Changes in N-terminal pro-B-type natriuretic peptide and incidence of diabetes: The Multi-Ethnic Study of Atherosclerosis (MESA).

AIMS: This study looked at whether the inverse association of circulating N-terminal pro-B-type natriuretic peptide (NT-proBNP) with incident diabetes is modified by changes in NT-proBNP (ΔNT-proBNP) levels. METHODS: Plasma NT-proBNP was assayed at baseline and 3.2 years later (visit 3) in the Multi-Ethnic Study of Atherosclerosis (MESA). ΔNT-proBNP was calculated as NT-proBNP visit3-NT-proBNP baseline. A Poisson distribution was fitted to determine the incidence density of diabetes, adjusted for age, race, gender, educational attainment, antihypertensive medication, total intentional exercise and plasma IL-6 levels. In the primary analysis (n=3236 without diabetes up to visit 3, followed for a mean of 6.3 years), incidence density was regressed for the following categories of baseline NT-proBNP: (1)<54.4 pg/mL; (2) 54.4-85.9 pg/mL; and (3) 86-54.2 pg/mL. This was crossed with categories of ΔNT-proBNP as medians (ranges): (1) -6.2 (-131-11.7) pg/mL; (2) 19.8 (11.8-30.1) pg/mL; (3) 44.0 (30.2-67.9) pg/mL; and (4) 111.2 (68.0-3749.9) pg/mL. RESULTS: The incidence density of diabetes followed a U-shaped association across categories of ΔNT-proBNP within categories of baseline NT-proBNP after adjusting for other covariates (P=0.02). At each level of baseline NT-proBNP, the incidence density of diabetes was lowest for small-to-moderate increases in NT-proBNP. CONCLUSION: This analysis suggests that NT-proBNP has a biphasic association with diabetes in which the risk of incident diabetes decreases within a 'physiological range' of ΔNT-proBNP, and plateaus or increases as NT-proBNP concentrations increase, probably in response to pathophysiological conditions leading to high levels of NT-proBNP.

Adiponectin is independently associated with NT-proBNP: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: To investigate the associations between selected adipokines and the N-terminal prohormone of B-type natriuretic peptide (NT-proBNP). METHODS AND RESULTS: As many as 1489 individuals enrolled in the Multi-Ethnic Study of Atherosclerosis were evaluated at 4 clinic visits about every 2 years. The evaluation included fasting venous blood, which was analyzed for NT-proBNP (at visits 1 and 3) and the adipokines adiponectin and leptin (at visits 2 and 3). The mean age was 64.8 ± 9.6 years and 48% were female. After multivariable adjustment, a 1-SD increment in adiponectin was associated with a 14 pg/ml higher NT-proBNP level (p < 0.01), while, compared to the 1st quartile of adiponectin, the 2nd, 3rd and 4th quartiles had 28, 45 and 67% higher NT-proBNP levels (p < 0.01 for all). For changes in NT-proBNP over the follow-up period, and after multivariable adjustment including baseline NT-proBNP, a 1-SD increment in adiponectin was associated with a 25 pg/ml absolute increase in NT-proBNP (p < 0.01), while those in the 2nd, 3rd and 4th quartiles of adiponectin were associated with increases of 5, 28 and 65 pg/ml (p = 0.74, 0.09 and <0.01, respectively). There was a significant interaction between adiponectin and sex for visit 3 NT-proBNP (p-interaction < 0.01), with significantly stronger associations in men. Leptin was not associated with NT-proBNP. CONCLUSION: Higher adiponectin, but not leptin, is significantly associated with higher levels of NT-proBNP, as well as with greater longitudinal increases in NT-proBNP. The associations were stronger in men.

ADQI 7: the clinical management of the Cardio-Renal syndromes: work group statements from the 7th ADQI consensus conference.

Many patients with heart failure have underlying renal dysfunction, and similarly, patients with kidney failure are prone to cardiac failure. This has led to the concept of cardio-renal syndromes, which can be an acute or chronic cardio-renal syndrome, when cardiac failure causes deterioration in renal function, or acute and/or chronic Reno-Cardiac syndrome, when renal dysfunction leads to cardiac failure. Patients who develop these syndromes have increased risk of hospital admission and mortality. Although there are clinical guidelines for managing both heart failure and chronic kidney disease, there are no agreed guidelines for managing patients with cardio-renal and/or Reno-Cardiac syndromes, as these patients have typically been excluded from clinical trials. We have therefore reviewed the currently available published literature to outline a consensus of current best clinical practice for these patients.

