylsalicylic acid (ASA) on platelet aggregation before and during a fish diet, already known to decrease the aggregability of platelets and to prolong the bleeding time, was studied in 10 healthy men. Two doses (3.5 and 10 mg/kg body weight) of ASA were given. Both doses equally decreased platelet aggregation to collagen and adenosine diphosphate (ADP). ASA, taken before the diet, diminished platelet aggregability to ADP by as much as did the diet alone. When ASA was administered during the diet, the effect on platelet aggregability to ADP was additive. Aggregation to collagen also decreased to the same extent as during the baseline period. The results, in conjunction with our earlier ones, indicate that the mechanism by which a fish diet delays primary haemostasis is different from the apparently similar effect of ASA. This raises the possibility of augmenting any antithrombotic effect of ASA by dietary means.

There is evidence that pathological aggregation of platelets in atherosclerotic arteries is initiated by hemorrhage through fissures in atheromatous plaques. Bleeding time determination reflects in vivo the physiologic function of platelets in their aggregation in injured vessels and can be used as a relevant model for primary hemostasis in investigations with antithrombotic aims. Acetylsalicylic acid is known to cause prolongation of bleeding time by inhibiting prostaglandin biosynthesis. Recent experiments have shown that dietary supplementation with omega-3 polyunsaturated fatty acids results in prolongation of bleeding time and decreased platelet aggregability. This paper is mainly concerned with the effect of different doses of aspirin (3.5 mg/kg, 5 mg/kg, and 10 mg/kg), and fish diets rich in omega-3 polyunsaturated fatty acids, on bleeding time and platelet aggregation. The effects of aspirin separately, as well as aspirin administration during dietary intervention, will be described. Administration of all three dose levels of aspirin prolonged bleeding time significantly (p less than 0.001). The effect of aspirin on bleeding time was dose-dependent and an optimum interval was found. A fish diet, rich in omega-3 polyunsaturated fatty acids, causes bleeding time prolongation and decreased platelet aggregability similar to those caused by aspirin. Aspirin taken during this diet prolonged bleeding time by more than the sum of the increases in bleeding time caused by aspirin and the diet with omega-3 polyunsaturated fatty acids, separately, but the synergism was not significantly more than additive. These observations suggest that fish diets affect primary hemostasis by mechanisms different from those of aspirin. Dietary intervention may therefore enhance the antithrombotic effects of aspirin.

The authors evaluated physiologic, psychologic and metabolic effects of a nine-week in-hospital training program on 14 men with severe disabling angina pectoris. The exercise program consisted of intensive interval training on an ergometer bicycle for two 30 min sessions daily. The physical performance increased by about 40% (p less than 0.001). Plasma insulin levels were reduced and glucose tolerance improved significantly. There was a decrease in plasma triglyceride and low-density lipoprotein (LDL) cholesterol levels, but no change in high-density lipoprotein (HDL) cholesterol, apolipoprotein AI and B concentrations. Plasma triglyceride (p less than 0.05) and LDL cholesterol (p less than 0.05) levels remained low three weeks after completion of the training period and the physical performance remained improved (p less than 0.01) even six months post-training. Four of the patients who had been disabled for at least five months were able to return to work. The authors suggest that comparatively short and intensive in-hospital rehabilitation of patients with coronary heart disease may be an attractive alternative to prolonged training on an outpatient basis, especially in patients with severe angina pectoris.

