Biomarker Commons

The kinetics of cardiopulmonary bypass: a dual-platform proteomics study of plasma biomarkers in pediatric patients undergoing cardiopulmonary bypass.

Artif Organs. 2012 Jan;36(1):E1-20

Authors: Umstead TM, Lu CJ, Freeman WM, Myers JL, Clark JB, Thomas NJ, Icitovic N, Chinchilli VM, Undar A, Phelps DS

Abstract
This study was designed to investigate the expression kinetics and patterns of plasma biomarkers throughout the pediatric cardiopulmonary bypass (CPB) procedure to help predict those patients most at risk for complications. This study sampled plasma from pediatric CPB patients at five time points before, during, and after CPB. A dual-platform proteomics approach was then utilized which incorporated two-dimensional difference gel electrophoresis (2D-DIGE) coupled with matrix-assisted laser desorption ionization-time-of-flight/time-of-flight tandem mass spectrometry, and multi-analyte profile (MAP) assays to identify changes in expression of plasma protein biomarkers and characterize the patterns of these changes. A combined total of 134 proteins were identified with significant changes between the two platforms, with 53 coming from 2D-DIGE, 90 from MAP, and nine proteins that were identified using both methods. The proteins were then divided into 12 major groups based on the expression patterns, and two of the most clinically relevant proteins having the greatest changes in expression were selected from each group to use as "predictor biomarkers." A potential model for prediction of patient outcome was then generated using these 24 proteins. The patterns of biomarker expression during pediatric CPB may provide insight into the prediction, prevention, or treatment of complications resulting from CPB, thereby helping to improve the outcomes of pediatric CPB patients and reduce the incidence of complications.

PMID: 22250822 [PubMed - indexed for MEDLINE]

Childhood adversity and immune and inflammatory biomarkers associated with cardiovascular risk in youth: a systematic review.

Brain Behav Immun. 2012 Feb;26(2):239-50

Authors: Slopen N, Koenen KC, Kubzansky LD

Abstract
BACKGROUND: Research suggests that adverse experiences in childhood affect the development of cardiovascular disease (CVD), and immune and inflammation dysregulation has been postulated to play role. However, it is unclear whether the effects of social adversity on immune-related biomarkers are evident in early life, and if these biomarkers may provide an early risk marker for targeting prevention and intervention. The purpose of this review is to evaluate research on the relationship between adversity and CVD-relevant immune biomarkers in youth, assess the consistency of the findings, and consider what additional research is needed.
METHODS: PubMed and PsycINFO searches were conducted through September 2011. Studies were selected using criteria related to the childhood exposure, biomarker outcome, age range, and sample selection. Twenty articles were identified, examining associations between childhood adversity and immune biomarkers (assessed during childhood) that are potential risk markers for CVD later in life.
RESULTS: Although childhood adversity was not consistently related to youth levels of inflammatory and other immune markers relevant to CVD, a trend toward positive findings was observed. No detectable patterns were evident based on measure of adversity, biomarker, study design, or sample size.
CONCLUSIONS: Overall, our findings suggest this avenue of research is worth continued investigation. We offer recommendations for future research related to (1) study design and sample, (2) definition and measurement of adversity, (3) statistical analysis, and (4) outcomes that will help distinguish whether there are immunologic alterations related to adversity and subsequent CVD risk that can be reliably detected in childhood.

PMID: 22138616 [PubMed - indexed for MEDLINE]

N-terminal pro-B-type natriuretic peptide and long-term mortality in non-ischaemic cardiomyopathy.

Wien Klin Wochenschr. 2011 Dec;123(23-24):738-42

Authors: Krackhardt F, Düngen HD, Trippel TD, Inkrot S, Tscholl V, Schlattmann P, Kehrt K, Haverkamp W

Abstract
AIM: The inactive N-terminal fragment of B-type natriuretic peptide is a strong predictor of mortality among patients with acute and chronic heart failure secondary to ischaemic heart disease. Its prognostic utility in patients with non-ischaemic heart disease is not well established. We therefore assessed the relationship of N-terminal proBNP levels and long-term mortality in patients with non-ischaemic cardiomyopathy.
METHODS: N-terminal proBNP was measured in serum samples of 156 patients who presented to a single academic centre with worsening heart failure secondary to non-ischaemic cardiomyopathy. The rate of death from all causes was determined after a mean follow-up of 8.9 years.
RESULTS: Multivariate analyses, using Cox proportional hazards models, established NT-proBNP and left ventricular diastolic diameter as predictors for cardiac mortality with estimated hazard ratios of 2.76 (95% confidence interval: 1.53, 4.98) and 1.06 (95% confidence interval: 1.02, 1.10), respectively.
CONCLUSION: This to date longest-term analysis of N-terminal proBNP and mortality in patients with proven non-ischaemic cardiomyopathy confirms this cardiac-specific biomarker as powerful, independent risk predictor. It is a superior prognostic determinant to New York Heart Association functional class and left ventricular ejection fraction.