Clinical applications of B-type natriuretic peptide (BNP) testing.

Many claims have been made in recent years regarding the utility of plasma B-type natriuretic peptide (BNP) concentration measurements in the diagnosis, risk stratification and monitoring of patients with heart failure. This paper summarizes the current evidence and provides guidance for practising clinicians. Overall, plasma BNP testing appears to be of most value in the diagnostic arena, where it is likely to improve the performance of non-specialist physicians in diagnosing heart failure. In clinical practice, BNP testing is best used as a 'rule out' test for suspected cases of new heart failure in breathless patients presenting to either the outpatient or emergency care settings; it is not a replacement for echocardiography and full cardiological assessment, which will be required for patients with an elevated BNP concentration. Although work is ongoing in establishing the 'normal' values of BNP, heart failure appears to be highly unlikely below a plasma concentration of 100 pg/ml. However, as BNP levels rise with age and are affected by gender, comorbidity and drug therapy, the plasma BNP measurement should not be used in isolation from the clinical context.

B-type natriuretic peptide in the diagnosis and management of congestive heart failure.

Finding a simple blood test that would aid in the diagnosis and management of patients with CHF clearly would have a favorable impact on the staggering costs associated with the disease. BNP, which is synthesized in the cardiac ventricles and correlates with LV pressure, amount of dyspnea, and the state of neurohormonal modulation, makes this peptide the first potential "white count" for heart failure. The fact that a point-of-care rapid assay for BNP has been approved by the FDA gives the clinician an opportunity to explore its potential usefulness. The author's data, and data from others, suggest that serial point-of-care testing of BNP will be of immense help in patients presenting to urgent care clinics with dyspnea. Additionally, BNP might serve as a screen for patients referred for echocardiography. A low BNP level makes echocardiographic indices of LV dysfunction (systolic and diastolic) highly unlikely. BNP also might be an effective way to improve the in-hospital management of patients admitted with decompensated CHF. In some instances, BNP levels may obviate the need for invasive hemodynamic monitoring and, in cases where such monitoring is used, may help tailor treatment of the decompensated patient. Finally, the role of BNP in the outpatient cardiac or primary care clinic may be one of critical importance in titration of therapies and in assessment of the state of neurohormonal compensation of the patient.

Practical approaches to treating patients with acute decompensated heart failure.

Finding a simple blood test to aid in the diagnosis and treatment of patients with congestive heart failure would have a favorable impact on the costs associated with the disease. B-type natriuretic peptide (BNP) is synthesized in the cardiac ventricles and correlates with left ventricular pressure, amount of dyspnea, and the state of neurohormonal modulation, making this peptide the first potential "white count" for heart failure. Data indicate that serial point-of-care testing of BNP should be helpful in patients presenting to urgent care clinics with dyspnea. BNP might serve as a screen for patients referred for echocardiography. A low BNP level makes echocardiographic indices of left ventricular dysfunction (both systolic and diastolic) highly unlikely. BNP may also be effective in improving in-hospital management of patients admitted with decompensated congestive heart failure. In some cases BNP levels may obviate the need for invasive hemodynamic monitoring and, when such monitoring is used, may help tailor treatment of decompensated patients. Finally, the role of BNP in outpatient cardiac or primary care clinics may be important in the titration of therapies and assessment of the state of neurohormonal compensation of patients.

Ninety-minute accelerated critical pathway for chest pain evaluation.

