Biomarker Commons

Triglycerides: how much credit do they deserve?

Med Clin North Am. 2012 Jan;96(1):39-55

Authors: Kohli P, Cannon CP

Abstract
In the modern era of statin therapy, major advances have been made in treating coronary heart disease. However, despite intensive treatment with statin therapy, residual cardiovascular risk persists and has been attributed to the persistence of atherogenic dyslipidemia and, in part, elevated triglycerides (TGs). In this review, the authors focus on the mechanism of elevated TGs and provide a discussion of the challenges of measuring TGs as a biomarker, its role in the pathogenesis of atherosclerotic heart disease, and results of several recent studies that have elucidated the relationship between TGs and cardiovascular morbidity and mortality.

PMID: 22391250 [PubMed - indexed for MEDLINE]

Urinary excretion of 8-oxo-7,8-dihydroguanine as biomarker of oxidative damage to DNA.

Arch Biochem Biophys. 2012 Feb 15;518(2):142-50

Authors: Loft S, Danielsen P, Løhr M, Jantzen K, Hemmingsen JG, Roursgaard M, Karotki DG, Møller P

Abstract
Oxidatively damaged DNA may be important in carcinogenesis. 8-Oxo-7,8-dihydroguanine (8-oxoGua) is an abundant and mutagenic lesion excised by oxoguanine DNA glycosylase 1 (OGG1) and measurable in urine or plasma by chromatographic methods with electrochemical or mass spectrometric detectors, reflecting the rate of damage in steady state. A common genetic OGG1 variant may affect the activity and was associated with increased levels of oxidized purines in leukocytes without apparent effect on 8-oxoGua excretion or major change in cancer risk. 8-OxoGua excretion has been associated with exposure to air pollution, toxic metals, tobacco smoke and low plasma antioxidant levels, whereas fruit and vegetable intake or dietary interventions showed no association. In rodent studies some types of feed may be source of 8-oxoGua in collected urine. Of cancer therapies, cisplatin increased 8-oxoGua excretion, whereas radiotherapy only showed such effects in experimental animals. Case-control studies found high excretion of 8-oxoGua in relation to cancer, dementia and celiac disease but not hemochromatosis, although associations could be a consequence rather than reflecting causality of disease. One prospective study found increased risk of developing lung cancer among non-smokers associated with high excretion of 8-oxoGua. Urinary excretion of 8-oxoGua is a promising biomarker of oxidatively damaged DNA.

PMID: 22239988 [PubMed - indexed for MEDLINE]

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]

Urinary F2-isoprostanes as a biomarker of reduced risk of type 2 diabetes.

Diabetes Care. 2012 Jan;35(1):173-4

Authors: Il'yasova D, Spasojevic I, Base K, Zhang H, Wang F, Young SP, Millington DS, D'Agostino RB, Wagenknecht LE

Abstract
OBJECTIVE: We have previously reported evidence of an inverse association between a urinary F(2)-isoprostane and type 2 diabetes risk in a pilot case-control study nested within the Insulin Resistance Atherosclerosis Study (IRAS). Here, we report the results from the study extended to the entire IRAS cohort.
RESEARCH DESIGN AND METHODS: This prospective study included 138 incident type 2 diabetes case and 714 noncase subjects. Four F(2)-isoprostanes (iPF2α-III; 2,3-dinor-iPF2α-III; iPF2α-VI; and 8,12-iso-iPF2α-VI) were assayed in baseline urine samples using liquid chromatography-tandem mass spectrometry.
RESULTS: Three F(2)-isoprostanes showed significant inverse associations with type 2 diabetes risk: the adjusted odds ratios were 0.52 (95% CI 0.39-0.67), 0.56 (0.42-0.73), 0.62 (0.48-0.79), and 0.91 (0.72-1.12) for iPF2α-III; 2,3-dinor-iPF2α-III; iPF2α-VI; and 8,12-iso-iPF2α-VI, respectively.
CONCLUSIONS: Our findings indicate that urinary F(2)-isoprostanes are inversely associated with type 2 diabetes risk beyond the traditional risk factors and may be useful in identifying high-risk populations.

PMID: 22100959 [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]

Do we now have a prognostic biomarker for progressive diabetic nephropathy?

J Am Soc Nephrol. 2012 Mar;23(3):376-7

Authors: Brosius FC, Saran R

PMID: 22323641 [PubMed - indexed for MEDLINE]

C-reactive protein promotes diabetic kidney disease in a mouse model of type 1 diabetes.

