Associations of Dehydroepiandrosterone Sulfate With Cardiometabolic Risk Factors in Prepubertal Children.

Context: Premature adrenarche (PA) has been associated with overweight and insulin resistance, but the associations of serum dehydroepiandrosterone sulfate (DHEAS) concentration with other cardiometabolic risk factors are uncertain. Objective: To examine the associations of serum DHEAS concentration with several cardiometabolic risk factors in children. Design: Cross-sectional data from the Physical Activity and Nutrition in Children Study. Participants: Population sample of 207 girls and 225 boys aged 7.6 ± 0.4 years. Main Outcome Measures: Cardiometabolic risk factors by serum DHEAS concentration. Results: DHEAS correlated positively with body mass index standard deviation score, body fat percentage, lean body mass, high-sensitivity C-reactive protein (hs-CRP), and alanine aminotransferase (ALT) when adjusted for age and sex. The associations of DHEAS with hs-CRP and ALT disappeared when adjusted also for body fat percentage. When further adjusted for birth weight SD score, DHEAS correlated negatively with low-density lipoprotein (LDL) cholesterol and LDL/high-density lipoprotein (HDL) cholesterol ratio. LDL cholesterol was lower in children with DHEAS ≥40 µg/dL than in those with DHEAS <40 µg/dL, adjusted for age, sex, and body fat percentage (86.5 vs 92.3 mg/dL, P = 0.029). This association strengthened after further adjustment for birth weight SD score (85.3 vs 92.3 mg/dL, P = 0.012). Conclusion: Higher DHEAS is not associated with an increased cardiometabolic risk in prepubertal children. Instead, it may be protective, evidenced by an association with lower LDL cholesterol and LDL/HDL cholesterol ratio. The increased cardiometabolic risk in PA shown in many studies may be due to low birth weight and childhood overweight associated with PA.

Participatory operations model for cost-efficient monitoring and modeling of river basins--A systematic approach.

The worldwide economic downturn and the climate change in the beginning of 21st century have stressed the need for cost efficient and systematic operations model for the monitoring and management of surface waters. However, these processes are still all too fragmented and incapable to respond these challenges. For example in Finland, the estimation of the costs and benefits of planned management measures is insufficient. On this account, we present a new operations model to streamline these processes and to ensure the lucid decision making and the coherent implementation which facilitate the participation of public and all the involved stakeholders. The model was demonstrated in the real world management of a lake. The benefits, pitfalls and development needs were identified. After the demonstration, the operations model was put into operation and has been actively used in several other management projects throughout Finland.

Serum hyperglycosylated human chorionic gonadotrophin at 14-17 weeks of gestation does not predict preeclampsia.

INTRODUCTION: Low first-trimester serum concentrations of hyperglycosylated human chorionic gonadotrophin (hCG-h) predict later preeclampsia. We studied whether serum hCG-h at 14-17 weeks of pregnancy also predicts preeclampsia alone or combined with placental growth factor (PlGF) and soluble vascular endothelial growth factor 1 (sVEGFR-1). METHODS: We conducted a nested case-control study comprising 55 women with subsequent preeclampsia, 21 with gestational hypertension, 30 with a small-for-gestational-age infant, and 83 controls. Serum concentrations of hCG-h, proportion of hCG-h to hCG (%hCG-h), PlGF, and sVEGFR-1 were converted to multiples of the medians (MoMs) adjusted for gestational age. RESULTS: Concentrations of hCG-h or %hCG-h did not differ between women with subsequent preeclampsia and controls. In women with subsequent preeclampsia, PlGF was lower (0.62 MoM) than in controls (P < 0.001). In receiver-operating characteristics curve analysis for the prediction of preeclampsia, the area under the curve for hCG-h or %hCG-h was not significantly different from 0.5, whereas that for PlGF was 0.746 (95% confidence interval, 0.656-0.836; P < 0.001). Combining hCG-h or %hCG-h with PlGF did not improve the prognostic value. CONCLUSIONS: Serum hCG-h did not improve prediction of preeclampsia in the second trimester.

Clustering of metabolic risk factors is associated with high-normal levels of liver enzymes among 6- to 8-year-old children: the PANIC study.

