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Background: The recently established international cystatin C calibrator makes it possible to develop non-laboratory specific glomerular filtration rate (GFR) estimating (eGFR) equations. This study compares the performance of the arithmetic mean of the revised Lund-Malmö creatinine and CAPA cystatin C equations (MEANLM-REV+CAPA), the arithmetic mean of the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) creatinine and cystatin C equations (MEANCKD-EPI), and the composite CKD-EPI equation (CKD-EPICREA+CYSC) with the corresponding single marker equations using internationally standardized calibrators for both cystatin C and creatinine., Methods: The study included 1200 examinations in 1112 adult Swedish patients referred for measurement of GFR (mGFR) 2008-2010 by plasma clearance of iohexol (median 51 mL/min/1.73 m2). Bias, precision (interquartile range, IQR) and accuracy (percentage of estimates ±30% of mGFR; P30) were compared., Results: Combined marker equations were unbiased and had higher precision and accuracy than single marker equations. Overall results of MEANLM-REV+CAPA/MEANCKD-EPI/CKD-EPICREA+CYSC were: median bias -2.2%/-0.5%/-1.6%, IQR 9.2/9.2/8.8 mL/min/1.73 m2, and P30 91.3%/91.0%/91.1%. The P30 figures were about 7-14 percentage points higher than the single marker equations. The combined equations also had a more stable performance across mGFR, age and BMI intervals, generally with P30 ≥90% and never <80%. Combined equations reached P30 of 95% when the difference between eGFRCREA and eGFRCYSC was <10% but decreased to 82% at a difference of ≥40%., Conclusions: Combining cystatin C and creatinine assays improves GFR estimations with P30 ≥90% in adults. Reporting estimates of both single and combined marker equations in clinical settings makes it possible to assess the validity of the combined equation based on the agreement between the single marker equations.

Background: The performance of creatinine-based glomerular filtration rate (GFR) estimating equations may vary in subgroups defined by GFR, age and body mass index (BMI). This study compares the performance of the Modification of Diet in Renal Disease (MDRD) study and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations with the revised Lund-Malmö equation (LM Revised), a new equation that can be expected to handle changes in GFR across the life span more accurately., Methods: The study included 3495 examinations in 2847 adult Swedish patients referred for measurement of GFR (mGFR) 2008-2010 by plasma clearance of iohexol (median 52 mL/min/1.73 m²). Bias, precision [interquartile range (IQR)] and accuracy [percentage of estimates ±10% (P₁₀) and ±30% (P₃₀) of mGFR] were compared., Results: The overall results of LM Revised/MDRD/CKD-EPI were: median bias 2%/8%/11%, IQR 12/14/14 mL/min/1.73 m², P₁₀ 40%/35%/35% and P₃₀ 84%/75%/76%. LM Revised was the most stable equation in terms of bias, precision and accuracy across mGFR, age and BMI intervals irrespective of gender. MDRD and CKD-EPI overestimated mGFR in patients with decreased kidney function, young adults and elderly. All three equations overestimated mGFR and had low accuracy in patients with BMI <20 kg/m², most pronounced among men., Conclusions: In settings similar to the investigated cohort LM Revised should be preferred to MDRD and CKD-EPI due to its higher accuracy and more stable performance across GFR, age and BMI intervals.

Background: Obesity is very costly for society and weight reduction is important to reduce obesity related diseases. We have evaluated the effect of weight reduction on CRP values to see if high sensitivity CRP could be used to provide persons on life style intervention programs with positive feedback., Methods: Study subjects (n = 26) were recruited to a life style intervention program aiming for weight loss among the laboratory staff at Uppsala University Hospital, Sweden. Blood samples for high sensitivity CRP were collected at inclusion and after 4 weeks. Body composition was estimated by measurements performed on an inexpensive bioimpedance analyzer., Results: CRP reduction was significantly associated with weight reduction after four weeks (p = 0.00005) and eight weeks (p = 0.0002). Data from the bioimpedance analyzer were not useful on an individual level., Conclusions: High sensitivity CRP could be used to provide positive feedback in workplace weight reduction programs.

Background: Patients with suspected or confirmed non-ST-elevation acute coronary syndrome (ACS) constitute a large and heterogeneous group. Measurements of renal function such as serum creatinine and estimation of creatinine clearance carry independent prognostic information in this population. Cystatin C is a new and better marker of renal function than creatinine. The aim was therefore to evaluate the prognostic value of cystatin C in this population., Methods and Results: Cystatin C was analyzed on admission in 726 patients admitted because of symptoms suggestive of an acute coronary syndrome and no ST-segment elevations. Patients were followed up with regard to death and myocardial infarction for a median of 40 and 6 months, respectively. The median cystatin C level was 1.00 mg/L (25th to 75th percentile, 0.83 to 1.24 mg/L). The risk of death during follow-up increased with increasing levels of cystatin C. In the group with non-ST-elevation ACS, patients in the second, third, and fourth quartiles had a relative risk of subsequent death of 1.8 (95% CI, 0.6 to 5.3), 3.2 (95% CI, 1.2 to 8.5), and 11.7 (95% CI, 4.7 to 29.3) compared with the lowest quartile. In Cox regression models including well-known predictors of outcome, cystatin C level was independently associated with mortality but not with the risk of subsequent myocardial infarction. In a comparison of the markers of renal function in receiver-operating curve analyses, cystatin C had the best ability to discriminate between survivors and nonsurvivors., Conclusions: A single measurement of cystatin C will substantially improve the early risk stratification of patients with suspected or confirmed non-ST-elevation ACS.

