Inhaled Long-acting Anticholinergics and Urinary Tract Infection in Individuals with COPD.

Inhaled, long-acting anticholinergic medication (LAA), commonly used for moderate-to-severe chronic obstructive pulmonary disease (COPD), has been shown to decrease COPD hospitalizations, emergency department visits, and acute exacerbations but has also been associated with urinary tract infection (UTI) in a prior meta-analysis. The objective of this study was to verify if there was an association between LAA and UTI in older individuals with COPD. A population-based, real-world cohort study using health administrative data from Ontario, Canada was conducted. Incidence of UTI was compared between older people with physician-diagnosed COPD, who were new users of inhaled long-acting anticholinergics and new users of inhaled corticosteroids-a reference medication used in similar clinical settings that has no known association with UTI. Propensity score matching was used to minimize the effects of confounding. An overall association between LAA and various measures of UTI in older individuals was not found. However, in a priori defined stratified analyses, men newly initiated on LAA were 75% more likely to develop a UTI than men newly started on an inhaled corticosteroid (hazard ratio 1.75; 95% confidence interval 1.05-2.92). No significant association was seen in women. In conclusion, older men with COPD newly started on LAA are at increased risk of UTI. Men considering an inhaled LAA should be informed of this risk and, if they decide to take it, be provided with appropriate monitoring.

Short-term exposure to antidepressant drugs and risk of acute angle-closure glaucoma among older adults.

Acute angle-closure glaucoma (AACG) is an ocular emergency that may be precipitated by certain types of medications. Antidepressant drugs can affect a number of neurotransmitters, which are involved in the regulation of the iris, which may precipitate AACG. We used a case-crossover study design to investigate the association between recent exposure to antidepressant drugs and AACG. We identified patients with AACG among adults aged 66 years or older between 1998 and 2010 in Ontario using linked population-based administrative databases. We identified intermittent users of antidepressant medications through prescription drug claims in the year preceding AACG. We determined antidepressant exposure in the period immediately before AACG and compared it with antidepressant exposure in 2 earlier control periods. We used conditional logistic regression to determine the odds ratio for antidepressant exposure in the hazard period compared with the control periods. A total of 6470 patients with AACG occurred during the study period. The mean age of the patients was 74.3 years, and 66% were female. Overall, 5.6% of individuals were intermittent users of antidepressant drugs in the year preceding AACG. The odds ratio for any antidepressant exposure in the period immediately preceding AACG was 1.62 (95% confidence interval, 1.16-2.26). An increased risk of AACG was also observed in several subgroups. We conclude that recent exposure to antidepressant drugs is associated with an increased risk of AACG. Clinicians should remain vigilant for the development of this uncommon but potentially serious adverse event after initiating antidepressant therapy.

Regional differences in process of care and outcomes for older acute myocardial infarction patients in the United States and Ontario, Canada.

BACKGROUND: Previous comparisons of acute myocardial infarction (AMI) treatment between the United States and Canada are limited because they compared selected patients from randomized trials, used administrative data that lacked clinical detail, or did not consider regional differences in AMI treatment. METHODS AND RESULTS: We compared medication use, invasive cardiac procedure use, and 30-day risk-standardized mortality rates of 38,886 fee-for-service Medicare beneficiaries hospitalized with AMI in the United States and 5634 similarly aged patients in Ontario, Canada, from 1998 and 2001. Baseline characteristics and illness severity across the US regions and Ontario were not substantially different. Cardiac catheterization use in AMI patients was significantly higher in the United States compared with Ontario (38.7% versus 16.8%, P<0.001), but significant regional variations existed, in which the northeastern United States had significantly lower utilization rates (25.6%) compared with other US regions. Beta-blocker use among ideal candidates was highest in the northeastern United States (77.6% versus 69.7% in the United States as a whole, P<0.001) and angiotensin-converting enzyme inhibitor use was highest in Ontario (69.1% versus 58.2% in the United States, P<0.001). Risk-standardized mortality rates at 30 days were not substantially different across the regions. CONCLUSIONS: Previous studies have suggested a clear divergence in invasive cardiac therapy for AMI patients between the United States and Canada on the basis of health care financing and structural differences. Our findings of similar treatment patterns in the northeastern United States and Ontario suggest that regional practices may have a greater impact on treatment patterns than the respective health care delivery systems.

