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Biomedical subjects

Allan S Jaffe

Publications and source records attributed to Allan S Jaffe.

At least 19 recordsLinked to original sources
PubMed2007

Long-term health outcomes associated with detectable troponin I concentrations.

BACKGROUND: Recent data suggest that older men with detectable cardiac troponin I (cTnI) concentrations that remain below the 99th percentile concentration cutoff are at increased risk for subsequent cardiovascular events. We designed this study to extend this observation by examining risk prediction in both men and women presenting to an emergency department with chest discomfort. METHODS: We obtained data for all-cause mortality and hospital discharges associated with either acute myocardial infarction (AMI) or congestive heart failure (CHF) for up to 8 years after the initial presentation in 448 patients who originally presented in 1996 with acute coronary syndrome (ACS). We performed retrospective analysis for cTnI (AccuTnI; Beckman Coulter) in frozen plasma samples based on the patients' reported time from onset of symptoms. Peak cTnI concentration was used for risk assessment. RESULTS: Patients with cTnI concentrations > or =0.02 microg/L (i.e., limit of detection), including those whose peak values remained below the 99th percentile (0.04 microg/L), were at greater risk for death and AMI/CHF readmissions at 2, 5, and 8 years of follow-up compared with those with peak cTnI <0.02 microg/L. All results were statistically significant (P <0.05) except for death within 2 years among patients with normal but detectable cTnI (0.02 to 0.03 microg/L), relative to the group with values <0.02 microg/L. Kaplan-Meier analyses indicated that both men and women with cTnI > or =0.02 microg/L had worse outcomes (P <0.001). CONCLUSION: Both men and women who present with possible ACS with detectable cTnI concentrations that remain below the 99th percentile are at a greater risk for future adverse events.

Aged↗
PubMed2006

Heart rate turbulence, depression, and survival after acute myocardial infarction.

OBJECTIVE: Depression is a risk factor for mortality after acute myocardial infarction (AMI), possibly as a result of altered autonomic nervous system (ANS) modulation of heart rate (HR) and rhythm. The purposes of this study were to determine: a) whether depressed patients are more likely to have an abnormal HR response (i.e., abnormal turbulence) to premature ventricular contractions (VPCs), and b) whether abnormal HR turbulence accounts for the effect of depression on increased mortality after AMI. METHODS: Ambulatory electrocardiographic data were obtained from 666 (316 depressed, 350 nondepressed) patients with a recent AMI; 498 had VPCs with measurable HR turbulence. Of these, 260 had normal, 152 had equivocal, and 86 had abnormal HR turbulence. Patients were followed for up to 30 (median = 24) months. RESULTS: Depressed patients were more likely to have abnormal HR turbulence (risk factor adjusted odds ratio = 1.8; 95% confidence interval [CI] = 1.0-3.0; p = .03) and have worse survival (odds ratio = 2.4; 95% CI = 1.2-4.6; p = .02) than nondepressed patients. When HR turbulence was added to the model, the adjusted hazard ratio for depression decreased to 1.9 (95% CI = 0.9-3.8; p = .08), and to 1.6 (95% CI = 0.8-3.4; p = .18) when a measure of HR variability (LnVLF) was added. The hazard was found to differ over time with depression posing little risk for mortality in year 1 but greater risk in years 2 and 3 of the follow up. CONCLUSION: ANS dysregulation may partially mediate the increased risk for mortality in depressed patients with frequent VPCs after an AMI.

Aged↗
PubMed2006

Time course of degradation of cardiac troponin I in patients with acute ST-elevation myocardial infarction: the ASSENT-2 troponin substudy.

Although measurement of troponin is widely used for diagnosing acute myocardial infarction (AMI), its diagnostic potential may be increased by a more complete characterization of its molecular appearance and degradation in the blood. The aim of this study was to define the time course of cardiac troponin I (cTnI) degradation in patients with acute ST-elevation myocardial infarction (STEMI). In the ASSENT-2 substudy, 26 males hospitalized with STEMI were randomized to 2 different thrombolytic drugs within 6 hours after onset of symptoms. Blood samples were obtained just before initiation of thrombolysis and at 30 minutes intervals (7 samples per patient). Western blot analysis was performed using anti-cTnI antibodies and compared with serum concentrations of cTnI. All patients exceeded the cTnI cutoff for AMI during the sampling period; at initiation of therapy, 23 had elevated cTnI values. All patients demonstrated 2 bands on immunoblot: intact cTnI and a single degradation product as early as 90 minutes after onset of symptoms. On subsequent samples, 15 of 26 patients showed multiple degradation products with up to 7 degradation bands. The appearance of fragments was correlated with higher levels of cTnI (P<0.001) and time to initiation of treatment (P=0.058). This study defines for the first time the initial time course of cTnI degradation in STEMI. Intact cTnI and a single degradation product were detectable on immunoblot as early as 90 minutes after onset of symptoms with further degradation after 165 minutes. Infarct size and time to initiation of treatment was the major determinant for degradation.

