Reference intervals for 24 laboratory parameters determined in 24-hour urine collections.

BACKGROUND: Reference intervals for many laboratory parameters determined in 24-h urine collections are either not publicly available or based on small numbers, not sex specific or not from a representative sample. METHODS: Osmolality and concentrations or enzymatic activities of sodium, potassium, chloride, glucose, creatinine, citrate, cortisol, pancreatic α-amylase, total protein, albumin, transferrin, immunoglobulin G, α1-microglobulin, α2-macroglobulin, as well as porphyrins and their precursors (δ-aminolevulinic acid and porphobilinogen) were determined in 241 24-h urine samples of a population-based cohort of asymptomatic adults (121 men and 120 women). For 16 of these 24 parameters creatinine-normalized ratios were calculated based on 24-h urine creatinine. The reference intervals for these parameters were calculated according to the CLSI C28-A3 statistical guidelines. RESULTS: By contrast to most published reference intervals, which do not stratify for sex, reference intervals of 12 of 24 laboratory parameters in 24-h urine collections and of eight of 16 parameters as creatinine-normalized ratios differed significantly between men and women. For six parameters calculated as 24-h urine excretion and four parameters calculated as creatinine-normalized ratios no reference intervals had been published before. For some parameters we found significant and relevant deviations from previously reported reference intervals, most notably for 24-h urine cortisol in women. Ten 24-h urine parameters showed weak or moderate sex-specific correlations with age. CONCLUSIONS: By applying up-to-date analytical methods and clinical chemistry analyzers to 24-h urine collections from a large population-based cohort we provide as yet the most comprehensive set of sex-specific reference intervals calculated according to CLSI guidelines for parameters determined in 24-h urine collections.

G-protein receptor kinase 4 polymorphism and response to antihypertensive therapy.

BACKGROUND: G-protein receptor kinase 4 polymorphism influences blood pressure regulation via modulation of dopamine receptor D1 in renal proximal tubular cells. We investigated the role of G-protein receptor kinase 4 polymorphism in the response to hypertensive therapy in patients with essential hypertension. METHODS: In a prospective study, we assessed the G-protein receptor kinase 4 polymorphisms R65L, A142V, and A486V in 100 hypertensive patients. We analyzed the association of the 3 gene variants on blood pressure control and response to antihypertensive therapy with single-locus analysis, haplotype analysis, and regression analysis. RESULTS: Hypertensive individuals with a homozygous double variant of 65 L and 142 V needed significantly more antihypertensive treatment (number of antihypertensives 2.59 vs 1.95, P = 0.043) and especially diuretic therapy (0.82 vs 0.49, P = 0.029) to reach the same mean arterial blood pressure than did homozygous carriers of only 1 variant or heterozygous/wild-type carriers of R65L, A142V, and A486V alleles. CONCLUSIONS: G-protein receptor kinase 4 polymorphism is associated with antihypertensive treatment response in patients with essential hypertension. Determination of G-protein receptor kinase 4 polymorphism may improve individual antihypertensive blood pressure control in patients with essential hypertension.

The magnitude of the plasma hepcidin response to oral iron supplements depends on the iron dosage.

BACKGROUND: Iron deficiency without anaemia is a common health problem, especially in young menstruating women. The efficacy of the usually recommended oral iron supplementation is limited due to increased plasma hepcidin concentration, which reduces iron absorption and leads to side effects such as intestinal irritation. This observation raises the question of how low-dose iron therapy may affect plasma hepcidin levels and whether oral iron intake dose-dependently affects plasma hepcidin production. METHODS: Fifteen non-anaemic women with iron deficiency (serum ferritin ≤30 ng/ml) received a single dose of 0, 6, 30, or 60 mg of elemental oral iron as ferrous sulfate on different days. Plasma hepcidin was measured before and seven hours after each dose. RESULTS: Subjects had an average age of 23 (standard deviation = 3.0) years and serum ferritin of 24 ng/ml (interquartile range = 16-27). The highest mean change in plasma hepcidin levels was measured after ingesting 60 mg of iron, increasing from 2.1 ng/ml (interquartile range = 1.6-2.9) to 4.1 ng/ml (interquartile range = 2.5-6.9; p < 0.001). Iron had a significant dose-dependent effect on the absolute change in plasma hepcidin (p = 0.008), where lower iron dose supplementation resulted in lower plasma hepcidin levels. Serum ferritin levels were significantly correlated with fasting plasma hepcidin levels (R2 = 0.504, p = 0.003) and the change in plasma hepcidin concentration after iron intake (R2 = 0.529, p = 0.002). CONCLUSION: We found a dose-dependent effect of iron supplementation on plasma hepcidin levels. Lower iron dosage results in a smaller increase in hepcidin and might thus lead to more efficient intestinal iron absorption and fewer side effects. The effectiveness and side effects of low-dose iron treatment in women with iron deficiency should be further investigated. This study was registered at the Swiss National Clinical Trials Portal (2021-00312) and ClinicalTrials.gov (NCT04735848).