Comparison of one-year outcome (death and rehospitalization) in hospitalized heart failure patients with left ventricular ejection fraction >50% versus those with ejection fraction <50%.

Heart failure (HF) with preserved systolic function (ejection fraction [EF] >50%) is common, yet no proven therapies exist. Large registries could shed light on what medications may or may not be useful to reduce hospitalization and mortality. The EFFECT Registry, which prospectively enrolled 9,943 patients admitted to the hospital for HF from 1999 to 2001 in 103 hospitals in Ontario, Canada, was used. Patients discharged alive were divided into those with EF >50% and EF <50%. Discharge medications (angiotensin-converting enzyme [ACE] inhibitors, beta blockers [BBs], spironolactone, and digoxin) were examined for their association with HF rehospitalization or death during 1 year. In the HF group with EF >50% (n = 1,026), 199 patients died within 1 year and 349 patients died or were hospitalized for HF within 1 year. In the HF group with EF <50% (n = 1,898), 427 patients died and 720 patients died or were hospitalized for HF. In the HF group with EF >50%, 67% were administered an ACE inhibitor; 32%, a BB; 37%, digoxin; and 12%, spironolactone. No differences were seen in adjusted survival for any medications (ACE inhibitors, BBs, digoxin, or spironolactone) examined in the HF group with EF >50% despite an adjusted survival benefit with ACE inhibitors (hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.77 to 0.94), BBs (HR 0.80, 95% CI 0.72 to 0.89), and spironolactone (HR 0.80, 95% CI 0.66 to 0.98) in patients with low EF. In conclusion, none of the medications proved to improve outcomes in patients with HF with low EF showed an association with outcomes in patients with HF and EF >50%, highlighting the need for randomized trial evidence to define therapies that will be beneficial in patients with HF and preserved systolic function.

Vascular versus myocardial dysfunction in acute coronary syndrome: are the adhesion molecules as powerful as NT-proBNP for long-term risk stratification?

OBJECTIVES: To determine if elevations of adhesion molecules in acute coronary syndrome (ACS) are useful for risk stratification. DESIGN AND METHODS: A cell adhesion array (Randox Ltd.) and NT-proBNP were measured in 216 ACS patients. RESULTS: Kaplan-Meier and Cox models indicate early elevations of NT-proBNP but not the adhesion molecules are predictive of future death/myocardial infarction. DISCUSSION: Elevations of adhesion molecules early after pain onset in ACS are not useful for long-term risk stratification.

"Upstream markers" provide for early identification of patients at high risk for myocardial necrosis and adverse outcomes.

BACKGROUND: For patients presenting with acute coronary syndrome (ACS) to the emergency department, early identification of those that are at high risk for subsequent myocardial necrosis or adverse outcomes would allow earlier or more aggressive treatment. We determined if a panel of biomarkers can be used to identify high risk patients. METHODS: A cohort (84 females/132 males) from our 1996 ACS study population that had EDTA specimens stored (-70 degrees C) was selected and the earliest available specimen was analyzed for 11 biomarkers (IL-6, IL-8, MCP-1, VEGF, L-selectin, P-selectin, E-selectin, ICAM-1, VCAM-1, NT-proBNP, cTnT). These data were linked to the existing cTnI and health outcome databases for this population. ROC curve analysis for myocardial necrosis (i.e., peak cTnI >0.04 microg/l) identified 3 candidate biomarkers. These 3 biomarkers were applied together to generate a panel test (2 of the 3 biomarkers increased for a positive result) and assessed for its ability to identify patients at risk for myocardial necrosis and the combined endpoint of death, myocardial infarction (MI) and heart failure (HF). RESULTS: The panel test (IL-6, NT-proBNP, E-selectin) alone detected 60% (95% CI: 49-69; false positive rate: 26%) of subjects that would be classified with myocardial necrosis. Kaplan-Meier and Cox proportional analyses indicated that patients positive by the biomarker panel (including those with cTnI < or =0.04 microg/l) had significantly worse outcomes (death/MI/HF) as compared to those negative by both cTnI and the panel test. CONCLUSION: A biomarker panel analyzed early after pain onset can identify individuals at risk for both myocardial necrosis and the combined endpoint of death/MI/HF. Additional prospective studies are required to assess this panel for both early MI detection and to further refine which health outcomes (death, MI, HF) are associated with positive panel results.