Adult↗
PubMed2006

Health outcomes categorized by current and previous definitions of acute myocardial infarction in an unselected cohort of troponin-naïve emergency department patients.

BACKGROUND: In a population originally classified for acute myocardial infarction (AMI) by the World Health Organization (WHO) definition, we compared the health outcomes after retrospectively reclassifying with the European Society of Cardiology and the American College of Cardiology (ESC/ACC) AMI definition, using the peak cardiac troponin I (cTnI) concentrations. The health outcomes were based on the WHO definition and occurred in an era that preceded the use of cardiac troponin biomarkers. METHODS: For 448 patients who presented to the emergency department with symptoms suggestive of cardiac ischemia in 1996, we obtained data for all-cause mortality and recurrent AMI for up to 1 year after the initial presentation. We performed retrospective analysis of the patients' frozen plasma samples to measure cTnI (AccuTnI, Beckman Coulter). RESULTS: At 30, 120, and 360 days, the risk for AMI/death in patients positive for AMI by only the ESC/ACC criteria was significantly lower than the risk in patients positive by both ESC/ACC and WHO criteria, and significantly higher than in patients negative according to both criteria. In a separate analysis, patients with a peak cTnI>0.10 microg/L were at greater risk for AMI/death than patients with cTnI concentrations of 0.04-0.10 microg/L. Patients negative by both definitions or with peak cTnI concentrations<0.04 microg/L had the highest event-free survival rates (92% and 94%, respectively) at 1 year. CONCLUSION: In a troponin-naïve population, patients classified as positive for AMI by only the ESC/ACC criteria have a prognosis that appears to be intermediate between those classified positive by both the WHO and ESC/ACC definitions and those who meet neither criteria.

Aged↗
PubMed2006

Redefinition of myocardial infarction: prospective evaluation in the community.

BACKGROUND: The 2000 European Society of Cardiology/American College of Cardiology definition for myocardial infarction (MI) combines ischemic symptoms, electrocardiographic changes, and troponin rather than creatine kinase levels. The use of troponins will increase the detection of MI by a magnitude to be quantified, and the clinical acceptance of the new definition is unknown. METHOD AND RESULTS: Subjects presenting to an Olmsted County facility with a troponin T value > or = 0.03 ng/mL between November 2002 and March 2005 were prospectively classified through the use of standardized MI criteria, relying on cardiac pain, Minnesota coding of the ECG, and troponin, creatine kinase, and its MB fraction measured simultaneously. Through the use of dynamic changes in troponin, 538 MIs were identified versus 327 with creatine kinase and 427 with only the MB fraction of creatine kinase. This represents a 74% (95% confidence interval [CI], 69% to 79%) increase above the number of MIs identified with creatine kinase and a 41% (95% CI, 37% to 46%) increase above the number identified with criteria including only its MB fraction. When relying on single values of troponin, increases in the number of MIs were always large but varied widely according to the threshold used for troponin. Cases meeting only troponin-based criteria were less likely to have electrocardiographic ST-segment elevation and had better survival than those identified with previous criteria. Clinician diagnoses mentioned MI in 42% (95% CI, 34% to 49%) of cases meeting only troponin-based criteria versus 74% (95% CI, 69% to 78%) for MIs meeting the previous criteria (P < 0.001). CONCLUSIONS: The prospective application of the new criteria in the community results in a large increase in the number of MIs and a change in case mix. The clinical acceptance of the new criteria is incomplete, and studies that rely exclusively on dismissal diagnoses to assess MI rates may underestimate the burden of disease as presently defined.

Biomarkers↗
PubMed2006

Lipoprotein-associated phospholipase A2 and prognosis after myocardial infarction in the community.