Rapid, efficient, and accurate evaluation of chest pain patients in the emergency department optimizes patient care from public health, economic, and liability perspectives. To evaluate the performance of an accelerated critical pathway for patients with suspected coronary ischemia that utilizes clinical history, electrocardiographic findings, and triple cardiac marker testing (cardiac troponin I [cTnI], myoglobin, and creatine kinase-MB [CK-MB]), we performed an observational study of a chest pain critical pathway in the setting of a large Emergency Department at the Veterans Affairs Medical Center in 1,285 consecutive patients with signs and symptoms of cardiac ischemia. The accelerated critical pathway for chest pain evaluation was analyzed for: (1) accuracy in triaging of patients within 90 minutes of presentation, (2) sensitivity, specificity, positive predictive value, and negative predictive value of cTnI, myoglobin, and CK-MB in diagnosing acute myocardial infarction (MI) within 90 minutes, and (3) impact on Coronary Care Unit (CCU) admissions. All MIs were diagnosed within 90 minutes of presentation (sensitivity 100%, specificity 94%, positive predictive value 47%, negative predictive value 100%). CCU admissions decreased by 40%. Ninety percent of patients with negative cardiac markers and a negative electrocardiogram at 90 minutes were discharged home with 1 patient returning with an MI (0.2%) within the next 30 days. Thus, a simple, inexpensive, yet aggressive critical pathway that utilizes high-risk features from clinical history, electrocardiographic changes, and rapid point-of-care testing of 3 cardiac markers allows for accurate triaging of chest pain patients within 90 minutes of presenting to the emergency department.

Utility of B-natriuretic peptide levels in identifying patients with left ventricular systolic or diastolic dysfunction.

PURPOSE: Although echocardiography is important for making the diagnosis of left ventricular dysfunction, its cost and lack of availability limit its use as a routine screening test. B-Natriuretic peptide levels accurately reflect ventricular pressure, and preliminary studies with a rapid assay have found that levels are sensitive and specific for diagnosing heart failure in patients with dyspnea. We hypothesized that B-natriuretic peptide levels obtained through the use of a rapid assay should correlate with echocardiographic abnormalities of ventricular function. SUBJECTS AND METHODS: We studied 400 patients who were referred for echocardiography at the San Diego Veteran's Healthcare System between June and August 2000 to evaluate ventricular function. B-natriuretic peptide levels were measured by a point-of-care immunoassay; cardiologists assessing left ventricular function were blinded to the assay results. Patients were grouped into those with normal ventricular function, systolic dysfunction only, diastolic dysfunction only, and both systolic and diastolic dysfunction. RESULTS: Mean (+/- SD) B-natriuretic peptide concentration was 416 +/- 413 pg/mL in the 253 patients diagnosed with abnormal left ventricular function, compared with 30 +/- 36 pg/mL in the 147 patients with normal left ventricular function. Patients with both systolic and diastolic dysfunction had the highest levels (675 +/- 423 pg/mL). The area under the receiver operating characteristic (ROC) curve for B-natriuretic peptide levels to detect any abnormal echocardiographic finding was 0.95 (91% confidence interval: 0.93 to 0.97). B-Natriuretic peptide levels were unable to differentiate systolic vs. diastolic dysfunction. In patients with symptoms of heart failure and normal systolic function, B-natriuretic peptide levels >57 pg/mL had a positive predictive value of 100% for diastolic abnormalities. CONCLUSIONS: A simple, rapid test for B-natriuretic peptide levels can reliably predict the presence or absence of left ventricular dysfunction on echocardiogram. For some patients, a normal level may preclude the need for echocardiography.

B-type natriuretic peptide levels: a potential novel "white count" for congestive heart failure.

Finding a simple blood test to aid in the diagnosis and treatment of patients with congestive heart failure could have a favorable impact on the costs associated with the disease. B-type natriuretic peptide (BNP) is synthesized in the cardiac ventricles, and its level correlates with left ventricular pressure, amount of dyspnea, and the state of neurohormonal modulation, thus making peptide the first potential "white count" for heart failure. Data indicate that serial point-of-care testing of BNP should be helpful in patients presenting to urgent care clinics with dyspnea. BNP may also serve as a screen for patients referred for echocardiography. A low BNP level makes left ventricular dysfunction (both systolic and diastolic) highly unlikely. BNP may also provide an effective means of improving in-hospital management of patients admitted with decompensated congestive heart failure. In some cases, BNP level observations may obviate the need for invasive hemodynamic monitoring and, when such monitoring is used, may help tailor treatment of the decompensated patient. Finally, the role of BNP in the outpatient cardiac or primary care clinic may be one of critical importance in titration of therapies as well as in assessing the state of neurohormonal compensation of the patient.