Elevated C-reactive protein in acute coronary syndrome presentation is an independent predictor of long-term mortality and heart failure.

OBJECTIVES: To assess the ability of C-reactive protein (CRP) to predict long-term outcomes in a chest pain population. DESIGN AND METHODS: CRP was measured at presentation in 446 emergency department patients with acute coronary syndromes. All-cause mortality and hospital discharges for acute myocardial infarction (AMI) and congestive heart failure (CHF) were obtained for up to 8 years following the event. RESULTS: Kaplan-Meier analyses indicated that patients with CRP concentrations above the American Heart Association scientific statement cut-off had a higher rate for death and CHF admissions. After adjusting for troponin concentrations, in a Cox proportional hazard model, only CRP concentrations indicative of an acute phase response (i.e., >7.44 mg/L) were associated with a significant risk for death after 5 years and CHF readmission after 2 years. CONCLUSIONS: Patients presenting early with chest pain with elevated CRP concentrations have a greater long-term risk for death and heart failure.

Effects of contemporary troponin assay sensitivity on the utility of the early markers myoglobin and CKMB isoforms in evaluating patients with possible acute myocardial infarction.

BACKGROUND: The 2003 American Heart Association (AHA) definition for myocardial infarction (MI) requires an "adequate set" (i.e. at least 6 h between measurements) of biomarkers and specifically troponin for the diagnosis of MI. The aim of the present study was to assess the performance of myoglobin, the CKMB isoforms, and cardiac troponin I (cTnI) in specimens earlier than the requisite 6 h after presentation, in a population originally characterized using World Health Organization (WHO) criteria. METHODS: In 1996, 228 acute coronary syndrome patients with an "adequate sample set" had their specimens assayed for CKMB isoforms and myoglobin. In 2003, the same specimens were analyzed with the AccuTnI troponin I assay and myoglobin (Beckman Coulter Access immunoassay). RESULTS: The clinical sensitivities for both myoglobin and the CKMB isoforms were >90% when the population was classified by WHO criteria. However the sensitivities were <70% when the ESC/ACC MI definition was used. Analyzing cTnI at earlier time points as long as there was at least 3 h between specimens or at least 1 specimen 6 h from pain onset did not misclassify subjects based on adverse outcomes in the year following their presentation. CONCLUSION: Contemporary assays for cTnI with increased analytical sensitivity reduce the utility of myoglobin and CKMB isoforms to rule-out an AMI.

Validation of the Thrombolysis In Myocardial Infarction (TIMI) risk index for predicting early mortality in a population-based cohort of STEMI and non-STEMI patients.

BACKGROUND: The Thrombolysis In Myocardial Infarction (TIMI) risk index for the prediction of 30-day mortality was developed and validated in patients with ST-segment elevation myocardial infarction (STEMI) who were being treated with thrombolytics in randomized clinical trials. When tested in clinical registries of patients with STEMI, the index performed poorly in an older (65 years and older) Medicare population, but it was a good predictor of early death among the more representative population on the National Registry of Myocardial Infarction-3 and -4 databases. It has not been tested in a population outside the United States or among non-STEMI patients. METHODS: The TIMI risk index was applied to the Enhanced Feedback for Effective Cardiac Treatment (EFFECT) study cohort of 11,510 acute MI patients from Ontario. The model's discriminatory capacity and calibration were tested in all patients and in subgroups determined by age, sex, diagnosis and reperfusion status. RESULTS: The TIMI risk index was strongly associated with 30-day mortality for both STEMI and non-STEMI patients. The C statistic was 0.82 for STEMI and 0.80 for non-STEMI patients, with overlapping 95% CI. The discriminatory capacity was somewhat lower for patients older than 65 years of age (0.74). The model was well calibrated. CONCLUSIONS: The TIMI risk index is a simple, valid and moderately accurate tool for the stratification of risk for early death in STEMI and non-STEMI patients in the community setting. Its routine clinical use is warranted.