OBJECTIVE: We evaluated the role of lipoprotein-associated phospholipase A2 (Lp-PLA2), an inflammatory biomarker, in defining risk after myocardial infarction (MI). METHODS AND RESULTS: Olmsted County, Minn, residents who experienced an MI meeting standardized criteria between 2003 and 2005 (n = 271) were prospectively identified and followed. Lp-PLA2 levels were measured at baseline and evaluated along with traditional risk indicators. Lp-PLA2 was modestly associated with total and low-density lipoprotein cholesterol, smoking, and age (inversely) but not with MI characteristics or severity, comorbidities, C-reactive protein, or the time from symptom onset to blood sampling. During the first year of follow-up, 42 deaths occurred. The survival estimates (95% confidence intervals [CI]) at 1 year were 92% (86% to 98%), 85% (78% to 93%), and 74% (65% to 84%) in the lowest, middle, and upper Lp-PLA2 tertiles, respectively (P = 0.007). After adjustment for age and sex, the hazard ratios for death in the middle and upper Lp-PLA2 tertiles were 2.20 (95% CI: 0.88 to 5.54) and 4.93 (95% CI: 2.10 to 11.60), compared with the lowest tertile, respectively (P(trend) < 0.001). Further adjustment for other risk indicators resulted in even stronger associations. Lp-PLA2 also contributed to risk discrimination as indicated by the increases in the area under the receiver operating characteristic curves obtained in each of the models examined (all P < or = 0.05). CONCLUSIONS: Among community subjects presenting with MI, increased Lp-PLA2 levels measured early after MI are strongly and independently associated with mortality and provide incremental value in risk discrimination over traditional predictors.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2006

Biomarkers in acute cardiac disease: the present and the future.

The use of biomarkers to aid diagnosis and treatment is increasing rapidly as genomics and proteomics help us expand the number of markers we can use and as an improved understanding of the pathophysiology of cardiac disease guides their use. However, as with all rapidly expanding fields, there is the risk of excessive enthusiasm unless we are circumspect about the data that guide the clinical use of these new tools. This review focuses first on how to use troponin, which at present is the best validated of the new markers, and will hopefully provide insight into how to use this biomarker more productively by distinguishing subsets of patients and by providing an understanding of the meaning of elevations in various clinical situations. The review then discusses the use as well as the knowledge gaps associated with emerging biomarkers such as B-type natriuretic peptide and C-reactive protein, which are increasingly moving toward more productive clinical use. Finally, it reflects on some of the large number of markers that are still in development.

Acute Disease↗
PubMed2006

Assessing the requirement for the 6-hour interval between specimens in the American Heart Association Classification of Myocardial Infarction in Epidemiology and Clinical Research Studies.

BACKGROUND: The American Heart Association (AHA) case definition for acute myocardial infarction (AMI) requires an "adequate set" of biomarkers: 2 measurements of the same marker at least 6 h apart. A sensitive troponin assay might detect significant changes in concentration earlier. We determined AMI prevalence, using protocols with shorter intervals between measurements, with and without incorporating the time from onset of symptoms. METHODS: The AHA case definition was used to retrospectively assign a diagnosis in 258 patients presenting to the emergency department with symptoms of cardiac ischemia. AMI was diagnosed if either specimen in an adequate set had a cardiac troponin I (cTnI) above the 99th percentile (AccuTnI >0.04 microg/L; Beckman Coulter) with a > or =20% change in concentration between specimens. We assessed positivity for AMI after progressively decreasing the time interval between specimens in specimen sets. In addition, for each patient, 2 additional specimen pairs were selected: pairs collected at least 1 h apart with 1 specimen being either > or =3 h after onset or > or =6 h after onset. RESULTS: When we used the AHA definition, the AMI prevalence was 35.7%. Prevalence was not significantly diminished when the interval between specimens was > or =5, > or =4, or > or= 3 h (36.4%, 34.5%, and 33.7%, respectively) compared with the AHA > or =6 h interval. When the time from onset of symptoms was included in the specimen selection algorithm, a 1-h interval was sufficient provided that at least one specimen was collected > or =6 h after onset (prevalence, 34.1%; P = 0.48 vs AHA definition). CONCLUSION: A sensitive cTnI assay in specimen sets with time intervals > or =3 h, or having one specimen > or =6 h after onset, gave an AMI prevalence equivalent to the AHA definition.

American Heart Association↗
PubMed2006

Baseline troponin level: key to understanding the importance of post-PCI troponin elevations.

