Robert Eggertsen

Ser49Gly of β1-adrenergic receptor is associated with effective β-blocker dose in dilated cardiomyopathy

Our objective was to evaluate the influence of polymorphisms at codons 49 and 389 of the β1‐adrenergic receptor (β1‐AR) on the response to β‐blockers and outcome in patients with dilated cardiomyopathy.

Screening for thyroid disease in a primary care unit with a thyroid stimulating hormone assay with a low detection limit.

In a study at a primary care centre in a predominantly rural area of Sweden the records of all patients with established thyroid disease were scrutinised and 2000 consecutive adult patients screened with an immunoenzymometric thyroid stimulating hormone assay. The aims of the study were fourfold: firstly, to assess the total burden of thyroid disease in primary care centres in Sweden; secondly, to assess the efficacy of clinical diagnosis of the disease in unselected populations of patients; thirdly, to assess the efficacy of clinical evaluation of treatment with thyroxine; and, lastly, to see whether a single analysis of the serum thyroid stimulating hormone concentration by recent methods would be enough to identify an abnormality of thyroid function. Of the roughly 17,400 adults in the study community, 111 women and 10 men were being treated for thyroid disease. Screening detected 68 patients (3.5%) not receiving thyroxine who had a serum thyroid stimulating hormone concentration of 0.20 mU/l or less, all of whom were followed up clinically. Fifty of these patients were also studied biochemically during follow up. Only nine of the 68 patients had thyroid disease (three with thyrotoxicosis requiring treatment), no evidence of the disease being found in the remainder. Sixteen patients had spontaneous hypothyroidism requiring treatment, and neither these nor three patients with thyrotoxicosis had been detected at the preceding clinical examination. Of 35 patients in whom thyroid disease was suspected clinically at screening, none had laboratory evidence of thyroid dysfunction. In this series 1.3% of all women in the study community (2.6% of all 50-59 year olds) and 0.1% of the men were being treated for thyroid disease at the primary care centre, roughly 1.0% of adults subjected to screening were found to have thyroid disease requiring treatment, and most patients with a thyroid stimulating hormone concentration of 0.20 mU/l or less did not have thyroid dysfunction. It is concluded that measuring the basal serum thyroid stimulating hormone concentration by present methods is insufficient for the biochemical assessment of thyroid dysfunction in unselected populations.

Haemodynamic Effects of Carvedilol, A New Beta-Adrenoceptor Blocker and Precapillary Vasodilator in Essential Hypertension

Carvedilol (BM 14190) is a new antihypertensive compound which combines beta-adrenoceptor blocking and precapillary vasodilating properties but is devoid of intrinsic sympathomimetic activity. The acute and long-term effects on blood pressure and regional haemodynamics (forearm plethysmography) were studied with carvedilol 25 mg b.i.d. or 50 mg b.i.d. Comparisons were made with propranolol 80 mg b.i.d. in a randomized double-blind placebo controlled trial comprised of 30 patients with essential hypertension. After a four-week placebo period active therapy was given for four weeks. Carvedilol administered acutely reduced blood pressure at both doses, delta 13/6 mmHg (P less than 0.001/P less than 0.01) and 17/10 mmHg (P less than 0.001/P less than 0.01). Resistance in the forearm fell significantly with the higher dose. This was in contrast to propranolol which only reduced heart rate acutely, and as expected caused a rise in forearm resistance. After four weeks both compounds had reduced blood pressure significantly and to the same extent. Blood flow was still significantly reduced with propranolol in contrast to the findings with carvedilol. We conclude that carvedilol given orally has a useful antihypertensive effect both acutely and during prolonged treatment. It is well tolerated and its haemodynamic profile is attractive.

Effect of coffee on ambulatory blood pressure in patients with treated hypertension

Abstract. Effects of caffeine on ambulatory blood pressure, heart rate, renin‐angiotensin system, and ANP were studied in patients treated for mild to moderate hypertension in a randomized, double‐blind, placebo‐controlled, cross‐over trial comparing 2 weeks of caffeine‐free diet with 2 weeks of regular coffee use. Twenty‐three patients (13 men; aged 28–74 years) with treated, mild to moderate essential hypertension and a regular intake of 3–4 cups of coffee daily completed the study.

