Changes in cardiac markers including B-natriuretic peptide in runners following the Boston Marathon.Department of Medicine, McLean Hospital, Belmont, MA; Clinical Laboratory and Nuclear Medicine Divisions, Massachusetts General Hospital Massachusetts General Hospital Health care The major teaching hospital for Harvard Medical School, widely regarded as one of the best health care centers in the world and Harvard Medical School Harvard Medical School (HMS) is one of the graduate schools of Harvard University. It is a prestigious American medical school located in the Longwood Medical Area of the Mission Hill neighborhood of Boston, Massachusetts. , Boston, MA
In contrast to nonspecific nonspecific /non·spe·cif·ic/ (non?spi-sif´ik)
1. not due to any single known cause.
2. not directed against a particular agent, but rather having a general effect.
1. elevations of myoglobin myoglobin (mī'əglō`bĭn), protein molecule isolated from the cells of vertebrate skeletal muscle that is both a structural and functional relative of hemoglobin, the oxygen-transport protein of the blood of higher animals. and creatine kinase creatine kinase /cre·a·tine ki·nase/ (ki´nas) an enzyme that catalyzes the phosphorylation of creatine by ATP to form phosphocreatine. MB (CK-MB CK-MB Creatine phosphokinase MB isoenzyme Cardiology A CK isoenzyme usually ↑ in acute MI; CK-MB may be ↑ in muscular dystrophy, polymyositis, myoglobinuria, malignancy–eg, lung CA. Cf Troponin I, Troponin T. ) in athletes due to exertional rhabdomyolysis rhabdomyolysis /rhab·do·my·ol·y·sis/ (-mi-ol´i-sis) disintegration of striated muscle fibers with excretion of myoglobin in the urine.
n. of trained skeletal muscle(1,2), reported increases in cardiospecific troponins after competition may indicate silent injury to the myocardium myocardium /myo·car·di·um/ (-kahr´de-um) the middle and thickest layer of the heart wall, composed of cardiac muscle.
hibernating myocardium see myocardial hibernation, under (3,4,5,6,7,8). We therefore undertook serial testing of multiple cardiac markers used to diagnose early- and late-stage myocardial myocardial /myo·car·di·al/ (-kahr´de-al) pertaining to the muscular tissue of the heart.
pertaining to the muscular tissue of the heart (the myocardium). injury in the same group of middle-aged runners before and sequentially after five Boston Marathons over 4 years. In addition to creatinine kinase MB (CK-MB) and myoglobin, cardiac TnI (cTnI) was tested by a qualitative rapid assay in 1997, a high-sensitivity reference method in 1998-2000, and a rapid quantitative method to detect acute myocardial infarction acute myocardial infarction (·kyōōtˑ mī·ō·karˑ·dē· (AMI) in 2001 together with cardiac troponin T (cTnT). Selective post-race single photon emission computed tomography single photon emission computed tomography
n. Abbr. SPECT
Tomographic imaging of local metabolic and physiological functions in tissues. (SPECT SPECT single-photon emission computed tomography.
single photon emission computed tomography
n See single photon emission computer tomography. ) Tc-99m sestamibi myocardial scintigraphy scintigraphy /scin·tig·ra·phy/ (sin-tig´rah-fe) the production of two-dimensional images of the distribution of radioactivity in tissues after the internal administration of a radiopharmaceutical imaging agent, the images being obtained and B-natriuretic peptide (BNP BNP B-type natriuretic peptide, brain natriuretic peptide Physiology A 32-residue peptide hormone produced predominantly in the ventricles, secreted in response to fluid overload–eg, CHF. See Atrial natriuretic peptide. ) levels were used to assess microinfarction and transient left ventricular dysfunction ventricular dysfunction,
n an abnormality in contraction and wall motion within the ventricles. respectively.
Participants were 82 runners with a mean age of 47 + 8 years attending the pre-race Scientific Symposia of the American Medical Athletic Association as entrants in the 10 1st to 10 5th Boston Athletic Association The Boston Athletic Association is a non-profit, organized sports association for the city of Boston, Massachusetts. It hosts such events as the world-renowned Boston Marathon. Marathons from 1997 to 2001. Medical and running histories obtained yearly by questionnaire indicated no smoking or known coronary heart disease coronary heart disease: see coronary artery disease.
coronary heart disease
or ischemic heart disease
Progressive reduction of blood supply to the heart muscle due to narrowing or blocking of a coronary artery (see atherosclerosis). , 25 training miles per week, and five prior marathons completed including a qualifying race under four hours in the prior year.