AIMS: The adverse prognostic significance of biomarker elevations after percutaneous coronary intervention (PCI) is well established. However, often baseline troponin values are not included in the analysis or sensitive criteria are not employed. Accordingly, we assessed the timing and magnitude of post-PCI troponin T (cTnT) levels and their relationships to outcomes in patients with and without pre-PCI baseline cTnT elevations using a sensitive assay and sensitive cut-off values. METHODS AND RESULTS: cTnT was measured at baseline (pre-PCI), 8 and 16 h post-PCI in 2352 patients. A cTnT elevation was defined as > or =0.03 ng/mL. No baseline cTnT elevations were detected in 1619 patients undergoing mostly (97%) non-urgent procedures (cTnT = 0.01 +/- 0.002 ng/mL; mean +/- SD). 733 patients had baseline cTnT elevations. Only the baseline troponin value had prognostic importance. Patients with elevated cTnT baseline levels had a higher overall cumulative 12-month death/MI rate of 11.1% compared with those without elevated baseline levels of 4.7% (P < 0.05). Neither the timing nor the magnitude of the post-procedure cTnT elevations was predictive of long-term death/MI rates when baseline elevations were included in the analysis. Similar findings were observed for baseline creatine kinase-MB (CK-MB) levels. Late increases in cTnT levels (16 h post-PCI) presaged in-hospital events only. CONCLUSION: Long-term prognosis is most often related to the baseline pre-PCI troponin value and not the biomarker response to the PCI. These results support a re-evaluation of the use of biomarker data in relation to PCI.

Aged↗
PubMed2006

Elevations of troponin in patients with epileptic seizures? What do they mean?

Cardiac troponin concentrations are important sensitive and specific markers for myocardial injury in clinical medicine. Troponin (TnT) elevations have been noted in some series in the setting of acute neurologic disease. We have previously reported that solitary seizures do not evoke elevations in TnT. The importance of this negative finding is exemplified by a patient who arrived at our clinic following a new onset seizure and in whom the cardiac TnT level was observed to rise. Triggered by this observation and by the knowledge that seizures alone would not do this, a subsequent targeted cardiologic workup documented what was believed to be an extension of a previously unrecognized myocardial infarction, with a seizure as its clinical presentation. Elevations of troponin should not be considered to be due to isolated seizures. This case illustrates the importance of having data concerning the response of troponin in various emergency and clinical situations.

Aged, 80 and over↗
PubMed2006

The impact of the ESC/ACC redefinition of myocardial infarction and new sensitive troponin assays on the frequency of acute myocardial infarction.

BACKGROUND: The prevalence of acute myocardial infarction (AMI) has increased due to the recent definitions, but the magnitude of this effect using contemporary highly sensitive troponin assays is unclear. The objective of this study is to compare the diagnosis of AMI using a contemporary troponin I (cTnI) biomarker and the 2003 American Heart Association (AHA) case definition with diagnoses made using the 1994 World Health Organization MONICA definition. METHODS: Contemporary troponin I measurements were performed with the Beckman Coulter AccuTnI assay (Chaska, MN) on plasma specimens originally assayed in 1996 for creatine kinase (CK)-MB mass from 486 emergency department patients presenting within 24 hours of onset of symptoms suggestive of cardiac ischemia. RESULTS: In a subgroup of 258 patients with 2 specimens drawn at least 6 hours apart (the AHA "adequate set of biomarkers"), AMI prevalence using CK-MB was 19.4% (95% CI 15.0-24.7) based on MONICA and 19.8% (15.4-25.1) based on the AHA case definition using the criterion for change of > or = 20% between specimens. Using cTnI as the biomarker of choice, under the AHA definition, the prevalence increased to as high as 35.7% (30.1-41.7, a relative increase of 84%, P < .001) using the 99th percentile cutoff. In 121 patients with a lower index of suspicion and without the requisite 6-hour interval between measurements, positivity increased from 5% with CK-MB by MONICA up to 12% to 16% with cTnI by AHA. CONCLUSIONS: A highly sensitive contemporary cTnI assay used with the AHA case definition results in a 62% to 84% increase in the frequency of AMI diagnosis compared with MONICA criteria.

Aged↗
PubMed2006

Prediction of medical morbidity and mortality after acute myocardial infarction in patients at increased psychosocial risk in the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) study.

