Risk of arrhythmias in 52 755 long-distance cross-country skiers: a cohort study.

AIMS: We aimed to investigate the association of number of completed races and finishing time with risk of arrhythmias among participants of Vasaloppet, a 90 km cross-country skiing event. METHODS AND RESULTS: All the participants without cardiovascular disease who completed Vasaloppet during 1989-98 were followed through national registries until December 2005. Primary outcome was hospitalization for any arrhythmia and secondary outcomes were atrial fibrillation/flutter (AF), bradyarrhythmias, other supraventricular tachycardias (SVT), and ventricular tachycardia/ventricular fibrillation/cardiac arrest (VT/VF/CA). Among 52 755 participants, 919 experienced arrhythmia during follow-up. Adjusting for age, education, and occupational status, those who completed the highest number of races during the period had higher risk of any arrhythmias [hazard ratio (HR)1.30; 95% CI 1.08-1.58; for ≥5 vs. 1 completed race], AF (HR 1.29; 95% CI 1.04-1.61), and bradyarrhythmias (HR 2.10; 95% CI 1.28-3.47). Those who had the fastest relative finishing time also had higher risk of any arrhythmias (HR 1.30; 95% CI 1.04-1.62; for 100-160% vs. >240% of winning time), AF (1.20; 95% CI 0.93-1.55), and bradyarrhythmias (HR 1.85; 95% CI 0.97-3.54). SVT or VT/VF/CA was not associated with finishing time or number of completed races. CONCLUSIONS: Among male participants of a 90 km cross-country skiing event, a faster finishing time and a high number of completed races were associated with higher risk of arrhythmias. This was mainly driven by a higher incidence of AF and bradyarrhythmias. No association with SVT or VT/VF/CA was found.

The positive effect of dietary vitamin D intake on bone mineral density in men is modulated by the polyadenosine repeat polymorphism of the vitamin D receptor.

INTRODUCTION: Few studies have considered the dietary influence of vitamin D intake on bone mineral density (BMD). Numerous studies have examined the association between VDR polymorphism and BMD, but no previous study has examined the joint influence of dietary vitamin D intake and VDR polymorphism on BMD. METHODS: We therefore conducted a study in 230 men aged 41-76 years of age. BMD was measured with DXA. A second bone scan was performed on average 2.7 years after the first investigation. Dietary habits were assessed by 14 dietary 24-h recall interviews. The polyadenosine (A) VDR genotypes were determined. RESULTS: Dietary vitamin D intake was associated with BMD at all sites, also after multivariate adjustment. Those in the highest quintile of intake had 9% higher femoral neck BMD (p = 0.004), 6% higher BMD at the lumbar spine (p = 0.06) and 5% higher total body BMD (p = 0.003) compared to men in the lowest quintile of dietary vitamin D intake. However, the positive association between vitamin D intake and BMD was especially apparent among those with the L/L polyadenosine (A) VDR genotype explaining between 10 and 15% of the variability in BMD depending on site (p < 0.004). There was furthermore a trend, in the lumbar spine, of less reduction in BMD with increasing vitamin D intake (p = 0.07) but not at the other sites. Calcium intake conferred no association with BMD. CONCLUSIONS: Our results indicate that the extent of positive association between dietary vitamin D intake and BMD in men is dependent on VDR polymorphism, a novel conceivable important gene-environmental interaction.

Survival after hip fracture.

Although it is known that overall mortality is increased after hip fracture, the influence of hip fracture risk factors on the subsequent mortality and cause of death has not been well studied. The objective of this study was to establish the survival after hip fracture in women and to assess the impact of comorbidity on mortality. We identified a complete population-based set of 2,245 incident hip fracture cases and 4,035 randomly selected population-based controls among women 50-81 years old in Sweden and followed these subjects for an average of 5 years through the Swedish National Inpatient and Cause-of-Death Registers. Information on factors related to hip fracture was obtained through linkage to hospital discharge data and through a mailed questionnaire. We studied excess mortality of hip fracture patients compared to controls using survival curves and proportional hazard regression models. During follow-up, 896 hip fracture patients (40%) and 516 (13%) controls died. The relative risk (RR) of death, adjusted for age and previous hospitalization for serious disease, was 2.3 (95% CI 2.0-2.5). Although the highest mortality risks were in the 1st 6 months post-fracture, RRs for fractures versus controls were increased for at least 6 years. Increased mortality was apparent both in those with evidence of comorbidity and those without. Hip fracture patients have a substantially increased risk of death that persists for at least 6 years post-fracture. The relative excess mortality is independent of comorbidity and known hip fracture risk factors.

Bone mineral density in relation to efficacy and side effects of budesonide and prednisolone in Crohn's disease.

