Rolf Gedeborg

Total mortality after changes in leisure time physical activity in 50 year old men: 35 year follow-up of population based cohort

Objective To examine how change in level of physical activity after middle age influences mortality and to compare it with the effect of smoking cessation. Design Population based cohort study with follow-up over 35 years. Setting Municipality of Uppsala, Sweden. Participants 2205 men aged 50 in 1970-3 who were re-examined at ages 60, 70, 77, and 82 years. Main outcome measure Total (all cause) mortality. Results The absolute mortality rate was 27.1, 23.6, and 18.4 per 1000 person years in the groups with low, medium, and high physical activity, respectively. The relative rate reduction attributable to high physical activity was 32% for low and 22% for medium physical activity. Men who increased their physical activity level between the ages of 50 and 60 continued to have a higher mortality rate during the first five years of follow-up (adjusted hazard ratio 2.64, 95% confidence interval 1.32 to 5.27, compared with unchanged high physical activity). After 10 years of follow-up their increased physical activity was associated with reduced mortality to the level of men with unchanged high physical activity (1.10, 0.87 to 1.38). The reduction in mortality associated with increased physical activity (0.51, 0.26 to 0.97, compared with unchanged low physical activity) was similar to that associated with smoking cessation (0.64, 0.53 to 0.78, compared with continued smoking). Conclusions Increased physical activity in middle age is eventually followed by a reduction in mortality to the same level as seen among men with constantly high physical activity. This reduction is comparable with that associated with smoking cessation.

Cardiovascular Diseases and Risk of Hip Fracture

CONTEXT Recent studies indicate common etiologies for cardiovascular disease (CVD) and osteoporotic fractures. OBJECTIVES To examine the relation between CVD and risk of hip fracture in twins and evaluate the relative importance of genetics and lifestyle factors in this association. DESIGN, SETTING, AND PARTICIPANTS A cohort of all 31,936 Swedish twins born from 1914-1944 was followed up from the age of 50 years. The National Patient Registry identified twins with CVDs and fractures from 1964 through 2005. Time-dependent exposures using Cox proportional hazard regression models were evaluated. MAIN OUTCOME MEASURE Time to hip fracture after diagnosis of CVD. RESULTS The crude absolute rate of hip fractures was 12.6 per 1000 person-years after a diagnosis of heart failure, 12.6 per 1000 person-years after a stroke, 6.6 per 1000 person-years after a diagnosis of peripheral atherosclerosis, and 5.2 per 1000 person-years after a diagnosis of ischemic heart disease compared with 1.2 per 1000 person-years for those without a CVD diagnosis. The multivariable-adjusted hazard ratio (HR) of hip fracture after a diagnosis of heart failure was 4.40 (95% confidence interval [CI], 3.43-5.63); after a stroke, the HR was 5.09 (95% CI, 4.18-6.20); after a diagnosis of peripheral atherosclerosis, the HR was 3.20 (95% CI, 2.28-4.50); and after an ischemic heart disease event, the HR was 2.32 (95% CI, 1.91-2.84). Identical twins without heart failure and stroke also had, after their co-twins had been exposed to these respective diseases, an increased rate of hip fracture. These sibling twins pseudoexposed for heart failure had a multivariable-adjusted HR of 3.74 (95% CI, 1.97-7.10) for hip fracture, whereas pseudoexposure for stroke had an HR of 2.29 (95% CI, 1.20-4.35). CONCLUSIONS A diagnosis of CVD was significantly associated with risk of subsequent hip fracture. Increased risks in co-twins without an index diagnosis suggest genetic factors in the association between CVD and osteoporotic fractures.