Screening of an Elderly Population in Primary Care for Primary Hyperparathyroidism

In order to assess the diagnostic outcome of a screening for primary hyperparathyroidism (PHPT) in an elderly population, we determined ionized calcium in serum from 368 individuals participating in a health control at Mölnlycke Primary Care Centre (200 women, 168 men; age range 75-95 years); four-fifths of the individuals living in their homes, the remainder in homes for aged or nursing homes. Intact parathyroid hormone was determined in the samples with oinized calcium concentration greater than mean + 3SD of the truncated population sample, and these individuals were also recalled for another blood sample. Moderate hypercalcaemia, probably due to PHPT, was found in eight individuals (2% of the complete sample, 3% of the women), five having neuropsychiatric or neuromuscular symptoms consistent with PHPT. Surgical intervention is probably indicated in only a small proportion of elderly patients. We conclude that optimal benefits in relation to costs of screening for PHPT in old people will depend on the availability of a safe and simple pharmacological treatment that could determine any causal relationship between hypercalcaemia and symptoms.

Determination of intrathyroidal iodine by X-ray fluorescence analysis in 60- to 65-year olds living in an iodine-sufficient area.

Objectives.  X‐ray fluorescence (XRF) is a non‐invasive method for determining the iodine content of the thyroid gland in vivo. In spite of the obvious clinical value of such a method in situations of iodine deficiency or iodine overload, the method has not so far been widely used. The objective was to investigate the applicability of the XRF method in a larger number of subjects.

Acute and Long-Term Hemodynamic Effects of Carvedilol, a Combined β-Adrenoceptor Blocking and Precapillary Vasodilating Agent, in Hypertensive Patients

Summary: The purpose of these studies was to investigate the hemodynamic effects of carvedilol, a compound with combined properties of nonselective &bgr;‐adrenoceptor blockade and precapillary vasodilatation. The acute effects were studied with invasive technique (dye dilution) in 10 patients taking 25 mg orally and noninvasively (forearm plethysmography) in 10 patients taking 25 mg and in 10 patients taking 50 mg orally, all with essential hypertension. Significant reductions of systolic and diastolic blood pressure (p < 0.05–0.001) were observed in all groups. Total peripheral resistance (TPR) did not change acutely whereas resistance in the forearm was reduced by 16% (p < 0.05; invasive group). When a comparison with propranolol (80 mg × 2) was made in a randomized double‐blind placebo controlled trial in 30 patients, carvedilol acutely reduced blood pressure significantly by 13/6 mg Hg (25 mg) and 17/10 mm Hg (50 mg) in contrast to propranolol. Resistance in the forearm fell significantly with 50 mg carvedilol, whereas propranolol caused a significant rise. After 4 weeks, both compounds had reduced blood pressure significantly. Blood flow was still reduced with propranolol in contrast to the findings with carvedilol. In conclusion, the summary of these studies shows that carvedilol given orally has a useful antihypertensive effect both acutely and during prolonged treatment, and it has an attractive hemodynamic profile, in agreement with the hemodynamic findings in essential hypertension.

Acute haemodynamic effects of carvedilol (BM 14190), a new combined beta-adrenoceptor blocker and precapillary vasodilating agent, in hypertensive patients

SummaryCarvedilol (BM 14190) is a new compound with combined nonselective beta-adrenoceptor blocking activity, devoid of ISA, and a precapillary vasodilating effect. Its acute haemodynamic effects were studied by invasive techniques in 10 patients given 25 mg carvedilol and noninvasively in 10 patients given 25 mg and in 10 given 50 mg orally. All had essential hypertension. In the invasive study intraarterial blood pressure was measured and cardiac output was determined by the dye-dilution method using Cardio-Green as the indicator. Peripheral haemodynamics in all 30 patients were studied in the forearm using strain gauge plethysmography. Measurements were made at rest before and repeatedly for 90 minutes after oral administration of one capsule of 25 mg or 50 mg carvedilol. Significant reductions in the systolic and diastolic blood pressures (p<0.05–0.001) were observed in all groups. Cardiac output showed a small, non-significant decrease from 5.8 l/min to 5.1 l/min. Total peripheral resistance did not change, whereas resistance in the forearm fell by 16% (p<0.05). These findings are different from what would have been expected acutely after administration of a pure beta-adrenoceptor blocking agent. They indicate that carvedilol possesses vasodilating activity in addition to its beta-adrenoceptor blocking effect.