BACKGROUND: We studied the associations of clustering of metabolic risk factors with plasma levels of alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) in healthy prepubertal children. METHODS: The subjects were a representative population sample of 492 children 6-8 years of age. We assessed body fat percentage (dual-energy X-ray absorptiometry), body mass index, waist circumference, systolic and diastolic blood pressure, glucose, insulin, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, ALT, GGT, and high-sensitivity C-reactive protein (hsCRP) and calculated a continuous metabolic syndrome score variable. We also used factor analysis to examine whether high-normal liver enzymes are a feature of metabolic syndrome among children. RESULTS: Children with overweight or obesity, defined by International Obesity Task Force (IOTF) criteria, had a 2.1-times higher risk of having ALT and a 4.5-times higher risk of having GGT in the highest fifth of its distribution than normal weight children. Children in the highest sex-specific third of metabolic syndrome score, body fat percentage, waist circumference, and insulin had a two to three times higher risk of being in the highest fifth of ALT and GGT. Moreover, children in the highest third of glucose and hsCRP had a 2.5-fold risk of being in the highest fifth of GGT. First-order factor analysis yielded three factors; the first included insulin, glucose, and triglycerides; the second waist circumference, insulin, GGT, and hsCRP; and the third HDL-C, triglycerides, waist circumference, and insulin. Second-order factor analysis yielded a single metabolic syndrome factor, explaining 64.1% of the variance. CONCLUSIONS: Clustering of metabolic risk factors, particularly excess body fat, is associated with high-normal levels of ALT and GGT in prepubertal children. High-normal levels of liver enzymes, especially GGT, and systemic low-grade inflammation could be considered features of metabolic syndrome among children. Subtle changes in liver function may play an important role in the pathogenesis of metabolic syndrome beginning in childhood.

Predictive value of procalcitonin decrease in patients with severe sepsis: a prospective observational study.

INTRODUCTION: This prospective study investigated the predictive value of procalcitonin (PCT) for survival in 242 adult patients with severe sepsis and septic shock treated in intensive care. METHODS: PCT was analyzed from blood samples of all patients at baseline, and 155 patients 72 hours later. RESULTS: The median PCT serum concentration on day 0 was 5.0 ng/ml (interquartile range (IQR) 1.0 and 20.1 ng/ml) and 1.3 ng/ml (IQR 0.5 and 5.8 ng/ml) 72 hours later. Hospital mortality was 25.6% (62/242). Median PCT concentrations in patients with community-acquired infections were higher than with nosocomial infections (P = 0.001). Blood cultures were positive in 28.5% of patients (n = 69), and severe sepsis with positive blood cultures was associated with higher PCT levels than with negative cultures (P = < 0.001). Patients with septic shock had higher PCT concentrations than patients without (P = 0.02). PCT concentrations did not differ between hospital survivors and nonsurvivors (P = 0.64 and P = 0.99, respectively), but mortality was lower in patients whose PCT concentration decreased > 50% (by 72 hours) compared to those with a < 50% decrease (12.2% vs. 29.8%, P = 0.007). CONCLUSIONS: PCT concentrations were higher in more severe forms of severe sepsis, but a substantial concentration decrease was more important for survival than absolute values.

Metabolic syndrome and the progression of carotid intima-media thickness in elderly women.

BACKGROUND: Although the metabolic syndrome can predict cardiovascular events in middle-aged individuals, data on its association with the progression of subclinical atherosclerosis, particularly in elderly women, are limited. We investigated the association of the metabolic syndrome with the progression of carotid intima-media thickness (IMT) in elderly women. METHODS: We performed a 12-year follow-up study in a population-based sample of 101 women (age range at baseline, 60-70 years). All study variables were measured at baseline and 12 years later. We used the National Cholesterol Education Program definition for metabolic syndrome (> or =3 of 5 risk factors) and quantified carotid IMT noninvasively by ultrasonography. RESULTS: The prevalence of metabolic syndrome increased from 13% at baseline to 46% after 12 years of follow-up (P<.001). The mean +/- SD IMT increased by 21% (from 1.05 +/- 0.31 mm to 1.27 +/- 0.38 mm) during 12 years (P<.001). Among the individuals without metabolic syndrome at baseline, the increase in carotid IMT was greater in 34 women who developed metabolic syndrome during 12 years (0.31 +/- 0.37 mm) than in 54 women who did not (0.16 +/- 0.25 mm) after adjustment for age, prevalent cardiovascular diseases, physical activity, smoking, alcohol intake, serum low-density lipoprotein cholesterol level, use of cholesterol-lowering medication, carotid IMT, and National Cholesterol Education Program metabolic risk score at baseline (P = .04 for difference). CONCLUSION: Incident metabolic syndrome is associated with accelerated progression of carotid IMT in elderly women.

Responses of the autonomic nervous system during periods of perceived high and low work stress in younger and older female teachers.

