Lars-Olof Hansson

Calculation of glomerular filtration rate expressed in mL/min from plasma cystatin C values in mg/L.

Larsson A, Malm J, Grubb A, Hansson L-O. Calculation of glomerular filtration rate expressed in mL/min from plasma cystatin C values in mg/L. 2004; 64: 25-30. The Cockcroft-Gault formula is often used to calculate the glomerular filtration rate (GFR) from plasma creatinine results. In Sweden this calculation is not usually done in the laboratory, but locally in the wards. These manual calculations could cause erroneous results. In several studies plasma cystatin C has been shown to be superior to plasma creatinine for estimation of GFR. One limitation of using cystatin C as a GFR marker is that there is no conversion formula transforming cystatin C expressed as mg/L to GFR expressed as mL/ min. In this study plasma creatinine and cystatin C were compared with iohexol clearance. A stronger correlation (p< 0.0001) was found between cystatin C and iohexol clearance (r2 = 0.91) than between creatinine and iohexol clearance (r2 = 0.84). From the correlation data a formula was calculated to convert cystatin C expressed as mg/L to GFR (mL/min). The formulas y = 77.24x−1.263 (Dade Behring cystatin C calibration) or y = 99.43x−1.5837 (DakoCytomation cystatin C calibration) are used to calculate GFR expressed in mL/min from the cystatin C value in mg/L and both results are reported to the referral doctor. These formulas can provide the clinicians with reliable and readily available GFR data based on single measurements of cystatin C concentrations.

High Serum S100B Levels for Trauma Patients without Head Injuries

OBJECTIVE Studies of patients with head trauma have demonstrated a correlation between a serum marker of brain tissue damage, namely S100B, and neuroradiological findings. It was recently demonstrated that the increases in serum S100B levels after heart surgery have extracerebral origins, probably surgically traumatized fat, muscle, and bone marrow. The current study examined multitrauma patients without head trauma, to determine whether soft-tissue and bone damage might confound the interpretation of elevated serum S100B concentrations for patients after head trauma. METHODS A commercial assay was used to determine serum S100B concentrations for a normal population (n = 459) and multitrauma patients without head injury (n = 17). Concentrations of the two subtypes of S100B (S100A1B and S100BB) were determined using separate noncommercial assays. RESULTS The mean serum S100B concentration for a normal healthy population was 0.032 microg/L (median, 0.010 microg/L; standard deviation, 0.040 microg/L). The upper 97.5% and 95% reference limits were 0.13 and 0.10 microg/L, respectively. No major age or sex differences were observed. Among trauma patients, serum S100B levels were highest after bone fractures (range, 2-10 microg/L) and thoracic contusions without fractures (range, 0.5-4 microg/L). Burns (range, 0.8-5 microg/L) and minor bruises also produced increased S100B levels. S100A1B and S100BB were detected in all samples. CONCLUSION Trauma, even in the absence of head trauma, results in high serum concentrations of S100B. Interpretation of elevated S100B concentrations immediately after multitrauma may be difficult because of extracerebral contributions. S100B may have a negative predictive value to exclude brain tissue damage after trauma. Similarly, nonacute S100B measurements may be of greater prognostic value than acute measurements.

Cystatin C A Novel Predictor of Outcome in Suspected or Confirmed Non–ST-Elevation Acute Coronary Syndrome

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.

Does singing promote well-being? : An empirical study of professional and amateur singers during a singing lesson

This study explored the possible beneficial effects of singing on well-being during a singing lesson. Eight amateur (2m, 6f, age 28–53 yrs) and eight professional (4m, 4f, age 26–49 yrs) singers who had been attending singing lessons for at least six months were included. Continuous ECG was recorded and computerized spectral analysis was performed. Serum concentrations of TNF-alpha, prolactin, cortisol, and oxytocin were measured before and 30 min after the lesson. Five visual analogue scales (VAS, sad-joyful, anxious-calm, worried-elated, listless-energetic, and tense-relaxed) were scored before and after the lesson. In addition, a semi-structured interview was performed.Heart rate variability analyses showed significant changes over time in the two groups for total power, and low and high frequency power. Power increased during singing in professionals, whereas there were no changes in amateurs. This indicates an ability to retain more “heart-brain connection,” i.e., more cardio-physiological fitness for singing in professional singers, compared to amateur singers. Serum concentration of TNF-alpha increased in professionals after the singing lesson, whereas the concentration in amateurs decreased. Serum concentrations of prolactin and cortisol increased after the lesson in the group of men and vice versa for women. Oxytocin concentrations increased significantly in both groups after the singing lesson. Amateurs reported increasing joy and elatedness (VAS), whereas professionals did not. However, both groups felt more energetic and relaxed after the singing lesson. The interviews showed that the professionals were clearly achievement-oriented, with focus on singing technique, vocal apparatus and body during the lesson. The amateurs used the singing lessons as a means of self-actualization and self-expression as a way to release emotional tensions. In summary, in this study, singing during a singing lesson seemed to promote more well-being and less arousal for amateurs compared to professional singers, who seemed to experience less well-being and more arousal.