Mitigation of the clinical significance of spurious elevations of cardiac troponin I in settings of coronary ischemia using serial testing of multiple cardiac markers.

The ability to differentiate between true positives, false positives, and sporadically elevated cardiac troponin levels has grown in importance as cardiac troponins assume an increasingly dominant role in the diagnosis of coronary syndromes. In a population sample of 1,000 patients who presented consecutively to a large urban hospital emergency room, 50 of 112 patients who had elevated troponin levels (> 0.6 ng/ml) during evaluation for myocardial injury were subsequently found to have had an isolated, spurious elevation of cardiac troponin, and not a diagnosed myocardial infarction. Logistic regression analysis shows that by hierarchically analyzing electrocardiographic changes with concurrent creating kinase-MB and myoglobin levels at the time of the troponin elevation, one may predict with 91% accuracy whether the troponin elevation is actually indicative of a myocardial infarction in a patient. Spurious troponin elevations may be a common occurrence, and if not detected, may result in an increased number of falsely diagnosed myocardial infarctions.

A rapid test for B-type natriuretic peptide correlates with falling wedge pressures in patients treated for decompensated heart failure: a pilot study.

OBJECTIVES: To determine if changes in B-type natriuretic peptide (BNP) levels can accurately reflect acute changes in pulmonary capillary wedge pressure during treatment of decompensated heart failure. BACKGROUND: Tailored therapy of decompensated congestive heart failure with hemodynamic monitoring is controversial. Other than the expense and complications of Swan-Ganz catheters, its use in titration of drug therapy has no conclusive end point. Because BNP reflects both elevated left ventricular pressure and neurohormonal modulation and has a short half-life, we hypothesized that levels of BNP would decline in association with falling wedge pressures. Final BNP levels would perhaps signify a new set point of neuromodulation. METHODS AND RESULTS: Twenty patients with decompensated New York Heart Association (NYHA) class III-IV congestive heart failure (CHF) undergoing tailored therapy were studied. BNP levels were drawn every 2 to 4 hours for the first 24 hours (active treatment phase) and then every 4 hours for the next 24 to 48 hours (stabilization period). Hemodynamic data was recorded simultaneously. In 15 patients whose wedge pressure responded to treatment in the first 24 hours, there was a significant drop in BNP levels (55%) versus nonresponders (8%). There was a significant correlation between percent change in wedge pressure from baseline per hour and the percent change of BNP from baseline per hour (r = 0.79, P <.05). When the wedge pressure was kept at a stable, low level during the stabilization phase, BNP levels continued to fall another 37% (937 +/- 140 pg/mL at 24 hours to 605 +/- 128 pg/mL). Patients who died (n = 4) had higher final BNP levels (1,078 +/- 123 pg/mL v 701 +/- 107 pg/mL). CONCLUSIONS: The data suggest that rapid testing of BNP may be an effective way to improve the in-hospital management of patients admitted with decompensated CHF. Although BNP levels will not obviate the need for invasive hemodynamic monitoring, it may be a useful adjunct in tailoring therapy to these patients.

Utility of B-natriuretic peptide as a rapid, point-of-care test for screening patients undergoing echocardiography to determine left ventricular dysfunction.