Plasma vitamin D and mortality in older men: a community-based prospective cohort study

BACKGROUND Vitamin D status is known to be important for bone health but may also affect the development of several chronic diseases, including cancer and cardiovascular diseases, which are 2 major causes of death. OBJECTIVE We aimed to examine how vitamin D status relates to overall and cause-specific mortality. DESIGN The Uppsala Longitudinal Study of Adult Men, a community-based cohort of elderly men (mean age at baseline: 71 y; n = 1194), was used to investigate the association between plasma 25-hydroxyvitamin D [25(OH)D] and mortality. Total plasma 25(OH)D was determined with HPLC atmospheric pressure chemical ionization mass spectrometry. Proportional hazards regression was used to compute hazard ratios (HRs). RESULTS During follow-up (median: 12.7 y), 584 (49%) participants died. There was a U-shaped association between vitamin D concentrations and total mortality. An approximately 50% higher total mortality rate was observed among men in the lowest 10% (<46 nmol/L) and the highest 5% (>98 nmol/L) of plasma 25(OH)D concentrations compared with intermediate concentrations. Cancer mortality was also higher at low plasma concentrations (multivariable-adjusted HR: 2.20; 95% CI: 1.44, 3.38) and at high concentrations (HR: 2.64; 95% CI: 1.46, 4.78). For cardiovascular death, only low (HR: 1.89; 95% CI: 1.21, 2.96) but not high (HR: 1.33; 95% CI: 0.69, 2.54) concentrations indicated higher risk. CONCLUSIONS Both high and low concentrations of plasma 25(OH)D are associated with elevated risks of overall and cancer mortality. Low concentrations are associated with cardiovascular mortality.

Prevention of Soccer-Related Knee Injuries in Teenaged Girls

BACKGROUND Knee injuries end many careers among female soccer players. The number of injuries can be anticipated to increase because of the increasing popularity of the sport worldwide and the higher incidence of knee injuries among young females compared with males. METHODS In a community-based intervention trial performed from February 1 through October 31, 2007, we sought to reduce the number of knee injuries among female soccer players aged 13 to 19 years (N = 1506), representing 97 teams from 2 Swedish counties. A physical exercise program designed exclusively for female soccer players was combined with education of athletes, parents, and coaches to increase awareness of injury risk. The training program aimed to improve motor skills, body control, and muscle activation. New acute knee injuries, diagnosed by the physician, were the main outcome measure. RESULTS Three knee injuries occurred in the intervention group and 13 occurred in the control group, corresponding to incidence rates of 0.04 and 0.20, respectively, per 1000 player hours. The preventive program was associated with a 77% reduction in knee injury incidence (crude rate ratio, 0.23; 95% confidence interval, 0.04-0.83). The noncontact knee injury incidence rate was 90% lower in the intervention group (crude rate ratio, 0.10; 95% confidence interval, 0.00-0.70). Adjustment for potential confounders strengthened the estimates. Forty-five of the 48 intervention teams (94%) reported a high adherence of at least 75%. CONCLUSION The incidence of knee injuries among young female soccer players can be reduced by implementation of a multifaceted, soccer-specific physical exercise program including education of individual players.

Determining vitamin D status: a comparison between commercially available assays.

Background Vitamin D is not only important for bone health but can also affect the development of several non-bone diseases. The definition of vitamin D insufficiency by serum levels of 25-hydroxyvitamin D depends on the clinical outcome but might also be a consequence of analytical methods used for the definition. Although numerous 25-hydroxyvitamin D assays are available, their comparability is uncertain. We therefore aim to investigate the precision, accuracy and clinical consequences of differences in performance between three common commercially available assays. Methodology/Principal Findings Serum 25-hydroxyvitamin D levels from 204 twins from the Swedish Twin Registry were determined with high-pressure liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (HPLC-APCI-MS), a radioimmunoassay (RIA) and a chemiluminescent immunoassay (CLIA). High inter-assay disagreement was found. Mean 25-hydroxyvitamin D levels were highest for the HPLC-APCI-MS technique (85 nmol/L, 95% CI 81–89), intermediate for RIA (70 nmol/L, 95% CI 66–74) and lowest with CLIA (60 nmol/L, 95% CI 56–64). Using a 50-nmol/L cut-off, 8% of the subjects were insufficient using HPLC-APCI-MS, 22% with RIA and 43% by CLIA. Because of the heritable component of 25-hydroxyvitamin D status, the accuracy of each method could indirectly be assessed by comparison of within-twin pair correlations. The strongest correlation was found for HPLC-APCI-MS (r = 0.7), intermediate for RIA (r = 0.5) and lowest for CLIA (r = 0.4). Regression analyses between the methods revealed a non-uniform variance (p<0.0001) depending on level of 25-hydroxyvitamin D. Conclusions/Significance There are substantial inter-assay differences in performance. The most valid method was HPLC-APCI-MS. Calibration between 25-hydroxyvitamin D assays is intricate.