The aim of this study was to examine the response of the autonomic nervous system in younger (mean age 31 yrs, n=14) and older (mean age 54 yrs, n=14) healthy female teachers during work periods of perceived high and low stress. In the younger participants, heart rate, cortisol excretion rate and psychosomatic symptoms were significantly higher during the high work stress period. The older participants experienced no decrease in their heart rate and cortisol excretion during the low stress period and they exhibited no significant decrease in blood pressure after the work in the evening during both periods. It may be concluded that the recovery from the stress in the older teachers was insufficient particularly in view of their elevated diastolic blood pressure during the low work stress period. Ergonomic and individually tailored measures in terms of work time control, specific relaxation techniques, and a part-time retirement may improve the stress management of older teachers.

Bone mineral density, body height, and vitamin D receptor gene polymorphism in middle-aged men.

BACKGROUND: Polymorphisms of the vitamin D receptor (VDR) gene have been suggested to account for some of the genetic variation in bone mass. However, the relationship has been controversial. It has been suggested that environmental factors such as physical activity may be one of the many reasons for this controversy.AIM. We investigated the possible interactions of VDR gene polymorphisms and low to moderate intensity exercise on bone mineral density (BMD) in a four-year controlled, randomized intervention trial in 140 middle-aged Finnish men. METHOD: The TaqI, FokI, and ApaI restriction fragment length polymorphism (RFLP)-markers of the VDR gene were evaluated. BMDs of the lumbar spine (L2-L4), femoral neck, and total proximal femur were measured with dual-energy X-ray absorptiometry (DXA). In addition, the relations of the VDR gene polymorphism with bone turnover markers (serum tartrate-resistant acid phosphatase (TRAP) 5b activity and serum osteocalcin concentration) were evaluated. RESULTS: At the randomization, the subjects with the VDR TaqI Tt or tt genotype had a greater body height than the subjects with TT genotype (P=0.001). In addition, the association of VDR TaqI polymorphism with femoral BMD was found. The Tt or tt genotype associated with higher femoral neck values than the TT genotype (P=0.003) at randomization. After adjusting the femoral neck for body height, the association remained (P=0.021). We did not find any association between VDR gene polymorphism and bone turnover markers or any interactions of VDR gene polymorphisms and exercise on BMD. CONCLUSIONS: The TaqI polymorphism may be associated with body height and femoral neck BMD values. The present findings also suggest that the VDR polymorphisms do not modify the effect of regular aerobic exercise on BMD. However, more randomized controlled exercise trials are needed to investigate the role of exercise intensity on VDR gene polymorphisms, and the role of VDR gene polymorphisms on BMD.

Effects of aerobic physical exercise on inflammation and atherosclerosis in men: the DNASCO Study: a six-year randomized, controlled trial.

BACKGROUND: Although regular physical activity is recommended for prevention of cardiovascular diseases, no data are available on its antiatherosclerotic effects in the general population. OBJECTIVE: To determine whether progressive aerobic exercise compared with usual activity slows progression of atherosclerosis in men. DESIGN: A 6-year randomized, controlled trial. SETTING: Eastern Finland. PARTICIPANTS: 140 middle-aged men randomly selected from the population registry. INTERVENTION: Low- to moderate-intensity aerobic exercise. MEASUREMENTS: Atherosclerosis was quantitated ultrasonographically as the mean intima-media thickness in the carotid artery at baseline and at years 2 through 6. RESULTS: On the basis of intention-to-treat analyses, a 19.5% net increase (P < 0.001) in ventilatory aerobic threshold was evident in the exercise group after 6 years. High-sensitivity C-reactive protein levels were statistically nonsignificantly lower in the exercise group than in the control group (P > 0.2). The progression of intima-media thickness in the carotid artery did not differ between the study groups (P > 0.2). A subgroup analysis that excluded men taking statins showed that the 6-year progression of intima-media thickness, adjusted for smoking and annual measures of low-density lipoprotein cholesterol level, systolic blood pressure, and waist circumference, was 40% less in the exercise group (0.12 mm [95% CI, -0.010 to 0.26 mm]) than in the control group (0.20 mm [CI, 0.05 to 0.35 mm]). LIMITATIONS: Only middle-aged white men were included. The intervention included mainly aerobic exercises. CONCLUSIONS: Aerobic physical exercise did not attenuate progression of atherosclerosis, except in a subgroup of men not taking statins.

Physical training and heart rate and blood pressure variability: a 5-yr randomized trial.