BACKGROUND: Although echocardiography is an important tool for making the diagnosis of left ventricular (LV) dysfunction, the cost of this procedure limits its use as a routine screening tool for this purpose. Brain natriuretic peptide (BNP) accurately reflects ventricular pressure, and preliminary studies have found it to be highly sensitive and highly specific in diagnosing congestive heart failure in the emergency department. We hypothesized that BNP might therefore be useful as a screening tool before echocardiography in patients with suspected LV dysfunction. METHODS: Subjects included patients referred for echocardiography to evaluate the presence or absence of LV dysfunction. Patients with known LV dysfunction were excluded from analysis. BNP was measured by a point-of-care immunoassay (Biosite Diagnostics, San Diego, Calif). The results of BNP levels were blinded from cardiologists making the assessment of LV function. Patients were divided into those with normal ventricular function, abnormal systolic ventricular function, abnormal diastolic function, and evidence of both systolic and diastolic dysfunction. RESULTS: Two hundred patients in whom LV function was unknown were studied. In the 105 patients (53%) whose ventricular function was subsequently determined to be normal by echocardiography, BNP levels averaged 37 +/- 6 pg/mL. This was significantly less than in those patients with either ultimate diastolic dysfunction (BNP 391 +/- 89 pg/mL (P <.001) or systolic dysfunction (BNP 572 +/- 115 pg/mL (P <.001). A receiver-operator characteristic curve showing the sensitivity and specificity of BNP against the echocardiography diagnosis revealed the area under the curve (accuracy) was 0.95. At a BNP level of 75 pg/mL was 98% specific for detecting the presence or absence of LV dysfunction by echocardiography. CONCLUSIONS: A simple, rapid test for BNP, which can be performed at the bedside or in the clinic, can reliably predict the presence or absence of LV dysfunction on echocardiogram. The data indicate that BNP may be an excellent screening tool for LV dysfunction and may, in fact, preclude the need for echocardiography in many patients.

Usefulness of cardiac troponin I in patients undergoing open heart surgery.

BACKGROUND: Significant myocardial injury during cardiac surgery is associated with a 10-fold increase in 2-year complication rates, yet there remains no clinical gold standard for diagnosis. Troponin I has complete cardiospecificity and is clinically used for diagnosis of myocardial infarction in other settings. METHODS AND RESULTS: One hundred consecutive patients undergoing open heart surgery (71 coronary artery bypass grafts and 29 aortic valve replacements) were enrolled and blood samples were drawn preoperatively, at 5 AM and 5 PM on days 1 and 2 after surgery, and at 5 AM for 3 more days. Twelve-lead electrocardiograms were performed daily and echocardiographic studies were performed on patients with either; electrocardiographic changes signifying likely myocardial damage, intraoperative complications, or elevated creatine kinase subfraction MB or troponin values. Seventeen patients had either new wall motion abnormalities or new Q waves all with peak cardiac troponin I >40 ng/mL. Stratification of patients by peak troponin values <40 and >60 ng/mL was highly predictive (P <.001) of days in intensive care unit, days on ventilator, development of new arrhythmia, and especially cardiac events. These postoperative variables also showed a stronger correlation with peak cardiac troponin I than did peak creatine kinase subfraction MB. CONCLUSION: Peak troponin I values detect myocardial infarction the day after heart surgery and predicts patient outcome.

Utility of B-type natriuretic peptide in the diagnosis of congestive heart failure in an urgent-care setting.

OBJECTIVES: The goal of this study was to evaluate the utility of a rapid "bedside" technique for measurement of B-type natriuretic peptide (BNP) in the diagnosis of congestive heart failure (CHF) in an urgent-care setting. BACKGROUND: B-type natriuretic peptide is a protein secreted from the cardiac ventricles in response to pressure overload. One potential application of measurements of BNP in blood is distinguishing dyspnea due to CHF from other causes. METHODS: B-type natriuretic peptide concentrations were measured in a convenience sample of 250 predominantly male (94%) patients presenting to urgent-care and emergency departments of an academic Veteran's Affairs hospital with dyspnea. Results were withheld from clinicians. Two cardiologists retrospectively reviewed clinical data (blinded to BNP measurements) and reached a consensus opinion on the cause of the patient's symptoms. This gold standard was used to evaluate the diagnostic performance of the BNP test. RESULTS: The mean BNP concentration in the blood of patients with CHF (n = 97) was higher than it was in patients without (1,076 +/- 138 pg/ml vs. 38 +/- 4 pg/ml, p < 0.001). At a blood concentration of 80 pg/ml, BNP was an accurate predictor of the presence of CHF (95%); measurements less than this had a high negative predictive value (98%). The overall C-statistic was 0.97. In multivariate analysis, BNP measurements added significant, independent explanatory power to other clinical variables in models predicting which patients had CHF. The availability of BNP measurements could have potentially corrected 29 of the 30 diagnoses missed by urgent-care physicians. CONCLUSIONS: B-type natriuretic peptide blood concentration measurement appears to be a sensitive and specific test to diagnose CHF in urgent-care settings.

