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Biomedical subjects

H Lithell

Publications and source records attributed to H Lithell.

At least 145 records · Page 8Linked to original sources

Hormone replacement therapy and the risk of stroke. Follow-up of a population-based cohort in Sweden.

BACKGROUND: The protective effect of postmenopausal estrogen replacement therapy on coronary heart disease has been shown in several studies. However, the effect on stroke is more controversial, and data on estrogen-progestin combinations are sparse. METHODS: A total of 23,088 women living in the Uppsala (Sweden) Health Care Region were identified from pharmacy records as having been prescribed noncontraceptive estrogens during 1977 through 1980. They were followed up from 1977 to 1983 for admissions to the hospital because of a first stroke (International Classification of Diseases, Eighth Revision, codes 430 through 438 and 344). The mean observation time was 5.8 years. The expected number was based on person-years in the cohort and incidence rates in the population of the region. RESULTS: Overall, 361 cases of first stroke were observed in the cohort, as compared with 403.2 expected (relative risk [RR], 0.90; 95% confidence limits, 0.81, 0.99). The RR for acute stroke (International Classification of Diseases, Eighth Revision, codes 431 through 436) was 0.85 (0.75, 0.97). In women younger than 60 years at entry who were prescribed estradiol compounds (1 to 2 mg) or conjugated equine estrogens (0.625 to 1.25 mg), the risk of any stroke was reduced by almost 30% (RR, 0.72; 0.58, 0.88) and the risk of acute stroke was reduced by 40% (RR, 0.61; 0.46, 0.79). Women prescribed a combined estradiol-levonorgestrel brand also had a lowered risk of stroke (RR, 0.61; 0.40, 0.88). Weak compounds (mainly estriol) showed no stroke-protective effect, nor was there any relationship between hormone replacement and risk of subarachnoid hemorrhage. CONCLUSION: Hormone replacement therapy with potent estrogens alone or cyclically combined with progestins can, particularly when started shortly after menopause, reduce the risk of stroke.

Cerebrovascular Disorders↗

Effects of small doses of bisoprolol on blood pressure and lipoprotein concentrations in hypertensive patients.

The effects of bisoprolol 2.5 and 5 mg per day on blood pressure, and lipoprotein and apolipoprotein concentrations were compared in 18 newly detected hypertensives in a double-blind, crossover study. All treatment results were related to the values at the end of a four-week placebo run-in period. Each of the two following treatment periods lasted for 3 months. The systolic and diastolic pressures in the supine position were reduced by 19.5/11.7 mm Hg and 14.6/10.4 mm Hg by 2.5 and 5 mg bisoprolol per day, respectively, with no significant difference in effect. Supine heart rate was reduced by 4.7 and 8.2 beats.min-1, respectively, (P = 0.0517 for different effects). The cholesterol concentration in low-density (LDL) and high-density (HDL) lipoproteins was reduced during both regimens, by about 0.3 and 0.1 mmol.l-1, respectively, difference not significant. Triglyceride concentrations were not significantly affected during either regimen. We conclude that, in this study population, treatment with bisoprolol 2.5 mg per day was equally effective as 5.0 mg per day in reducing blood pressure. The effects on lipoprotein concentrations were small and included an unexpected reduction in LDL-cholesterol concentration. A low dose of a highly selective beta-adrenoceptor blocker like bisoprolol appears to retain the blood pressure reducing capacity and has lost most of the unfavourable effects on lipoproteins characteristic of higher doses.

Adult↗

Decreased peripheral blood flow in the pathogenesis of the metabolic syndrome comprising hypertension, hyperlipidemia, and hyperinsulinemia.

Major cardiovascular risk factors, such as hypertension, hyperlipidemia, and diabetes, often cluster in the same individuals. It has been claimed that obesity, hyperinsulinemia, insulin resistance, and a deranged intracellular handling of ions have pathogenetic importance in the development of this metabolic syndrome. However, a decrease in peripheral blood flow is another factor found in all the different facets of this syndrome. An increased peripheral resistance and a rarefaction of skeletal vessels are often seen in hypertensive subjects. Also, the insulin resistance so commonly seen in hypertension may be a consequence of a decreased blood flow because insulin resistance is associated with a decreased capillarization in skeletal muscle. Furthermore, the activity of skeletal muscle lipoprotein lipase, the key enzyme involved in the removal of triglycerides from the circulation, is known to be related to skeletal muscle vascularization. Because enhanced sympathetic activity has been associated with vascular hypertrophy and rarefaction of vascularization, overactivity in this part of the autonomic nervous system may lead to structural changes that will decrease the blood flow in peripheral tissues and thereby induce the metabolic syndrome of cardiovascular risk factors, particularly in individuals who, for genetic reasons, have decreased capillarization at the onset.