Objective: Overexpression of elastolytic cysteine and aspartic proteases, known as cathepsins, is implicated in atherogenesis. The potential significance of imbalance in expression between cathepsins and their inhibitor cystatin C in cardiovascular disease has been highlighted by the demonstration of cystatin C deficiency in human atherosclerosis and abdominal aortic aneurysms., Methods and Results: We identified and characterized physiologically relevant polymorphisms in the promoter region of the cystatin C gene that influence cystatin C production and used these polymorphisms as a tool to examine the significance of cystatin C in coronary atherosclerosis in vivo in humans. Seven polymorphisms, all in strong-linkage disequilibrium, were identified in the cystatin C gene, of which 2 promoter polymorphisms (-82G/C and -78T/G) were functional in vitro in electromobility shift and transient transfection assays. Genotyping of 1105 individuals (237 survivors of a first myocardial infarction before age 60 and 2 independent groups comprising a total of 868 healthy individuals) revealed that the plasma cystatin C concentration was significantly lower in carriers of the mutant haplotype. Furthermore, the mutant haplotype was associated with a higher average number of stenoses per coronary artery segment in unselected postinfarction patients (N=237) undergoing routine coronary angiography., Conclusions: These results provide human evidence for an important role of cystatin C in coronary artery disease.

Objective: To illustrate the geographical West-to-East division of coronary heart disease (CHD) by comparing a population from Sweden, that represents a Western country to a population from Estonia, that represents an Eastern country. Estonia has an approximately 2-4-fold higher CHD prevalence for 55-year-old women and men, respectively, than Sweden., Design: Randomized screening of 35- and 55-year-old men and women in Sollentuna county, Sweden and Tartu county, Estonia. Eight hundred subjects, 100 from each cohort, were invited to participate in the study, 272 Swedes and 277 Estonians participated., Setting: Preventive cardiology, administered by a primary health care centre at the Karolinska Hospital, Sweden and a cardiology centre at Tartu University Hospital, Estonia., Main Outcome Measures: The CHD risk factors (smoking, blood pressure, concentrations of lipoproteins, fibrinogen, and glucose) and certain environmental factors and attitudes related to CHD risk by questionnaires (fat-type and alcohol ingestion, self-assessed rating of CHD susceptibility)., Results: Of the 55-year-old men, 57% smoked in Estonia and 20% smoked in Sweden. Similar, although less pronounced differences showing higher smoking prevalence, were seen for 35-year-old Estonian men and women, whilst for 55-year-old women, less than 20% smoked in either country. Estonian 55-year-old women had lower HDL cholesterol and higher LDL cholesterol serum concentrations than Swedish 55-year-old women. Estonians reportedly ate food containing more saturated fats than Swedes, as indicated by the scale-score questionnaire. Estonians, relative to Swedes, rated their chance of developing CHD higher, and paradoxically, Estonians did to a much lesser degree believe that life style influences the risk of developing CHD., Conclusions: Elevated smoking prevalence is a striking difference between the Estonian and Swedish populations likely to explain the much higher CHD prevalence in Estonian men. The lower HDL cholesterol and higher LDL cholesterol in Estonian 55-year-old women may explain the higher CHD prevalence in Estonian women. Furthermore, the SWESTONIA CHD study (i.e. comparison between Sweden and Estonia) shows several environmental differences between the countries populations related to fat content in food, alcohol drinking patterns, and views on CHD risk and the importance of lifestyle intervention, that could contribute to the higher CHD prevalence in Estonia.

Background: The present study is part of a longitudinal study of recently resettled refugees with the aim of learning which factors in their daily life influence health as measured by self-report and stress-responsive hormones., Methods: In a group of recently resettled refugees with a high incidence of posttraumatic stress disorder (PTSD), diagnosed by structured interview, self-rated symptoms of PTSD were followed three times over a period of 9 months after inclusion in the study. Eighty-six individuals were included in the study and 58 subjects (67.4%) completed it. Blood samples were drawn at each examination for assessment of hormone levels., Results: After adjustment for age, dehydroepiandrosterone sulphate (DHEA-s) was observed to be higher in non-depressed PTSD cases than in non-PTSD without depression. There was an interaction between PTSD and depression regarding DHEA-s levels. DHEA-s correlated significantly with changes in self-rated symptoms of PTSD at last follow-up; the greater the increase in PTSD symptoms, the greater the increase in plasma DHEA-s. The variation of DHEA-s levels in relation to changes in self-rated health in non-PTSD showed the opposite pattern, although not reaching significance., Conclusions: The finding of changes in DHEA-s should encourage further studies of the role of altered steroid metabolism in PTSD., (Copyright 2002 S. Karger AG, Basel)