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Biomedical subjects

H Lithell

Publications and source records attributed to H Lithell.

At least 163 records · Page 9Linked to original sources
PubMed1992

The risk of acute myocardial infarction after oestrogen and oestrogen-progestogen replacement.

OBJECTIVE: To determine the relative risk of developing a first acute myocardial infarction after treatment with oestrogens alone or oestrogen-progestogen combinations. DESIGN: Prospective cohort study utilizing a prescription-based and record linkage system for a follow-up period from 1977 to 1983. Average individual observation time was 5.8 years. SETTING: The entire female population of the Uppsala Health Care Region (1.4 million inhabitants), one-sixth of the total Swedish population. SUBJECTS: 23,174 women aged 35 years and older, identified from pharmacy records as having been prescribed non-contraceptive oestrogens during 1977-1980. OUTCOMES: Admissions to hospitals for first acute myocardial infarctions. RESULTS: Overall, 227 cases of a first acute myocardial infarction were observed as against 281:1 expected, RR = 0.81 (95% confidence limits 0.71 to 0.92). Women who were younger than 60 years at entry into the study and prescribed oestradiol compounds (1-2 mg) or conjugated oestrogens (0.625-1.25 mg) showed a significant 30% reduction of the relative risk (RR = 0.69, 0.54 to 0.86). Those prescribed a combined oestradiol-levonorgestrel brand also demonstrated a significantly lowered relative risk (RR = 0.53, 0.30 to 0.87). The risk estimates were near unity during the first year of follow-up but decreased during subsequent years. Exposure to the weak oestrogen oestriol did not alter the risk. CONCLUSION: Hormonal replacement therapy with oestrogens alone, and maybe also when cyclically combined with progestogens, can reduce the risk of acute myocardial infarction.

Adult↗
PubMed1992

The metabolic and circulatory response to beta-blockade in hypertensive men is correlated to muscle capillary density.

Both haemodynamic and metabolic variables have been shown to be related to the fibre composition and capillary density of skeletal muscle in man. In the present study, the change of several metabolic variables during beta-blockade was investigated and related to muscle fibre composition and capillary density in 28 men with essential hypertension. They had been given atenolol (50 mg/day) or metoprolol (200 mg/day) or propranolol (160 mg/day) for 4-12 months. Serum triglycerides increased during treatment and individual changes were significantly inversely correlated with capillary density. Insulin concentrations in the fasting state and at the end of an i.v. glucose tolerance test were significantly higher during beta-blockade, and individual changes were inversely correlated with capillary density. Furthermore, body weight increased and heart rate decreased, changes that were also correlated with capillary density. It is concluded that many of the previously but poorly understood large interindividual differences in response to beta-blocker treatment may be explained by the degree of development of the capillary net in muscle tissue. Obesity, physical training as well as genetic factors are known determinants of capillary density.

Adrenergic beta-Antagonists↗
PubMed1992

Metabolic effects of pindolol and propranolol in a double-blind cross-over study in hypertensive patients.

Metabolic effects of pindolol and propranolol were investigated in a randomised study of double-blind, double-dummy design in 39 Caucasians with newly detected hypertension. Each active treatment period was 6 months long. A euglycaemic hyperinsulinaemic clamp test was done to measure insulin sensitivity, and i.v. glucose tolerance was investigated with insulin determinations. Lipoprotein concentrations were quantified and lipoprotein lipase activities were determined in muscle and adipose tissue and in plasma after heparin injection. The blood pressure was significantly reduced by both regimes. The insulin sensitivity index was decreased by 34% during propranolol treatment and by 17% during pindolol treatment. The insulin concentrations in plasma were elevated at the end of the i.v. glucose tolerance test but were not high enough to compensate for the insulin resistance, so HbA1c and glucose concentrations were increased. A significant reduction of lipoprotein lipase activity in skeletal muscle during propranolol treatment probably explains the pronounced increase in serum triglyceride concentration during propranolol treatment despite lower free fatty acids and higher lipoprotein lipase activity in adipose tissue. These changes of lipoprotein lipase activity were not correlated to the changes in insulin sensitivity. In summary, the metabolic effects were significantly less pronounced with pindolol than with propranolol, which probably can be ascribed to the agonistic effect of pindolol on beta 2 adrenoceptors.

Aged↗
PubMed1992

Insulin resistance and cardiovascular drugs.