PMID: 22105112 [PubMed - indexed for MEDLINE]

Elevated E-selectin and diastolic blood pressure in diabetic children.

Eur J Clin Invest. 2012 Mar;42(3):303-9

Authors: Maggio AB, Farpour-Lambert NJ, Montecucco F, Pelli G, Marchand LM, Schwitzgebel V, Mach F, Aggoun Y, Beghetti M

Abstract
BACKGROUND: Cardiovascular risk markers are related to micro-angiopathy in children with type 1 diabetes (T1DM), but there is no information about their relationship with blood pressure (BP) and endothelial function.
MATERIALS AND METHODS: This was a case-control study including 29 children with T1DM (mean age 10·5 ± 2·7 years, disease duration: 3·8 ± 2·2 years) and 39 healthy controls (mean age: 9·8 ± 2·7 years). We assessed 24-h ambulatory BP, vascular function and serum level of lipids, vascular cell adhesion molecule-1 (VCAM-1; ICAM) and selectins (E-selectin; P-selectin).
RESULTS: The subject groups had similar physical characteristics and lipids level, except body mass index (BMI) which was higher in T1DM than in healthy children (18·6 ± 2·6 vs. 16·7 ± 2·5 kg/m(2), P = 0·003). Children with T1DM had increased 24 h diastolic BP z-score (0·62 ± 0·9 vs. -0·65 ± 0·8, P < 0·001), even after adjustment for BMI, as well as higher VCAM-1 concentration (492 ± 346 vs. 340 ± 225 ng/mL, P = 0·039) compared to healthy subjects. Diastolic BP z-scores were associated with disease duration, E-selectin and triglyceride levels in the T1DM group (P < 0·05). E-selectin was also related to triglycerides, otherwise there were no relationships between vascular function, markers and BP.
CONCLUSION: E-selectin, an early atherosclerosis biomarker, is positively associated with diastolic BP values in children with T1DM, despite relatively short disease duration.

PMID: 21880038 [PubMed - indexed for MEDLINE]

Evolving role of biomarkers in acute cerebrovascular disease.

Ann Neurol. 2012 Mar;71(3):289-303

Authors: Kernagis DN, Laskowitz DT

Abstract
The development of a clinically validated biomarker of acute cerebral ischemia would have the potential to facilitate the use of time-sensitive reperfusion strategies, allow for individualization of patient care by predicting relative risk of hemorrhage and volume of penumbral tissue, and add valuable prognostic information for patients presenting with acute stroke. Additionally, a stroke biomarker might benefit early stage clinical research by serving as a surrogate measure of ischemic injury. Although at present there are no clinically validated biomarkers of acute stroke, previous studies have focused on markers associated with different components of the ischemic cascade, including microglial activation, inflammation, oxidative stress, neuronal injury, hemostasis, and endothelial dysfunction. Evolving technologies have provided high throughput approaches to investigate potential gene and protein signatures, and methods to measure newly discovered markers of cell death and immune responses. Prior to defining the clinical utility of stroke biomarkers, it is critical to understand the inherent limitations of a biomarker-based approach and define its potential value for providing adjunctive diagnostic and prognostic information. The identification and validation of a clinically relevant biomarker, or panel of markers, of stroke will ultimately require incorporation of both stringent research design and assessment in the clinical context in which the marker will be used.

PMID: 22451199 [PubMed - indexed for MEDLINE]

Plasma biomarker may help to distinguish acute CVST from non-thrombotic CVSS in emergency.

Int J Stroke. 2012 Feb;7(2):183-4

Authors: Meng R, Konakondla S, Wang X, Lo EH, Ding Y, Ji X

PMID: 22264373 [PubMed - indexed for MEDLINE]

TRV: a physiological biomarker in sickle cell disease.

