Some pharmacological and elastic characteristics of isolated subcutaneous small arteries from patients with essential hypertension.

OBJECTIVE: To investigate the elastic characteristics of the wall of isolated subcutaneous resistance arteries from patients with essential hypertension, the response of the vessels to endothelium-dependent and -independent vasodilators and the dependence on calcium. METHODS: Subcutaneous resistance arteries were isolated from 16 patients with never-treated essential hypertension and from 16 normotensive controls matched for age and sex. The vessels were mounted in a myograph for isometric force development. The passive elastic characteristics were determined and then the response to acetylcholine, nitroprusside, felodipine, caffeine and calcium (in the presence of noradrenaline and prazosin or yohimbine) were determined. RESULTS: Young's elastic modulus as a function of wall stress was similar in the two groups of vessels. The relaxation of vessels from hypertensive and normotensive in response to acetylcholine, nitroprusside and felodipine was also similar. However, the response to caffeine was increased in vessels from the hypertensive patients, although the relationship between the dependence on the effect of calcium on the behaviour of arteries from hypertensives and controls was similar in the presence of prazosin and yohimbine. CONCLUSIONS: The altered morphology of subcutaneous resistance arteries from hypertensives is not caused by a change in the elastic characteristics of the wall material. The data support our previous observation of abnormal calcium handling in vessels from hypertensives, although they do not support the hypothesis that a generalized abnormality in endothelium-dependent or endothelium-independent relaxation is of importance in essential hypertension.

Metoprolol versus thiazide diuretics in hypertension. Morbidity results from the MAPHY Study.

The present study in hypertensive men (40-64 years old) with untreated diastolic blood pressure above 100 mm Hg was aimed at investigating whether metoprolol (n = 1,609) given as initial treatment would lower the risk for coronary events (sudden death and myocardial infarction) more effectively than thiazide diuretics (n = 1,625). A substantial part of this study was the metoprolol arm of the Heart Attack Primary Prevention in Hypertension (HAPPHY) study. The HAPPHY study was a pooling of the effect of different beta-blockers, mainly metoprolol and atenolol, in which no favorable effect in relative risk was observed for atenolol as compared with diuretics. In the present study, 255 patients suffered definite coronary events during follow-up; 25% of these events were fatal, 39% were acute myocardial infarctions, and 36% were silent myocardial infarctions. The risk for coronary events was significantly lower in patients on metoprolol than in patients on diuretics (111 versus 144 cases, p = 0.001, corresponding to 14.3 versus 18.8 cases/1,000 patient years and a relative risk of 0.76 at the end of the trial; 95% confidence interval 0.58-0.98). This difference in risk has potentially important implications for clinical practice because of the large number of hypertensive patients who are at increased risk for coronary events. Because a placebo group, for ethical reasons, could not be included, relative risk can only be expressed in relation to diuretics. There was no difference between the two treatment groups in baseline characteristics, blood pressure during follow-up, or stroke rates. Thus, the difference in risk for coronary events is probably mediated via mechanisms other than blood pressure control. However, present data might suggest that different beta-blockers may have different efficacy in preventing coronary events. The reasons for this possibility are as yet unknown.

Primary prevention of sudden cardiovascular death in hypertensive patients. Mortality results from the MAPHY Study.

In a randomized primary prevention trial including 3,234 men with mild to moderate uncomplicated hypertension, the effect of the beta-blocker metoprolol or a thiazide diuretic as an initial antihypertensive therapy was compared regarding the risk of sudden cardiovascular death during a follow-up ranging from 2.3 to 10.8 years (median of 4.2 years). Only men aged 40 to 64 years were included in the study. The randomization of patients into the metoprolol (n = 1,609) or diuretic group (n = 1,625) was performed after stratification for age, smoking habits, serum cholesterol, and systolic blood pressure. At baseline the two treatment groups were well matched. Metoprolol was given in a mean dose of 174 mg daily and the mean dose of thiazide diuretic was either 46 mg hydrochlorothiazide daily or 4.4 mg bendroflumethiazide daily. Identical blood pressure control was achieved using the fixed therapeutic schedule. Total and cardiovascular mortality were significantly lower for metoprolol than for diuretics, owing to fewer deaths from coronary heart disease and stroke. Of the cardiovascular deaths, 78% were classified as sudden cardiovascular deaths (occurred within 24 h after the onset of symptoms). There were significantly fewer sudden cardiovascular deaths in the metoprolol group compared to the diuretic group (32 v 45, P = .017). The present results suggest that initial antihypertensive therapy with metoprolol is associated with a lesser incidence of sudden cardiovascular deaths than initial diuretic treatment in uncomplicated hypertension.

Decreased coronary heart disease in hypertensive smokers. Mortality results from the MAPHY study.

