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Objectives: To evaluate effects of postmenopausal hormone replacement therapy (HRT) on von Willebrand factor, factor (F)VIII, factor (F)VII, fibrinogen, antithrombin (AT) III, prothrombin fragments 1 and 2, protein C, total and free protein S, plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) and resistance to activated protein C., Design: Part 1: double blind randomized trial for 3 months. Part 2: open study for 9 months., Setting: Department of Endocrinology, University Hospital, Malmö, Sweden., Subjects: Fifty-one postmenopausal women with a history of amenorrhoea of at least 6 months and body mass index > or = 24 kg m-2 participated in part 1 and 46 participated in part 2., Intervention: Randomization for placebo (n=24) or HRT (n=27). HRT was given as 2 mg oestradiol valerate for the first 3 months, with the addition of 10 mg medroxyprogesterone for 10 days every third month thereafter., Measurements: At baseline and after 3 and 12 months., Results: During 0-3 months in the HRT group, FVII increased (P < 0.01), whereas fibrinogen, AT III and total protein S all decreased (P < 0.001 for all). Changes in variables were expressed as Delta-values. After 3 months Delta-values differed between groups for fibrinogen (P < 0.05), AT III (P < 0.001), total protein S (P < 0.001), and PAI-1 (P < 0.001). During 0-12 months, fibrinogen, total protein S, tPA (P < 0.01 for all) and AT III (P < 0.05) decreased. In the control group, all variables were unchanged during the study, except for increases (P < 0.05) in total protein S after 3 and 12 months, and a decrease (P < 0.01) in FVIII after 12 months. After 12 months Delta-values differed for fibrinogen (P < 0.05), AT III (P < 0.05) and total protein S (P < 0.001)., Conclusions: Unopposed oestrogen substitution was associated with both potentially beneficial effects, such as decreases in fibrinogen, and potentially thrombogenic effects such as decreasing AT III and protein S and increasing FVII. During prolonged follow-up and addition of progesterone, differences between groups concerning FVII were attenuated. These data suggest that effects of HRT upon coagulation are most pronounced early after institution of unopposed treatment.

Objectives: To study muscle fibre characteristics and glycogen synthase activity in relation to peripheral glucose disposal in skeletal muscle in hypertension-prone men., Design: The hyperinsuliemic euglycemic clamp method was used to calculate insulin sensitivity index (M/I). Muscle biopsies were performed for the analysis of slow-twitch (ST) and fast twitch (FT, low insulin sensitivity and low capillarisation compared to ST fibres) muscle fibres, capillarisation (number of capillaries per fibre) and diffusional index (mean area per fibre divided by capillarisation) of muscle fibres, capillary density (capillaries mm(-2) muscle fibre) and glycogen synthase activity., Subjects: Thirty-two young, healthy, normotensive men with a family history of hypertension (REL) were compared to 2 5 age-matched men with no family history of hypertension (CON) and similar body mass index (BMI)., Results: REL had a lower M/I (P = 0.021), lower capillarisation (P = 0.04) and a tendency of a lower diffusional index of subgroup b of FT muscle fibres (P = 0.10) compared to CON. Glycogen synthase activity did not differ between the groups., Conclusions: Men with a family history of hypertension have less capillaries per FTb fibre and greater diffusion distance from the capillary to the muscle cell compared to controls, which may be a contributory factor to the lower insulin sensitivity in the former group. However, additional investigations are needed to study the causality in this association.

Objective: Resistance to activated protein C (APC resistance), caused by a single point mutation in the factor V gene (FV:R506Q), is a major risk factor for venous thrombosis. As the significance of this mutation among unselected outpatients with deep-vein thrombosis (DVT) is not established, we have studied its prevalence among consecutive outpatients attending the emergency room due to a clinically suspected DVT., Design, Setting and Subjects: The FV:R506Q mutation was determined in 223 consecutive Swedish outpatients with clinically suspected DVT, and in 288 healthy controls. Using phlebography, the patients were classified as DVT-positive or DVT-negative., Main Outcome Measure: The prevalence of FV:R506Q mutation., Results: The prevalence of the FV:R506Q mutation was 28% (28/99) in the DVT-positive subgroup (relative risk: 3.1; 95% CI: 1.7-5.5), and 23% (28/124) in the DVT negative subgroup (relative risk: 2.0; 95% CI: 1.1-3.6), as compared to 11% (32/288) in the control group. In the DVT-positive subgroup, the FV:R506Q mutation was most common among younger patients with primary thrombosis (47%) and least common among older patients with secondary thrombosis (19%). The high prevalence of FV:R506Q mutation among DVT-negative patients was associated with a high frequency of previous venous thrombosis. Thus, 46% (13/28) of the DVT-negative FV:R506Q carriers had a history of thrombosis, compared with only 22% (21/96) of the DVT-negative patients lacking the mutation (P = 0.01)., Conclusion: To sum up, the FV:R506Q mutation is present in more than a quarter of Swedish DVT-positive outpatients with clinically suspected DVT, indicating that APC-resistance is a major thrombotic risk factor contributing to the high incidence of venous thrombosis in Sweden.