Pediatr Blood Cancer. 2012 Jun;58(6):831-2

Authors: Kato GJ

PMID: 22180092 [PubMed - indexed for MEDLINE]

Admission glucose does not improve GRACE score at 6 months and 5 years after myocardial infarction.

Cardiology. 2011;120(4):227-34

Authors: de Mulder M, van der Ploeg T, de Waard GA, Boersma E, Umans VA

Abstract
OBJECTIVE: Admission plasma glucose (APG) is a biomarker that predicts mortality in myocardial infarction (MI) patients. Therefore, APG may improve risk stratification based on the GRACE risk score.
METHODS: We collected data on baseline characteristics and long-term (median 55 months) outcome of 550 MI patients who entered our hospital in 2003 and 2006. We determined the GRACE risk score at admission for each patient, which was entered in a logistic regression model, together with APG, to evaluate their prognostic value for 6-month and 5-year mortality.
RESULTS: Patients with APG ≥7.8 mmol/l had a higher mortality than those with APG levels <7.8 mmol/l; 6 months: 13.7 versus 3.6%, p value <0.001; 5 years: 20.4 versus 11.1%, p value 0.003. After adjustment for the GRACE risk score variables, APG appeared a significant predictor of 6-month and 5-year mortality, adjusted OR 1.17 (1.06-1.29) and 1.12 (1.03-1.22). The combination of the GRACE risk score and APG increased the model's performance (discrimination C-index 0.87 vs. 0.85), although the difference was not significant (p = 0.095). Combining the GRACE risk score and APG reclassified 12.9% of the patients, but the net reclassification improvement was nonsignificant (p = 0.146).
CONCLUSION: APG is a predictor of 6-month and 5-year mortality, each mmol/l increase in APG being associated with a mortality increase of 17 and 12%, respectively, independent of the GRACE risk score. However, adding APG to the GRACE model did not result in significantly improved clinical risk stratification.

PMID: 22343543 [PubMed - indexed for MEDLINE]

Telomeres, atherosclerosis, and the hemothelium: the longer view.

Annu Rev Med. 2012;63:293-301

Authors: Aviv A, Levy D

Abstract
The model we propose to explain the links between atherosclerosis and telomere dynamics (birth telomere length and its age-dependent shortening) in leukocytes takes cues from three facts: atherosclerosis is a disease of the vascular endothelium; the hematopoietic system and the vascular endothelium share a common embryonic origin; interindividual variation in leukocyte telomere length (LTL) in the general population has a genetic explanation. The model posits that LTL dynamics mirror telomere dynamics in hematopoietic stem cells (HSCs), where telomere length is an index of HSC reserves. Diminished HSC reserves at birth, their accelerated attrition rate afterward, or both are are reflected in shortened LTL during adulthood-a phenomenon that confers increased risk for atherosclerosis. We explain how telomere length in HSCs serves as both a biomarker of atherosclerosis and a determinant of its development. Our model comes down to this proposition: Shortened LTL predicts increased atherosclerotic risk because the injurious component of atherosclerosis exceeds the repair capacity of HSC reserves, which largely depend on HSC telomere length.

PMID: 22017444 [PubMed - indexed for MEDLINE]

Prediction of haematoma expansion with the CTA spot sign: a useful biomarker?

Lancet Neurol. 2012 Apr;11(4):294-5

Authors: Wardlaw JM

PMID: 22405629 [PubMed - indexed for MEDLINE]

Combined cardiac magnetic resonance imaging and C-reactive protein levels identify a cohort at low risk for defibrillator firings and death.

Circ Cardiovasc Imaging. 2012 Mar;5(2):178-86

Authors: Wu KC, Gerstenblith G, Guallar E, Marine JE, Dalal D, Cheng A, Marbán E, Lima JA, Tomaselli GF, Weiss RG