BACKGROUND: Patients with myocardial infarction (MI) are at further increased risk for untoward events when patients also exhibit low social support and/or depression. The ENRICHD study was the largest controlled trial in post-MI patients attempting to treat these psychological comorbidities and provides an opportunity to examine the medical and psychological characteristics that may affect risk in this population. METHODS: We analyzed the baseline characteristics and their relationship to the primary end point of long-term mortality and recurrent infarction and to the secondary end points of overall mortality and cardiovascular mortality in 2481 post-MI patients. Cox proportional hazards models were used to predict the risk of these outcomes over a mean of 2.5 years of follow-up. RESULTS: Death or nonfatal MI occurred in 24.1%, all-cause mortality in 13.7%, and cardiovascular mortality in 8.4% of the sample (62% of the total). Age, heart failure, pulmonary disease, Killip class, ejection fraction, an elevated creatinine, the use of non-angiotensin-coverting enzyme asodilators, prior MI, diabetes, depression, and bypass surgery after acute MI were all significant multivariable predictors. CONCLUSIONS: The medical predictors of adverse events in post-MI patients with low social support and/or depression were similar to those of patients with MI in other clinical trials.

Area Under Curve↗
PubMed2006

B-type natriuretic peptide in the assessment of acute lung injury and cardiogenic pulmonary edema.

OBJECTIVE: The role of plasma B-type natriuretic peptide (BNP) in critically ill patients with acute pulmonary edema is controversial. We postulated that a low BNP level would exclude cardiac dysfunction as the principal cause of pulmonary edema and therefore help in the diagnosis of acute lung injury. DESIGN: A retrospective derivation cohort was followed by a prospective validation cohort of consecutive patients with acute pulmonary edema admitted to three intensive care units. BNP was measured within 24 hrs from onset. Critical care experts blinded to BNP results integrated clinical data with the course of disease and response to therapy and served as the reference standard. SETTING: Three intensive care units at the tertiary center. PATIENTS: Consecutive critically ill patients with acute pulmonary edema. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In a derivation cohort of 84 patients, a BNP threshold of <or=250 pg/mL had a specificity of 87% and sensitivity of 48% for the diagnosis of acute lung injury. High specificity of BNP (90%, likelihood ratio of 3.9) was confirmed in a validation cohort of 120 consecutive patients, 52 (43%) of whom had acute lung injury. Notably, 32% of patients with acute lung injury had concomitant cardiac dysfunction. The median time from the onset of pulmonary edema to BNP testing was 3 hrs. The accuracy of BNP (area under receiver operator curve, 0.71) was comparable with pulmonary artery occlusion pressure (area under receiver operator curve, 0.66) and superior to ejection fraction (area under receiver operator curve, 0.60) in subgroups of patients in whom these tests were performed. The accuracy of BNP improved when patients with renal insufficiency were excluded (area under receiver operator curve, 0.82). CONCLUSION: When measured early after the onset of acute pulmonary edema, a BNP level of <250 pg/mL supports the diagnosis of acute lung injury. The high rate of cardiac and renal dysfunction in critically ill patients limits the discriminative role of BNP. No level of BNP could completely exclude cardiac dysfunction.

Acute Disease↗
PubMed2006

Lipoprotein-associated phospholipase A2: review and recommendation of a clinical cut point for adults.

Recently, several epidemiologic studies have demonstrated an association between plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) concentration and risk of subsequent cardiovascular events. Several major commercial and reference laboratories across the United States are now offering Lp-PLA2 testing for clinical use to evaluate cardiovascular risk and as a guide to intensity of therapy in individuals at intermediate risk for developing coronary heart disease. Each laboratory has established its own cut points, or "decision values," for Lp-PLA2, which vary from the 50th to the 95th percentile values of individual populations tested at each site. Uniform reporting of cut points has not been achieved. The purpose of this manuscript is to recommend appropriate decision values for Lp-PLA2, endorsed by a consensus panel of laboratorians and clinicians from the major laboratories where the test is performed. These coauthors possess considerable experience with assessment of cardiovascular risk marker decision values in general and are familiar with the validation of the Lp-PLA2 immunoassay and the Lp-PLA2 clinical studies conducted thus far. An ideal risk marker, studied in an ideal population, might yield a consistent cut point associated with a sudden increase in cardiovascular risk. While acknowledging that additional studies will be required to test and refine the recommended decision value, this article reviews the most current information with which to provide guidance to practicing clinicians regarding Lp-PLA2 levels. Since several studies have demonstrated increased risk associated with the second and third tertiles vs. the first tertile for Lp-PLA2, the 50th percentile cut point (235 ng/mL) is recommended as a conservative cut point associated with increased risk for cardiovascular disease. This cut point is not proposed as a treatment target, but rather as a level above which clinicians should consider a patient to be at higher risk for cardiovascular events, independent of established risk factors, high- and low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