Hemodynamics↗

On the diversity of insulin secretion and sensitivity in subjects with impaired glucose tolerance.

Insulin secretion and sensitivity are basic characteristics determining the glucose tolerance. The aim of this study was to investigate if derangements in these two main characteristics were generally found in subjects with impaired glucose tolerance (IGT). The early insulin response at the intravenous glucose tolerance test (IVGTT) in 42 subjects with IGT was found to be correlated to the glucose tolerance (r = -0.38, p < 0.01 vs, fasting glucose and r = 0.35, p < 0.02, vs the k-value of IVGTT) while fasting insulin was found to be closely correlated to insulin sensitivity, measured by the euglycemic clamp method (r = -0.83, p < 0.003, n = 11). Using data obtained at the IVGTT's in the IGT subjects, different patterns of insulin secretion were found representing different combinations of impairments in insulin secretion and sensitivity. However, in the majority of the IGT subjects a marked decrease in the early insulin response and a fasting hyperinsulinemia were found. The present study suggest such a characterization by the IVGTT to be of importance for a better understanding of the dynamic interplay between insulin secretion and sensitivity in IGT subjects.

Blood Glucose↗

Hypertension and hyperlipidemia. A review.

In a recent meta-analysis of 13 studies of antihypertensive treatment, it was demonstrated that the reduction of risk for coronary artery disease was 14% compared with the 20% to 25% expected for a diastolic blood pressure reduction of 5 to 6 mm Hg according to observational studies. In contrast, the obtained effect on stroke reduction was of the same order as that expected for a given blood pressure reduction. A meta-analysis of 22 lipid-lowering studies indicated a reduction in risk of coronary artery disease that is consistent with epidemiologic observations, indicating a difference in risk of 20% to 30% for a 10% difference in cholesterol concentration. Many cross-sectional studies have demonstrated that hypertensive men and women are metabolically different from normotensive subjects. These differences include a disturbed glucose metabolism due to insulin resistance that may also be the basis of the observed lipid abnormalities and even of the hypertension itself. Some of the drugs used in the treatment of hypertension produce changes in metabolism such that insulin resistance becomes worse and lipid abnormalities become still more pronounced. In the case of treatment with beta-blockers, there is a change in lipoprotein composition that may indicate an increased tendency toward oxidation, which may render the lipoproteins more atherogenic. It is obvious that the metabolic profile in hypertensive patients warrants consideration and, furthermore, that the metabolic effects of different drugs should be taken into account when starting treatment.

Female↗

On the relationships between mineral metabolism, obesity and fat distribution.

Alterations in calcium metabolism have been associated with cardiovascular risk factors. An altered binding of calcium to plasma proteins and raised levels of parathyroid hormone (PTH) have been described in morbid obesity. In the present study, indices of mineral metabolism were related to obesity (body mass index, BMI) and fat distribution (waist to hip ratio, w/h) in 194 subjects with a wide range of BMI and w/h. The ratio of total serum calcium to plasma ionized calcium (Ca2+) was found to be significantly correlated to both BMI (r = 0.20, P < 0.02) and w/h (r = 0.22, P < 0.005). Serum phosphate was also correlated to both of the indices of obesity in an inverse way (r = -0.24, P < 0.0008 for BMI and r = -0.33, P < 0.0001 for w/h). These relationships were still significant when the influences of age, sex and serum creatinine were included in the multiple regression analysis. This kind of analysis also disclosed that w/h was superior to BMI as a determinant of serum phosphate and the total calcium/Ca2+ ratio in serum. PTH was not significantly correlated to any of the indices of obesity. In conclusion, fat distribution rather than obesity per se was found to be associated with an altered mineral metabolism.

Adipose Tissue↗

The influence of pretransplant lipoprotein abnormalities on the early results of renal transplantation.