Abstract
BACKGROUND: Annually, ≈80,000 Americans receive guideline-based primary prevention implantable cardioverter-defibrillators (ICDs), but appropriate firing rates are low. Current selection criteria for ICDs rely on left ventricular ejection fraction, which lacks sensitivity and specificity. Because scar-related myocardial tissue heterogeneity is a substrate for life-threatening arrhythmias, we hypothesized that cardiac magnetic resonance identification of myocardial heterogeneity improves risk stratification through (1) its association with adverse cardiac events independent of clinical factors and biomarker levels and (2) its ability to identify particularly high- and low-risk subgroups.
METHODS AND RESULTS: In 235 patients with chronic ischemic and nonischemic cardiomyopathy with a left ventricular ejection fraction of ≤35% undergoing clinically indicated primary prevention ICD implantation, gadolinium-enhanced cardiac magnetic resonance was prospectively performed to quantify the amount of heterogeneous myocardial tissue (gray zone [GZ]) and dense core scar. Serum high-sensitivity C-reactive protein (hsCRP) and other biomarkers were assayed. The primary end point was appropriate ICD shock for ventricular tachycardia/fibrillation or cardiac death, which occurred in 45 (19%) patients at a 3.6-year median follow-up. On univariable analysis, only diuretics, hsCRP, GZ, and core scar were associated with outcome. After multivariable adjustment, GZ and hsCRP remained independently associated with outcome (P<0.001). Patients in the lowest tertile for both GZ and hsCRP (n=42) were at particularly low risk (0.7% per year event rate), whereas those in the highest tertile for both GZ and hsCRP (n=32) had an event rate of 16.1% per year, P<0.001.
CONCLUSIONS: In a cohort of primary prevention ICD candidates, combining a myocardial heterogeneity index with an inflammatory biomarker identified a subgroup with a very low risk for adverse cardiac events, including ventricular arrhythmias. This novel approach warrants further investigation to confirm its value as a clinical risk stratification tool. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00181233.

PMID: 22267750 [PubMed - indexed for MEDLINE]

Physicians' actions and influence, such as aggressive blood pressure control, greatly improve the health of diabetes patients.

Health Aff (Millwood). 2012 Jan;31(1):140-9

Authors: Gray B, Schuetz CA, Weng W, Peskin B, Rosner B, Lipner RS

Abstract
Managing diabetes and preventing its associated morbidities require active partnerships between physicians and patients. Studies to date lack the level of detail to quantify the degree to which interventions that are more controlled by physicians influence outcomes versus those that are more controlled by patients. Using the Archimedes model, we simulated a thirty-year clinical trial and compared the effects of three sets of interventions over which physicians have progressively less control: compliance with process-of-care standards, such as conducting foot and retinal exams and screening for signs of early kidney disease; control of biomarkers, such as hemoglobin A1c and blood pressure; and lifestyle modifications, such as patients' switching to healthier diets and losing weight. We found that if all US adults diagnosed with type 2 diabetes met quality targets in all of these areas, they would experience a nearly 16 percent increase in quality-adjusted life-years and a nearly 23 percent reduction in fifteen-year mortality over the thirty-year simulation period. Meeting aggressive biomarker targets yielded the most benefit. Meeting conservative biomarker targets came next, followed closely by meeting process-of-care standards. The incremental benefits of complying fully with diet and smoking cessation yielded the least benefit. Thus, through measures more readily within their control, and through collaboration with their patients, physicians have a substantial opportunity to improve outcomes. These findings can inform policy makers' rational resource allocation decisions and the design of programs to improve diabetes care.

PMID: 22232104 [PubMed - indexed for MEDLINE]

Safety and efficiency of a chest pain diagnostic algorithm with selective outpatient stress testing for emergency department patients with potential ischemic chest pain.

Ann Emerg Med. 2012 Apr;59(4):256-264.e3

Authors: Scheuermeyer FX, Innes G, Grafstein E, Kiess M, Boychuk B, Yu E, Kalla D, Christenson J

Abstract
STUDY OBJECTIVE: Chest pain units have been used to monitor and investigate emergency department (ED) patients with potential ischemic chest pain to reduce the possibility of missed acute coronary syndrome. We seek to optimize the use of hospital resources by implementing a chest pain diagnostic algorithm.
METHODS: This was a prospective cohort study of ED patients with potential ischemic chest pain. High-risk patients were referred to cardiology, and patients without ECG or biomarker evidence of ischemia were discharged home after 2 to 6 hours of observation. Emergency physicians scheduled discharged patients for outpatient stress ECGs or radionuclide scans at the hospital within 48 hours. Patients with positive provocative test results were immediately referred back to the ED. The primary outcome was the rate of missed diagnosis of acute coronary syndrome at 30 days.
RESULTS: We prospectively followed 1,116 consecutive patients who went through the chest pain diagnostic algorithm, of whom 197 (17.7%) were admitted at the index visit and 254 (22.8%) received outpatient testing on discharge. The 30-day acute coronary syndrome event rate was 10.8%, and the 30-day missed acute coronary syndrome rate was 0% (95% confidence interval 0% to 2.4%). Of the 120 acute coronary syndrome cases, 99 (82.5%) were diagnosed at the index ED visit, and 21 patients (17.5%) received the diagnosis during outpatient stress testing.
CONCLUSION: In ED patients with chest pain, a structured diagnostic approach with time-focused ED decision points, brief observation, and selective application of early outpatient provocative testing appears both safe and diagnostically efficient, even though some patients with acute coronary syndrome may be discharged for outpatient stress testing on the index ED visit.

