Effects of two low-dose oral contraceptives on circulating components of the coagulation and fibrinolytic systems.

We studied the effects on plasma levels of coagulation and fibrinolysis factors of two currently used "sub-50" oral contraceptive preparations (OCs), one containing 750 micrograms lynestrenol and 37.5 micrograms ethinyl estradiol (LYN-EE) and the other containing 150 micrograms levonorgestrel and 30 micrograms ethinyl estradiol (LNG-EE), in groups of about 25 women aged 21 +/- 2 years. After 3 months, plasminogen levels increased in the two experimental groups (LYN-EE and LNG-EE), by 40% and 32%, respectively. This change was positively correlated with changes in ceruloplasmin levels, indicating that an estrogenic effect might be involved. Histidine-rich glycoprotein concentration decreased by 26% and 16%, respectively. Tissue-type plasminogen activator (t-PA) activity increased by 260% and 167%; t-PA antigen decreased by 12% and 18%, and t-PA inhibitor activity decreased by 31% and 32%, respectively. In the coagulation system, in both groups factor XII increased by 47% and 34%, respectively. The main inhibitor of factor XII, C1-inactivator, decreased slightly, but this was significant only in the LNG-EE group. The von Willebrand factor antigen fell by 8% and 9%, whereas factor VIII activity did not change. Antithrombin III antigen decreased by 14% in both groups. Factor IX activity increased by 15% and 21%. The difference in hormonal effects of both preparations was reflected by the increases in sex hormone binding globulin (by 130% and 21%) and ceruloplasmin (by 98% and 51%), indicating that LYN-EE had a more estrogenic potency than LNG-EE. In a control group of 25 matched subjects, who were observed simultaneously, we found no significant changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Advances in clinical fibrinolysis.

The discovery of a fast-acting plasminogen activator inhibitor has resulted in the notion that the balance between tissue-type plasminogen activator and its inhibitor determines the net fibrinolytic activity of blood. The inhibitor shows a rapidly fluctuating acute-phase pattern, which may be important in relation to thrombosis in acute disease. Other newly discovered modulators of the fibrinolytic system include histidine-rich glycoprotein, tetranectin and thrombospondin. The role of fibrin as a cofactor in its own dissolution is further elucidated with emphasis on local aspects. Therapeutic inhibition of overactive fibrinolysis by various drugs needs careful monitoring. Prophylactic stimulation of fibrinolysis is possible, e.g. by stanozolol or other drugs that lower inhibitor levels, but its proven value is as yet limited. Results of clinical trials with activators of the fibrinolytic system as thrombolytic agents are discussed in relation to the physiology of the fibrinolytic system.

Effect of low-dose oral contraceptives on lipoproteins and lipolytic enzymes: differences between two commonly used preparations.

Changes in circulating lipoproteins, which may be related to the risk for atherosclerotic vascular disease, were studied in a control group and in two groups of 24 or 26 women using different preparations of low-dose oral contraceptives for 3 months. One preparation contained 150 micrograms levo-norgestrel and 30 micrograms ethinylestradiol (Stediril-d 150/30); the other contained 750 micrograms lynestrenol and 37.5 micrograms ethinylestradiol (Ministat). No significant changes were found with either of the preparations in serum cholesterol or high density lipoprotein cholesterol (HDL-C) levels. Apolipoprotein A-II levels increased during Ministat treatment from 50.4 to 61.4 mg/dL and during Stediril-d 150/30 treatment from 52.7 to 58.9 mg/dL (both P less than 0.001). These changes differed significantly from each other (P less than 0.01). Apolipoprotein A-I levels increased significantly during use of Ministat only. Apolipoprotein B in low density lipoprotein increased by about 20% (P less than 0.001) in both groups. Post-heparin lipoprotein lipase activity did not change, but hepatic lipase activity decreased to the same extent in both groups (P less than 0.001). Reductions in post-heparin lipase activity were not correlated with increases in HLD-C.

High density lipoprotein cholesterol and apolipoprotein A-I levels in 32-33-year-old women on steroid contraceptives-differences between two frequently used low-estrogen pills.

High density lipoprotein cholesterol and apolipoprotein A-I levels were measured in about one thousand 32-33-year-old women taking part in a cardiovascular screening programme. After corrections for differences in smoking habits and use of alcoholic drinks women on various types of steroid contraceptives had widely different levels of high density lipoprotein cholesterol and apolipoprotein A-I. Lowest levels were found in users of lynestrenol-containing minipills (progestagen-only pills) and highest levels in lynestrenol-containing minipills. Of the two commonly used low-estrogen pills ("sub-50 pills") one type (containing levonorgestrel) was associated with elevated and the other (containing lynestrenol) with depressed levels of high density lipoprotein cholesterol and apolipoprotein A-I as compared with the reference group of non-users of oral contraceptives.

Diurnal levels of lipids, glucose and insulin in type IV hyperlipidemic patients on high carbohydrate and high fat diet: comparison with normals.

