External validation of the Garvan nomograms for predicting absolute fracture risk: The Tromso study

Background: Absolute risk estimation is a preferred approach for assessing fracture risk and treatment decision making. This study aimed to evaluate and validate the predictive performance of the Garvan Fracture Risk Calculator in a Norwegian cohort. Methods: The analysis included 1637 women and 1355 aged 60+ years from the Tromsø study. All incident fragility fractures between 2001 and 2009 were registered. The predicted probabilities of non-vertebral osteoporotic and hip fractures were determined using models with and without BMD. The discrimination and calibration of the models were assessed.Reclassification analysis was used to compare the models performance. Results: The incidence of osteoporotic and hip fracture was 31.5 and 8.6 per 1000 population in women, respectively; in men the corresponding incidence was 12.2 and 5.1. The predicted 5-year and 10-year probability of fractures was consistently higher in the fracture group than the non-fracture group for all models. The 10-year predicted probabilities of hip fracture in those with fracture was 2.8 (women) to 3.1 times (men) higher than those without fracture. There was a close agreement between predicted and observed risk in both sexes and up to the fifth quintile. Among those in the highest quintile of risk, the models over-estimated the risk of fracture. Models with BMD performed better than models with body weight in correct classification of risk in individuals with and without fracture. The overall net decrease in reclassification of the model with weight compared to the model with BMD was 10.6% (p = 0.008) in women and 17.2% (p = 0.001) in men for osteoporotic fractures, and 13.3% (p = 0.07) in women and 17.5% (p = 0.09) in men for hip fracture. Conclusions: The Garvan Fracture Risk Calculator is valid and clinically useful in identifying individuals at high risk of fracture. The models with BMD performed better than those with body weight in fracture risk prediction

The impact of carotid plaque presence and morphology on mortality outcome in cardiological patients

BACKGROUND: Carotid plaque severity and morphology can affect cardiovascular prognosis. We evaluate both the importance of echographically assessed carotid artery plaque geometry and morphology as predictors of death in hospitalised cardiological patients. METHODS: 541 hospitalised patients admitted in a cardiological division (age = 66 ± 11 years, 411 men), have been studied through ultrasound Duplex carotid scan and successively followed-up for a median of 34 months. Echo evaluation assessed plaque severity and morphology (presence of heterogeneity and profile). RESULTS: 361 patients showed carotid stenosis (67% with <50% stenosis, 18% with 50–69% stenosis, 9% with >70% stenosis, 4% with near occlusion and 2% with total occlusion). During the follow-up period, there were 83 all-cause deaths (15% of the total population). Using Cox's proportional hazard model, age (RR 1.06, 95% CI 1.03–1.09, p = 0.000), ejection fraction > 50% (RR = 0.62, 95% CI 0.4–0.96, p = 0.03), treatment with statins (RR = 0.52, 95% CI 0.29–0.95, p = 0.34) and the presence of a heterogeneous plaque (RR 1.6; 95% CI, 1.2 to 2.14, p = 0.002) were independent predictors of death. Kaplan – Meier survival estimates have shown the best outcome in patients without plaque, intermediate in patients with homogeneous plaques and the worst outcome in patients with heterogeneous plaques (90% vs 79% vs 73%, p = 0.0001). CONCLUSION: In hospitalised cardiological patients, carotid plaque presence and morphology assessed by ultrasound are independent predictors of death

The association between timed up and go test and history of falls: The Tromsø study

BACKGROUND: Fall-related injuries in older adults are a major health problem. Although the aetiology of falls is multifactorial, physical factors are assumed to contribute significantly. The "Timed up and go test" (TUG) is designed to measure basic mobility function. This report evaluates the association between TUG times and history of falls. METHODS: A retrospective, observational, population-based study was conducted on 414 men and 560 women with mean age 77.5 (SD 2.3). TUG time and falls during the previous 12 months were recorded. Covariates were age, sex, medical history and health-related mobility problems. Means, confidence intervals and test characteristics for TUG were calculated. Odds ratios and influence of covariates were examined by logistic regression. RESULTS: The mean TUG time was 11.1s (SD 2.5) among male non-fallers and 13.0s (SD 7.8) among fallers. The difference was 1.9s (95%CI 0.9–3.0). The odds ratio for fallers being in the upper quartile was 2.1 (95%CI 1.4–3.3). Adjusted for covariates, the odds ratio was (OR = 1.8, 95%CI 1.1–2.9). The corresponding mean was 13.0s (SD 5.74) among female non-fallers and 13.9s (SD 8.5) among fallers. The difference was 0.9 (95%CI -0.3–2.1). The odds ratio for fallers being in upper quartile was 1.0 (95%CI 0.7–1.4). The area under the ROC curve was 0.50 (95%CI 0.45–0.55) in women and 0.56 (95%CI 0.50–0.62) in men. CONCLUSION: TUG is statistically associated with a history of falls in men but not in women. The ability to classify fallers is poor, and the clinical value of the association is therefore limited

Effect of genetically low 25-hydroxyvitamin D on mortality risk: Mendelian randomization analysis in 3 large European cohorts