Diabetologia. 2011 Oct;54(10):2713-23

Authors: Liu F, Chen HY, Huang XR, Chung AC, Zhou L, Fu P, Szalai AJ, Lan HY

Abstract
AIMS/HYPOTHESIS: Although C-reactive protein (CRP) has been implicated as a risk factor in diabetes, its pathogenic importance in diabetic kidney disease (DKD) remains unclear. The present study investigated the potential role of CRP in DKD.
METHODS: Diabetes was induced by streptozotocin in human CRP transgenic and wild-type mice for assessment of kidney injury at 24 weeks by real-time PCR, immunohistochemistry and western blot analysis. In vitro, the pathogenic effect of CRP was investigated using human kidney tubular epithelial cells cultured with high glucose and/or CRP.
RESULTS: We found that CRP transgenic mice developed much more severe diabetic kidney injury than wild-type mice, as indicated by a significant increase in urinary albumin excretion and kidney injury molecule-1 abundance, enhanced infiltration of macrophages and T cells, and upregulation of pro-inflammatory cytokines (IL-1β, TNFα) and extracellular matrix (collagen I, III and IV). Enhanced renal inflammation and fibrosis in CRP transgenic mice was associated with upregulation of CRP receptor, CD32a, and over-activation of the TGF-β/SMAD and nuclear factor κB signalling pathways. In vitro, CRP significantly upregulated pro-inflammatory cytokines (IL-1β, TNFα, monocyte chemoattractant protein-1 [MCP-1]) and pro-fibrotic growth factors (TGF-β1, connective tissue growth factor [CTGF]) via CD32a/64. CRP was induced by high glucose, which synergistically promoted high glucose-mediated renal inflammation and fibrosis.
CONCLUSIONS/INTERPRETATION: CRP is not only a biomarker, but also a mediator in DKD. Enhanced activation of TGF-β/SMAD and nuclear factor κB signalling pathways may be the mechanisms by which CRP promotes renal inflammation and fibrosis under diabetic conditions.

PMID: 21744073 [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]

Urinary markers of nucleic acid oxidation and long-term mortality of newly diagnosed type 2 diabetic patients.

Diabetes Care. 2011 Dec;34(12):2594-6

Authors: Broedbaek K, Siersma V, Henriksen T, Weimann A, Petersen M, Andersen JT, Jimenez-Solem E, Stovgaard ES, Hansen LJ, Henriksen JE, Bonnema SJ, Olivarius Nde F, Poulsen HE

Abstract
OBJECTIVE: We analyzed data from a cohort of 1,381 newly diagnosed type 2 diabetic patients to test the hypothesis that urinary markers of nucleic acid oxidation are independent predictors of mortality.
RESEARCH DESIGN AND METHODS: We examined the relationship between urinary excretion of markers of DNA oxidation (8-oxo-7,8-dihydro-2'-deoxyguanosine [8-oxodG]) and RNA oxidation (8-oxo-7,8-dihydroguanosine [8-oxoGuo]) and long-term mortality using Cox proportional hazards regression.
RESULTS: After multivariate adjustment, the hazard ratios for all-cause and diabetes-related mortality of patients with 8-oxoGuo levels in the highest quartile compared with those in the lowest quartile were 1.44 (1.12-1.85) and 1.54 (1.13-2.10), respectively. Conversely, no significant associations between 8-oxodG and mortality were found in the adjusted analyses.
CONCLUSIONS: Urinary excretion of the RNA oxidation marker 8-oxoGuo measured shortly after diagnosis of type 2 diabetes predicts long-term mortality independently of conventional risk factors. This finding suggests that 8-oxoGuo could serve as a new clinical biomarker in diabetes.

PMID: 21994431 [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]

'Personalized medicine' to identify genetic risks for type 2 diabetes and focus prevention: can it fulfill its promise?

Health Aff (Millwood). 2012 Jan;31(1):43-9

Authors: Spiegel AM, Hawkins M

Abstract
Public health measures are required to address the worldwide increase in type 2 diabetes. Proponents of personalized medicine predict a future in which disease treatment and, more important, prevention will be tailored to high-risk individuals rather than populations and will be based on genetic and other new biomarker tests. Accurate biomarker tests to identify people at risk for diabetes could allow more-targeted and perhaps individualized prevention efforts. DNA variants conferring higher risk for type 2 diabetes have been identified. However, these account for only a small fraction of genetic risk, which limits their practical predictive value. Nor has identification of these variants yet led to new, individualized prevention methods. Further research is needed to identify genomic and other types of biomarkers that could accurately predict risk and facilitate targeted prevention.

PMID: 22232093 [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]