Eighteen healthy sedentary males took part in supervised bicycle training for 50 minutes three to five times a week. Twelve subjects (group A) trained for 6 weeks at heavy intensity, and six subjects (group B) trained for 12 weeks at moderate intensity. Maximal oxygen uptake increased by about 20% (P < 0.01). Body weight and composition as well as diet remained unchanged. After 6 weeks plasma high-density lipoprotein (HDL) cholesterol concentrations had increased by 7% (P < 0.05) in all subjects. The increase was most marked in group B at 14% (P < 0.05) compared to 3% in group A (ns). Apolipoprotein AI (apo AI) increased by about 7% in both groups (P < 0.01). After 12 weeks HDL cholesterol and apo AI levels had almost returned to initial values. Measurements of HDL components showed increases of 6% to 12% in free cholesterol, cholesteryl ester (P < 0.05), and phospholipid (P < 0.01); whereas, the minor triglyceride fraction decreased by 20% (P < 0.01). Zonal ultracentrifugation in four subjects revealed a preferential rise of about 35% in the HDL2 subfraction, increasing the HDL2HDL3 ratio by about 20%. In parallel, the composition of the lipoprotein classes changed. The protein moiety of all classes, except low-density lipoprotein (LDL), expanded at the expense of the core components cholesteryl ester and triglyceride. Hepatic lipase (HL) activity decreased by 6% (P < 0.05), and lipoprotein lipase (LPL) activity in adipose tissue increased by about 50% (P < 0.05) during the first 6 weeks of training, while LPL activity in postheparin plasma and skeletal muscle did not change. The transient rise in HDL cholesterol levels was correlated (P < 0.05) to the elevation of adipose tissue LPL activity. The alterations in HDL concentration were also related to changes in body composition and diet, especially to an increase in fat intake.

Plasma lipoprotein concentrations were followed in 21 men with acute myocardial infarction. HDL and LDL cholesterol concentrations showed similar time-courses with average maximal decreases of about 20%, 10-14 days after onset of symptoms. The decrease in HDL levels (measured as HDL cholesterol and apolipoprotein AI) was significantly correlated to the inflammatory response, as reflected by plasma orosomucoid concentrations, and to the extent of myocardial injury, as mirrored by serum activities of lactate dehydrogenase. In samples drawn 10 days after myocardial infarction we found marked changes in the ability of the patients' sera to enhance the activity of purified lipoprotein lipase. The maximal activating ability (at saturating serum concentrations) increased by about 30%; however, at suboptimal serum concentrations, the activating ability of the patients' sera declined (50% higher serum concentrations were required to reach half maximal reaction rate). The altered activation characteristics were correlated to the changes in HDL concentrations. By affecting the activity of lipoprotein lipase and thereby the rate of intravascular lipoprotein metabolism, this phenomenon may contribute to the lipoprotein alterations seen after myocardial infarction.

Triglycerides, cholesterol and phospholipids in serum and high density lipoproteins (HDL) were assessed in 11 women with previous gestational diabetes before and repeatedly during 6 months of low dose progestogen (lynoestrenol = LYN) contraceptive administration. Eight of these women also were followed in an identical manner during non-hormonal contraception (IUD) and 6 of them during combined oral contraceptive administration (EE + LYN). During the use of IUD or LYN administration neither serum nor HDL lipids changed. The combined OC, EE + LYN, increased serum triglycerides progressively: 73% (P less than 0.01) after 6 months concomitant with a 100%-increment of HDL triglycerides (P less than 0.01) HDL-cholesterol and -phospholipids were not consistently changed. The EE + LYN induced alterations differed from the effects of LYN alone (P less than 0.01). During the use of IUD or LYN administration neither serum nor HDL lipids changed. The combined OC, EE + LYN, increased serum triglycerides progressively: 73% (P less than 0.01) after 6 months concomitant with a 100%-increment of HDL triglycerides (P less than 0.01). HDL-cholesterol and -phospholipids were not consistently changed. The EE + LYN induced alterations differed from the effects of LYN alone (P less than 0.01). These results suggest that low dose progestogens, such as LYN, could be considered as contraceptive alternatives in women with gestational diabetes. However, combined OC should be avoided in these patients. The present findings differ from those obtained in insulin-dependent diabetics and suggest that a diabetic prediposition enhances the effects of synthetic oestrogens and/or diminishes some of the effects of progestogens on lipid metabolism.

