Henrik Schirmer

Persistent postsurgical pain in a general population: prevalence and predictors in the Tromsø study.

TOC summary Persistent pain after surgery is common, but prevalence of clinically relevant pain may be overestimated. Sensory abnormalities are associated with pain and more intense pain. ABSTRACT Population‐based data on the prevalence of persistent postsurgical pain are scarce. This study aimed to assess the prevalence of persistent postsurgical pain in a general population and to describe associated physical, social, and psychological factors, including symptoms of nerve injury and sensitization. A cross‐sectional survey was performed in northern Norway with questionnaire items covering surgery, pain, and sensory abnormalities in the area of surgery. Of the 12,982 participants, 24.0% (3111) had undergone one or more surgical procedures during the 3 years preceding the survey. Of these, 2043 had the surgery performed more than 3 months before the investigation. Persistent pain in the area of surgery was reported by 40.4% of the patients (826 of 2043), moderate or severe pain by 18.3% (373 of 2043). Hypoesthesia, hyperesthesia, or both was reported by 24.5% (501 of 2043). There were strong associations between sensory abnormalities and persistent pain, increasingly with higher pain intensities; odds ratios were 2.68 for hypoesthesia and 6.27 for hyperesthesia. Of the 826 individuals reporting persistent pain in the anatomical area of surgery, 51.0% reported chronic pain when questioned without specific reference to the surgery. The present study supports evidence from clinical studies of persistent postsurgical pain, indicating a high prevalence, but reveals large discrepancies in report of pain, depending on the questions asked and the context in which the questions are presented. Strong associations between sensory abnormalities and pain indicate neuropathic mechanisms in a major proportion of cases.

The evolving epidemiology of valvular aortic stenosis. The Tromsø Study

Objective To assess prevalence, incidence, prognosis and progression of degenerative valvular aortic stenosis (AS). Setting The Tromsø Study and the University Hospital of North Norway. Design Population based prospective study. Population Over a 14 year span we performed three repeated echocardiographic examinations (1994, 2001 and 2008) of a random sample of initially 3273 participants. Data from the only hospital serving this population were included. Results There were 164 subjects with AS. Prevalence consistently increased with age, average values being 0.2% in the 50–59 year cohort, 1.3% in the 60–69 year cohort, 3.9% in the 70–79 year cohort and 9.8% in the 80–89 year cohort. The incidence rate in the study was 4.9‰/year. The mean annual increase in mean transvalvular pressure gradient was 3.2 mm Hg. The increase was lower in mild AS than in more severe disease, disclosing a non-linear development of the gradient, but with large individual variations. Mortality was not significantly increased in the asymptomatic AS-group (HR=1.28), nor in those who received aortic valve replacement (n=34, HR=0.93), compared with the general population. Conclusion This is the first study to document the incidence and prognosis of AS in a general population with surgery as a treatment option. It reveals an accelerated progression of the aortic mean gradient as the disease advances. The prognosis of AS seems to be comparable with the normal population in the asymptomatic stage and after successful surgery, indicating that the follow-up and timing of surgery has been adequate for this patient group.

Endogenous sex hormones and the prospective association with cardiovascular disease and mortality in men: the Tromsø Study

OBJECTIVE To study the impact of endogenous testosterone levels in community-dwelling men on later risk for myocardial infarction (MI) and all-cause, cardiovascular disease (CVD), and ischemic heart disease (IHD) mortality. DESIGN Population-based prospective cohort study. METHODS For the analyses, we used a cohort of 1568 randomly selected men, with sex-hormone data participating in the fourth Tromsø Study (1994-1995). Defined end points were first-ever MI (fatal or nonfatal), all-cause, CVD, and IHD mortality. A committee performed thorough ascertainment of end points, following a detailed protocol. Complete ascertainment of end points was until 30 September 2007 for all-cause mortality, until 31 December 2005 for CVD/IHD mortality, and until 31 December 2004 for first-ever MI. The prospective association between total and free testosterone and end points were examined using Cox proportional hazard regression, allowing for multivariate adjustment for age and cardiovascular risk factors. RESULTS During follow-up, there were 395 deaths from all causes, 130 deaths from CVD and 80 deaths from IHD, while 144 men experienced a first-ever MI. There was a significant increase in all-cause mortality risk for men with free testosterone in the lowest quartile (<158 pmol/l) compared with the higher quartiles after age adjustment hazard ratios (HR 1.24, 95% confidence interval, CI 1.01-1.53) and after multivariate adjustments (HR 1.24, 95% CI 1.01-1.54). Total testosterone was not associated with mortality risk. Likewise, there were no significant changes in risk for first-ever MI across different total or free testosterone levels. CONCLUSION Men with free testosterone levels in the lowest quartile had a 24% increased risk of all-cause mortality.