Under certain circumstances the effect of insulin to promote glucose uptake in peripheral tissues is reduced because of a resistance to insulin action. This insulin resistance and the resulting hyperinsulinaemia are now recognised as common background factors that may be responsible for hypertension, hyperlipidaemia, decreased thrombolysis and also impaired glucose tolerance and diabetes. Hyperinsulinaemia has also been identified as an independent risk factor for coronary heart disease and promotes smooth muscle cell growth and plaque formation. A series of studies have now demonstrated that treatment with selective beta-blockers as well as thiazide diuretics impair insulin sensitivity by 15-30% and causes a compensatory increase in insulin concentrations. Furthermore, lipoprotein concentrations are affected in an unfavourable way. This is in contrast to the drugs belonging to ACE-inhibitors, calcium-channel blockers and alpha 1-blocker classes that are either neutral or may have the opposite effects in these respects.

Antihypertensive Agents↗
PubMed1992

Metabolic cardiovascular risk factors and the renin-aldosterone system in essential hypertension.

Impairment of glucose and lipid metabolism is common in hypertensive subjects. In the present study the relationships between indices of lipid and glucose metabolism and the renin-aldosterone system were studied in 37 untreated hypertensive subjects (DBP greater than 95 mmHg). Fasting insulin and the early insulin response at an intravenous glucose tolerance test were both correlated to plasma renin activity (r = 0.48, P less than 0.003 and r = 0.55, P less than 0.002, respectively) while HDL-cholesterol was found to be inversely related to the urinary excretion of aldosterone (r = 0.35, P less than 0.03). These relations were still significant when influences of age, sex, obesity (BMI) and serum creatinine were taken into account in the multiple regression analysis. In conclusion, hyperinsulinaemia and low levels of HDL-cholesterol were found in hypertensive subjects with a high activity of the renin-aldosterone system and might explain the high incidence of cardiovascular diseases found in this group.

Adult↗
PubMed1991

Risk factors for coronary heart disease in New Zealand and Sweden: Dunedin and Uppsala compared.

OBJECTS: to compare men and women over the age of 35 years in Dunedin (New Zealand) and Uppsala (Sweden) in respect of anthropometric values, dietary habits and certain coronary heart disease risk factors in view of known differences in coronary mortality between the two countries. METHODS: one hundred and ninety-five Dunedin and 94 Uppsala residents were chosen randomly from the respective populations, in the former city by electoral roll, in the latter by use of unique personal number. Measurements of height, weight, waist/hip ratio, blood pressure, blood lipids were made and dietary and smoking habits assessed. RESULTS: the Swedes were taller and leaner than the New Zealanders. Blood pressure and smoking habits were not significantly different but total blood cholesterol levels were lower in Uppsala men and women. Blood triglycerides were higher in Dunedin women but high density lipoprotein cholesterol levels tended to be lower in men and women in Uppsala. CONCLUSIONS: it was found by analysis of variance that the blood lipid level differences between the two populations could be explained by body mass index. Correction of lipid values for the waist/hip ratio partly explained the higher cholesterol values in Dunedin but diet differences may also have been contributory. The differences in coronary mortality between the population of New Zealand and Sweden are compatible with the view that our blood cholesterol findings reflect the different levels of risk.

Adult↗
PubMed1991

Different aetiologies of type 2 (non-insulin-dependent) diabetes mellitus in obese and non-obese subjects.

Insulin responses to intravenous glucose infusion and glucose utilization during hyperinsulinaemic euglycaemic clamp were determined in a large homogeneous group of 65-year-old male subjects. Twenty-eight had untreated Type 2 (non-insulin-dependent) diabetes mellitus and the remaining 44 control subjects had a normal glucose tolerance. Diabetic patients with abdominal obesity displayed peripheral insulin resistance in combination with defective insulin secretion, whereas non-obese diabetic patients showed only a secretory defect. Thus, Type 2 diabetes in obese and non-obese elderly male subjects may take two forms where the cause of hyperglycaemia differs.

Aged↗
PubMed1991

Blood pressure response during long-term treatment with magnesium is dependent on magnesium status. A double-blind, placebo-controlled study in essential hypertension and in subjects with high-normal blood pressure.

