Measurement of a Plasma Stroke Biomarker Panel and Cardiac Troponin T in Marathon Runners Before and After the 2005 Boston Marathon

Saenz, Adam J.; Lee-Lewandrowski, Elizabeth; Wood, Malissa J.; Neilan, Tomas G.; Siegel, Arthur J.; Januzzi, James L.; Lewandrowski, Kent

doi:10.1309/d7quf0hjmcyyyy5a

Cited by 52 publications

(29 citation statements)

References 15 publications

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“…19 For example, D-dimer is a crosslinked fibrin degradation product. Although previously demonstrated to be elevated after acute stroke, 20 -23 D-dimer is elevated in any clinical circumstance in which both clot formation and subsequent fibrinolysis are increased, including deep venous thrombosis, pulmonary embolism, disseminated intravascular coagulation, acute myocardial infarction, surgery, and trauma.…”

Section: Discussionmentioning

confidence: 99%

Clinical Usefulness of a Biomarker-Based Diagnostic Test for Acute Stroke

Laskowitz

Kasner

Saver

et al. 2009

Stroke

201

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Background and Purpose-One of the significant limitations in the evaluation and management of patients with suspected acute cerebral ischemia is the absence of a widely available, rapid, and sensitive diagnostic test. The objective of the current study was to assess whether a test using a panel of biomarkers might provide useful diagnostic information in the early evaluation of stroke by differentiating patients with cerebral ischemia from other causes of acute neurological deficit. Methods-A total of 1146 patients presenting with neurological symptoms consistent with possible stroke were prospectively enrolled at 17 different sites. Timed blood samples were assayed for matrix metalloproteinase 9, brain natriuretic factor, D-dimer, and protein S100␤. A separate cohort of 343 patients was independently enrolled to validate the multiple biomarker model approach. Results-A diagnostic tool incorporating the values of matrix metalloproteinase 9, brain natriuretic factor, D-dimer, and S-100␤ into a composite score was sensitive for acute cerebral ischemia. The multivariate model demonstrated modest discriminative capabilities with an area under the receiver operating characteristic curve of 0.76 for hemorrhagic stroke and 0.69 for all stroke (likelihood test PϽ0.001). When the threshold for the logistic model was set at the first quartile, this resulted in a sensitivity of 86% for detecting all stroke and a sensitivity of 94% for detecting hemorrhagic stroke. Moreover, results were reproducible in a separate cohort tested on a point-of-care platform. Conclusions-These results suggest that a biomarker panel may add valuable and time-sensitive diagnostic information in the early evaluation of stroke. Such an approach is feasible on a point-of-care platform. The rapid identification of patients with suspected stroke would expand the availability of time-limited treatment strategies. Although the diagnostic accuracy of the current panel is clearly imperfect, this study demonstrates the feasibility of incorporating a biomarker based point-of-care algorithm with readily available clinical data to aid in the early evaluation and management of patients at high risk for cerebral ischemia.

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Section: Discussionmentioning

confidence: 99%

Clinical Usefulness of a Biomarker-Based Diagnostic Test for Acute Stroke

Laskowitz

Kasner

Saver

et al. 2009

Stroke

201

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“…Although investigators have explored the eVects of an acute bout of exercise on MMP concentrations in skeletal muscle (Carmeli et al 2005;Rullman et al 2007) and plasma (Saenz et al 2006;Tayebjee et al 2005), the eVects of exercise training on circulating MMP concentrations have not been elucidated. Since serum concentrations of MMPs are reported to peak within a relatively short time period following a single bout of exercise, it is possible that post-training serum concentrations of MMPs represent the eVects of repeated bouts of exercise that have initiated adaptive responses in skeletal muscle.…”

Section: Introductionmentioning

confidence: 99%

Effects of exercise training on the matrix metalloprotease response to acute exercise

et al. 2009

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Matrix metalloproteases (MMPs) in the circulation are thought to modulate the activation of growth factors, cytokines, and angiogenesis, facilitating physiological adaptations to exercise training. The purpose of this work was to characterize serum MMP-1, MMP-2, MMP-3, and MMP-9 concentrations pre- and post-eight weeks of exercise training. We tested the hypothesis that exercise training would influence serum MMP concentrations in response to an acute resistance exercise test (ARET). Participants were randomized into an 8-week training program (5 days per week) that emphasized callisthenic (CT, N = 8) or resistance (RT, N = 8) exercise. Serum MMP concentrations (MMP-1, -2, -3, -9) were assessed in men (N = 16) in response to an acute bout of high-intensity resistance exercise (six sets of 10-RM squats with 2-min inter-set rest periods) both before and after 8 weeks of training. Training resulted in a temporal shift in the peak MMP-1 concentration from post-ARET to mid-ARET in both groups. Post-training, MMP-9 concentrations were increased immediately after the ARET in the CT group as compared to pre-training ARET concentrations. RT did not alter MMP-3 and -9 concentrations. These data suggest that the mode of exercise training influences the MMP response to an acute bout of exercise, revealing a possible role of MMPs in initiating training-specific adaptations.

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“…Elevated serum creatine kinase as an index of exertional rhabdomyolysis in runners after "hitting the wall" was accompanied by neutrophilia, increased interleukin-6, C-reactive protein and matrix metallo-proteinase-9 [6][7][8][9]. Inflammation by this paradigm may render previously silent low-profile coronary atherosclerotic plaques vulnerable to rupture leading to acute myocardial infarction [10].…”

Section: Discussionmentioning

confidence: 99%

The rationale for pre-race aspirin to protect susceptible runners from sudden cardiac death during marathons: Deconstructing the Pheidippides conundrum

Siegel¹

2013

WJCD

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Objectives: While endurance exercise such as training for marathons is cardioprotective, cardiac arrests and sudden death occur in previously healthy runners during races predominantly in middle-aged males due to atherosclerotic heart disease. Recent evidence related to this problem is reviewed herein including epidemiologic studies and findings related to acute cardiac risk in asymptomatic middle-aged male runners during races. Method: Literature review related to the above. Findings: The risks of cardiac arrest and sudden death were 1 in 57,002 and 1 in 171,005 respectively in runners with a mean age of 49.7 years among 1,710,052 participants in marathons in the United States since 1980. Atherosclerotic heart disease was the cause of death in over 90% of cases in two retrospective studies and a greater than two-fold increase in cardiac arrests was observed in middle-aged men in the latter half of a 10-year prospective registry beginning in the year 2000. Asymptomatic middle-aged male runners showed elevated biomarkers of inflammation such as interleukin-6, C-reactive protein together with procoagulant effects including in vivo platelet activation, indicating susceptibility to atherothrombosis. Conclusions: Antithrombotic prophylaxis is evidencebased by validated clinical paradigms to prevent cardiac arrest and sudden death in susceptibile marathon runners at high risk for atherothrombosis during races.

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Measurement of a Plasma Stroke Biomarker Panel and Cardiac Troponin T in Marathon Runners Before and After the 2005 Boston Marathon

Cited by 52 publications

References 15 publications

Clinical Usefulness of a Biomarker-Based Diagnostic Test for Acute Stroke

Clinical Usefulness of a Biomarker-Based Diagnostic Test for Acute Stroke

Effects of exercise training on the matrix metalloprotease response to acute exercise

The rationale for pre-race aspirin to protect susceptible runners from sudden cardiac death during marathons: Deconstructing the Pheidippides conundrum

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