Increase in serum S100A1-B and S100BB during cardiac surgery arises from extracerebral sources

BACKGROUND Elevated levels of serum S100B after coronary artery bypass grafting may arise from extracerebral contamination. Serum S100B content was analyzed in several tissues, and the two dimers S100A1-B and S100BB were analyzed separately in blood. METHODS Serum, shed blood, marrow, fat, and muscle were studied in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass using suction either to the cardiotomy reservoir (group 1, n = 10) or to a cell-saving device (group 2, n = 10), or operated on off-pump (group 3, n = 10). RESULTS Serum S100B was sixfold higher in group 1 than in groups 2 and 3, which were identical. The same ratio between S100A1-B and S100BB was found in all groups. When compared with serum, S100B was 10(2) to 10(4) times higher in marrow, fat, muscle tissue, and shed blood. CONCLUSIONS Separate analysis of S100A1-B and S100BB did not distinguish between S100B of cerebral and extracerebral origin. The concept that S100B only originates in astroglial and Schwann cells is wrong. Fat, muscle, and marrow in mediastinal blood contain high levels of S100B. Cardiopulmonary bypass caused no increase in S100B.

Self-rated health is related to levels of circulating cytokines.

Objective: Self-rated health is a powerful and independent predictor of long-term health, but its biological basis is unknown. Because factors associated with poor self-rated health (eg, pain, daily discomforts, and low energy and fitness) resemble symptoms of a generalized cytokine-induced sickness response, we examined the relationship between circulating cytokines and self-rated health. Methods: In 265 consecutive primary health care patients (174 women and 91 men), we examined self-rated and physician-rated health, circulating levels of interleukin (IL)-1β, IL-1 receptor antagonist (IL-1ra), IL-6, and tumor necrosis factor (TNF)-&agr; as determined from plasma samples using high-sensitivity enzyme-linked immunoassay. Results: Self-rated health correlated with levels of IL-1β (r = 0.27; p < .001), IL-1ra (r = 0.19; p < .05) and TNF-&agr; (r = 0.46; p < .001) in women but not in men. Thus, poorer subjective health was associated with higher levels of inflammatory cytokines. Even when controlling for age, education, physical health, and diagnoses in multiple regression analyses, self-rated health was an independent and more robust predictor of cytokine levels than physician-rated health. Conclusions: The present findings suggest that an individuals health perception may be coupled to circulating cytokines. Because epidemiological research established that self-rated health predicts morbidity and mortality, the biological correlates and mechanisms of self-rated health need to be understood.

Predictors of the first cardiovascular event in patients with systemic lupus erythematosus - a prospective cohort study

IntroductionCardiovascular disease (CVD) is a major cause of premature mortality among Systemic lupus erythematosus (SLE) patients. Many studies have measured and evaluated risk factors for premature subclinical atherosclerosis, but few studies are prospective and few have evaluated risk factors for hard endpoints, i.e. clinically important cardiovascular events (CVE). We investigated the impact of traditional and lupus associated risk factors for the first ever CVE in a longitudinal cohort of SLE patients.MethodsA total of 182 SLE patients (mean age 43.9 years) selected to be free of CVE were included. Cardiovascular and autoimmune biomarkers were measured on samples collected after overnight fasting at baseline. Clinical information was collected at baseline and at follow up. End point was the first ever CVE (ischemic heart, cerebrovascular or peripheral vascular disease or death due to CVD). Impact of baseline characteristics/biomarkers on the risk of having a first CVE was evaluated with Cox regression.ResultsFollow up was 99.5% after a mean time of 8.3 years. Twenty-four patients (13%) had a first CVE. In age-adjusted Cox regression, any positive antiphospholipid antibody (aPL), elevated markers of endothelial activation (von Willebrand factor (vWf), soluble vascular cellular adhesion molecule-1 (sVCAM-1)) and fibrinogen predicted CVEs. Of SLE manifestations, arthritis, pleuritis and previous venous occlusion were positively associated with future CVEs while thrombocytopenia was negatively associated. Among traditional risk factors only age and smoking were significant predictors. In a multivariable Cox regression model age, any positive aPL, vWf and absence of thrombocytopenia were all predictors of the first CVE.ConclusionsIn addition to age, positive aPL, biomarkers indicating increased endothelial cell activity/damage, and absence of thrombocytopenia were independent predictors of CVEs in this prospective study. Our results indicate that activation of the endothelium and the coagulation system are important features in SLE related CVD. Furthermore, we observed that the risk of CVEs seems to differ between subgroups of SLE patients.