Both experimental and epidemiological studies support the idea of magnesium supplementation in essential hypertension. We added 15 mmol Mg to a free diet in 71 subjects with mild essential hypertension or a high-normal blood pressure in a double-blind, placebo-controlled study over 6 months. The treatment, which raised urinary magnesium excretion 30%, induced no general effects on the blood pressure. However, when the changes in blood pressure in the actively treated group were related to the pretreatment magnesium status, a correlation was found between pretreatment urinary magnesium excretion and the induced change in supine blood pressure (P less than .05) with a blood pressure reduction in subjects with a low pretreatment urinary excretion of magnesium, and a pressor effect in the subjects with the highest pretreatment levels of urinary magnesium. The induced change in blood pressure was furthermore found to be inversely correlated to the changes in serum magnesium and urinary excretion of sodium (P less than .03) induced by treatment indicating that both a direct calcium antagonist action of magnesium at the cellular level as well as a diuretic effect of the increased magnesium load might be involved in the blood pressure effects of magnesium. Pretreatment serum potassium concentration also appeared to be a predictor of the induced change in standing blood pressure (P less than .03). In conclusion, magnesium supplementation does not seem to be effective in unselected mild hypertensive subjects or in subjects with a high-normal blood pressure and can therefore not be generally recommended.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1991

Cardiovascular risk factors in primary hyperparathyroidism: a 15-year follow-up of operated and unoperated cases.

The need for treatment of mild and apparently asymptomatic primary hyperparathyroidism (HPT) is questioned, but a raised incidence of cardiovascular disease has been regarded as evidence in favour of surgery. While it is well known that several risk factors for cardiovascular disease (hypertension, hyperlipidaemia and diabetes mellitus/impaired glucose tolerance) are overrepresented in HPT, it is not known whether surgery provides long-term normalization in these respects and reduces the risk of premature death. In a 15-year follow-up of a cohort of 172 subjects in whom mild hypercalcaemia was initially detected during a health screening, it was found that 56 subjects had died. 17 individuals had been operated on for HPT, 47 individuals were persistently hypercalcaemic, while 45 subjects had serum calcium within the normal range (seven individuals were lost to follow-up). There had been no significant differences in blood pressure between these groups of mildly hypercalcaemic patients and age- and sex-matched controls at the initial screening, but at follow-up blood pressure was significantly higher not only in subjects with persistent hypercalcaemia, but also in those who had been successfully operated on for HPT. Neither of the hypercalcaemic groups showed any significant deviations from the controls with regard to indices of lipid or glucose metabolism. These findings suggest that there is no simple cause-and-effect relationship to account for the propensity toward high blood pressure in primary HPT. Consequently it cannot be assumed that surgery for HPT will eliminate the increased risk of cardiovascular disease in patients with mild HPT.

Cardiovascular Diseases↗
PubMed1991

Effects of antihypertensive treatment on insulin sensitivity with special reference to ACE inhibitors.

In 1984, the suspicion that pharmacological treatment may worsen the insulin resistance and associated metabolic abnormalities in lipid and carbohydrate metabolism and contribute to the relative failure of antihypertensive treatment to produce more than marginal reductions in cardiovascular morbidity and mortality led us to start a series of trials aimed at elucidating how antihypertensive drugs affect insulin sensitivity. These trials, which included assessment of insulin sensitivity by the euglycemic insulin clamp, showed that beta-adrenergic blockade and thiazide diuretic treatment (hydrochlorothiazide) increase insulin resistance and basal plasma insulin, whereas Ca(2+)-channel antagonists (verapamil and diltiazem), with the exception of the negative effect of nifedipine, are metabolically neutral. alpha-Adrenergic blockade with prazosin and angiotensin-converting enzyme (ACE) inhibition with captopril enhance insulin sensitivity. The mechanisms underlying the positive effects of ACE inhibition and beta-adrenergic blockade are largely unknown, but hemodynamic factors (vasodilation) may contribute by improving the access of glucose and insulin to skeletal muscle. The drugs, which were favorable or neutral with respect to insulin sensitivity, caused no changes in lipids or glucose homeostasis. In contrast, beta-blockers, except pindolol, had negative effects on triglycerides and high-density lipoprotein cholesterol, and thiazide diuretics caused adverse effects on total serum cholesterol, low-density lipoprotein cholesterol, and total and very-low-density lipoprotein triglyceride. The metabolic action of antihypertensive drugs is an important factor to consider in the choice of a proper treatment strategy in both diabetic and nondiabetic patients with hypertension.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Reduction in serum alkaline phosphatase levels by treatment with active vitamin D (alphacalcidol) in primary and secondary hyperparathyroidism and in euparathyroid individuals.