Quality of care and outcomes of older patients with heart failure hospitalized in the United States and Canada.

BACKGROUND: Health care expenditure per person is significantly higher in the United States compared with Canada, but whether there are differences in quality of care of many conditions is unknown. We compared the process of care and outcomes of patients with heart failure, the most common cause of hospitalization for individuals 65 years and older in both countries. METHODS: We compared processes of care and 30-day and 1-year risk-standardized mortality rates among 28,521 US Medicare beneficiaries and 8180 similarly aged patients in Ontario, Canada, hospitalized with heart failure from 1998 to 2001. RESULTS: More US patients underwent left ventricular ejection fraction assessment during hospitalization compared with Canadian patients (61.2% vs 41.7%, P<.001). At discharge, patients in the United States were prescribed beta-blockers more frequently (28.7% vs 25.4%, P<.001) but angiotensin-converting enzyme inhibitors less frequently (54.3% vs 63.4%, P<.001). Among ideal candidates, prescription of beta-blockers (32.5% vs 29.7%, P = .08) or angiotensin-converting enzyme inhibitors (78.3% vs 77.6%, P = .68) was not significantly different between the 2 countries. The US patients had lower risk characteristics on admission and lower crude mortality rates at 30 days and 1 year. Thirty-day risk-standardized mortality was significantly lower for the US patients (8.9% vs 10.7%, P<.001), but 1-year risk-standardized mortality was no longer significantly different (32.2% vs 32.3%, P = .98). CONCLUSION: Patients with heart failure who are hospitalized in the United States had lower short-term mortality at 30 days, but 1-year mortality rates were not significantly different between the United States and Canada.

Ethnic Differences in Mental Illness Severity: A Population-Based Study of Chinese and South Asian Patients in Ontario, Canada.

OBJECTIVE: Little is known about the sociocultural determinants of mental illness at hospital presentation. Our objective was to examine ethnic differences in illness severity at hospital admission among Chinese, South Asian, and the general population living in Ontario, Canada. METHODS: We conducted a large, population-based, cross-sectional study of psychiatric inpatients aged from 19 to 105 years who were discharged between 2006 and 2014. A total of 133,588 patients were classified as Chinese (n = 2,582), South Asian (n = 2,452), or the reference group (n = 128,554) using a validated surnames algorithm (specificity: 99.7%). Diagnoses were based on DSM-IV criteria. We examined the association between ethnicity and 4 measures of disease severity: involuntary admissions, aggressive behaviors, and the number and frequency of positive symptoms (ie, hallucinations, command hallucinations, delusions, and abnormal thought process) (Positive Symptoms Scale, Resident Assessment Instrument-Mental Health [RAI-MH]). RESULTS: After adjusting for sociodemographic characteristics, immigration status, and discharge diagnosis, Chinese patients had greater odds of involuntary admissions (odds ratio [OR] = 1.79; 95% CI, 1.64-1.95) and exhibiting severe aggressive behaviors (OR = 1.36; 95% CI, 1.23-1.51) and ≥ 3 positive symptoms (OR = 1.39; 95% CI, 1.24-1.56) compared to the general population. South Asian ethnicity was also an independent predictor of most illness severity measures. The association between Chinese ethnicity and illness severity was consistent across sex, diagnostic and immigrant categories, and first-episode hospitalization. CONCLUSIONS: Chinese and South Asian ethnicities are independent predictors of illness severity at hospital presentation. Understanding the role of patient, family, and health system factors in determining the threshold for hospitalization is an important future step in informing culturally specific care for these large and growing populations worldwide.

Association between lipid testing and statin therapy in acute myocardial infarction patients.