Effects of treatment with a commercially available St John's Wort product (Movina) on cholesterol levels in patients with hypercholesterolemia treated with simvastatin.

Objective. To assess the effect of treatment with a St Johns Wort product (Movina®) on cholesterol levels (total cholesterol, LDL-cholesterol, and HDL-cholesterol) in patients with hypercholesterolemia on treatment with a stable dose of simvastatin. Design. Controlled, randomized, open, crossover pharmacodynamic study. Setting. Two primary healthcare centres. Intervention. Patients were treated with Movina® one tablet (containing 300 mg of Hypericum perforatum) twice daily and control (a commercially available multivitamin tablet, Vitamineral®). The trial started with a run-in period of 4 weeks. Then the treatment order between control and active treatment was decided (randomization using sealed envelopes). The duration of each treatment period was 4 weeks and simvastatin treatment was kept unchanged during the whole study period (12 weeks). Subjects. Twenty-four patients with hypercholesterolemia treated with a stable dose of simvastatin (10–40 mg daily) for at least three months. Main outcome measures. Assessments of total cholesterol, HDL- cholesterol, LDL-cholesterol, and triglycerides were performed in the morning with the patients in a fasting condition. Results. All patients completed the study. LDL-cholesterol was significantly increased during active treatment compared with control. Thus, the mean LDL-cholesterol after 4 weeks’ active treatment was 2.72 mmol/L compared with 2.30 mmol/L after treatment with control (p <0.0001). An increase in total-cholesterol was also observed (5.08 mmol/L compared with 4.56 mmol/L, p <0.0001). Conclusion. Products containing St Johns Wort should not be given to patients with hypercholesterolemia who are on treatment with simvastatin.

Validation of a 4-item score predicting hip fracture and mortality risk among elderly women.

PURPOSE One in 4 Swedish women experiences a hip fracture, an event that has high concomitant morbidity and mortality. We developed and validated a clinical predictor of fracture and mortality risk, the Fracture and Mortality (FRAMO) Index. METHODS This was a population-based prospective cohort study with a baseline questionnaire and 2-year outcomes of hip fracture, fragility fracture, and death. The questionnaire was sent to 1,498 women aged 70 years or older in 3 rural populations, asking them about their age, weight, height, mobility, previous fractures, smoking, medication use, and housing. Some women were also asked about previous vertebral radiographs. We defined 2 risk models before outcome data collection and subsequently renamed 1 model (age =80 years, weight <60 kg, previous fragility fracture, and the need to use arms to rise from the sitting position) the FRAMO Index. We used logistic regression analysis to study the association between the FRAMO Index and outcomes in all participants. RESULTS The participation rate was 83% in this elderly female population (N = 1,248). The 63% of women with 0 to 1 risk factor had a 2-year hip fracture risk of 0.8% and mortality risk of 3.2%. In contrast, women with 2 to 4 risk factors had a 2-year hip fracture risk of 5.4% (odds ratio = 7.5; 95% confidence interval, 3.0–18.4) and mortality risk of 23.7% (odds ratio = 9.5; 95% confidence interval, 6.0–14.9). These differences remained significant after adjustment for age as a continuous variable. Mortality increased with the number of risk factors. The proportion of women reporting previous vertebral fractures was higher among the group specifically questioned about vertebral radiographs (P <.001). CONCLUSIONS The FRAMO Index identified the majority of women who experienced hip fractures during a 2-year follow-up, who might have been candidates for intensified preventive measures. The FRAMO Index, based on 4 binary risk factors, would be practical for routine use in primary care.