Use of calcium supplements and the risk of coronary heart disease in 52–62-year-old women: The Kuopio Osteoporosis Risk Factor and Prevention Study

Background

To analyse prospectively the effect of calcium or calcium + D supplementation on coronary heart disease (CHD) in 52–62-year-old women.

Methods and results

10,555 52–62-year-old women from the population-based Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) who did not have CHD at baseline were followed for nearly 7 years in 1994–2001. Information about use of calcium supplements and health events was obtained from two repeated questionnaires in 1989 and 1994. Information about causes of death during the follow-up was obtained from the Statistics Finland. Information about CHD and other disease morbidity before and during the follow-up was obtained from the Registry of Specially Refunded Drugs of the Finnish Social Insurance Institution (SII). Cox's proportional-hazards models were used to estimate the risk of CHD morbidity related to the use of calcium supplements. At baseline, 2723 women reported current use of calcium or calcium + D supplementation. During the follow-up, CHD was diagnosed in 513 women. Compared to non-users of calcium/calcium + D supplements, the multivariate adjusted hazard ratio (HR) of CHD was 1.24 (95% CI 1.02–1.52) in women who used these supplements. The multivariate adjusted HR for CHD morbidity in postmenopausal women who used calcium/calcium + D supplements was 1.26 (95% CI 1.01–1.57).

Conclusions

Calcium or calcium + D supplementation appears to increase the risk of CHD among women before old age.     

Cell-free plasma DNA as a predictor of outcome in severe sepsis and septic shock

BACKGROUND: Increased concentrations of cell-free DNA have been found in plasma of septic and critically ill patients. We investigated the value of plasma DNA for the prediction of intensive care unit (ICU) and hospital mortality and its association with the degree of organ dysfunction and disease severity in patients with severe sepsis. METHODS: We studied 255 patients with severe sepsis or septic shock. We obtained blood samples on the day of study inclusion and 72 h later and measured cell-free plasma DNA by real-time quantitative PCR assay for the beta-globin gene. RESULTS: Cell-free plasma DNA concentrations were higher at admission in ICU nonsurvivors than in survivors (median 15 904 vs 7522 genome equivalents [GE]/mL, P < 0.001) and 72 h later (median 15 176 GE/mL vs 6758 GE/mL, P = 0.004). Plasma DNA values were also higher in hospital nonsurvivors than in survivors (P = 0.008 to 0.009). By ROC analysis, plasma DNA concentrations had moderate discriminative power for ICU mortality (AUC 0.70-0.71). In multiple regression analysis, first-day plasma DNA was an independent predictor for ICU mortality (P = 0.005) but not for hospital mortality. Maximum lactate value and Sequential Organ Failure Assessment score correlated independently with the first-day plasma DNA in linear regression analysis. CONCLUSIONS: Cell-free plasma DNA concentrations were significantly higher in ICU and hospital nonsurvivors than in survivors and showed a moderate discriminative power regarding ICU mortality. Plasma DNA concentration was an independent predictor for ICU mortality, but not for hospital mortality, a finding that decreases its clinical value in severe sepsis and septic shock.     

Heparan sulfate and syndecan-1 are essential in maintaining murine and human intestinal epithelial barrier function

