On certain genetic and metabolic risk factors for carotid stenosis and stroke

The present study evaluated genetic and metabolic factors influencing the risk of acute cerebrovascular disease (CVD) and internal carotid artery stenosis (ICA stenosis) in a Swedish community. The threonine (T) containing protein of the FABP2 A54T gene polymorphism has a greater affinity for long chain fatty acids (FFAs) than the alanine (A) containing protein. This altered affinity for FFAs has been shown to affect the intestinal absorption of fatty acids and consequently the fatty acid composition of serum lipids, in particularly postprandially. Endothelium derived NO is a potent vasodilator and antiatherogenic agent. Asymmetric dimethyl arginine (ADMA) is an endogenous competitive inhibitor of endothelial nitric oxide synthase (eNOS). ADMA has been shown to be involved in the pathogenesis of atherosclerotic disease, and ADMA inhibits eNOS by displacement of L-arginine from the enzyme, which in turn is believed to affect the amount of NO available within the endothelium. The FABP2 A54T gene polymorphism was analyzed in 407 patients with acute CVD and also in a subset of these patients whose carotids had been evaluated with ultrasound. Both the FABP2 polymorphism and a common polymorphism of the eNOS gene, Glu298Asp, were analyzed in a different population consisting of 54 matched pairs of patients with ICA stenosis and controls. ADMA levels were measured in both study populations. We found that the T54 allele was more frequent in patients with transient ischaemic attacks (TIA), and that the TT genotype was more prevalent in young, non-smoking patients with CVD than in controls. Increased concentrations of ADMA were observed in cardio-embolic infarction and TIA, but not significantly in non-cardio-embolic infarction nor in haemorrhagic stroke. In multivariate logistic regression models, CVD increased across quartiles of ADMA in all subgroups, but this association was only significant in the TIA group. A decreased arginine/ADMA ratio, a measure of NO availability was associated with CVD in the entire study population. Patients with severe carotid stenosis had significantly higher ADMA levels than the controls. Allele and genotype frequencies of the FABP2 and eNOS polymorphisms did not differ between patients with ICA stenosis and controls. Our results indicate that ADMA is a strong marker for TIA and severe ICA stenosis, and that relative defiency of arginine, measured as L-arginine/ADMA, is present in acute CVD. We also conclude that a common polymorphism of the FABP2 gene increases susceptibility to ischaemic stroke and TIA.Figure 4 on page 17 is publshed with kind permisson from The Journal of Physiology (http://jp.physoc.org/).</p

Modestly degraded microarchitecture and high serum levels of osteopontin in Swedish females with anorexia nervosa

Purpose Adult women with long-time anorexia nervosa (AN) are believed to have osteopenia (T-score &amp;lt;= 1.0) in 93 % and osteoporosis (T-score &amp;lt;= 2.5) in 38 %. Bone microarchitecture assessed by Trabecular Bone Score (TBS) predicts osteoporotic fractures. Our aim was to evaluate the microarchitecture in adult females with AN by determining TBS and to identify factors potentially associated with TBS, such as bone turnover markers. Methods 20 female patients with AN (DSM IV), aged 27.8 +/- 4.4 years, BMI 16.6 +/- 0.6 kg/m(2) and duration of illness of 8.5 +/- 5 years had previously been evaluated with dual-energy X-ray absorptiometry (DXA). TBS measurements were now obtained, using iNsight software, from spinal DXA images. Serum levels of bone turnover markers were determined in patients and healthy normal-weight controls. Results Compared to controls serum values of osteopontin were higher (p = 0.009). BMD in patients with AN was reduced by at least 1.0 SD at one or more skeletal sites in 65 % of patients and by at least 2.5 SD in 20 %. Only one of the patients (5%) had suffered a fracture. TBS (mean 1.35 +/- 0.06; median 1.36 (1.23-1.44) was in the lower normal range (&amp;gt;= 1.35). 40 % of patients showed partially (&amp;gt; 1.20 and &amp;lt; 1.35) but none showed a fully degraded micro-architecture. Conclusions In Swedish AN patients we found a low reduction of BMD and fracture history. The bone microarchitecture, evaluated for the first time for this group by TBS, was only modestly compromised, and to a lesser extent than expected for this group of patients with AN.Funding Agencies|Linnaeus University; Medical Research Council of Southeast Sweden (FORSS)</p

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On certain genetic and metabolic risk factors for caroti

A cost analysis of systematic vitamin D supplementation in the elderly versus supplementation based on assessed requirements

