Effect of interleukin-1 blockade with anakinra on leukocyte count in patients with ST-segment elevation acute myocardial infarction.

Leukocytosis is a common finding in patients with ST elevation myocardial infarction (STEMI) and portends a poor prognosis. Interleukin 1-ß regulates leukopoiesis and pre-clinical studies suggest that anakinra (recombinant human interleukin-1 [IL-1] receptor antagonist) suppresses leukocytosis in myocardial infarction. However, the effect of IL-1 blockade with anakinra on leukocyte count in patients with STEMI is unknown. We reviewed the white blood cell (WBC) and differential count of 99 patients enrolled in a clinical trial of anakinra (n = 64) versus placebo (n = 35) for 14 days after STEMI. A complete blood cell count with differential count were obtained at admission, and after 72 h, 14 days and 3 months. After 72 h from treatment, anakinra compared to placebo led to a statistically significant greater percent reduction in total WBC count (- 35% [- 48 to - 24] vs. - 21% [- 34 to - 10], P = 0.008), absolute neutrophil count (- 48% [- 60 to - 22] vs. - 27% [- 46 to - 5], P = 0.004) and to an increase in absolute eosinophil count (+ 50% [0 to + 100] vs. 0% [- 50 to + 62], P = 0.022). These changes persisted while on treatment at 14 days and were no longer apparent at 3 months after treatment discontinuation. We found that in patients with STEMI IL-1 blockade with anakinra accelerates resolution of leukocytosis and neutrophilia. This modulation may represent one of the mechanisms by which IL-1 blockade improves clinical outcomes.

European position paper on the management of patients with patent foramen ovale. Part II - Decompression sickness, migraine, arterial deoxygenation syndromes and select high-risk clinical conditions.

Patent foramen ovale (PFO) is implicated in the pathogenesis of a number of medical conditions but to date only one official position paper related to left circulation thromboembolism has been published. This interdisciplinary paper, prepared with the involvement of eight European scientific societies, reviews the available evidence and proposes a rationale for decision making for other PFO-related clinical conditions. In order to guarantee a strict evidence-based process, we used a modified grading of recommendations, assessment, development, and evaluation (GRADE) methodology. A critical qualitative and quantitative evaluation of diagnostic and therapeutic procedures was performed, including assessment of the risk/benefit ratio. The level of evidence and the strength of the position statements were weighed and graded according to predefined scales. Despite being based on limited and observational or low-certainty randomised data, a number of position statements were made to frame PFO management in different clinical settings, along with suggestions for new research avenues. This interdisciplinary position paper, recognising the low or very low certainty of existing evidence, provides the first approach to several PFO-related clinical scenarios beyond left circulation thromboembolism and strongly stresses the need for fresh high-quality evidence on these topics.

Interleukin-1 Blockade Inhibits the Acute Inflammatory Response in Patients With ST-Segment-Elevation Myocardial Infarction.

Background ST-segment-elevation myocardial infarction is associated with an intense acute inflammatory response and risk of heart failure. We tested whether interleukin-1 blockade with anakinra significantly reduced the area under the curve for hsCRP (high sensitivity C-reactive protein) levels during the first 14 days in patients with ST-segment-elevation myocardial infarction (VCUART3 [Virginia Commonwealth University Anakinra Remodeling Trial 3]). Methods and Results We conducted a randomized, placebo-controlled, double-blind, clinical trial in 99 patients with ST-segment-elevation myocardial infarction in which patients were assigned to 2 weeks treatment with anakinra once daily (N=33), anakinra twice daily (N=31), or placebo (N=35). hsCRP area under the curve was significantly lower in patients receiving anakinra versus placebo (median, 67 [interquartile range, 39-120] versus 214 [interquartile range, 131-394] mg·day/L; P<0.001), without significant differences between the anakinra arms. No significant differences were found between anakinra and placebo groups in the interval changes in left ventricular end-systolic volume (median, 1.4 [interquartile range, -9.8 to 9.8] versus -3.9 [interquartile range, -15.4 to 1.4] mL; P=0.21) or left ventricular ejection fraction (median, 3.9% [interquartile range, -1.6% to 10.2%] versus 2.7% [interquartile range, -1.8% to 9.3%]; P=0.61) at 12 months. The incidence of death or new-onset heart failure or of death and hospitalization for heart failure was significantly lower with anakinra versus placebo (9.4% versus 25.7% [P=0.046] and 0% versus 11.4% [P=0.011], respectively), without difference between the anakinra arms. The incidence of serious infection was not different between anakinra and placebo groups (14% versus 14%; P=0.98). Injection site reactions occurred more frequently in patients receiving anakinra (22%) versus placebo (3%; P=0.016). Conclusions In patients presenting with ST-segment-elevation myocardial infarction, interleukin-1 blockade with anakinra significantly reduces the systemic inflammatory response compared with placebo. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01950299.