Patients with protein-losing enteropathy (PLE) fail to maintain intestinal epithelial barrier function and develop an excessive and potentially fatal efflux of plasma proteins. PLE occurs in ostensibly unrelated diseases, but emerging commonalities in clinical observations recently led us to identify key players in PLE pathogenesis. These include elevated IFN-gamma, TNF-alpha, venous hypertension, and the specific loss of heparan sulfate proteoglycans from the basolateral surface of intestinal epithelial cells during PLE episodes. Here we show that heparan sulfate and syndecan-1, the predominant intestinal epithelial heparan sulfate proteoglycan, are essential in maintaining intestinal epithelial barrier function. Heparan sulfate- or syndecan-1-deficient mice and mice with intestinal-specific loss of heparan sulfate had increased basal protein leakage and were far more susceptible to protein loss induced by combinations of IFN-gamma, TNF-alpha, and increased venous pressure. Similarly, knockdown of syndecan-1 in human epithelial cells resulted in increased basal and cytokine-induced protein leakage. Clinical application of heparin has been known to alleviate PLE in some patients but its unknown mechanism and severe side effects due to its anticoagulant activity limit its usefulness. We demonstrate here that non-anticoagulant 2,3-de-O-sulfated heparin could prevent intestinal protein leakage in syndecan-deficient mice, suggesting that this may be a safe and effective therapy for PLE patients.     

Temporal cortex dopamine D2/3 receptor binding in major depression

The aim of this study was to assess the dopamine function of the temporal cortex in major depressive disorder using [¹²³I]epidepride to image D_2/3 receptor binding sites. Ten major depressives and 10 healthy controls were selected from a general population sample for single-photon emission computed tomography imaging. Among the major depressives there was a strong bilateral correlation between the scores on the 21-item Hamilton Depression Rating Scale and D_2/3 receptor binding. Dopaminergic abnormalities may be present in the temporal cortices of major depressives.     

Language Abilities of Children with Asperger Syndrome

Current diagnostic taxonomies (ICD-10, DSM-IV) emphasize normal acquisition of language in Asperger syndrome (AS). Although many linguistic sub-skills may be fairly normal in AS there are also contradictory findings. There are only few studies examining language skills of children with AS in detail. The aim of this study was to study language performance in children with AS and their age, sex and IQ matched controls. Children with AS had significantly lower scores in the subtest of Comprehension of Instructions. Results showed that although many linguistic skills may develop normally, comprehension of language may be affected in children with AS. The results suggest that receptive language processes should be studied in detail in children with AS.     

Grip Strength May Facilitate Fracture Prediction in Perimenopausal Women with Normal BMD: A 15-Year Population-Based Study

The aim of the present study was to investigate the ability of grip strength measurements to predict fracture risk in perimenopausal women according to bone mineral density (BMD). A random sample of 971 perimenopausal women from the Kuopio Osteoporosis Risk Factor and Prevention study cohort was measured with dual-energy X-ray absorptiometry (DXA) at the femoral neck and grip strength with a pneumatic squeeze dynamometer in 5-year intervals from baseline (1989-1991). Fractures during the 15-year follow-up were recorded based on self-reports and validated from medical records. In the total sample and in osteopenic or osteoporotic women (T score < -1, n = 284) grip strength was not significantly associated with fracture-free survival rate (P = nonsignificant in Cox regression). In women with normal baseline BMD (N-BMD, T score > -1, n = 687) the lowest grip strength quartile had a significantly lower fracture-free survival rate in the Cox proportional hazard model (P = 0.005, hazard ratio [HR] = 2.0). In the multivariate Cox regression model, T score and grip strength were the only significant predictors of 15-year fracture-free survival in the N-BMD group and a risk index (RI) was formed according to HRs of these two variables. High RI (0-5 points) was associated with significantly lower 15-year fracture-free survival rate (P = 0.001, HR = 0.137) in the N-BMD group. In contrast, 5-year T score was no better a predictor of fractures in the baseline N-BMD group (P = 0.04, HR = 0.36). In conclusion, grip strength predicts 15-year fracture-free survival in perimenopausal women with N-BMD, while 5-year DXA does not seem to be any better a predictor of fracture risk. DXA measurements could be coupled with simple and cost-effective grip strength measurements. Controlling BMD in women with N-BMD could be abandoned.     

Assessment of postoperative sedation level with spectral EEG parameters.