PMID: 22221842 [PubMed - indexed for MEDLINE]

Basal ganglia hyperintensity on T1-weighted MRI in Rendu-Osler-Weber disease.

J Magn Reson Imaging. 2012 Feb;35(2):426-30

Authors: Oikonomou A, Chatzistefanou A, Zezos P, Mintzopoulou P, Vadikolias K, Prassopoulos P

Abstract
The purpose of this study was to evaluate possible central nervous system (CNS) involvement in Rendu-Osler-Weber (ROW) disease in magnetic resonance imaging (MRI). Three patients with symptomatic ROW disease underwent brain MRI. Brain MRI depicted in all three of them increased signal intensity on T1-weighted images involving the globus pallidus and cerebral crura bilaterally. Laboratory studies of the two men showed iron deficiency anemia, while all three of them had normal liver function tests and increased manganese blood concentration. Gastroscopy and colonoscopy revealed a gastric and a cecal arteriovenous malformation (AVM) in the first one, while pulmonary and hepatic computed tomography (CT) angiography did not detect any intrahepatic shunts. Liver ultrasound in the second one revealed dilatation of intrahepatic artery branches consistent with intrahepatic shunts, while it was normal in the third patient. Chest radiographs were normal in all three patients. Pallidal T1 hyperintensity on T1-weighted imaging may be a biomarker of manganese overload in ROW disease.

PMID: 22127848 [PubMed - indexed for MEDLINE]

Circulating levels of a biomarker of collagen metabolism are associated with health-related quality of life in patients with chronic heart failure.

Qual Life Res. 2012 Feb;21(1):143-53

Authors: Chatzikyriakou SV, Tziakas DN, Chalikias GK, Stakos D, Papazoglou D, Lantzouraki A, Thomaidi A, Boudoulas H, Konstantinides S

Abstract
PURPOSE: Assessment of circulating levels of collagen-derived peptides has been proposed as a useful tool to monitor indirectly myocardial collagen metabolism in chronic heart failure (CHF) patients. The potential link between circulating concentrations of collagen metabolism biomarkers and health-related quality of life (HRQOL) has not been adequately evaluated. With the present study, we investigated the association between serum levels of collagen-derived peptides and HRQOL.
METHODS: We studied 280 consecutive outpatients (of mean age 67 ± 10 years, 180 men) with CHF. Serum concentrations of carboxy-terminal telopeptide of collagen type I (CITP)-a marker of collagen type I degradation-were measured in all patients both at baseline and during a period of 6 months follow-up. HRQOL was assessed by Minnesota living with heart failure questionnaire (MLHFQ).
RESULTS: CITP levels were significantly associated with MLHFQ scores both at baseline (r = 0.231, P < 0.001) and at 6 months follow-up (r = 0.145, P = 0.044). CITP levels remained significantly associated with MLHFQ score in multivariable linear regression analysis. Higher CITP levels were observed with higher MLHFQ scores (poor HRQOL) both at baseline (P = 0.001) and at 6 months (P = 0.041). Unadjusted analysis demonstrated a significant relationship between increasing CITP levels during 6 months follow-up and worsening HRQOL (r = 0.204, P = 0.001). The aforementioned correlation remained significant in multivariable linear regression analysis.
CONCLUSION: Our findings show that increased CITP levels are associated with poorer HRQOL in patients with CHF. These findings are consistent with a link between a pathophysiologic mechanism, i.e., collagen metabolism and patient self-assessed health status in CHF.

PMID: 21598062 [PubMed - indexed for MEDLINE]

Biomarkers in acute myocardial injury.