BACKGROUND & AIMS: Osteoporosis frequently occurs in Crohn's disease, often because of corticosteroids. Budesonide as controlled release capsules is a locally acting corticosteroid with low systemic bioavailability. We investigated its effects on bone compared with prednisolone. METHODS: In 34 international centers, 272 patients with Crohn's disease involving ileum and/or colon ascendens were randomized to once daily treatment with budesonide or prednisolone for 2 years at doses adapted to disease activity. One hundred eighty-one corticosteroid-free patients had active disease (98 had never received corticosteroids, corticosteroid naive; 83 had received corticosteroids previously, corticosteroid exposed), and 90 had quiescent disease, receiving long-term low doses of corticosteroids, corticosteroid-dependent; in 1 patient, no efficacy data were obtained. Bone mineral density and fractures were assessed in a double-blinded fashion; disease activity, side effects, and quality of life were monitored. RESULTS: Neither the corticosteroid-free nor the corticosteroid-dependent patients treated with budesonide differed significantly in bone mineral density from those receiving prednisolone. However, corticosteroid-naive patients receiving budesonide had smaller reductions in bone mineral density than those on prednisolone (mean, -1.04% vs -3.84%; P = .0084). Treatment-emergent corticosteroid side effects were less frequent with budesonide. Efficacy was similar in both groups. CONCLUSIONS: Treatment with budesonide is associated with better preserved bone mass compared with prednisolone in only the corticosteroid-naive patients with active ileocecal Crohn's disease. In both the corticosteroid-free and corticosteroid-dependent groups, budesonide and prednisolone were equally effective for up to 2 years, but budesonide caused fewer corticosteroid side effects.

[Management of asymptomatic primary hyperparathyroidism. New North American guidelines discussed from a Swedish perspective]. / Handläggning av asymtomatisk primär hyperparatyreoidism. Nya nordamerikanska rekommendationer diskuteras i ett svenskt perspektiv.

Primary hyperparathyroidism (HPT) is a common endocrine disease, in most cases without obvious symptoms of hypercalcemia and parathyroid hormone excess. The only curative treatment outside clinical trials is parathyroidectomy. Many patients are undiagnosed and left untreated, and the indications for curative treatment are still controversial. In 1990, NIH presented recommendations on the management of asymptomatic HPT, which was defined as HPT without symptoms and signs of renal or bone disease. Since then many studies have shed new light on mainly the cardiovascular complications and increased mortality of the disease, and the 1990 recommendations have been questioned. A workshop in 2002 revised the recommendations for handling of asymptomatic HPT in the United States. These recommendations are discussed from a Swedish perspective together with recent data on mortality in a large Swedish HPT cohort.

Two years of treatment with recombinant human growth hormone increases bone mineral density in men with idiopathic osteoporosis.

We have investigated the effects of GH treatment on bone turnover, bone size, bone mineral density (BMD), and bone mineral content (BMC) in 29 men, 27-62 yr old, with idiopathic osteoporosis. The patients were randomly assigned to treatment with GH, either as continuous treatment with daily injections of 0.4 mg GH/d (group A, n = 14) or as intermittent treatment with 0.8 mg GH/d for 14 d every 3 months (group B, n = 15). All patients were treated with GH for 24 months, with a follow-up period of 12 months, and also received 500 mg calcium and 400 U vitamin D3 daily during all 36 months. Fasting morning urine and serum samples were obtained for assay of IGF-I, bone markers, and routine laboratory tests at baseline, after 1, 12, 24, and 36 months. Body composition, BMD, and BMC were determined by dual-energy x-ray absorptiometry at baseline and every 6 months. After 2 yr, there was an increase in BMD in lumbar spine (by 4.1%) in group A, and in total body (by 2.6%) in group A and (by 2.7%) in group B. BMC of the total body and lean body mass increased, whereas fat mass decreased in both treatment groups. After 36 months, the BMD and BMC in lumbar spine and total body had increased further in both groups. We conclude that 2 yr of intermittent or continuous treatment with GH in men with idiopathic osteoporosis results in an increase in BMD and BMC that is sustained for at least 1 yr post treatment.

Six months of hormone replacement therapy does not influence muscle strength in postmenopausal women.

OBJECTIVES: Postmenopausal hormone replacement therapy (HRT) has positive effects on fracture incidence before any effects on bone mineral density can be demonstrated. This has been attributed to increased muscle strength by HRT. This study was designed to evaluate the effect of 6 months of HRT on muscle strength in postmenopausal women. METHODS: Forty postmenopausal women, aged 60-78 were included in the study. They were randomly divided in two groups with 20 women in each group. One group received Menorest 50 microg/24 h (estradiol 4.3 mg) and Gestapuran 2.5 mg (medroxyprogesteron) daily and the other group received placebo treatment. The study was conducted as a double blinded, prospective and placebo controlled trial. Hand grip strength, isokinetic knee flexion and extention, and physical activity were measured before treatment, after 3 and 6 months. Physical activity was estimated using a classification system of physical activity. A JAMAR hydraulic hand dynamometer and a Cybex II dynamometer were used to evaluate muscle strength. RESULTS: Hand grip strength in the right hand, increased significantly in both groups (HRT P<0.001 and placebo P<0.01) and in the left hand in the HRT group (P<0.01). However, there were no differences in muscle strength between the two groups. There was no significant change in isokinetic knee flexion or extension after 6 months in either of the groups. The estimated physical activity increased slightly in the placebo group, but there was no significant difference compared to the treatment group. CONCLUSIONS: Our data suggest that 6 months of HRT does not influence muscle strength in postmenopausal women.