The present primary prevention study aimed at investigating whether metoprolol given as initial antihypertensive treatment would lower cardiovascular complications of high blood pressure to a greater extent than thiazide diuretics. Patients were randomized to metoprolol (n = 1,609, 8,110 patient-years) or a thiazide diuretic (n = 1,625, 8,070 patient-years). At randomization, 535 patients in the metoprolol group and 524 patients in the diuretic group were classified as smokers. Blood pressure control during follow-up was equally effective regardless of smoking habits at randomization. Cardiovascular and coronary heart disease mortality was three to four times higher in smokers than in nonsmokers, underlining the importance of smoking as a risk factor. Total and cardiovascular mortality were significantly lower for the metoprolol group than for the thiazide diuretic group in the whole study population (p = 0.028 and p = 0.012), as well as in smokers (p = 0.013 and p = 0.016). Coronary heart disease mortality was significantly lower for patients on metoprolol than for patients on diuretics in the whole study population (p = 0.048) as well as in smokers (p = 0.021). The results suggest that initial antihypertensive therapy with metoprolol is associated with a lesser incidence of total, cardiovascular, and coronary heart disease mortality as compared with initial diuretic treatment, both in the whole study population and in smokers. The favorable effect of metoprolol must be mediated via mechanisms other than the blood pressure-lowering effect of metoprolol because equal blood pressure control was achieved with both types of medication, irrespective of smoking habits at randomization.

[Primary Waldenström's macroglobulinemia. Report of a case with pulmonary involvement]. / Macroglobulinaemia primaria Waldenström. Et tilfaelde med lungeaffektion.

A rare case of Waldenström's macroglobulinaemia is presented. In this case, the lymphoplasmacytoid cell infiltration which is characteristic of the disease was demonstrable only in the lungs.

Late nervous system disorders in cured malignant lymphoma: a clinical and neuropathological study.

A 53-year-old woman was treated for and cured of low grade malignant lymphoma, localized to the neck, by irradiation and chemotherapy. One year later she developed signs of damage to the spinal cord with slight paraparesis of the lower extremities, which remained stationary for seven years. Then, new and rapidly progressive central and peripheral neurological symptoms developed. About one year later the patient died. At autopsy a malignant glioma of the right temporal lobe and radiation damage to the spinal cord were found. Lymphocytic infiltrations in the peripheral nerves and muscles of the lower extremities were also seen. A severe neurogenic atrophy was present but no relapse of malignant lymphoma was found. Depressed immune defense is suggested to be the cause of the pathological changes of the nervous system in this case. The inflammation of the peripheral nerves might be due to activation of a latent virus infection.

Effect of propranolol treatment on bone mass, bone mineral content, bone remodelling, parathyroid function and vitamin D metabolism in hyperthyroidism.

The effect of propranolol 160-640 mg/day for 3 months on the accelerated loss of bone matrix and mineral in hyperthyroidism was studied in seventeen patients. A rise in serum thyroxine (P less than 0.01) during the first 3 weeks was followed by a fall (P less than 0.02). Serum triiodothyronine declined during the study (P less than 0.02). The enhanced bone mineral mobilization and collagen turnover continued during treatment and the bone mineral content decreased 3.2% (P less than 0.01). The secondary adaptive changes in serum parathyroid hormone and vitamin-D metabolites and in renal phosphate handling stayed unchanged. Iliac crest bone biopsies after tetracycline double-labelling showed initially a high bone turnover (P less than 0.01) with a reduced amount of cortical and trabecular bone (P less than 0.05). Following treatment bone formation rate decreased at both cellular and tissue level (P less than 0.01). No significant changes were observed in the amount of cortical and trabecular bone. The investigation shows that propranolol, in contrast to antithyroid medication, lacks any curative effect on the accelerated bone loss in hyperthyroidism.

Serum levels of vitamin D metabolites and bone remodelling in hyperthyroidism.

Serum levels of 25-hydroxyvitamin DF, 24,25-dihydroxyvitamin D and 1,25-dihydroxyvitamin D were measured in 25 untreated hyperthyroid patients in whom histomorphometric evaluations of iliac crest bone biopsies were performed after in vivo tetracycline doublelabeling. The serum concentration of 25-hydroxyvitamin D was normal. The serum concentration of 1,25-dihydroxyvitamin D was reduced (p less than 0.02) compared to normal whereas the serum concentration of 24,25-dihydroxyvitamin D was increased (p less than 0.02). The bone changes were characterized by an enhanced turn-over in trabecular and cortical bone leading to an increased porosity of cortical bone and mobilisation of bone mineral. The observed changes in vitamin D metabolism could be explained by a reduced renal 1-alpha-hydroxylase activity secondary to hypercalcaemia with suppressed parathyroid secretion and hyperphosphataemia. The bone changes were unrelated to the serum levels of vitamin D metabolites. In trabecular bone the appositional rate and mineralization rates of osteoid were increased and the mineralization lag time was shortened showing that the mineralization and formation of osteoid in the hyperthyroid state can progress with an enhanced rate in spite of a reduced mean serum level of the active vitamin D metabolite, 1,25-dihydroxyvitamin D.