Low testosterone and sex hormone-binding globulin levels and high estradiol levels are independent predictors of type 2 diabetes in men

OBJECTIVE To study the impact of endogenous sex hormone levels in community-dwelling men on later risk for type 2 diabetes. DESIGN Population-based prospective cohort study. METHODS For the analyses, 1454 men who participated in the fourth Tromsø study (1994-1995) were used. Cases of diabetes were retrieved and validated until 31.12.05 following a detailed protocol. The prospective association between sex hormones and diabetes was examined using Cox proportional hazard regression analysis, allowing for multivariate adjustments. RESULTS There was a significantly lowered multi-adjusted risk for later diabetes with higher normal total testosterone levels, both linearly per s.d. increase (hazard ratio (HR) 0.71, confidence interval (CI) 0.54-0.92) and in the higher quartiles of total testosterone than in the lowest quartiles (HR 0.53, CI 0.33-0.84). A reduced multi-adjusted risk for incident diabetes was also found for men with higher sex hormone-binding globulin (SHBG) levels, both linearly per s.d. increase (HR 0.55, CI 0.39-0.79) and when comparing the third (HR 0.38, CI 0.18-0.81) and the fourth quartile (HR 0.37, CI 0.17-0.82) to the lowest quartile. The associations with total testosterone and SHBG were no longer significant after inclusion of waist circumference to the multivariate models. Estradiol (E(2)) was positively associated with incident diabetes after multivariate adjustments including waist circumference when comparing the second (HR 0.49, CI 0.26-0.93) and the third (HR 0.51, CI 0.27-0.96) quartile to the highest quartile. CONCLUSION Men with higher E(2) levels had an increased risk of later diabetes independent of obesity, while men with lower total testosterone and SHBG had an increased risk of diabetes that appeared to be dependent on obesity.

Baseline serum 25‐hydroxyvitamin D concentrations in the Tromsø Study 1994–95 and risk of developing type 2 diabetes mellitus during 11 years of follow‐up

Diabet. Med. 27, 1107–1115 (2010)

Polymorphisms Related to the Serum 25-Hydroxyvitamin D Level and Risk of Myocardial Infarction, Diabetes, Cancer and Mortality. The Tromsø Study

Objective Low serum 25(OH)D levels are associated with cardiovascular risk factors, and also predict future myocardial infarction (MI), type 2 diabetes (T2DM), cancer and all-cause mortality. Recently several single nucleotide polymorphisms (SNPs) associated with serum 25-hydroxyvitamin D (25(OH)D) level have been identified. If these relations are causal one would expect a similar association between these SNPs and health. Methods DNA was prepared from subjects who participated in the fourth survey of the Tromsø Study in 1994–1995 and who were registered with the endpoints MI, T2DM, cancer or death as well as a randomly selected control group. The endpoint registers were complete up to 2007–2010. Genotyping was performed for 17 SNPs related to the serum 25(OH)D level. Results A total of 9528 subjects were selected for genetic analyses which were successfully performed for at least one SNP in 9471 subjects. Among these, 2025 were registered with MI, 1092 with T2DM, 2924 with cancer and 3828 had died. The mean differences in serum 25(OH)D levels between SNP genotypes with the lowest and highest serum 25(OH)D levels varied from 0.1 to 7.8 nmol/L. A genotype score based on weighted risk alleles regarding low serum 25(OH)D levels was established. There was no consistent association between the genotype score or individuals SNPs and MI, T2DM, cancer, mortality or risk factors for disease. However, for rs6013897 genotypes (located at the 24-hydroxylase gene (CYP24A1)) there was a significant association with breast cancer (P<0.05). Conclusion Our results do not support nor exclude a causal relationship between serum 25(OH)D levels and MI, T2DM, cancer or mortality, and our observation on breast cancer needs confirmation. Further genetic studies are warranted, particularly in populations with vitamin D deficiency. Trial Registration ClinicalTrials.gov NCT01395303