Hypovitaminosis D is common among older people and treatment with vitamin D is associated with reduced risk of falls and fractures. This paper provides a cost analysis of assessing the vitamin D status of and providing the pharmaceuticals for elderly citizens in Kalmar County, Sweden (population approximately 230,000). Four hypothetical interventions were analyzed: (a) systematic vitamin D/calcium supplementation to all elderly (≥75 years), (b) assessment of vitamin D status in elderly and supplementation to those with insufficient levels, (c) systematic vitamin D/calcium supplementation to all nursing-home residents, and (d) assessment of vitamin D status in nursing-home residents and supplementation to those with insufficient levels. The calculations were based on an estimated reduction in overall costs due to the assessed number of hip fractures after vitamin D/calcium supplementation. The annual net economic benefit of vitamin D/calcium supplementation was estimated at (a) €304,000, (b) €860,000, (c) €755,000, and (d) €740,000. The provision of systematic vitamin D supplementation to nursing-home residents would provide a substantial net economic benefit to society and assessment of the vitamin D status before starting supplementation does not seem to be necessary. Although assessment of all elderly citizens would be more comprehensive, the true proportion with insufficient vitamin D levels in the general population is uncertain and to reaching consensus on the most advantageous daily vitamin D intake, vitamin D blood levels are necessary. Also, systematic supplementation to all elderly would result in other outcomes that could be worth the cost, but that remains to be evaluated.Betydelsen av bra D-vitaminstatus för äldres häls

Assessing heart rate variability in type 1 diabetes mellitus—Psychosocial stress a possible confounder

Abstract Background Autonomic neuropathy (AN) commonly arises as a long‐term complication in diabetes mellitus and can be diagnosed from heart rate variability (HRV), calculated from electrocardiogram recordings. Psychosocial stress also affects HRV and could be one of several confounders for cardiac AN. The present work investigated the impact of psychosocial stress on HRV in individuals with type 1 diabetes mellitus (T1DM) and assessed the use of salivary cortisol as a biomarker for psychosocial stress in this context. Methods A total of 167 individuals 6–60 years old (113 with T1DM and 54 healthy controls) underwent 24‐hr ECG recordings with HRV analysis. Salivary cortisol was sampled thrice during the registration day. Perceived psychosocial stress along with other factors of possible importance for the interpretation of HRV was documented in a diary. Results Heart rate variability (high‐frequency power during sleep) was reduced (p < .05) with older age, longer diabetes duration, higher mean glucose levels, physical inactivity, and perceived psychosocial stress. Salivary cortisol levels in the evening were increased (p < .05) in women in ovulation phase, in individuals with preceding hypoglycemia or with hyperglycemia. The amplitude of salivary cortisol was reduced (p < .05) with the presence of perceived psychosocial stress, but only in adult healthy controls, not in individuals with diabetes. Conclusion Psychosocial stress might be a confounder for reduced HRV when diagnosing cardiac AN in T1DM. Salivary cortisol is, however, not a useful biomarker for psychosocial stress in diabetes since the physiological stress of both hypoglycemia and hyperglycemia seems to overrule the effect of psychosocial stress on cortisol

A novel index to assess low energy fracture risks in patients prescribed antiepileptic drugs

Objective To develop an index assessing the risks of low energy fractures (LEF) in patients prescribed antiepileptic drugs (AED) by exploring five previously suggested risk factors; age, gender, AED-type, epilepsy diagnosis and BMI. Methods In a population-based retrospective open cohort study we used real world data from the Electronic Health Register (EHR) in Region Kalmar County, Sweden. 23 209 patients prescribed AEDs at any time from January 2008 to November 2018 and 23 281 matching controls were followed from first registration in the EHR until the first documented LEF, disenrollment (or death) or until the end of the study period, whichever came first. Risks of LEF measured as hazard rate ratios in relation to the suggested risk factors and in comparison to matched controls were analyzed using Cox regression. The index was developed using a linear combination of the statistically significant variables multiplied by the corresponding regression coefficients. Results Data from 23 209 patients prescribed AEDs and 2084 documented LEFs during a follow-up time of more than 10 years resulted in the Kalmar Epilepsy Fracture Risk Index (KEFRI). KEFRI = Age-category x (1.18) + Gender x (-0.51) + AED-type x (0.29) + Epilepsy diagnosis-category x (0.31) + BMI-category x (-0.35). All five previously suggested risk factors were confirmed. Women aged 75 years and older treated with an inducing AED against epilepsy and BMIs of 25 kg/m(2) or below had 48 times higher LEF rates compared to men aged 50 years or younger, treated with a non-inducing AED for a condition other than epilepsy and BMIs above 25 kg/m(2). Conclusion The KEFRI is the first weighted multifactorial assessment tool estimating risks of LEF in patients prescribed AEDs and could serve as a feasible guide within clinical practice

A comparison in women with newly diagnosed diabetes between those with and without a history of gestational diabetes : a new perspective