Raised levels of alkaline phosphatases (ALP) are seen in conditions with a high bone turn-over, such as in primary and secondary hyperparathyroidism (HPT). To study the effects of active vitamin D treatment on ALP, alphacalcidol (1-alpha-hydroxyvitamin D3), was given to patients with primary HPT as well as HPT secondary to chronic renal failure and also to healthy, euparathyroid subjects. Oral alphacalcidol (1 microgram daily) significantly reduced serum ALP (3.2 +/- 1.1 to 2.8 +/- 1.2 mu kat/l, p less than 0.05) in a 6-month double-blind, placebo-controlled study in patients with mild primary HPT, and alphacalcidol given intravenously to uremic subjects induced a reduction in serum ALP levels (3.5 +/- 3.1 to 2.6 +/- 1.7 mu kat/l, p less than 0.05) during a 4 months' study. A reduction in serum ALP was also seen in the euparathyroid subjects (2.4 +/- 0.77 to 2.2 +/- 0.64 mu kat/l, p = 0.03). This study indicates that treatment with active vitamin D is effective in reducing the increased bone turnover seen in subjects with both primary and secondary HPT.

Aged↗
PubMed1991

Potassium and blood pressure.

The relationships between serum potassium and urinary excretion of potassium and blood pressure were determined in an unmedicated adult population with a wide range of blood pressure (mean arterial blood pressure 100-130 mm Hg, n = 71). Inverse correlations between both serum potassium concentration and urinary excretion of potassium and standing (but not supine) mean blood pressure were seen (r = -0.41, p less than 0.005 and r = -0.33, p less than 0.01 respectively). These relationships persisted also when the influences of age, sex, obesity and kidney function were taken into account in a multiple regression analysis. The present observation is in accordance with previous reports of an association between potassium metabolism and blood pressure.

Aged↗
PubMed1991

No major metabolic alterations accompany the hypotensive effect of active vitamin D.

A hypotensive effect of active vitamin D treatment (alphacalcidol 1 mg daily) has previously been reported in three double-blind, placebo-controlled studies over 4-6 months in subjects with mild primary hyperparathyroidism (HPT), intermittent hypercalcemia and essential hypertension. The commonly used antihypertensive drugs, thiazides and betablockers, both induce impairments in both glucose and lipid metabolism and the thiazides are known to cause an elevation of serum urate. The effects of vitamin D treatment on these metabolic variables were recorded in these studies. Alphacalcidol did not induce any changes in fasting glucose HbA1c or insulin, serum triglycerides, cholesterol or serum urate in any of the treated groups. Neither was HDL cholesterol affected, except for a rise seen in the HPT subjects. It is therefore concluded that no major metabolic alterations in glucose or lipid metabolism or serum urate accompany the hypotensive effect of vitamin D.

Aged↗
PubMed1991

Expression of lipoprotein lipase in different human subcutaneous adipose tissue regions.

Steady state expression of lipoprotein lipase was compared in abdominal and gluteal subcutaneous adipose tissue of nonobese men and women. In both regions enzyme activity and lipoprotein lipase mRNA levels were significantly higher in women than in men. In men the enzyme activity was higher in abdominal than in gluteal adipose tissue (P less than 0.01) whereas the opposite was observed in women (P less than 0.05). In both sexes, however, lipoprotein lipase mRNA levels were threefold higher in the abdominal as compared to the gluteal site, whether they were determined in isolated fat cells or in fat segments (P less than 0.01). This regional difference persisted when the mRNA values were expressed as a function of the mRNA concentration for beta-actin. There was a correlation between the two adipose tissue regions as regards the values for enzyme activity and mRNA level (r = 0.6-0.8). Northern blot analysis revealed two mRNA species of 3.5 and 3.7 kilobases, respectively. It is concluded that there are regional variations in the steady state expression of lipoprotein lipase in human subcutaneous adipose tissue. This involves site variations in gene expression as well as posttranslational modification of lipoprotein lipase enzyme activity and may contribute to the characteristic variations in adipose tissue mass and distribution between men and women.

Abdomen↗