A rapid bedside test for B-type peptide predicts treatment outcomes in patients admitted for decompensated heart failure: a pilot study.

OBJECTIVES: The goal of this study was to determine if B-type natriuretic peptide (BNP) levels predict outcomes of patients admitted with decompensated heart failure. BACKGROUND: Treatment of decompensated congestive heart failure (CHF) has often been based on titration of drugs to relieve patient's symptoms, a case that could be made for attempting to also treat neurohormonal abnormalities. Because BNP reflects both elevated left ventricular pressure as well as neurohormonal modulation, we hypothesized that BNP might be useful in assessing outcomes in patients admitted with decompensated CHF. METHODS: We followed 72 patients admitted with decompensated New York Heart Association class III to IV CHF, measuring daily BNP levels. We then determined the association between initial BNP measurement and the predischarge or premoribund BNP measurement and subsequent adverse outcomes (death and 30-day readmission). RESULTS: Of the 72 patients admitted with decompensated CHF, 22 end points occurred (death: n = 13, readmission: n = 9). In these patients, BNP levels increased during hospitalization (mean increase, 233 pg/ml, p < 0.001). In patients without end points, BNP decreased (mean decrease 215 pg/ml). Univariate analysis revealed that the last measured BNP was strongly associated with the combined end point. In patients surviving hospitalization, BNP discharge concentrations were strong predictors of subsequent readmission (area under the receiver operator curve of 0.73). CONCLUSIONS: In patients admitted with decompensated CHF, changes in BNP levels during treatment are strong predictors for mortality and early readmission. The results suggest that BNP levels might be used successfully to guide treatment of patients admitted for decompensated CHF.

B-type natriuretic peptide levels: diagnostic and therapeutic potential.

A blood test that would aid in the diagnosis and management of patients with congestive heart failure would have a favorable impact on the staggering costs of the disease. B-type naturetic peptide (BNP) is synthesized in the cardiac ventricles and its release is directly proportional to ventricular volume expansion and pressure overload. Levels of BNP correlate with left ventricular pressure, amount of dyspnea, and the state of neurohumoral modulation. BNP also correlates closely with New York Heart Association classification. A cut point of 100 pg/mL appears to discriminate patients with congestive heart failure from those without congestive heart failure. Measurement of BNP may also be an excellent screening tool for LV dysfunction. Key Words: Natriuretic peptides; neurohormonal; left-ventricular pressure;

B-type natriuretic peptide (BNP) levels: diagnostic and therapeutic potential.

Finding a simple blood test that would aid in the diagnosis and management of patients with CHF would clearly have a favorable impact on the staggering costs associated with the disease. B-type natriuretic peptide (BNP) may be the first potential "white count" for heart failure. The fact that a point-of-care, rapid assay for BNP has recently been approved by the FDA gives the clinician an opportunity to explore its potential usefulness. Data suggest that serial point-of-care testing of BNP will be of immense help in patients presenting to urgent care clinics with dyspnea. Additionally, BNP might serve as a screen for patients referred for echocardiography, and might also be an effective way to improve the in-hospital management of patients admitted with decompensated CHF. Finally, the role of BNP in the outpatient cardiac or primary care clinic may be one of critical importance in titration of therapies as well as assessment of the state of the patient's neurohormonal compensation.

A prospective study of an algorithm using cardiac troponin I and myoglobin as adjuncts in the diagnosis of acute myocardial infarction and intermediate coronary syndromes in a veteran's hospital.