Lipoprotein patterns were investigated before and after renal transplantation in a prospective study including 151 patients. Kidney graft losses during the first 6 months were associated with higher total cholesterol (P = 0.03), LDL cholesterol (P = 0.003) and LDL triglyceride levels (P = 0.01) before transplantation. Patients with serum cholesterol > or = 6.9 mmol l-1 before transplantation had more acute rejections (1.7 vs. 0.9), a worse graft function and more vascular intimal hyperplasia and glomerular mesangial changes in transplant biopsies at 6 months. Patients with serum creatinine levels exceeding 160 mumol l-1 at 6 months had more severe lipid disorders already before transplantation. Serum creatinine at 6 months was influenced by the number of acute rejection episodes (P = 0.0001) and the age of the donor (P = 0.009) while the number of acute rejections was found to be related to pretransplant total cholesterol levels (P = 0.0086) and the age of the recipient (P = 0.025). In conclusion, pretransplant lipoprotein disturbances have an impact on the early outcome of renal transplantation. Since there is a progression of hyperlipidaemia following transplantation, this may have an influence also on the cardiovascular morbidity and late graft dysfunction.

Adolescent↗

Cardiovascular risk factors in treated hypertensives--a nation-wide, cross-sectional study in Sweden.

Hypertensive patients still face a considerable risk of cardiovascular disease in spite of drug treatment in many studies. This may partly be explained by metabolic disturbances, both primarily linked to hypertension but also secondarily influenced by anti-hypertensive drugs themselves. In order to evaluate residual cardiovascular risk factors we investigated 1915 treated hypertensives (912 males, 1003 females) attending 128 health centres from all parts of Sweden. Mean blood pressure was 148/91 mmHg for males and 151/90 for females, but a substantial proportion of all patients were not well controlled, having a diastolic blood pressures > or = 100 mmHg (17% males, 12% females). Total cholesterol and HDL-cholesterol were 6.03 and 1.25 mmol l-1 for males, and 6.40 and 1.50 for females. The corresponding figures for serum triglycerides were 2.03 and 1.72 mmol l-1, respectively. In all, 38% of the hypertensives had hypercholesterolaemia (> or = 6.5 mmol l-1) and 27% hypertriglyceridaemia (> or = 2.3 mmol l-1). The lipid/lipoprotein findings may also be influenced by the various anti-hypertensive drugs used in Sweden. The prevalence of smoking and diabetes mellitus were 25% and 11% for men, and for women 24% and 9%. In conclusion, Swedish hypertensives show evidence of significant residual cardiovascular risk factors in spite of treatment. This may be of importance for future relative and absolute cardiovascular risk. It is time to re-evaluate the effectiveness of our management and care of hypertensive patients.

Antihypertensive Agents↗

Peripheral glucose metabolism and insulin sensitivity in Alzheimer's disease.

Twenty-four patients with Alzheimer's disease and matched controls were examined with reference to metabolic parameters such as peripheral insulin and glucose metabolism, serum lipid concentrations and blood pressure levels. Blood glucose levels and insulin response were measured during an intravenous glucose tolerance test and peripheral insulin sensitivity was estimated with the hyperinsulinemic euglycemic clamp technique. There were no differences recorded between the two groups in glucose metabolism, triglyceride, cholesterol or HDL-cholesterol levels. The patients with Alzheimer's disease had significantly lower blood pressure levels, which partly could be explained by ongoing treatment with neuroleptics and antidepressives. Previous findings of higher insulin levels in Alzheimer's disease could not be verified.

Aged↗

Is it hyperinsulinemia or insulin resistance that is related to hypertension and other metabolic cardiovascular risk factors?