Transl Res. 2012 Apr;159(4):252-64

Authors: Kehl DW, Iqbal N, Fard A, Kipper BA, De La Parra Landa A, Maisel AS

Abstract
Acute coronary syndrome (ACS) is a significant cause of morbidity and mortality worldwide. The proper diagnosis of ACS requires reliable and accurate biomarker assays to detect evidence of myocardial necrosis. Currently, troponin is the gold standard biomarker for myocardial injury and is used commonly in conjunction with creatine kinase-MB (CK-MB) and myoglobin to enable a more rapid diagnosis of ACS. A new generation of highly sensitive troponin assays with improved accuracy in the early detection of ACS is now available, but the correct interpretation of assay results will require a careful consideration of assay characteristics and the clinical setting prior to incorporation into routine practice. B-type natriuretic peptides, copeptin, ischemia-modified albumin, heart-type fatty-acid-binding protein, myeloperoxidase, C-reactive protein, choline, placental growth factor, and growth-differentiation factor-15 make up a promising group of other biomarkers that have shown the ability to improve prognosis and diagnosis of ACS compared with traditional markers.

PMID: 22424429 [PubMed - indexed for MEDLINE]

Cardiovascular biomarkers in chronic kidney disease.

J Ren Nutr. 2012 Jan;22(1):120-7

Authors: Park SH, Stenvinkel P, Lindholm B

Abstract
Cardiovascular disease (CVD) is the major cause of death in patients with advanced chronic kidney disease (CKD). Recent studies have suggested that novel risk factors, uremia- or dialysis-related, are of great importance, as they act synergistically with the highly prevalent traditional risk factors for CVD in CKD patients. Whereas an ideal single biomarker, i.e., one that adds relevant prognostic information in clinical practice over and above that provided by conventional (Framingham) risk factors, has yet to be identified, combinations of several biomarkers or repeated measurements of biomarkers may increase the explanatory power of prognostic information provided by traditional risk factors to predict cardiovascular outcomes. However, because the increase of predictive power is modest, clinical assessment of patient status still remains the cornerstone tool for predicting risk for CVD. On the other hand, the search for better biomarkers may reveal novel pathways linked to CVD that need to be explored in CKD patients. This brief review summarizes some emerging and potentially clinically applicable CVD biomarkers in CKD patients, especially focusing on inflammation and vascular calcification that may provide additional information to conventional risk factors.

PMID: 22200428 [PubMed - indexed for MEDLINE]

Geographic variation in cardiovascular inflammation among healthy women in the Women's Health Study.

PLoS One. 2011;6(11):e27468

Authors: Clark CR, Coull B, Berkman LF, Buring JE, Ridker PM

Abstract
BACKGROUND: Geographic variation in traditional cardiovascular disease (CVD) risk factors has been observed among women in the US. It is not known whether state-level variation in cardiovascular inflammation exists or could be explained by traditional clinical risk factors and behavioral lifestyle factors.
METHODS AND RESULTS: We used multilevel linear regression to estimate state-level variation in inflammatory biomarker patterns adjusted for clinical and lifestyle characteristics among 26,029 women free of CVD. Participants derived from the Women's Health Study, a national cohort of healthy middle-aged and older women. Inflammatory biomarker patterns (plasma levels of high-sensitivity C-reactive protein (hsCRP), soluble intercellular adhesion molecule-1 (sICAM-1), and fibrinogen) were compared to state-level patterns of traditional CVD risk factors and global risk scores. We found that all three inflammatory biomarkers exhibited significant state-level variation including hsCRP (lowest vs. highest state median 1.3 mg/L vs. 2.7 mg/L, unadjusted random effect estimate 1(st) to 99(th) percentile range for log hsCRP 0.52, p<.001), sICAM-1 (325 ng/ml vs. 366ng/ml, unadjusted random effect estimate 1(st) to 99(th) percentile range 0.44, p<.001), and fibrinogen (322 mg/dL vs. 367 mg/dL, unadjusted random effect estimate 1(st) to 99(th) percentile range 0.41, p = .001). Neither demographic, clinical or lifestyle characteristics explained away state-level effects in biomarker patterns. Southern and Appalachian states (Arkansas, West Virginia) had the highest inflammatory biomarker values. Regional geographic patterns of traditional CVD risk factors and risk scores did not completely overlap with biomarkers of inflammation.
CONCLUSIONS: There is state-level geographic variation in inflammatory biomarkers among otherwise healthy women that cannot be completely attributed to traditional clinical risk factors or lifestyle characteristics. Future research should aim to identify additional factors that may explain geographic variation in biomarkers of inflammation among healthy women.