Norethisterone acetate (NET), levonorgestrel (NORG) and medroxyprogesterone acetate (MPA) were administered to oophorectomized women to evaluate the effects on individual serum phospholipids as well as serum lecithin and cholesterol ester fatty acid composition. Blood samples were drawn after a 3-week period without hormonal replacement therapy and after 3 weeks on each progestogen. NORG reduced cepahlin and lecithin with a concomitant increase in lysolecithin. This shift in individual phospholipids has previously been induced by exogenous androgens. The 17C-alkylated synthetic progestogens NET and NORG but not the non-alkylated MPA caused a redistribution among the 1-position fatty acids of serum lecithin with an increase in palmitic concomitant with a decrease in stearic acid. These findings indicate differences between 19-nortestosterone derivatives and 17-hydroxyprogesterone derivatives in effect on individual serum phospholipids and in influence on liver lecithin synthesis as judged from serum lecithin fatty acid composition.

Intravenous glucose tolerance tests (IVGTT) with simultaneous assessment of plasma insulin and analyses of the fatty acid composition of serum lecithin and cholesterol esters were performed in 11 women with previous gestational diabetes before and repeatedly during 6 months' administration of a low-dose progesterone (lynestrenol = LYN). 8 of these women were also followed in an identical manner during 6 months of nonhormonal contraception (intrauterine device = IUD) and additionally 6 of these women were followed also during the use of a combined oral contraceptive (OC) (ethinyl estradiol + lynestrenol - EE + LYN). LYN did not alter the IVGTT or plasma insulin but decreased the proportion of polyunsaturated fatty acids (PUFA) in serum lecithin (p less than 0.01) and cholesterol esters (p less than 0.01) where oleic acid was reciprocally increased (p less than 0.05). After 6 months' use of IUD, on the other hand, the k value of IVGTT increased by 45% (p less than 0.01) without significant changes in plasma insulin. In both lecithin and cholesterol ester PUFA increased (p less than 0.05) and cholesterol ester oleate decreased (p less than 0.01); i.e., virtually the reversal of the changes seen during LYN administration. The combined OC, EE + LYN, caused a decrease in the k value by 27% (p less than 0.05) which was apparent even when compared to the effects of LYN alone. EE + LYN also increased (p less than 0.05) lecithin palmitate and decreased stearate (p less than 0.05) and had a concomitant tendency to lower PUFA and increase oleic acid in both lecithin and cholesterol esters. These results indicate that LYN has little influence on the glucose tolerance in women predisposed to diabetes but may provide poorer conditions for dietary treatment of subclinical diabetes than do nonhormonal IUDs. The combined CO, EE + LYN, on the other hand, promptly diminishes glucose tolerance and may also have an unfavorable influence on liver metabolism.

Twenty-three young women with insulin-dependent diabetes were randomly allocated to contraceptive treatment with either a progestogen only (Lynestrenol 0.5 mg) (LYN) or a combined oral contraceptive (OC) (ethinyl estradiol 50 micrograms + lynestrenol 2.5 micrograms) (EE + LYN). After six months treatment the medication was withdrawn for at least two months, after which the patients were placed on the other preparation. Diabetes control and serum and high density lipoprotein (HDL) lipids were assessed before and after 1, 3 and 6 months of treatment. Low-dose LYN administration did not alter the insulin requirement, blood glucose or body weight while the combined EE + LYN treatment increased the insulin requirement (p less than 0.01) without altering blood glucose or body weight. Low-dose LYN reduced serum triglycerides (p less than 0.001), serum cholesterol (p less than 0.001) and serum phospholipids (p less than 0.01) without affecting HDL lipids, while EE + LYN gave an inconsistent increase in serum triglycerides (p less than 0.01) but no change in HDL lipids. These findings confirm our earlier results and we conclude that EE + LYN influences diabetes control slightly more (although still not seriously) than the low-dose LYN. It is suggested that insulin-dependent diabetics (in contrast to non-diabetics) are more sensitive to the influence of 19-norprogestogens than to alkylated estrogens, with respect to lipid metabolism.

Twentythree young women with insulin-dependent diabetes were randomly allocated to contraceptive treatment with either a progestogen only (Lynestrenol 0.5 mg) (LYN) or a combined oral contraceptive (OC) (ethinyl estradiol 50 μg + lynestrenol 2.5 μg) (EE + LYN). After six months treatment the medication was withdrawn for at least two months, after which the patients were placed on the other preparation.