Spirulina is an effective dietary source of zeaxanthin to humans.

Zeaxanthin is a predominant xanthophyll in human eyes and may reduce the risk of cataracts and age-related macular degeneration. Spirulina is an algal food that contains a high concentration of zeaxanthin. In order to determine the zeaxanthin bioavailability of spirulina for dietary supplementation in humans, spirulina was grown in nutrient solution with ²H2O for carotenoid labelling. Single servings of ²H-labelled spirulina (4.0-5.0 g) containing 2.6-3.7 mg zeaxanthin were consumed by fourteen healthy male volunteers (four Americans and ten Chinese) with 12 g dietary fat. Blood samples were collected over a 45 d period. The serum concentrations of total zeaxanthin were measured using HPLC, and the enrichment of labelled zeaxanthin was determined using LC-atmospheric pressure chemical ionisation-MS (LC-APCI-MS). The results showed that intrinsically labelled spirulina zeaxanthin in the circulation was detected at levels as low as 10 % of the total zeaxanthin for up to 45 d after intake of the algae. A single dose of spirulina can increase mean serum zeaxanthin concentration in humans from 0.06 to 0.15 µmol/l, as shown in our study involving American and Chinese volunteers. The average 15 d area under the serum zeaxanthin response curve to the single dose of spirulina was 293 nmol × d/µmol (range 254-335) in American subjects, and 197 nmol × d/µmol (range 154-285) in Chinese subjects. It is concluded that the relative bioavailability of spirulina zeaxanthin can be studied with high sensitivity and specificity using ²H labelling and LC-APCI-MS methodology. Spirulina can serve as a rich source of dietary zeaxanthin in humans.

[CME: Harmful Alcohol Consumption in the Elderly]. / CME: Riskanter Alkoholkonsum im Alter.

CME: Harmful Alcohol Consumption in the Elderly Abstract. Harmful alcohol consumption is an increasing clinical problem in many patients. Often excessive alcohol consumption is not addressed in clinical practice and there is still a high level of stigmatization around this topic. The early recognition and early therapeutic intervention are crucial for success. The general practitioner plays a key role in the (early) diagnosis, initiation and follow-up of alcohol-related problems. In this article the ideal procedures for the recognition of high-risk consumption are summarized. In daily practice, an ideal tool is the 'brief intervention' approach. The major steps and procedures for brief intervention for alcohol misuse are summarized and discussed.

[CME/Answers: Harmful Alcohol Consumption in the Elderly]. / CME/Antworten: Riskanter Alkoholkonsum im Alter.

CME/Answers: Harmful Alcohol Consumption in the Elderly Abstract. Harmful alcohol consumption is an increasing clinical problem in many patients. Often excessive alcohol consumption is not addressed in clinical practice and there is still a high level of stigmatization around this topic. The early recognition and early therapeutic intervention are crucial for success. The general practitioner plays a key role in the (early) diagnosis, initiation and follow-up of alcohol-related problems. In this article the ideal procedures for the recognition of high-risk consumption are summarized. In daily practice, an ideal tool is the 'brief intervention' approach. The major steps and procedures for brief intervention for alcohol misuse are summarized and discussed.

Age-Dependency of Cardiometabolic Risk and Protective Factors in Females Living in a Countryside Area of Switzerland.

We investigated the effect of age on cardiometabolic risk and protective factors in females living in a countryside area of Switzerland. For this cross-sectional analysis, data from 268 female adults, who live in two neighboring countryside villages in Italian-speaking Switzerland were retained. 89 study participants were premenopausal, 82 climacteric and 97 postmenopausal. Television viewing time, short duration of sleep, overweight, blood pressure, levels of atherogenic lipids and glycated hemoglobin significantly increased with age. Walking time also significantly increased with age. Tobacco smoking was more common among premenopausal women. It is concluded that in these countryside villages climacteric and postmenopausal women generally have an unfavorable cardiometabolic risk profile. On the other side, low physical activity and smoking are, compared to premenopausal and climacteric women, less prevalent in postmenopausal women.