Blood samples were drawn the day before and within four and 24 hours after the race. In 1997, whole blood was immediately tested by rapid assay for CK-MB, myoglobin and cTnI using Cardiac STATus' CK-MB/Myoglobin and Cardiac STATus' Troponin I troponin I
A subunit of troponin found in muscle and cartilage that inhibits the formation of blood vessels and is under investigation as a potential cancer therapy. Point-of-Care Test Kits (Princeton Bio Meditech Corp., Princeton, NJ) with sera frozen at -70o for reference testing. Sequential sera were similarly obtained and frozen from 20, 17, and 14 runners in 1998-2000 for measurement of CK-MB, myoglobin and cTnI by an ACS (Asynchronous Communications Server) See network access server. : 180 instrument (Bayer Corporation, Tarrytown, NY). In 2001, CK-MB, myoglobin, and cTnI were measured by a rapid quantitative fluorescence immunoassay Immunoassay
An assay that quantifies antigen or antibody by immunochemical means. The antigen can be a relatively simple substance such as a drug, or a complex one such as a protein or a virus. using Triage triage
Division of patients for priority of care, usually into three categories: those who will not survive even with treatment; those who will survive without treatment; and those whose survival depends on treatment. [R] Cardiac Panel (Biosite[R] Diagnostics, Inc., San Diego, CA), cTnT by an electrochemiluminescence immunoassay on the Elecsys 1010 analyzer (Roche Diagnostics Corp., Indianapolis, IN), and BNP by the Triage[R] BNP Test (Biosite[R] Diagnostics, Inc., San Diego, CA). SPECT sestamibi myocardial perfusion imaging myocardial perfusion imaging A technique in which the regional distribution of blood throughout the myocardium, is determined by injecting a radiopharmaceutical–eg, 201Tl. was performed at rest the morning after the 1998 race in five finishers after injection with 30m Ci Tc-99m sestamibi (Cardiolite[R], Dupont Pharmaceuticals, North Billerica, MA). The student-paired T test (Sigma Stat, Jandal jandal
NZ a rubber-soled sandal attached to the foot by a thong between the big toe and the next toe Scientific) was used to compare results from runners providing three sequential samples.
Changes in cardiac markers were measured before and after a total of 104 races among 82 runners with 15 subjects participating multiple times over four years. Results of qualitative rapid assays for CK-MB, myoglobin, and cTnI before and sequentially after the 1997 Boston Marathon are shown in Table 1 with positive tests confirmed by corresponding reference methods. CK-MB/myoglobin rapid assays were positive pre-race in 17 and 14 of 40 runners respectively and in all runners (n=41) within four and 24 hours (n= 13) post race. Rapid assays for cTnI were positive in two asymptomatic runners with levels remaining elevated up to 72 hours post-race.
Using the same reference method in 51 runners in 1998-2000, there were significant increases from pre-race to within four hours after competition for all markers with persistent increases in CK-MB and cTnI within 24 hours post-race (see Figure 1). Serum myoglobin (nl<110ng/ml) rose 38.4-fold from 47 + 5 ng/ml pre-race to 1811 + 340 ng/ml (p<.0001) within four hours post-race, returning to baseline within 24 hours (n=37, 1998-1999). Serum CK-MB (nl<6.6 ng/ml) rose 4.9-fold from 2.8 + .5 ng/ml pre-race to 13.8 + 1.4 ng/ml (p<.0001) within four hours and 13.5-fold to 38 + 6.9 ng/ml (p<.0001) within 24 hours post-race (n=51, 1998-2000). Mean values for cTnI (nl<1.5ng/ml) rose 6.5-fold within the normal range from .02 + .005 ng/ml pre-race to .14 + .02 ng/ml (p=.0013) and 0.14 + 0.4 ng/ml (p=.0013) within four and 24 hours post-race, respectively (n=51, 1998-2000).