BACKGROUND: Accurate and cost-effective evaluation of acute chest pain has been problematic for years. The high prevalence of missed myocardial infarctions (MI) has led to conservative triage behavior on the part of physicians, leading to expensive admissions to coronary care units. New algorithms are sorely needed for more rapid and accurate triage of patients with chest pain to appropriate treatment settings. HYPOTHESIS: We sought to test an algorithm for rapid diagnosis of MI and acute coronary syndromes using cardiac troponin I (cTnI) and myoglobin as adjuncts to creatine kinase (CK)-MB. We hypothesized our algorithm would be both sensitive and specific at early time points, and would allow safe stratification of patients not ruling in by conventional CK-MB criteria. METHODS: This was a 6-month prospective study of 505 consecutive patients who presented with chest pain at a university-affiliated veteran's hospital. The percentage of MIs at various time points was identified using combinations of markers. Safety outcomes were assessed by follow-up of patients discharged home. Cost savings analysis was assessed by surveying the physicians as to whether the use of the algorithm affected their disposition of patients. Forty-nine patients ruled in for MI. Using the combination of cTnI, 2-h doubling of myoglobin, and CK-MB, 37 (76%) ruled in at the time of presentation, 43 (88%) at 2 h, and 100% by 6 h. RESULTS: Cardiac troponin I plus a 2-h myoglobin was as accurate as the combination of all three markers and performed better than CK-MB in detecting patients presenting late and as a predictor for complications when CK-MB was normal. Of the 456 patients with normal markers after 6 h, only 140 were sent to the coronary care unit (CCU), and 176 were sent home. A 3-month follow-up showed minimal adverse events. One-half of physicians completing a survey stated the use of markers changed their disposition of patients, leading to an estimated 6-month cost savings of a half-million dollars. CONCLUSIONS: We developed an algorithm using troponin I and myoglobin as adjuncts to usual CK-MB levels that allowed for rapid and accurate assessment of patients with acute MI. It also afforded physicians important input into their decision making as to how best to triage patients presenting with chest pain. Their comfort in sending home certain subgroups of patients who otherwise would have been admitted to the CCU was rewarded with a good short-term prognosis and a large cost savings to the hospital.

Leukocyte adhesion molecule expression and T cell naïve/memory status following isoproterenol infusion.

This study examined adhesion molecules on peripheral leukocytes following a 30-min infusion of the beta-adrenergic agonist isoproterenol in 23 healthy subjects. In response to isoproterenol, the number of CD8 +CD62L- T cells and both CD62L+ and CD62L-natural killer (NK) (CD3 CD16+ 56+) cells increased markedly in circulation (p < 0.001). In addition, the surface density of CD62L was significantly lower on both CD8+ and CD4+ T cells (p < 0.001). Plasma levels of soluble CD62L remained unchanged, arguing against an isoproterenol-induced shedding of L-selectin. In contrast to CD62L, the surface density of the beta2 integrin LFA-1 (CD11a) was higher on circulating lymphocytes (p < 0.001) (but not monocytes or lymphocytes) post-infusion. Isoproterenol also led to a mobilization of memory/activated CD8+CD29high T cells (p < 0.01), but had no significant effect on the number of circulating CD8+ CD45RA+ CD62L+ naïve T cells. beta blockade with the non-specific antagonist propranolol eliminated these isoproterenol-induced effects.

Peripheral blood mononuclear cell-endothelial adhesion in human hypertension following exercise.

OBJECTIVE: To determine the effects of hypertension and exercise on interleukin-6 (IL-6) levels and mononuclear cell adhesion to endothelial cells. DESIGN: Twelve hypertensive and 33 normotensive volunteers were studied prior to and following exhaustive exercise. End points were stimulated IL-6 levels and peripheral blood mononuclear cell (PBMC) CD11a (LFA-1) expression and in vitro PBMC adhesion to human umbilical venous endothelial cells (HUVEC). RESULTS: In response to exercise, all subjects showed a significant increase in lymphocyte CD11a a density and in IL-6 levels (P < 0.001). Compared to normotensives, hypertensives showed significantly greater mean density of CD11a on lymphocytes (P< 0.05) and on monocytes (P < 0.05). In response to exercise, hypertensive subjects showed a twofold greater increase in IL-6 as compared to normotensives (+ 240 pg/ml versus + 123 pg/ml, respectively; P< 0.05). PBMC adhesion to HUVEC was increased in hypertensives but decreased in normotensives following exercise (P< 0.03). CONCLUSION: The findings suggest that exercise leads to increased mononuclear cell adhesion to endothelial cells in patients with hypertension, possibly through cytokine-induced activation of mononuclear cell CD11a. These findings, coupled with prior data indicating increased endothelial activation in hypertension, may be relevant to the increased risk of atherosclerosis in human hypertension.