BACKGROUND: Clinical guidelines recommend lipid testing in all hospitalized acute myocardial infarction (AMI) patients. Inhospital lipid testing has also been proposed as a quality indicator for AMI care, but little is known about its use or importance. We sought to examine rates of inhospital lipid testing and its association with statin therapy at hospital discharge. METHODS: We performed an analysis using medical chart abstraction data that included demographic and comprehensive clinical information for patients hospitalized in Ontario, Canada, with an AMI from 1999 to 2001. RESULTS: Among 11,468 patients, inhospital lipid testing was performed in 6,019 (52.5%) patients and in 4,169 (36.4%) patients within 24 hours of admission. Patients who had lipid testing were significantly more likely to be discharged on statin therapy compared with patients not tested (41.4% vs 23.0%, P < .001). In addition, inhospital lipid testing was strongly associated (odds ratio 3.61, 95% CI 3.15-4.14) with statin therapy prescription at hospital discharge after adjusting for other clinical, physician, and hospital factors. CONCLUSIONS: Despite endorsements from practice guidelines, less than half of all admitted AMI patients received lipid testing within 24 hours of hospital admission. Because inhospital lipid testing was strongly associated with the initiation of statin therapy at discharge, many opportunities to initiate statin therapy were lost. Efforts to increase the use of lipid testing in hospitalized AMI patients may translate into higher rates of lipid-lowering therapy and improved patient outcomes.

The evaluation of a formalized queue management system for coronary angiography waiting lists.

BACKGROUND: Lengthy waiting lists for coronary angiography have been described in many health care systems worldwide. The extent to which formal queue management systems may improve the prioritization and survival of patients in the angiography queue is unknown. OBJECTIVE: To prospectively evaluate the performance of a formal queue management system for patients awaiting coronary angiography in Ontario. METHODS: The coronary angiography urgency scale, a formal queue management system developed in 1993 using a modified Delphi panel, allocates recommended maximum waiting times (RMWTs) in accordance with clinical necessity. By using a provincial clinical registry, 35,617 consecutive patients referred into the coronary angiography queue between April 1, 2001, and March 31, 2002, were prospectively tracked. Cox proportional hazards models were used to examined mortality risk across urgency after adjusting for additional clinical and comorbid factors. RESULTS: Good agreement was determined in urgency ratings between scores from the coronary angiography urgency scale and implicit physician judgement, which was obtained independently at the time of the index referral (weighted kappa = 0.49). The overall mortality in the queue was 0.3% (0.47%, 0.26% and 0.13% for urgent, semiurgent and elective patients, respectively). Urgency, as specified by the coronary angiography urgency scale, was the strongest predictor of death in the queue (P<0.001). However, when patients were censored according to their RMWTs, mortality was similar across different levels of urgency. Consequently, up to 18.5 deaths per 10,000 patients could have potentially been averted had patients been triaged and undergone coronary angiography within the RMWT as specified by the coronary angiography urgency scale. CONCLUSIONS: The incorporation of the coronary angiography urgency scale as a formal queue management system may decrease mortality in the coronary angiography queue. The authors recommend its implementation in health care systems where patients experience excessive waiting time delays for coronary angiography.

Variability in Antibiotic Use Across Nursing Homes and the Risk of Antibiotic-Related Adverse Outcomes for Individual Residents.

IMPORTANCE: Antibiotics are frequently and often inappropriately prescribed to patients in nursing homes. These antibiotics pose direct risks to recipients and indirect risks to others residing in the home. OBJECTIVE: To examine whether living in a nursing home with high antibiotic use is associated with an increased risk of antibiotic-related adverse outcomes for individual residents. DESIGN, SETTING, AND PARTICIPANTS: In this longitudinal open-cohort study performed from January 1, 2010, through December 31, 2011, we studied 110,656 older adults residing in 607 nursing homes in Ontario, Canada. EXPOSURES: Nursing home-level antibiotic use was defined as use-days per 1000 resident-days, and facilities were classified as high, medium, and low use according to tertile of use. Multivariable logistic regression modeling was performed to assess the effect of nursing home-level antibiotic use on the individual risk of antibiotic-related adverse outcomes. MAIN OUTCOMES AND MEASURES: Antibiotic-related harms included Clostridium difficile, diarrhea or gastroenteritis, antibiotic-resistant organisms (which can directly affect recipients and indirectly affect nonrecipients), allergic reactions, and general medication adverse events (which can affect only recipients). RESULTS: Antibiotics were provided on 2,783,000 of 50,953,000 resident-days in nursing homes (55 antibiotic-days per 1000 resident-days). Antibiotic use was highly variable across homes, ranging from 20.4 to 192.9 antibiotic-days per 1000 resident-days. Antibiotic-related adverse events were more common (13.3%) in residents of high-use homes than among residents of medium-use (12.4%) or low-use homes (11.4%) (P < .001); this trend persisted even among the residents who did not receive antibiotic treatments. The primary analysis indicated that residence in a high-use nursing home was associated with an increased risk of a resident experiencing an antibiotic-related adverse event (adjusted odds ratio, 1.24; 95% CI, 1.07-1.42; P = .003). A sensitivity analysis examining nursing home-level antibiotic use as a continuous variable confirmed an increased risk of resident-level antibiotic-related harms (adjusted odds ratio, 1.004 per additional day of nursing home antibiotic use; 95% CI, 1.001-1.006; P = .01). CONCLUSIONS AND RELEVANCE: Antibiotic use is highly variable across nursing homes; residents of high-use homes are exposed to an increased risk of antibiotic-related harms even if they have not directly received these agents. Antibiotic stewardship is needed to improve the safety of all nursing home residents.