Diurnal levels of serum triglyceride (TG), cholesterol, free fatty acids (FFA), glucose and insulin were measured in three type IV hyperlipidemic patients on a fixed solid 65% carbohydrate and a 65% fat diet when in steady state conditions in a metabolic unit. The carbohydrate-rich food was divided into either three or eight equivalent portions, differently spaced over the day and night. The fat-rich food was given in three equivalent portions only. The diurnal TG profiles on these diets showed the same characteristics as those found in normals, but increments and mean levels were considerably higher. On the carbohydrate-rich diet, mean TG levels decreased during the study. This was not seen either on the fat-rich diet or in normals. In contrast to our findings in normals, chylomicrons formed the major contribution to the serum TG pattern. FFA levels were markedly higher on the high-fat than on the carbohydrate-rich diet, but not different from those in normals. Postprandial glucose responses did not differ significantly between the diets. Insulin responses were markedly higher on the carbohydrate-rich than on the fat-rich food. Glucose levels did not differ from those in normals. Insulin levels were significantly higher in the patients. Cholesterol showed minimal fluctuations, parallel to the TG pattern, which could be attributed to chylomicron cholesterol.

Influence of meal frequency on diurnal lipid, glucose and insulin levels in normal subjects on a high fat diet; comparison with data obtained on a high carbohydrate diet.

Diurnal levels of serum triglyceride (TG) were measured in six normal persons consuming a fixed solid 65% fat diet under steady state conditions in a metabolic unit. The food was divided into either three or eight similar portions, differently spaced over the day and night. The diurnal TG-profiles on this diet were practically identical to those found under comparable conditions on a 65% carbohydrate diet [1]. Mean diurnal TG values did not significantly differ with varying meal frequency. Free fatty acid levels, however, were significantly higher on a high fat diet. Post-prandial glucose and insulin reponses did not significantly differ whether a high fat diet or a high carbohydrate diet was consumed. We conclude that the composition of the diet is of little importance in determining diurnal TG patterns when the diet consists of normal food stuffs, but that these patterns are dependent on meal frequency and distribution.

High-density lipoprotein cholesterol, monthly variation and association with cardiovascular risk factors in 1000 forty-year-old Dutch citizens.

High density lipoprotein cholesterol (HDL chol) levels were measured in about 1000 forty-year-old residents of the town of Leiden, The Netherlands. Mean levels (+/- S.D.) in women were 48.0 +/- 11.0 mg/dl; in men 42.5 +/- 10.7 mg/dl. In March mean levels in women were about 5 mg/dl lower than in June (P less than 0.001); in men there was a similar difference between mean levels in April and June (P less than 0.002). HDL chol levels were negatively related to smoking habits, relative body weight, and in women to use of oral contraceptives. Weak positive and negative correlations between HDL chol and serum cholesterol, respectively, were found in subgroups with high and low HDL chol levels, respectively.

The influence of meal frequency on diurnal lipid, glucose and cortisol levels in normal subjects.

Diurnal levels of serum triglyceride, cholesterol, free fatty acids, glucose, and cortisol were measured in four normal persons on a fixed solid 65% carbohydrate diet under steady state conditions in a metabolic unit. Triglyceride levels in all subjects showed similar patterns, which unexpectedly did not bear a simple relation to meal frequency or distribution. With three equivalent meals per day at 09.00, 12.00 and 17.00 hours, 'fasting' triglyceride levels increased by about 0.3 g/l from a minimum value between 03.00 and 05.00 hours in the morning till before breakfast. After breakfast there was a continued rise till about 15.00 hours and then a overall fall in spite of the meal at 17.00 hours. Isocaloric change to eight equivalent meals, consumed between 09.00 and 23.00 hours, resulted in a similar although slightly more even triglyceride pattern. On eight equivalent meals, spaced evenly over the entire 24 h period, a different pattern was found with lower triglyceride values at daytime than at night. Increase in meal frequency did not result in a lowering of mean diurnal triglyceride levels. The cholesterol pattern followed the triglyceride pattern most clearly in subjects with high triglyceride levels. Glucose showed the expected postprandial increments. Cortisol rhythm did not change on varying meal frequency.

Primary hyperlipoproteinemia in xanthomatosis.

Blood lipid values, clinical data and effects of therapy are reported on 74 patients with hyperlipidemia and xanthomatosis. A natural subdivision into two groups was observed on the basis of low density lipoprotein lipid values: one corresponding to Frederickson's type II, characterized by elevated low density lipoproteins, tendinous xanthomata, absence of eruptive xanthomata and a high incidence of cardiovascular diseases and the other resembling Frederickson's type III, with elevated very low density lipoproteins, eruptive xanthomata, xanthomata striata palmaria, elevated cholesterol/triglyceride ratios in the very low density lipoproteins and irregular appearance of floating beta lipoproteins. The latter group consisted of 32 patients in whom cardiovascular symptoms were relatively rare, despite mean cholesterol levels of 500 mg/dl.