Aims: Previous gestational diabetes mellitus (GDM) entails increased risk of future diabetes. We describe the characteristics of women with previous GDM and compare with no previous GDM from the cohort Diabetes in Kalmar and Kronoberg (DKK) of 1248 adults, 40% women, with new diabetes, and factors affecting age and C-peptide levels at diagnosis of diabetes. Methods: Age-at-diagnosis of diabetes, BMI, hypertension, hyperlipidemia, smoking, physical activity, and pre-existing myocardial infarction, stroke, or peripheral arterial insufficiency were registered at ordinary care visits close to diagnosis of diabetes, for the 43 women (9.4% of 456 from DKK with complete data for this analysis) with self-reported previous GDM (yes/no) and 86 controls without it, matched for date of diagnosis of diabetes. Blood samples were centrally analyzed for GADA and C-peptide for classification of diabetes. Results: Women with previous GDM had lower mean age-at-diagnosis of diabetes, 53.4 vs 65.0 years, lower systolic blood pressure (SBP), 131.2 vs 137.5 mmHg, and fewer had pre-existing hypertension than without previous GDM (p < 0.001–0.05). Among antibody negative women with previous GDM, BMI (p = 0.024), hypertension (p = 0.023) and hyperlipidemia (p < 0.001) were associated with higher levels of C-peptide, while physical activity was inversely associated (p = 0.035), and SBP (p = 0.02) and hypertension (p = 0.016) were associated with age-at-diagnosis of diabetes. Conclusions: Women with previous GDM were a decade younger and had lower prevalence of hypertension at diagnosis of diabetes; C-peptide levels were associated with BMI, hypertension, and hyperlipidemia and showed a tendency to be lower, possibly indicating a phenotype with higher risk of overt cardiovascular disease later in life

Older Swedish Adults with High Self-Perceived Health Show Optimal 25-Hydroxyvitamin D Levels Whereas Vitamin D Status Is Low in Patients with High Disease Burden

Controversy pervades the definition of adequate and optimal vitamin D status. The Institutes of Medicine have recommended serum 25(OH) D levels above 50 nmol/L based upon evidence related to bone health, but some experts, including the Endocrine Society and International Osteoporosis Foundation, suggest a minimum serum 25(OH) D level of 75 nmol/L to reduce the risk of falls and fractures in older adults. In a cross-sectional study, we compared vitamin D status in people amp;gt;= 75 years selected from four groups with a frailty phenotype, combined with a control group free from serious illness, and who considered themselves completely healthy. Only 13% of the 169 controls were vitamin D deficient (S-25(OH) D) amp;lt; 50 nmol/L), in contrast with 49% of orthopedic patients with hip fractures (n = 133), 31% of stroke patients (n = 122), 39% of patients visiting the hospitals emergency department amp;gt;= 4 times a year (n = 81), and 75% of homebound adult residents in long-term care nursing homes (n = 51). The mean vitamin D concentration of the healthy control group (74 nmol/L) was similar to a suggested optimal level based on physiological data and mortality studies, and much higher than that of many officially recommended cut-off levels for vitamin D deficiency (amp;lt; 50 nmol/L). The present study provides a basis for planning and implementing public guidelines for the screening of vitamin D deficiency and vitamin D treatment for frail elderly patients.Funding Agencies|Kamprad family foundation</p

Depression was associated with younger age, female sex, obesity, smoking, and physical inactivity, in 1027 patients with newly diagnosed type 2 diabetes : a Swedish multicentre cross-sectional study

Background: Depression is a risk factor for type 2 diabetes (T2D) and cardiovascular disease (CVD). The aims were to explore the prevalence of depression, anxiety, antidepressant use, obesity, Hemoglobin A1c > 64 mmol/mol, life-style factors, pre-existing CVD, in patients with newly diagnosed T2D; to explore associations with depression; and to compare with Swedish general population data. Methods: Multicentre, cross-sectional study. Inclusion criteria: adults with serologically verified newly diagnosed T2D. Included variables: age, sex, current depression and anxiety (Hospital Anxiety and Depression Scale), previous depression, antidepressant use, obesity (BMI ≥ 30 and ≥ 40 kg/m2), Hemoglobin A1c, pre-existing CVD. Logistic regression analyses were performed. Results: In 1027 T2D patients, aged 18–94 years, depression was associated with age (per year) (inversely) (odds ratio (OR) 0.97), anxiety (OR 12.2), previous depression (OR 7.1), antidepressant use (OR 4.2), BMI ≥ 30 kg/m2 (OR 1.7), BMI ≥ 40 kg/m2 (OR 2.3), smoking (OR 1.9), physical inactivity (OR 1.8), and women (OR 1.6) (all p ≤ 0.013). Younger women (n = 113), ≤ 59 years, compared to younger men (n = 217) had higher prevalence of current depression (31% vs 12%), previous depression (43 vs 19%), anxiety (42% vs 25%), antidepressant use (37% vs 12%), BMI ≥ 30 kg/m2 (73% vs 60%) and BMI ≥ 40 kg/m2) (18% vs 9%), and smoking (26% vs 16%) (all p ≤ 0.029). Older women (n = 297), ≥ 60 years, compared to older men (n = 400) had higher prevalence of previous depression (45% vs 12%), anxiety (18% vs 10%), antidepressant use (20% vs 8%), BMI ≥ 30 kg/m2 (55% vs 47%), BMI ≥ 40 kg/m2 (7% vs 3%) (all p ≤ 0.048), but not of current depression (both 9%). Compared to the Swedish general population (depression (women 11.2%, men 12.3%) and antidepressant use (women 9.8%, men 5.3%)), the younger women had higher prevalence of current depression, and all patients had higher prevalence of antidepressant use. Conclusions: In patients with newly diagnosed T2D, the younger women had the highest prevalence of depression, anxiety, and obesity. The prevalence of depression in young women and antidepressant use in all patients were higher than in the Swedish general population. Three risk factors for CVD, obesity, smoking, and physical inactivity, were associated with depression