Primary hyperparathyroidism revisited in menopausal women with serum calcium in the upper normal range at population-based screening 8 years ago.

Population-based screening showed 2.1% prevalence of primary hyperparathyroidism (pHPT) in postmenopausal women. Individuals with total serum (s)-calcium levels of 2.55 mmol/L or more at screening were diagnosed with pHPT when subsequent analysis supported inappropriately elevated intact parathormone (PTH) levels in relation to even normal s-calcium levels. The arbitrary diagnostic criteria were validated by parathyroidectomy. Herein we reinvestigated biochemical signs of pHPT in women not diagnosed with pHPT due to s-calcium 2.50 to 2.54 mmol/L (group A, n = 160) at screening or due to appropriate PTH levels on two occasions after screening (group B, n = 70). Altogether, 99 women in group A and 47 in group B underwent reinvestigation 8.8 years after screening when they were 65 to 84 years old. The s-calcium levels averaged 2.56 mmol/L and had increased in group A (mean 0.04 mmol/L) and decreased in group B (mean 0.05 mmol/L). A total of 48 and 18 females (48%, 38%), respectively, met the previously validated criteria of pHPT. Altogether 21% of them were hypercalcemic (range 2.60-3.12 mmol/L). Subgroup analysis showed that PTH had not increased with time (n = 47) and that atherogenic blood lipids, but not glucose levels, were similar in pHPT patients and matched controls (n = 37). Assuming the existence of pHPT already at screening, the prevalence of pHPT could be adjusted to 3.4%. Even the most liberal diagnostic criteria utilized at pHPT screening seemed to underdiagnose the disease by inefficient cutoff limits for s-calcium and PTH. Because one-fifth of the women with pHPT progressed to hypercalcemia, long-term follow-up is advocated for those with s-calcium in the upper normal range.

Dual X-ray absorptiometry of hip, heel ultrasound, and densitometry of fingers can discriminate male patients with hip fracture from control subjects: a comparison of four different methods.

Few studies have examined different bone densitometry techniques to determine male hip fracture risk. We conducted a case-control study of 31 noninstitutionalized men, mean age 77 yr, with a first hip fracture and compared the results with 68 randomly selected age-matched control subjects. The methods used were dual X-ray absorptiometry (DXA) of the proximal femur, quantitative ultrasound (QUS) of the heel and fingers, and radiographic absorptiometry of the fingers. Case patients had significantly lower values (4-17%; p < 0.01) for all methods. The odds ratios for every SD reduction in bone values were 4.8 (95% confidence interval [CI]: 2.3-9.9) for DXA of the femoral neck, 2.2 (95% CI: 1.2-3.9) for QUS of the heel, 2.0 (95% CI: 1.2-3.3) for QUS of the phalanges, and 3.1 (95% CI: 1.5-6.6) for radiographic absorptiometry of the phalanges. The results indicate a strong capability of DXA of the femoral neck to distinguish between men with a first hip fracture and control subjects. Furthermore, ultrasound of the heel and fingers as well as radiographic absorptiometry proved capable of discriminating men with hip fractures from control subjects.

Normalized dyslipidaemia after parathyroidectomy in mild primary hyperparathyroidism: population-based study over five years.

OBJECTIVE: Postmenopausal women are at increased risk of primary hyperparathyroidism (pHPT). Secondary dyslipidaemia in pHPT has attracted little attention, although morbidity and mortality associated with cardiovascular diseases have been reported to be increased in these patients. DESIGN: A population-based screening programme was used to recruit postmenopausal women with mild, asymptomatic pHPT (mean serum calcium 2.57 +/- 0.12 mmol/l) and matched controls. MEASUREMENTS AND PATIENTS: Serum lipids, lipoprotein fractions and influences of treatment for the parathyroid disease were studied in 87 case-control pairs (mean age 67 years), 69 of whom completed a 5-year follow-up period. RESULTS: pHPT was characterized by decreased serum high-density lipoprotein (HDL)-cholesterol, increased total triglycerides, very-low-density lipoprotein (VLDL)-triglycerides and VLDL-cholesterol levels and an elevated atherogenic index. The differences were more pronounced in the cases with serum parathyroid hormone levels in the normal range and were inversely correlated to the serum parathyroid hormone level. Parathyroidectomy, with or without additive hormone replacement therapy, normalized the dyslipidaemia. Five-year surveillance of pHPT without treatment was associated with a maintained increase in total triglycerides and the atherogenic index and a decrease in HDL-cholesterol levels. CONCLUSION: Proatherosclerotic dyslipidaemia characterizes mild pHPT and is effectively reversed by parathyroidectomy. As dyslipidaemia might contribute to the increased risk of cardiovascular diseases and death observed in pHPT, the findings favour operative intervention rather than conservative surveillance in mild, asymptomatic pHPT in postmenopausal females.