We studied the effect of regular physical activity on cardiac and vascular autonomic modulation during a 5-yr controlled randomized training intervention in a representative sample of older Finnish men. Heart rate variability (HRV) and blood pressure variability (BPV) are markers of cardiac and vascular health, reflecting cardiac and vascular autonomic modulation. One hundred and forty randomly selected 53- to 63-yr-old men were randomized into two identical groups: an intervention (EX) group and a reference (CO) group, of which 89 men remained until the final analysis (EX: n = 47; CO: n = 42). The EX group trained for 30-60 min three to five times a week with an intensity of 40-60% of maximal oxygen consumption. The mean weekly energy expenditure of the training program for the 5-yr training period was 3.80 MJ, and 71% of the EX group exceeded the mean. The EX group had a significantly (P < 0.01) higher oxygen consumption at ventilatory aerobic threshold (VO2VT) than the CO group at the 5-yr time point. VO2VT had a tendency to increase in the EX group and decrease in the CO group (interaction P < 0.001) from the baseline to the 5-yr time point. Peak performance did not change. Low-frequency power of R-R interval variability decreased in the EX group (P < 0.01, by 6%) from the baseline to the 5-yr time point. BPV did not change. In conclusion, low-intensity regular exercise training did not prevent HRV from decreasing or change BPV in 5 yr in older Finnish men.

Physical exercise and blood pressure with reference to the angiotensinogen M235T polymorphism.

We investigated the role of the angiotensinogen (AGT) gene M235T polymorphism in determining blood pressure (BP) response to moderate intensity exercise in a 6-yr randomized controlled trial in 140 middle-aged men. Sitting, supine, and standing blood pressures were measured annually. Of the randomized men, 86% participated in the trial for 6 yr. Submaximal cardiorespiratory fitness increased by 16% in the exercise group. In the M homozygotes, sitting systolic BP decreased by 1.0 mmHg in the exercise but increased by 14.6 mmHg in the reference group (P = 0.007 for net effect). Sitting and supine diastolic BP decreased by 6.2 and 3.3 mmHg in the exercise but increased by 2.8 and 3.2 mmHg in the reference group (P = 0.026 and 0.024 for net effects), respectively. Regular moderate intensity exercise attenuates aging-related increase in systolic BP and decreases diastolic BP among the M homozygotes of the AGT gene M235T polymorphism.

Effects of endurance training on heart rate and blood pressure variability.

PURPOSE: To study the influences of a 1-year controlled, randomized endurance exercise training period on heart rate (HR) and blood pressure variability in a representative sample of Finnish men in their late middle age. METHODS AND RESULTS: Subjects were 140 sedentary men aged 53-63 years. The men were randomized into two identical groups: an intervention (EX) and a reference (CO) group. One hundred and twelve of them remained in the final analysis (EX: n=59, CO: n=53). EX trained for 30-60 min three to five times a week with the intensity of 40-60% of maximal oxygen consumption. In EX, 1 year of regular exercise training increased oxygen consumption at respiratory compensation threshold by 11% (P < or = 0.001) in a maximal cardiorespiratory test. Total power and very low frequency power of R-R interval variability (ms2) tended to increase in the EX group by 26 and 42% and to decrease in the CO group by 13 and 10% (interaction P<0.05 and P<0.01), respectively. There were no significant changes in blood pressure variability. CONCLUSION: Regular low- to moderate-intensity exercise training could retard the declining tendency in cardiac autonomic nervous function in older men during 1 year.

Renal effects of uranium in drinking water.

Animal studies and small studies in humans have shown that uranium is nephrotoxic. However, more information about its renal effects in humans following chronic exposure through drinking water is required. We measured uranium concentrations in drinking water and urine in 325 persons who had used drilled wells for drinking water. We measured urine and serum concentrations of calcium, phosphate, glucose, albumin, creatinine, and beta-2-microglobulin to evaluate possible renal effects. The median uranium concentration in drinking water was 28 microg/L (interquartile range 6-135, max. 1,920 microg/L) and in urine 13 ng/mmol creatinine (2-75), resulting in the median daily uranium intake of 39 microg (7-224). Uranium concentration in urine was statistically significantly associated with increased fractional excretion of calcium and phosphate. Increase of uranium in urine by 1 microg/mmol creatinine increased fractional excretion of calcium by 1.5% [95% confidence interval (CI), 0.6-2.3], phosphate by 13% (1.4-25), and glucose excretion by 0.7 micromol/min (-0.4-1.8). Uranium concentrations in drinking water and daily intake of uranium were statistically significantly associated with calcium fractional excretion, but not with phosphate or glucose excretion. Uranium exposure was not associated with creatinine clearance or urinary albumin, which reflect glomerular function. In conclusion, uranium exposure is weakly associated with altered proximal tubulus function without a clear threshold, which suggests that even low uranium concentrations in drinking water can cause nephrotoxic effects. Despite chronic intake of water with high uranium concentration, we observed no effect on glomerular function. The clinical and public health relevance of the findings are not easily established, but our results suggest that the safe concentration of uranium in drinking water may be within the range of the proposed guideline values of 2-30 microg/L.