Use of valve surgery in Canada.

BACKGROUND: To date, although clinical databases have been used to report on single centre or regional valve surgery outcomes, neither clinical nor administrative data have been used to examine rates of valve surgery use across large geographical regions. The objective of the present study was to use administrative data to evaluate use of valve surgery over time and across Canada. METHODS: All cases of aortic valve replacement (AVR), mitral valve replacement (MVR), mitral valve repair (MV repair), combined AVR and coronary artery bypass grafting (CABG), and combined MVR/MV repair and CABG between fiscal years 1994/95 and 1999/2000 were identified using hospital discharge abstract data obtained from the Canadian Institute of Health Information. Age- and sex-adjusted rates of valve surgery were then calculated by province and by procedure type. RESULTS: Rates of valve surgery for all procedure types increased between fiscal years 1994/95 and 1999/2000 with the exception of MVR, which remained relatively constant. Significant variation in rates of valve surgery was found between male and female residents. Similar variation was also demonstrated across provinces by year and by procedure type. CONCLUSION: There was a trend toward increased use of valve surgery over time for most procedures. Variation in rates of valve surgery exists across provinces. These results provide a starting point from which to track future trends in use and outcomes for these major procedures.

The use of a cytokine panel to define the long-term risk stratification of heart failure/death in patients presenting with chest pain to the emergency department.

OBJECTIVE: To determine if a cytokine panel could be informative regarding subsequent heart failure(HF)/death. DESIGN AND METHODS: In 216 subjects presenting with chest pain to an emergency department in 1996, EDTA plasma (-70 degrees C) was thawed for IL-6, MCP-1, IL-10, VEGF, EGF measurement. RESULTS: Subjects with any three cytokines elevated were at higher risk for HF/death compared to those with < or = two cytokines elevated. DISCUSSION: A cytokine panel might be useful for risk stratification for HF/death.

Secular trends in acute coronary syndrome hospitalization from 1994 to 2005.

BACKGROUND: Acute coronary syndrome (ACS) is one of the most frequent reasons for hospitalization worldwide. Although substantial advances have been made in the prevention and treatment of coronary artery disease, their impact on the rates of ACS hospitalization is unclear. METHODS: Data from the Canadian Institute for Health Information Discharge Abstract Database were used to estimate secular trends in ACS hospitalization. A total of 1.3 million ACS hospitalizations in Canada from April 1, 1994, to March 31, 2006, were examined. Overall hospitalization rates were standardized for age and sex using 1991 Canadian census data, and hospitalization rates were also stratified by age group, sex and Canadian province to assess trends in each subgroup. RESULTS: The Canadian age- and sex-standardized ACS hospitalization rate was 508 per 100,000 persons in 1994, and 317 per 100,000 persons in 2005 - a relative reduction of 37.8% and an average annual relative reduction of 3.9% per year. Declines in ACS hospitalization rates were observed among men (annual relative reduction 3.9%, relative reduction 39.0%) and women (annual relative reduction 3.8%, relative reduction 35.8%). Declining trends were also observed among patients of different age groups and among patients hospitalized across all Canadian provinces. INTERPRETATION: Over the past decade, a substantial decline in ACS hospitalization rates occurred, which has not been previously observed. This finding is likely due to improvements in primary and secondary prevention of coronary artery disease. The present study's data should provide important insights and guidance for future health care planning in Canada.