OBJECTIVES: Several sedation scores have been developed, but still a need exists for an objective method to monitor sedation level during intensive care. Our study presents a procedure for finding a combination of electroencephalogram (EEG) characteristics, which could be used in estimating sedation level.METHODS: We measured EEG in 29 cardiac surgical patients prior to and after the cardiac bypass grafting operation at different sedation levels. The clinical assessment of sedation levels was evaluated with the Ramsay Score. Spectral EEG parameters were computed and a linear model to predict postoperative sedation level was constructed by using principal component analysis and regression analysis.RESULTS: Sedation levels modified all computed spectral EEG parameters. The model based on optimal combination of EEG parameters predicted the observed Ramsay Score value with a prediction probability of 88%.CONCLUSIONS: This study suggests that a combination of spectral EEG parameters may discriminate between 3 sedation levels: awake, moderate sedation and deep sedation.     

Subtle changes in ADMA and l-arginine concentrations in normal pregnancies are unlikely to account for pregnancy-related increased flow-mediated dilatation

BACKGROUND: Our objective was to investigate whether serum concentrations of asymmetric dimethylarginine (ADMA) or l-arginine correlate to hyperlipidemia or endothelial function in normal pregnancy compared with the non-pregnant subjects. METHODS AND RESULTS: As a part of population-based, prospective cohort Cardiovascular Risk in Young Finns study conducted in Finland we examined 57 pregnant Finnish women throughout gestation and 62 control women matched for age and smoking. Serum glucose, triglycerides (TG), total cholesterol (TC), low-density cholesterol (LDL-C), high-density cholesterol (HDL-C) and ADMA, symmetric dimethylarginine (SDMA) and l-arginine were determined concomitantly with endothelium-dependent brachial artery flow-mediated dilation (FMD), measured by ultrasound. All serum lipid concentrations were significantly higher in pregnant women than in non-pregnant women (P < 0.001 for each). The mean serum ADMA concentration in pregnant women was significantly lower compared with the non-pregnant controls (0.513 micromol l(-1) +/- 0.0593 versus 0.577 micromol l(-1) +/- 0.0710, P < 0.001). Lowered ADMA concentrations did not correlate statistically to FMD in these healthy pregnant women but FMD was enhanced towards the end of pregnancy. CONCLUSIONS: ADMA and l-arginine concentrations fall in normal pregnancy despite marked hypercholesterolemia. Endothelium-dependent vasodilation is enhanced in normal pregnancy but is not statistically correlated to maternal serum ADMA or l-arginine concentrations.     

Blood pressure and heart rate variability analysis of orthostatic challenge in normal human pregnancies

The aim of the present study was to evaluate pregnancy-related changes in autonomic regulatory functions in healthy subjects. We studied cardiovascular autonomic responses to head-up tilt (HUT) in 28 pregnant women during the third trimester of pregnancy and 3 months after parturition. The maternal ECG and non-invasive beat-to-beat blood pressure were recorded in the horizontal position (left-lateral position) and during HUT in the upright position. Stroke volume was assessed from blood pressure signal by using the arterial pulse contour method. Heart rate variability (HRV) was analysed in frequency domain, and baroreflex sensitivity by the cross-spectral and the sequence methods. In the horizontal position, all frequency components of HRV were lower during pregnancy than 3 months after parturition (P < 0.01 to <0.001), while pregnancy had no influence on normalized low frequency and high frequency powers. During pregnancy haemodynamics was well balanced with only minor changes in response to postural change while haemodynamic responses to HUT were more remarkable after parturition. In pregnant women HRV and especially its very low frequency component increased in response to HUT, whereas at 3 months after parturition the direction of these changes was opposite. Parasympathetic deactivation towards term is likely to contribute to increased heart rate and cardiac output at rest, whereas restored sympathetic modulation with modest responses may contribute stable peripheral resistance and sufficient placental blood supply under stimulated conditions. It is important to understand cardiovascular autonomic nervous system and haemodynamic control in normal pregnancy before being able to judge whether they are dysregulated in complicated pregnancies.