Post-race SPECT sestamibi myocardial imaging was normal in five runners in 1998 including a 47 year old asymptomatic subject concurrent with a cTnI of 3.1 ng/ml selected because of positive rapid assays for cTnI in the prior year. A 72 year old runner with a normal post-race scan was hospitalized for transient chest pain later the same day with nondiagnostic electrocardiograms and a two-fold increase in cTnI from 0.6 ng/ml pre-race to 1.2 ng/ml post-race. Stress SPECT sestamibi cardiac imaging remained normal in both of these runners six weeks later. Three other runners with normal scans showed no post-race increase in cTnI, including a 56 year old Iron Man triathlete tri·ath·lete
One who competes in a triathlon. with a custom-programmed permanent cardiac pacemaker (Telectronics 1256, Denver, CO) placed in 1995 for idiopathic complete heart block.
Quantitative rapid assays in 2001 showed increases in CK-MB and myoglobin at both post-race time points (p<0.005) with no change in cTnI or cTnT (see Figure 2). BNP levels were within normal limits (<100 pg/ml) post-race in all subjects but increased from 16.7 + 4.5 pg/ml to 48.6 + 10.2 pg/ml within 24 hours post-race (p=0.0006). All runners remained free of cardiac events over four years while completing subsequent marathons with comparable finishing times averaging four hours and 20 minutes.
In contrast to reported increases in cardiac troponins in endurance athletes based on single values after competition (6,7,8), we extended previous studies using serial testing to assess the time course of release in the same group of runners over four years. Because of positive qualitative rapid assays for cTnI in some runners in 1997, we undertook subsequent testing with an assay for cTnI providing low-end analytical sensitivity designed to detect minor degrees of myocardial damage as used to differentiate unstable angina from non-ST segment elevation myocardial infarction in patients with acute coronary syndromes (9, 10). This high-sensitivity showed a 6.5-fold increase in cTnI at both post-race time points in each subgroup and in 51 runners over three years with a consistency seen with true-positive rather than sporadic or spurious elevations(11). SPECT sestamibi Tc-99m myocardial imaging was negative in five runners in 1998 concurrent in one asymptomatic subject with a cTnI level of 3.1 ng/ml, which may represent necrosis of cardiomyocytes below the threshold for detection by SPECT myocardial imaging as with prior antimyosin myocardial scintigraphy(12). Another 72 year old runner with normal imaging was hospitalized hours later for transient chest pain, with a two-fold post-race increase in cTnI to 1.2 ng/ml compatible with unstable angina. Follow-up stress SPECT sestamibi cardiac imaging was negative six weeks later in both of these runners who remained asymptomatic while completing subsequent races with comparable finishing times.
Based upon changes in cTnI in runners as predictive of poor prognosis in patients with acute coronary syndromes(13,14), we undertook testing for cTnI and cTnT in 2001 using rapid quantitative methods designed to detect AMI (15). While confirming post-race increases in myoglobin and CK-MB as early-stage markers of AMI, there was no change in cTnT or cTnI as late-stage markers up to 24 hours after competition. Despite post-race increases in novel inflammatory markers for cardiovascular risk in these same runners (16), there was no apparent increase in cardiac events in these middle-aged male runners over four years. Further studies including younger and elite athletes and runners rehabilitated after treatment for ischemic Ischemic
An inadequate supply of blood to a part of the body, caused by partial or total blockage of an artery.
Mentioned in: Antiangiogenic Therapy, Subarachnoid Hemorrhage, Ventricular Fibrillation
ischemic or other heart disease are indicated to assess the prognostic role of cardiac troponins as shown in patients with heart disease (13, 17).
Regarding exercise-related myocardial stunning as reported in endurance athletes after competition(7), BNP as a surrogate marker of transient left ventricular dysfunction (18, 19) remained normal. An increase in BNP within the normal range at 24 hours post-race (p = 0.006) deserves study as a possible mechanism for hyponatremia Hyponatremia Definition
The normal concentration of sodium in the blood plasma is 136-145 mM. Hyponatremia occurs when sodium falls below 130 mM. Plasma sodium levels of 125 mM or less are dangerous and can result in seizures and coma. and noncardiogenic pulmonary edema as may occur in endurance athletes after competition (20).