Dietary calcium intake and risk of fracture and osteoporosis: prospective longitudinal cohort study.

Objective To investigate associations between long term dietary intake of calcium and risk of fracture of any type, hip fractures, and osteoporosis. Design A longitudinal and prospective cohort study, based on the Swedish Mammography Cohort, including a subcohort, the Swedish Mammography Cohort Clinical. Setting A population based cohort in Sweden established in 1987. Participants 61 433 women (born between 1914 and 1948) were followed up for 19 years. 5022 of these women participated in the subcohort. Main outcome measures Primary outcome measures were incident fractures of any type and hip fractures, which were identified from registry data. Secondary outcome was osteoporosis diagnosed by dual energy x ray absorptiometry in the subcohort. Diet was assessed by repeated food frequency questionnaires. Results During follow-up, 14 738 women (24%) experienced a first fracture of any type and among them 3871 (6%) a first hip fracture. Of the 5022 women in the subcohort, 1012 (20%) were measured as osteoporotic. The risk patterns with dietary calcium were non-linear. The crude rate of a first fracture of any type was 17.2/1000 person years at risk in the lowest quintile of calcium intake, and 14.0/1000 person years at risk in the third quintile, corresponding to a multivariable adjusted hazard ratio of 1.18 (95% confidence interval 1.12 to 1.25). The hazard ratio for a first hip fracture was 1.29 (1.17 to 1.43) and the odds ratio for osteoporosis was 1.47 (1.09 to 2.00). With a low vitamin D intake, the rate of fracture in the first calcium quintile was more pronounced. The highest quintile of calcium intake did not further reduce the risk of fractures of any type, or of osteoporosis, but was associated with a higher rate of hip fracture, hazard ratio 1.19 (1.06 to 1.32). Conclusion Gradual increases in dietary calcium intake above the first quintile in our female population were not associated with further reductions in fracture risk or osteoporosis.

Plasma 25-Hydroxyvitamin D Levels and Fracture Risk in a Community-Based Cohort of Elderly Men in Sweden

CONTEXT Blood levels of 25-hydroxyvitamin D [25(OH)D] is the generally accepted indicator of vitamin D status, but no universal reference level has been reached. OBJECTIVE The objective of the study was to determine the threshold at which low plasma 25(OH)D levels are associated with fractures in elderly men and clarify the importance of low levels on total fracture burden. DESIGN AND PARTICIPANTS In the Uppsala Longitudinal Study of Adult Men, a population-based cohort (mean age, 71 yr, n = 1194), we examined the relationship between 25(OH)D and risk for fracture. Plasma 25(OH)D levels were measured with high-pressure liquid chromatography-mass spectrometry. SETTING The study was conducted in the municipality of Uppsala in Sweden, a country with a high fracture incidence. MAIN OUTCOME MEASURE Time to fracture was measured. RESULTS During follow-up (median 11 yr), 309 of the participants (26%) sustained a fracture. 25(OH)D levels below 40 nmol/liter, which corresponded to the fifth percentile of 25(OH)D, were associated with a modestly increased risk for fracture, multivariable-adjusted hazard ratio 1.65 (95% confidence interval 1.09-2.49). No risk difference was detected above this level. Approximately 3% of the fractures were attributable to low 25(OH)D levels in this population. CONCLUSIONS Vitamin D insufficiency is not a major cause of fractures in community-dwelling elderly men in Sweden. Despite the fact that cutaneous synthesis of previtamin D during the winter season is undetectable at this northern latitude of 60 degrees, only one in 20 had 25(OH)D levels below 40 nmol/liter, the threshold at which the risk for fracture started to increase. Genetic adaptations to limited UV light may be an explanation for our findings.