Prevalence of ideal cardiovascular health in a community-based population - results from the Swiss Longitudinal Cohort Study (SWICOS).

AIMS OF THE STUDY: The American Heart Association (AHA) developed a concept to measure cardiovascular health in populations. We aimed to analyse participants in the Swiss Longitudinal Cohort Study (SWICOS) according to the AHA concept. METHODS: We analysed cardiovascular health according to the AHA concept in all 474 participants of the prospective, population-based SWICOS study who were 18 years or older. The AHA concept uses seven health metrics of known cardiovascular risk factors (blood pressure, total cholesterol, blood glucose, smoking, body weight, physical activity and diet), and classifies each health metric according to three levels (ideal, intermediate and poor) using pre-defined cut-offs. RESULTS: Ideal cardiovascular health for three or more of the seven health metrics was found in 259 participants (54.9%; 95% confidence interval [CI] 50.1-59.4%), but a relevant number of participants (n = 213, 45.1%, 95% CI 40.6-49.7%) showed ideal cardiovascular health for only two or fewer of the seven health metrics. Poor cardiovascular health for three or more of the seven health metrics was found in 40 participants (8.5%; 95% CI 6.1-11.4%); a majority of 432 participants (91.5%; 95% CI 88.6-93.9%) showed a poor level for only two or fewer of the seven health metrics. CONCLUSIONS: Overall, we found favourable results for cardiovascular health in the population-based SWICOS cohort. Nevertheless, we see the need for further health prevention campaigns given the fact that a relevant proportion of the participants could optimise their cardiovascular health.

[Thoughts about Light and Sleep]. / Mach nicht zu viel «blau¼.

Thoughts about Light and Sleep Abstract. Many aspects of health and disease are mainly determined by the constant change between light and darkness during a solar day. The resulting physiological rhythms correspond to the circadian rhythm, which was one of the most central drivers in the evolution of humans. However, over the last 20-30 years, these natural rhythms of the change of light and darkness are being increasingly ignored by modern societies. It is well known that these rhythms are modulators of many physiological pathways and any desynchronization or misalignment will activate different pathophysiological pathways, which contribute to the risk of chronic diseases. Light pollution by widespread illumination of our environment and the night sky and uncontrolled man-made use of any light source plays a key role in the pathogenesis of sleep disturbances. Blue light exposure in the evening from any artificial light source (especially from electronic device screens) is of special relevance in this context. In this article a few key facts concerning light, sleep and diseases are presented. We should by all means account for the effects of light and darkness and stop any further light pollution.

[Alcohol and the Bariatric Patient: When One Drink Becomes Two Drinks]. / «Ich bin plötzlich so besäuselt!¼ Alkoholstoffwechsel und Bariatrie: wenn ein Drink zu zwei Drinks wird CME-Fragen.

Alcohol and the Bariatric Patient: When One Drink Becomes Two Drinks Abstract. Moderate consumption of alcohol is a risk factor for weight gain and obesity. Alcohol affects all components of the energy balance. Alcohol consumption is - as in the general population - also a widespread phenomenon in obese and bariatric patients. As a function of the bariatric surgery technique, alcohol metabolism is altered: gastric bypass surgery and sleeve gastrectomy lead to a faster absorption of alcohol, higher peak alcohol concentration and a longer alcohol persistence in the circulation. Further reward mechanisms for alcohol are changed, so that alcohol consumption is enhanced and promoted, with an increased risk to develop alcohol dependency. It is time to address these issues in the daily practice and to fill the existing research gaps.

Protocol of the Swiss Longitudinal Cohort Study (SWICOS) in rural Switzerland.