TABLE 1 Results of Cardiac Markers Before and After the 1997 Boston Marathon * <4 h <24 h Before After After Race Race Race (n = 40) (n = 41) (n = 13) Myoglobin (+) (nl <150 ng/ml) 14 41 13 CK-MB (+) (nl <5.0 ng/ml) 17 41 13 CTnl (+) (nl <0.2 ng/ml) 1 2 1 * Qualitative rapid assays for myoglobin and CK-MB were positive before the race in 14 and 17 of 40 runners, respectively, and in all 41 and 13 subjects within 4 and 24 hours after the race; cTnl rapid assays were positive in 2 asymptomatic runners (as shown). FIGURE 1 Results of cardiac markers before and after the 1998 to 2000 Boston Marathons: CK-MB, myoglobin, and cTnl increased from before the race to both postrace time points. 1998-1999 Boston 1998-2000 Boston Marathon (N=37) Marathon (N=51) Myoglobin CK-MB NORMAL <110 NG/ML NORMAL <6.6 NG/ML Pre-Race 47 [+ or -] 5 2.8 [+ or -] 0.5 4 hrs Post Race 1811 [+ or -] 340 13.8 [+ or -] 1.4 * 24 hrs Post Race 304 [+ or -] 41 38.0 [+ or -] 6.9 * 1998-2000 Boston Marathon (N=51) cTnl NORMAL <1.5 NG/ML Pre-Race .022 [+ or -] .005 4 hrs Post Race .144 [+ or -] .024 * 24 hrs Post Race .142 [+ or -] .037 * * p <0.05. Note: Table made from bar graph FIGURE 2 Results of cardiac markers in marathon runners before and after the 2001 Boston Marathon. Quantitative rapid assays for CK-MB and myoglobin showed significant increases within 4 and 24 hours after the race compared with prerace levels, whereas changes in cTnl and cTnT were not significant. BNP stayed within normal limits but increased significantly within 24 hours after the race. 2001 Boston Marathon (N=11) Myoglobin CK-MB (NORMAL = <107 NG/ML) (NORMAL = <4.3 NG/ML) Pre-Race 95 [+ or -] 2.3 [+ or -] 0.5 4 hrs Post Race >500 * 20.1 [+ or -] 4.5 * 24 hrs Post Race 379 [+ or -] 43 * 47.1 [+ or -] 13.4 * BNP (Normal = <100 pg/ml) Pre-Race 16.7 [+ or -] 4.5 4 hrs Post Race 18.4 [+ or -] 4.4 24 hrs Post Race 48.6 [+ or -] 10.2 * * p <0.005. Note: Table made from bar graph cTnl cTnT (NORMAL = <0.2 NG/ML) (NORMAL = <0.1 NG/ML) Pre-Race .009 [+ or -] .009 <0.01 4 hrs Post Race .027 [+ or -] .027 .041 [+ or -] .013 24 hrs Post Race .001 [+ or -] .001 <0.01 cTnl & cTnT (ng/ml) [+ or -] S.E. Note: Table made from bar graph
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AHB Assault Helicopter Battalion
AHB Air Historical Branch
AHB Attack Helicopter Battalion
AHB Automatic Half Barriers
AHB Aussie Home Brewers
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Used to express disdain for something deemed stupid or obvious, especially a self-evident remark.
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"Reprinted from The American Journal of Cardiology, Vol. 88, pp. 918-920, Copyright 2001, with permission from Excerpia Medica medica (māˑ·dē·k , Inc."
Contents in Brief: In contrast to non-specific post-race elevations in myoglobin and CK-MB as early-stage markers for AMI due to exertional rhabdomyolysis of trained skeletal muscle, late-stage markers including cTnI and cTnT remained negative by rapid quantitative methods within 24 hours after competition. A 6.5-fold increase in cTnI by high-sensitivity methods as predictive of poor outcome in patients with acute coronary syndromes occurred in these middle-aged male runners without evidence for microinfarction by SPECT-sestamibi myocardial scintigraphy, left ventricular dysfunction by BNP, or apparent risk for cardiac events over four years.
Address correspondence and reprint requests to:
Kent Lewandrowski, M.D.
Department of Clinical
Laboratories, Gray 5
Massachusetts General Hospital
Fruit Street, Belmont MA 02114 (USA)
Telephone: (617) 726-2275
Fax: (617) 726-9206