AIM OF STUDY: Epidemiologic and clinical studies have shown a close association between hypertension, hyperlipidemia and glucose intolerance. A metabolic imbalance has been proposed. As both hyperinsulinemia and insulin resistance appear to be of pathogenetic importance in this metabolic syndrome, we studied these features in hypertensive and normotensive subjects. METHODS: Glucose disposal under a hyperinsulinemic clamp was measured and different indices of hyperinsulinemia were obtained with the intravenous glucose tolerance test. The results were evaluated in relation to different cardiovascular risk factors assessed in 194 adult subjects selected from a health screening. RESULTS: Both hyperinsulinemia and the glucose disposal (clamped) value were significantly correlated with blood pressure (r = 0.36 and -0.42, respectively; both P < 0.0001), free fatty acids (r = 0.20 and -0.29, respectively; both P < 0.0005), serum triglycerides (r = 0.33 and -0.39, respectively; both P < 0.0001), high-density lipoprotein (HDL) cholesterol (r = -0.31 and 0.41, respectively; both P < 0.001) and fasting glucose (r = 0.45 and -0.44, respectively; both P < 0.0001). Multiple regression analysis with age, sex and obesity as confounding variables showed that insulin resistance was superior to hyperinsulinemia in the relationships with blood pressure and indices of hyperlipidemia (elevated free fatty acids, serum triglycerides and low HDL cholesterol), but both insulin sensitivity and hyperinsulinemia were significantly related to fasting glucose. CONCLUSIONS: Insulin sensitivity was more closely related to blood pressure, serum triglycerides and HDL cholesterol than hyperinsulinemia, but both insulin sensitivity and the insulin levels were associated with fasting glucose. Thus, insulin resistance is more important than hyperinsulinemia as a determinant of the constellation of cardiovascular risk factors comprising hypertension, glucose intolerance and hyperlipidemia.

Adult↗

Calcium metabolism and sodium sensitivity in hypertensive subjects.

A pattern of negative calcium balanced with lowered levels of serum ionized calcium (Ca2+) and increased urinary excretion of calcium has been reported in hypertensive men. In the present study, ten untreated hypertensive subjects were salt loaded (20 g NaCl) for one week after a week on a low salt diet (< 3 g). The change in mean blood pressure (MBP) at the end of the high compared with the low salt diet was called salt sensitivity and was related to indexes of mineral metabolism. It was found that salt sensitivity was significantly correlated with both plasma ionized calcium (Ca2+) and serum calcium concentrations (both r = 0.64, P < 0.05) on the different diets. These relationships were strongest when sodium sensitivity was measured in the standing position during the low salt intake suggesting a role for an increased sympathetic tone. Salt loading increased the urinary excretion of calcium by 95% and also induced reductions in haemoglobin, serum albumin and serum calcium (P < 0.001). Ca2+, on the other hand, remained constant after salt loading. In conclusion, low levels of plasma ionized calcium and serum calcium were mainly found in hypertensive subjects with a low sensitivity to salt. Salt loading induced an increased calciuresis, haemodilution and possibly a shift of calcium from its protein-bound to its ionized form. The findings support the view that calcium metabolism is related to the regulation of BP.

Aged↗

Metabolic cardiovascular risk factors and sodium sensitivity in hypertensive subjects.

Hypertension has previously been suggested to be a part of a metabolic syndrome also involving hyperlipidemia, hyperinsulinemia, and decreased insulin sensitivity. In the present study, 10 untreated hypertensive subjects were challenged with a high-salt diet (20 g NaCl) for 1 week after 7 days on a low-salt diet (less than 3 g). The difference in mean blood pressure (MBP) at the end of the high-salt diet v the low-salt diet was denoted salt sensitivity. We related the salt sensitivity to indices of glucose and lipid metabolism and studied the effect of salt deprivation on these metabolic variables. Salt sensitivity was found to be significantly correlated to HDL cholesterol (r = 0.79, P less than .007), insulin sensitivity (M value at the euglycemic clamp, r = 0.68, P less than .003), and fasting serum insulin (r = 0.69, P less than .04). Salt deprivation induced an increase in fasting insulin (P less than .03), but did not significantly affect any other indices of glucose and lipid metabolism. In conclusion, our study shows that hyperinsulinemia, decreased sensitivity to insulin, and low levels of HDL cholesterol were most commonly seen in hypertensive subjects with a low sodium sensitivity. A putative mechanism might be an increased activity in pressor systems also affecting glucose and lipid metabolism.

Aged↗

Fasting insulin, calcium metabolism and the electrocardiogram in hypertensive subjects.