INTRODUCTION: Increased longevity and consequent major changes in demographics and population lifestyles necessitate new approaches to reduce the burden of ageing-related diseases (including cardiovascular disease) and maintain an optimal quality of life. This study aims to examine and longitudinally follow health status and disease risk factors in a Swiss rural cohort, evaluating all health-related research and practice disciplines to assure development of new implementable and successful preventive strategies for healthy ageing. METHODS AND OBJECTIVES: Small Swiss villages with low migration rates will be selected for this study. 2 villages (Cama/Lostallo) have already been selected as initial study sites. All residents (age ≥6 years, no upper age limit) are eligible. The target enrolment number per village is 300. Examinations and measurements encompass medical history, anthropometry, cardiac and vascular health, pulmonary function, physical performance, nutritional, mental and emotional status, biochemical and molecular analyses. Follow-up examinations (identical to baseline) will be performed after 5 and 10 years, and in 10-year intervals thereafter. The major objective is to assess, and observe change in, health status over time in a prospective manner. Secondary objectives are to: (1) identify 'hidden' (asymptomatic and/or unrecognised) health problems which enhance risk for chronic diseases; (2) identify barriers to accessing healthcare and adapting health behaviours; (3) evaluate efficacy of present preventive strategies and recommendations; (4) evaluate knowledge and attitude towards ongoing health programmes and public health recommendations; (5) monitor change and progress towards the national health objectives; (6) formulate new preventive strategies and recommendations based on the findings and knowledge base of the past 10 years; (7) formulate models for successful prevention of chronic diseases and for healthy ageing. ETHICS AND DISSEMINATION: The Ethics Committee of Nordwest-und Zentralschweiz approved this study (EKNZ 2014-209). It is registered at ClinicalTrials.gov (NCT02282748). Findings will be disseminated through scientific articles/presentations and public events.

Effect of vitamin D3 on self-perceived fatigue: A double-blind randomized placebo-controlled trial.

BACKGROUND: Vitamin D deficiency is frequent and has been associated with fatigue in uncontrolled trials. METHODS: This is the first double-blind placebo-controlled clinical trial to investigate the efficacy of per os vitamin D3 (cholecalciferol) in treating fatigue among otherwise healthy persons with low serum 25-hydroxyvitamin D (25(OH)D) levels. We enrolled 120 individuals (mean age 29 ±â€Š6 years, 53% women) presenting with fatigue and vitamin D deficiency (serum 25(OH)D < 20 µg/L). Participants were randomized to a single oral dose of 100,000 units of vitamin D or placebo. The primary endpoint was intra-individual change in the fatigue assessment scale (FAS) at 4 weeks after treatment. RESULT: The mean age of the participants was 29 ±â€Š6 years, 53% were women. Mean FAS decreased significantly more in the vitamin D group (-3.3 ±â€Š5.3; 95% confidence interval [CI] for change -14.1 to 4.1) compared with placebo (-0.8 ±â€Š5.3; 95% CI for change -9.0 to 8.7); (P = 0.01). Amelioration of fatigue was reported more frequently in vitamin D than in placebo group (42 [72%] vs. 31 [50%]; P = 0.01; odds ratio [OR] 2.63, 95% CI for OR 1.23-5.62). Among all participants, improvement in fatigue score correlated with the rise in 25(OH)D level (R = -0.22, P = 0.02). CONCLUSION: Vitamin D treatment significantly improved fatigue in otherwise healthy persons with vitamin D deficiency.This study was registered at the www.ClinicalTrials.gov Protocol ID NCT02022475.

Prevalence and determinants of chronic kidney disease in the Swiss population.

QUESTIONS UNDER STUDY: The prevalence of chronic kidney disease (CKD) is increasing worldwide, corresponding to an increased risk of cardiovascular disease. The latest study on prevalence of CKD involving the three linguistic regions of Switzerland dates back to 2002-2003 and definitions have changed since then. We aimed to assess the current prevalence and determinants of CKD in the Swiss general population. METHODS: We analysed the data of 1353 participants from a cross-sectional population-based survey performed in 2010-2012 in the three linguistic regions of Switzerland. The prevalence of CKD and the derived cardiovascular risk categories were assessed according to the Kidney Disease - Improving Global Outcomes (KDIGO) 2012 classification, using estimated glomerular filtration rate (GFR; CKD-Epidemiological Collaboration equation) and albuminuria level. Multivariate logistic regression was used to analyse factors associated with CKD. RESULTS: We included 660 men and 693 women, equally distributed in four age categories (15-29, 30-44, 45-59 and over 60 years). The overall prevalence of CKD was 10.4%. The prevalence in the low, moderate, high and very high risk KDIGO categories were 89.6%, 8.4%, 1.6% and 0.5%, respectively. The prevalence of CKD was similar in all linguistic regions. In multivariate analysis, female gender, older age, diabetes and uric acid were independently associated with CKD in persons ≥45 y. In younger participants, diabetes and lower educational level were associated with CKD. CONCLUSIONS: In the general Swiss population, CKD affects one in ten adults. Subjects older than 60 years, as well as patients with diabetes and hypertension, show a high prevalence of CKD. Systematic screening may be recommended in this population.