Seasonal Genetic Influence on Serum 25-Hydroxyvitamin D Levels: A Twin Study

Background Although environmental factors, mainly nutrition and UV-B radiation, have been considered major determinants of vitamin D status, they have only explained a modest proportion of the variation in serum 25-hydroxyvitamin D. We aimed to study the seasonal impact of genetic factors on serum 25-hydroxyvitamin D concentrations. Methodology/Principal findings 204 same-sex twins, aged 39–85 years and living at northern latitude 60°, were recruited from the Swedish Twin Registry. Serum 25-hydroxyvitamin D was analysed by high-pressure liquid chromatography and mass spectrometry. Genetic modelling techniques estimated the relative contributions of genetic, shared and individual-specific environmental factors to the variation in serum vitamin D. The average serum 25-hydroxyvitamin D concentration was 84.8 nmol/l (95% CI 81.0–88.6) but the seasonal variation was substantial, with 24.2 nmol/l (95% CI 16.3–32.2) lower values during the winter as compared to the summer season. Half of the variability in 25-hydroxyvitamin D during the summer season was attributed to genetic factors. In contrast, the winter season variation was largely attributable to shared environmental influences (72%; 95% CI 48–86%), i.e., solar altitude. Individual-specific environmental influences were found to explain one fourth of the variation in serum 25-hydroxyvitamin D independent of season. Conclusions/Significance There exists a moderate genetic impact on serum vitamin D status during the summer season, probably through the skin synthesis of vitamin D. Further studies are warranted to identify the genes impacting on vitamin D status.

Identification of Incident Injuries in Hospital Discharge Registers

Background: Hospital discharge data on injuries constitute a potentially powerful data source for epidemiologic studies. However, reliable identification of incident injury admissions is necessary. The objective of this study was to develop a prediction model for identifying incident hospital admissions, based on variables derived from a hospital discharge register. Methods: There were 743,022 hospital admissions for injury in Sweden 1998–2004. Of these, 23,920 were in the county of Uppsala and 24% of these people had previous injury admissions. To determine if these admissions were new injuries or readmissions for earlier injuries, we reviewed 817 randomly selected hospital records. A prediction model for incident injury admissions was developed on the basis of patient age, type of admission (urgent or elective), time interval from the previous injury admission, main diagnosis, and department type. Results: The final prediction model showed good discrimination (c-statistic = 0.969). This model was applied to the validation dataset using the optimal cut-off level, and the resulting sensitivity and specificity were adjusted according to the proportion with a previous injury admission in each injury category. The injury with the highest proportion of possible readmissions was hip contusion (35%). Nevertheless, using the prediction model, incident hip contusions were identified with a sensitivity of 94% (95% confidence interval = 93%–95%) and a specificity of 95% (94%–97%). The accuracy was higher for all other injury categories. Conclusions: Incident injury admissions can be accurately separated from readmissions using a prediction model based on information derived from hospital discharge data.

Simply Ask Them About Their Balance—Future Fracture Risk in a Nationwide Cohort Study of Twins

The principal causal components of an osteoporotic fracture are a fall and weakened bone strength. While bone quality measures have been frequently studied, the ability of simple measures of impaired balance to predict fracture risk has received less attention. Computer-assisted telephone interviews were conducted between 1998 and 2000 among 24,598 Swedish twins aged 55 years or older. Impaired balance at the time of interview was reported by 2,890 (12%) of the twins. Twin pairs who were discordant with regard to impaired balance were selected for analysis and followed for fractures through 2005. In a pairwise analysis, the odds ratio for hip fracture was 3.13 (95% confidence interval (CI): 1.62, 6.05) among twins with impaired balance as compared with their co-twins with normal balance. When previously recognized clinical risk factors for osteoporotic fracture were considered in the model, the odds ratio for hip fracture with impaired balance was 3.88 (95% CI: 1.40, 10.72). Approximately 40% of all hip fractures were attributable to impaired balance. The odds ratios for any fracture and any osteoporotic fracture for twins with impaired balance were 2.00 (95% CI: 1.29, 3.11) and 2.39 (95% CI: 1.49, 3.82), respectively. These results imply that self-reported impaired balance is a novel and readily assessed risk factor for future fractures in the elderly.