Source at https://doi.org/10.3390/nu11010074.The aim of this study was to determine if increased mortality associated with low levels of serum 25-hydroxyvitamin D (25(OH)D) reflects a causal relationship by using a Mendelian randomisation (MR) approach with genetic variants in the vitamin D synthesis pathway. Individual participant data from three European cohorts were harmonized with standardization of 25(OH)D according to the Vitamin D Standardization Program. Most relevant single nucleotide polymorphisms of the genes CYP2R1 (rs12794714, rs10741657) and DHCR7/NADSYN1 (rs12785878, rs11234027), were combined in two allelic scores. Cox proportional hazards regression models were used with the ratio estimator and the delta method for calculating the hazards ratio (HR) and standard error of genetically determined 25(OH)D effect on all-cause mortality. We included 10,501 participants (50.1% females, 67.1±10.1 years) of whom 4003 died during a median follow-up of 10.4 years. The observed adjusted HR for all-cause mortality per decrease in 25(OH)D by 20 nmol/L was 1.20 (95% CI: 1.15–1.25). The HR per 20 nmol/L decrease in genetically determined 25(OH)D was 1.32 (95% CI: 0.80–2.24) and 1.35 (95% CI of 0.81 to 2.37) based on the two scores. In conclusion, the results of this MR study in a combined sample from three European cohort studies provide further support for a causal relationship between vitamin D deficiency and increased all-cause mortality. However, as the current study, even with ~10,000 participants, was underpowered for the study of the effect of the allele score on mortality, larger studies on genetics and mortality are needed to improve the precision

Sex-differential genetic effect of phosphodiesterase 4D (PDE4D) on carotid atherosclerosis

<p>Abstract</p> <p>Background</p> <p>The phosphodiesterase 4D (PDE4D) gene was reported as a susceptibility gene to stroke. The genetic effect might be attributed to its role in modulating the atherogenic process in the carotid arteries. Using carotid intima-media thickness (IMT) and plaque index as phenotypes, the present study sought to determine the influence of this gene on subclinical atherosclerosis.</p> <p>Methods</p> <p>Carotid ultrasonography was performed on 1013 stroke-free subjects who participated in the health screening programs (age 52.6 ± 12.2; 47.6% men). Genotype distribution was compared among the high-risk (plaque index ≥ 4), low-risk (index = 1-3), and reference (index = 0) groups. We analyzed continuous IMT data and further dichotomized IMT data using mean plus one standard deviation as the cutoff level. Because the plaque prevalence and IMT values displayed a notable difference between men and women, we carried out sex-specific analyses in addition to analyzing the overall data. Rs702553 at the PDE4D gene was selected because it conferred a risk for young stroke in our previous report. Previous young stroke data (190 cases and 211 controls) with an additional 532 control subjects without ultrasonic data were shown as a cross-validation for the genetic effect.</p> <p>Results</p> <p>In the overall analyses, the rare homozygote of rs702553 led to an OR of 3.1 (p = 0.034) for a plaque index ≥ 4. When subjects were stratified by sex, the genetic effect was only evident in men but not in women. Comparing male subjects with plaque index ≥ 4 and those with plaque index = 0, the TT genotype was over-represented (27.6% vs. 13.4%, p = 0.008). For dichotomized IMT data in men, the TT genotype had an OR of 2.1 (p = 0.032) for a thicker IMT at the common carotid artery compared with the (AA + AT) genotypes. In women, neither IMT nor plaque index was associated with rs702553. Similarly, SNP rs702553 was only significant in young stroke men (OR = 1.8, p = 0.025) but not in women (p = 0.27).</p> <p>Conclusions</p> <p>The present study demonstrates a sex-differential effect of PDE4D on IMT, plaque index and stroke, which highlights its influence on various aspects of atherogenesis.</p

Progressively Increasing Fracture Risk With Advancing Age After Initial Incident Fragility Fracture: The Tromso Study

The risk of subsequent fracture is increased after initial fractures; however, proper understanding of its magnitude is lacking. This population-based study examines the subsequent fracture risk in women and men by age and type of initial incident fracture. All incident nonvertebral fractures between 1994 and 2009 were registered in 27,158 participants in the TromsO Study, Norway. The analysis included 3108 subjects with an initial incident fracture after the age of 49 years. Subsequent fracture (n=664) risk was expressed as rate ratios (RR) and absolute proportions irrespective of death. The rates of both initial and subsequent fractures increased with age, the latter with the steepest curve. Compared with initial incident fracture rate of 30.8 per 1000 in women and 12.9 per 1000 in men, the overall age-adjusted RR of subsequent fracture was 1.3 (95% CI, 1.2-1.5) in women, and 2.0 (95% CI, 1.6-2.4) in men. Although the RRs decreased with age, the absolute proportions of those with initial fracture who suffered a subsequent fracture increased with age; from 9% to 30% in women and from 10% to 26% in men, between the age groups 50-59 to 80+ years. The type of subsequent fracture varied by age from mostly minor fractures in the youngest to hip or other major fractures in the oldest age groups, irrespective of type and severity of initial fracture. In women and men, 45% and 38% of the subsequent hip or other major fractures, respectively, were preceded by initial minor fractures. The risk of subsequent fracture is high in all age groups. At older age, severe subsequent fracture types follow both clinically severe and minor initial incident fractures. Any fragility fracture in the elderly reflects the need for specific osteoporosis management to reduce further fracture risk