Effect of orlistat on postprandial lipemia, NMR lipoprotein subclass profiles and particle size.

Evidence suggests that metabolic phenomena during postprandial lipemia may be important in the pathogenesis of atherosclerosis. Both lipid concentrations and lipoprotein subclass patterns may be important cardiovascular risk modifiers. The pancreatic lipase inhibitor orlistat reduces fat absorption by 30% and is used for the treatment of overweight and obesity. We evaluated the effect of orlistat on postprandial lipemia and lipoprotein particle distribution after moderate-and high-fat meals in healthy volunteers. In this double-blind, randomized, cross-over study, 10 healthy young men received orlistat 120 mg plus a high-fat meal (HFO), orlistat plus a moderate-fat meal (MFO) or placebo plus a high-fat meal (HFP). Plasma triacylglycerol, glucose, insulin, and free fatty acids were measured at baseline (fasting) and postprandially for 8h. Lipoprotein subclass profile was assessed by nuclear magnetic resonance spectroscopy. The 8h postprandial mean triacylglycerol area under the curve (AUC) was significantly lower with MFO and HFO (0.79 versus 1.33 mmol/lh) versus HFP (4.33 mmol/lh; p=0.02). Mean change in large VLDL subclass concentration during the 4-8h and mean VLDL size after 8h was significantly lower with HFO and MFO versus HFP (p<0.001). Small HDL particle concentration decreased significantly with HFP versus MFO or HFO (p<0.001). There was no significant difference in postprandial concentrations of glucose, insulin or free fatty acids on the different regimens. The lowering of postprandial triacylglycerol AUC, shorter postprandial lipemia, lower concentration of large triacylglycerol-rich particles and decrease of VLDL particle size supports the hypothesis of a less atherogenic postprandial lipoprotein profile following orlistat ingestion.

[Circadian rhythms and chronic diseases]. / Zirkadiane Rhythmik und chronische Erkrankungen.

Everything in nature and life is occurring in a rhythmic manner. The major "Zeitgeber" is the change of light and dark during a 24 h day. This circadian rhythm is besides others reflected in circadian rhythms of behaviors or different biochemical parameters. A disruption of the circadian rhythm has a high pathophysiological potential. In this article a few basic issues about the role of circadian rhythms and the pathophysiological importance of desynchronisation are reviewed.

[Help me--I do not tolerate my statin]. / Hilfe--ich vertrage den Cholesterinsenker nicht!

Statins represent the most widely prescribed drugs. Accordingly, in daily practice statin-related muscle pain and other myopathic sensations are frequently seen. In this practice review the clinical approach to statin myopathy is discussed.

Association of urinary calcium excretion with serum calcium and vitamin D levels.

BACKGROUND AND OBJECTIVES: Population-based data on urinary calcium excretion are scarce. The association of serum calcium and circulating levels of vitamin D [25(OH)D2 or D3] with urinary calcium excretion in men and women from a population-based study was explored. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS: Multivariable linear regression was used to explore factors associated with square root-transformed 24-hour urinary calcium excretion (milligrams per 24 hours) taken as the dependent variable with a focus on month-specific vitamin D tertiles and serum calcium in the Swiss Survey on Salt Study. RESULTS: In total, 624 men and 669 women were studied with mean ages of 49.2 and 47.0 years, respectively (age range=15-95 years). Mean urinary calcium excretion was higher in men than in women (183.05 versus 144.60 mg/24 h; P<0.001). In adjusted models, the association (95% confidence interval) of square root urinary calcium excretion with protein-corrected serum calcium was 1.78 (95% confidence interval, 1.21 to 2.34) mg/24 h per milligram per deciliter in women and 0.59 (95% confidence interval, -0.11 to 1.29) mg/24 h per milligram per deciliter in men. Men in the third 25(OH)D3 tertile had higher square root urinary calcium excretion than men in the first tertile (0.99; 95% confidence interval, 0.36 to 1.63 mg/24 h per nanogram per milliliter), and the corresponding association was 0.32 (95% confidence interval, -0.22 to 0.85) mg/24 h per nanogram per milliliter in women. These sex differences were more marked under conditions of high urinary sodium or urea excretions. CONCLUSIONS: There was a positive association of serum calcium with urinary calcium excretion in women but not men. Vitamin 25(OH)D3 was associated with urinary calcium excretion in men but not women. These results suggest important sex differences in the hormonal and dietary control of urinary calcium excretion.