Features of the metabolic syndrome and the risk of non-vertebral fractures : The Tromso Study

Owing to a technical error, a number of non-vertebral fractures had not been included in the database. Owing to changes in the informed consents for some of the participants, at the time of repeated analyses, the study cohort changed from 27,159 to 26,905 participants. A total of 1,882 non-vertebral fractures (not 1,249 as stated in the publication) were registered. After excluding all subjects with missed measurements of any metabolic syndrome criteria (n=152), 750 men and 1108 women (not 438 men and 789 women as stated in the publication) suffered non-vertebral fractures. The risk estimates of the associations between having three or more of the metabolic syndrome criteria and nonvertebral fractures and changed to (RR 0.81, 95% CI 0.64– 1.04) in men and (RR 0.78, 95% CI 0.65–0.93) in women. The trend towards reduced fracture risk by increasing mean BP in men was no longer significant (Fig. 2). We apologize for any inconvenience caused by this unfortunate error. Osteoporos Int (2009) 20:839 DOI 10.1007/s00198-009-0847-8

Impact of cardiovascular risk factors on cognitive function: The Tromsø study

Background and purpose:  The role of cardiovascular risk factors in the pathogenesis of cognitive impairment and dementia remains still unclear. We examined the impact of cardiovascular risk factors on cognitive function in a large longitudinal population study.

Combined analyses and extended follow-up of two randomized controlled homocysteine-lowering B-vitamin trials

Abstract.  Ebbing M., Bønaa K.H., Arnesen E., Ueland P.M., Nordrehaug J.E., Rasmussen K., Njølstad I., Nilsen D.W., Refsum H., Tverdal A., Vollset S.E., Schirmer H., Bleie Ø., Steigen T., Midttun Ø., Fredriksen Å., Pedersen E.R., Nygård O. (From the Departments of 1Heart Disease, Haukeland University Hospital, Bergen; Heart Disease, University Hospital of North Norway; Department of Community Medicine, University of Tromsø, Tromsø; Institute of Medicine, University of Bergen, Bergen; Department of Clinical Medicine, University of Tromsø, Tromsø; Department of Cardiology, Stavanger University Hospital, Stavanger; Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway; Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, UK; Division of Epidemiology, the Norwegian Institute of Public Health, Oslo; Department of Public Health and Primary Health Care, University of Bergen; Bevital AS, Bergen; Norway) Combined Analyses and Extended Follow‐Up of Two Randomized Controlled Homocysteine‐Lowering B‐Vitamin Trials. J Intern Med 2010; 268: 367–382.

No Effect of High-Dose Vitamin D Supplementation on Glycemic Status or Cardiovascular Risk Factors in Subjects With Prediabetes

OBJECTIVE In observational studies, low serum 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with insulin resistance and other risk factors for cardiovascular disease. RESEARCH DESIGN AND METHODS We present 1-year data from an ongoing 5-year trial in 511 individuals with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) randomly assigned to 20,000 IU/week vitamin D3 or placebo. An oral glucose tolerance test was performed at baseline and after 1 year. RESULTS Mean baseline serum 25(OH)D was 59.9 nmol/L and 61.1 nmol/L in the vitamin D and placebo groups, respectively, and increased by 45.8 nmol/L and 3.4 nmol/L, respectively. With adjustment for baseline concentrations, no differences in measures of glucose metabolism, insulin secretion or sensitivity, blood pressure, or hs-CRP were found after 1 year. There was a slight, but significant decrease in total and LDL cholesterol in the vitamin D group compared with the placebo group, but as there was also a decrease in HDL cholesterol, the change in the total/HDL cholesterol ratio did not differ significantly. Only analyzing subjects with 25(OH)D <50 nmol/L did not change the results. CONCLUSIONS This study shows that vitamin D supplementation does not improve glycemic indices, blood pressure, or lipid status in subjects with IFG and/or IGT.