Generation of a New Cystatin C–Based Estimating Equation for Glomerular Filtration Rate by Use of 7 Assays Standardized to the International Calibrator

BACKGROUND Many different cystatin C-based equations exist for estimating glomerular filtration rate. Major reasons for this are the previous lack of an international cystatin C calibrator and the nonequivalence of results from different cystatin C assays. METHODS Use of the recently introduced certified reference material, ERM-DA471/IFCC, and further work to achieve high agreement and equivalence of 7 commercially available cystatin C assays allowed a substantial decrease of the CV of the assays, as defined by their performance in an external quality assessment for clinical laboratory investigations. By use of 2 of these assays and a population of 4690 subjects, with large subpopulations of children and Asian and Caucasian adults, with their GFR determined by either renal or plasma inulin clearance or plasma iohexol clearance, we attempted to produce a virtually assay-independent simple cystatin C-based equation for estimation of GFR. RESULTS We developed a simple cystatin C-based equation for estimation of GFR comprising only 2 variables, cystatin C concentration and age. No terms for race and sex are required for optimal diagnostic performance. The equation, [Formula: see text] is also biologically oriented, with 1 term for the theoretical renal clearance of small molecules and 1 constant for extrarenal clearance of cystatin C. CONCLUSIONS A virtually assay-independent simple cystatin C-based and biologically oriented equation for estimation of GFR, without terms for sex and race, was produced.

Risk factors for cardiovascular mortality in patients with systemic lupus erythematosus, a prospective cohort study

IntroductionSystemic lupus erythematosus (SLE) is a chronic autoimmune disease. Cardiovascular disease (CVD) is common and a major cause of mortality. Studies on cardiovascular morbidity are abundant, whereas mortality studies focusing on cardiovascular outcomes are scarce. The aim of this study was to investigate causes of death and baseline predictors of overall (OM), non-vascular (N-VM), and specifically cardiovascular (CVM) mortality in SLE, and to evaluate systematic coronary risk evaluation (SCORE).Methods208 SLE patients were included 1995-1999 and followed up after 12 years. Clinical evaluation, CVD risk factors, and biomarkers were recorded at inclusion. Death certificates and autopsy protocols were collected. Causes of death were divided into CVM (ischemic vascular and general atherosclerotic diseases), N-VM and death due to pulmonary hypertension. Predictors of mortality were investigated using multivariable Cox regression. SCORE and standardized mortality ratio (SMR) were calculated.ResultsDuring follow-up 42 patients died at mean age of 62 years. SMR 2.4 (CI 1.7-3.0). 48% of deaths were caused by CVM. SCORE underestimated CVM but not to a significant level. Age, high cystatin C levels and established arterial disease were the strongest predictors for all- cause mortality. After adjusting for these in multivariable analyses, only smoking among traditional risk factors, and high soluble vascular cell adhesion molecule-1 (sVCAM-1), high sensitivity C-reactive protein (hsCRP), anti-beta2 glycoprotein-1 (abeta2GP1) and any antiphospholipid antibody (aPL) among biomarkers, remained predictive of CVM.ConclusionWith the exception of smoking, traditional risk factors do not capture the main underlying risk factors for CVM in SLE. Rather, cystatin C levels, inflammatory and endothelial markers, and antiphospholipid antibodies (aPL) differentiate patients with favorable versus severe cardiovascular prognosis. Our results suggest that these new biomarkers are useful in evaluating the future risk of cardiovascular mortality in SLE patients.

Human Evidence That the Cystatin C Gene Is Implicated in Focal Progression of Coronary Artery Disease

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.