Objectives: To describe the size, overlap and mortality of four cardiovascular risk groups, in order to give a scientific background for the prevention of cardiovascular disease in a representative urban population., Setting: Section of Preventive Medicine, Department of Medicine, Malmö University Hospital, Malmö, Sweden., Subjects: Between 1974 and 1984 22444 men born between 1949 and 1921, constituting 75% of the total male population in these age groups, took part in a comprehensive screening examination aimed at detecting risk factors for cardiovascular disease., Interventions: Those at high-risk of developing cardiovascular disease were referred to their general practitioner or to special clinics for hypertension, hyperlipidaemia and diabetes. The follow-up, which lasted until the end of 1991, averaged 12.2 years., Main Outcome Measures: Total death (n = 1450) and death from ischaemic heart disease (IHD) (n = 471)., Results: Hypertension was found in 13%, hypercholesterolaemia in 19% and diabetes mellitus in 2.6% of the subjects; 49% of the subjects smoked. Multiple risk factors were found in over 17% of the total cohort. Despite the intervention, all-cause mortality during follow-up was increased three-fold in smokers and in men with hypercholesterolaemia, four-fold in hypertensive men and five-fold in men with diabetes, compared to men with no risk factors. The vast majority of deaths (81%) occurred in men who smoked, had hypertension or had high serum cholesterol. Ischaemic heart disease (IHD) was increased five-fold in smokers, seven-fold in men with hypercholesterolaemia, nine-fold in hypertensive men and 12-fold in men with diabetes. Again, the vast majority of IHD deaths (86%) occurred in the first three categories. Combinations of risk factors substantially increased total mortality as well as IHD mortality., Conclusions: The large proportion (64%) of the population with risk factors for cardiovascular disease and the substantially (5-12-fold) increased IHD mortality in those risk groups, calls for actions aimed at preventing premature IHD deaths. Such action should include measures directed towards the whole population and comprehensive treatment programmes for high-risk individuals, including intervention to stop smoking. The substantial overlap between risk factors calls for one high-risk clinic caring for all risk groups.

A case of tongue necrosis in a patient with temporal arteritis who was taking ergotamine is described, and the role of ergotamine tartrate in provoking the tongue necrosis is considered. The literature on this unusual complication is critically reviewed, and the value of a carotid angiography in assessing the tongue ischaemia is exemplified.

Low sodium and potassium adenosine triphosphatase (ATPase) activity has been proposed as a mechanism behind diabetic neuropathy. In this study the platelet ATPase activity and platelet noradrenaline efflux rate were determined in 47 insulin-dependent diabetes mellitus (IDDM) patients and 20 controls. Ulnar motor conduction velocities, tested in a subgroup, were lower in patients than in controls (52.7 +/- 1.3 m s-1 vs. 61.3 +/- 1.4 m s-1; P less than 0.001). Platelet ATPase activity tended to be increased in the patients compared with the controls (29.9 +/- 1.0 x 10(-3) min-1 vs. 26.9 +/- 1.1 x 10(-3) min-1; NS). In ulnar nerve function tested subjects, ATPase activity was higher in patients than in controls (31.2 +/- 1.7 x 10(-3) min-3 vs. 25.9 +/- 1.3 x 10(-3) min-1; P less than 0.01). The platelet noradrenaline efflux rate tended to be higher in patients with lower brake indices, a sign of autonomic neuropathy, than in controls (29.0 +/- 3.0 x 10(-3) min-1 vs. 21.2 +/- 0.9 x 10(-3) min-1; P less than 0.05). The platelet ATPase activity was not decreased in IDDM patients, however, a connection between diabetic autonomic neuropathy and platelet transmittor leakage was indicated.