PMID: 22102899 [PubMed - indexed for MEDLINE]

Urinary angiotensinogen levels in relation to renal involvement of Henoch-Schonlein purpura in children.

Nephrology (Carlton). 2012 Jan;17(1):53-7

Authors: Mao YN, Liu W, Li YG, Jia GC, Zhang Z, Guan YJ, Zhou XF, Liu YF

Abstract
AIM: To investigate whether urinary angiotensinogen (UAGT) levels are correlated with renal involvement of Henoch-Schonlein purpura (HSP) in children, and to explore whether UAGT has any relation to the severity of HSP.
METHODS: The study sample consisted of 107 patients (50 boys and 57 girls, 6.68±2.41 years) with clinical diagnosis of HSP. A 24 h urine sample was collected before treatment. UAGT levels were measured in patients with HSP in the acute and convalescent phases by enzyme linked immunosorbent assay.
RESULTS: Urinary angiotensinogen/urinary concentration of creatinine levels were significantly higher in proteinuric HSP in the acute phase and the convalescent phase (32.02±3.95 and 25.31±4.11 µg/g) compared with those with HSP without renal involvement (17.26±2.60 and 15.14±3.81 µg/g) and those with hematuric HSP (19.70±2.21 and 17.28±3.62 µg/g) (P<0.0001 and P<0.01, respectively). Using matched urine samples from the same patients, UAGT/urinary concentration of creatinine (UCr) levels of proteinuric HSP patients were significantly lower in the convalescent phase (25.31 ± 4.11 µg/g, P<0.01) than in the acute phase (32.02±3.95 µg/g). UAGT/UCr levels showed positive correlation with 24 h urine protein or serum creatinine in both hematuric HSP and proteinuric HSP groups during the acute phase (P<0.05).
CONCLUSIONS: Urinary angiotensinogen levels were remarkably high in the acute phase in the patients with proteinuric HSP, suggesting increased UAGT may indicate a series of functional changes in the kidney and it may be used as a potential biomarker of severity of HSP to monitor the progression of HSP with renal involvement.

PMID: 21854508 [PubMed - indexed for MEDLINE]

Relations between plasma ox-LDL and carotid plaque among Chinese Han ethnic group.

Neurol Res. 2011 Jun;33(5):460-6

Authors: Fang R, Zhang N, Wang C, Zhao X, Liu L, Wang Y, Xu J, Wang X, Liu Z, Wang Y

Abstract
OBJECTIVES: To study the relationship between plasma oxidized low-density lipoprotein (ox-LDL) and carotid plaque, including plaque stability, of patients with acute ischemic stroke among Chinese Han ethnic group.
METHODS: A total of 181 patients with acute ischemic stroke were recruited and enrolled. The subjects were divided into a carotid plaque group and a no-plaque group by carotid ultrasound. The stability of carotid atheromas was assessed by ultrasound echo density, and the carotid plaque group was further divided into a vulnerable plaque group and a stable plaque group based on the echo results.
RESULTS: The study showed that the correlation between age [odds ratio (OR): 1.047; 95% confidence interval (CI): 1.014-1.082; P<0.01] and carotid plaque was significant. Plasma ox-LDL (OR: 1.020; 95%CI: 1.010-1.030; P<0.001) was also found to be significantly correlated with carotid plaque. Age was irrelevant to plaque stability (P = 0.0685). The ox-LDL of the vulnerable plaque group was found to be significantly higher than that of the stable plaque group (P = 0.015). By measuring the plasma ox-LDL in patients with ischemic stroke, the proportion under the receiver operating characteristic curve of vulnerable carotid plaques was 0.690 with a 95%CI of 0.613-0.767 (P<0.001). The point of cut-off was 94.5943, the sensitivity was 0.805, and the specificity was 0.505.
CONCLUSION: The plasma ox-LDL level and age are possible risk factors for carotid plaque among patients with ischemic stroke of the Chinese Han ethnic group. This study suggests that ox-LDL could be used as a biomarker in screening for vulnerable carotid plaque in clinical practice.

PMID: 21669113 [PubMed - indexed for MEDLINE]