Is a pattern of increasing biomarker concentrations important for long-term risk stratification in acute coronary syndrome patients presenting early after the onset of symptoms?

BACKGROUND: Guidelines for treatment of acute coronary syndrome (ACS) recommend observing a rise or fall in cardiac troponin (cTn) concentrations for assessing acute injury. It is unknown whether a rising pattern presages a more adverse long-term prognosis than elevations that do not change. The present study assessed whether a rising pattern of cardiac biomarkers was more prognostic than simple elevations. METHODS: We measured N-terminal pro-brain natriuretic peptide (NT-proBNP) (Roche), cTnT (Roche) and cTnI (Beckman Coulter) in 212 ACS patients. These biomarkers were measured in coincident EDTA and heparin plasma samples available from at least 2 different time points, an early first specimen obtained a median of 2 hours after onset of symptoms, interquartile range (IQR) 2-4 hours, and a later second specimen obtained at 9 hours, IQR 9-9 hours. The cTn concentration in the second specimen was used to classify myocardial necrosis (cTnI >0.04 ug/L; cTnT >0.01 ug/L). Outcomes [death, myocardial infarction (MI), heart failure (HF)] were obtained >8 years after the initial presentation. For patients with myocardial necrosis and a cTn concentration ratio (second/first measured concentrations) > or =1.00, the concentration ratios and the absolute concentrations in the second specimen were used to assess prognosis after 4 years. RESULTS: In myocardial necrosis, the relative change (cTn2/cTn1) was greater for cTnI than for cTnT (P <0.01), whereas the relative change in NT-proBNP was the same regardless of which troponin was used to classify necrosis (P = 0.71). The concentration ratio for cTnI, cTnT, and NT-proBNP was not useful for risk stratification (i.e., death/MI/HF; P > or =0.15). CONCLUSIONS: A rise in cardiac troponin or NT-proBNP concentration in ACS patients presenting early after onset of pain is not helpful for long-term prognosis.

Risk stratification for heart failure and death in an acute coronary syndrome population using inflammatory cytokines and N-terminal pro-brain natriuretic peptide.

BACKGROUND: Inflammation in acute coronary syndrome (ACS) can identify those at greater long-term risks for heart failure (HF) and death. The present study assessed the performance of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1) (cytokines involved in the activation and recruitment of leukocytes) in addition to known biomarkers [e.g., N-terminal pro-brain natriuretic peptide (NT-proBNP)] for predicting HF and death in an ACS population. METHODS: In a cohort of 216 ACS patients, NT-proBNP (Elecsys; Roche) and IL-6, IL-8, and MCP-1 (evidence investigator; Randox) were measured in serial specimens collected early after symptom onset (n = 723). We collected at least 2 specimens from each participant: an early specimen (median 2 h; interquartile range 2-4 h) and a later specimen (9 h; 9-9 h), and used the later specimens' biomarker concentrations for risk stratification. RESULTS: An increase in both IL-6 and NT-proBNP was observed but not for IL-8 or MCP-1 early after pain onset. Kaplan-Meier analysis demonstrated that individuals with increased NT-proBNP (>183 ng/L) or cytokines (IL-6 > 6.4 ng/L; above upper limit of normal for IL-8 or MCP-1) had a greater probability of death or HF in the following 8 years (P <0.05). In a Cox proportional hazard model adjusted for both CRP and troponin I, increased IL-6, MCP-1, and NT-proBNP remained significant risk factors. Combining all 3 biomarkers resulted in a higher likelihood ratio for death or HF than models restricted to any 2 of these biomarkers. CONCLUSION: IL-6, MCP-1, and NT-proBNP are independent predictors of long-term risk of death or HF, highlighting the importance of identifying leukocyte activation and recruitment in ACS patients.