Changes in both calcium and insulin metabolism have been described in essential hypertension. Low levels of plasma ionized calcium (Ca2+) and high levels of insulin have previously been associated with vascular complications and coronary heart disease. In the present study, indices of calcium metabolism and fasting serum insulin were related to electrocardiographic (ECG) variables in 58 patients with untreated hypertension. Fasting insulin was found to be related to heart rate (r = 0.47, P < 0.001), diastolic interval (r = -0.39, P < 0.004) and electrical axis (r = -0.29, P < 0.03) while Ca2+ was found to be correlated with the QRS amplitude (r = -0.32, P < 0.03) and diastolic interval (r = 0.37, P < 0.02). Furthermore, non-ionized serum calcium was correlated with the QRS duration (r = 0.36, P < 0.02), ST-segment interval (r = -0.49, P < 0.002) and QT interval (QoT, r = -0.42, P < 0.008). These correlations were still significant when the influences of age, sex, obesity, blood pressure and heart rate were taken into account in the multiple regression analysis. In conclusion, the present study demonstrates that calcium and insulin metabolism are related to several basic characteristic functions of the heart, such as the systolic and diastolic function, as well as to signs of left ventricular hypertrophy.

Adult↗

Plasma ionized calcium and cardiovascular risk factors in mild primary hyperparathyroidism: effects of long-term treatment with active vitamin D (alphacalcidol).

Primary hyperparathyroidism (HPT) has been associated with hypertension, hyperinsulinaemia, hypertriglyceridaemia and hyperuricaemia. In the present study, plasma ionized calcium (Ca2+) was studied in relation to cardiovascular risk factors in 20 subjects with mild hypertension. Plasma Ca2+ was found to be negatively correlated with fasting serum insulin, triglycerides and urate, and with diastolic blood pressure (DBP). However, after the interaction of the different risk factors had been taken into account in the multiple regression analysis, only the relationship between Ca2+ and serum insulin was significant (r = 0.55, P less than 0.01). In a previous double-blind, placebo-controlled study 1 micrograms alphacalcidol, a synthetic analogue of 1,25 dihydroxy-vitamin D3, induced a decrease in blood pressure in mild HPT subjects. In the present study, the highest dose that did not further aggravate the hypercalcaemia was given in a long-term study over a 12-month period to 18 mild HPT subjects (average dose, 1.75 micrograms daily). The treatment induced a reduction in body weight of 0.9 kg (P less than 0.05) and an increase in serum urate from 330 +/- 92 to 380 +/- 104 mmol l-1 (P less than 0.01). A reduction in blood pressure was only observed at the end of the study, from 142 +/- 17/86.6 +/- 9.1 to 139 +/- 13/82.9 +/- 8.9 mmHg (P less than 0.05 for DBP). The reduction in systolic blood pressure was significantly correlated with the reduction in body weight induced by treatment (r = 0.63, P less than 0.02). No consistent changes in glucose or lipid metabolism were induced by treatment.

Blood Glucose↗

Polyunsaturated fatty acids may impair blood glucose control in type 2 diabetic patients.

Fifteen patients with Type 2 diabetes were given two diets rich in either saturated fat or polyunsaturated fat in alternate order over two consecutive 3-week periods on a metabolic ward. Both diets contained the same amount of fat, protein, carbohydrates, dietary fibre, and cholesterol. The proportions of saturated, monounsaturated and polyunsaturated fatty acids in the saturated fat diet were 16, 10, and 5%-energy and in the polyunsaturated fat diet (PUFA) 9, 10, and 12%-energy. The PUFA diet contained a high proportion of n-3 fatty acids. Metabolic control improved significantly in both dietary periods, due to both qualitative dietary changes and a negative energy balance. The serum lipoprotein concentrations decreased on both diets but the serum lipids were significantly lower after the PUFA diet (serum triglycerides -20%, p = 0.001; serum cholesterol -5%, p = 0.03; VLDL-triglycerides -29%, p less than 0.001; and VLDL-cholesterol -31%, p = 0.001) than after the saturated fat diet. Average blood glucose concentrations during the third week were significantly higher fasting (+15%, p less than 0.01), and during the day at 1100 h (+18%, p less than 0.001) and 1500 h (+17%, p = 0.002) on PUFA than on the saturated fat diet. Significantly higher blood glucose levels were also recorded with a standard breakfast, while the sum of the insulin values was lower (-19%, p = 0.01). HbA1c did not differ significantly between the two dietary periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