Comparative cardiac toxicity of anthracyclines in vitro and in vivo in the mouse.

PURPOSE: The antineoplastic efficacy of anthracyclines is limited by their cardiac toxicity. In this study, we evaluated the toxicity of doxorubicin, non-pegylated liposomal-delivered doxorubicin, and epirubicin in HL-1 adult cardiomyocytes in culture as well as in the mouse in vivo. METHODS: The cardiomyocytes were incubated with the three anthracyclines (1 µM) to assess reactive oxygen generation, DNA damage and apoptotic cell death. CF-1 mice (10/group) received doxorubicin, epirubicin or non-pegylated liposomal-doxorubicin (10 mg/kg) and cardiac function was monitored by Doppler echocardiography to measure left ventricular ejection fraction (LVEF), heart rate (HR) and cardiac output (CO) both prior to and 10 days after drug treatment. RESULTS: In HL-1 cells, non-pegylated liposomal-doxorubicin generated significantly less reactive oxygen species (ROS), as well as less DNA damage and apoptosis activation when compared with doxorubicin and epirubicin. Cultured breast tumor cells showed similar sensitivity to the three anthracyclines. In the healthy mouse, non-pegylated liposomal doxorubicin showed a minimal and non-significant decrease in LVEF with no change in HR or CO, compared to doxorubicin and epirubicin. CONCLUSION: This study provides evidence for reduced cardiac toxicity of non-pegylated-liposomal doxorubicin characterized by attenuation of ROS generation, DNA damage and apoptosis in comparison to epirubicin and doxorubicin.

Comparison of the feasibility and effectiveness of transradial coronary angiography via right versus left radial artery approaches (from the PREVAIL Study).

It remains undefined if transradial coronary angiography from a right or left radial arterial approach differs in real-world practice. To address this issue, we performed a subanalysis of the PREVAIL study. The PREVAIL study was a prospective, multicenter, observational survey of unselected consecutive patients undergoing invasive cardiovascular procedures over a 1-month observation period, specifically aimed at assessing the outcomes of radial approach in the contemporary real world. The choice of arterial approach was left to the discretion of the operator. Prespecified end points of this subanalysis were procedural characteristics. Of 1,052 patients consecutively enrolled, 509 patients underwent transradial catheterization, 304 with a right radial and 205 with a left radial approach. Procedural success rates were similar between the 2 groups. Compared to the left radial group, the right radial group had longer procedure duration (46 ± 29 vs 33 ± 24 minutes, p <0.0001) and fluoroscopy time (765 ± 787 vs 533 ± 502, p <0.0001). At multivariate analysis, including a parsimonious propensity score for the choice of left radial approach, duration of procedure (beta coefficient 11.38, p <0.001) and total dose-area product (beta coefficient 11.38, p <0.001) were independently associated with the choice of the left radial artery approach. The operator's proficiency in right/left radial approach did not influence study results. In conclusion, right and left radial approaches are feasible and effective to perform percutaneous procedures. In the contemporary real world, however, the left radial route is associated with shorter procedures and lower radiologic exposure than the right radial approach, independently of an operator's proficiency.

Blocking interleukin-1 as a novel therapeutic strategy for secondary prevention of cardiovascular events.

The inflammatory hypothesis of atherosclerosis postulates that inflammation within the plaque promotes plaque progression and complications. Interleukin-1 (IL-1) is a key pro-inflammatory cytokine responsible for the amplification of the inflammatory response following injury. Animal studies show that IL-1 blockade is effective in limiting atherosclerosis and atherothrombosis and improving outcomes in acute myocardial infarction and ischemic stroke. Preliminary data in patients with acute myocardial infarction, ischemic stroke, and heart failure are promising. A large secondary prevention trial with canakinumab in patients with prior acute myocardial infarction is currently ongoing. Many unanswered questions remain regarding the optimal use of IL-1 blockade and the preferred agent.

Fenoldopam and acute renal failure in cardiac surgery: a meta-analysis of randomized placebo-controlled trials.

OBJECTIVE: Because at present no pharmacologic prevention or treatment of acute kidney injury seems to be available, the authors updated a meta-analysis to investigate the effects of fenoldopam in reducing acute kidney injury in patients undergoing cardiac surgery, focusing on randomized placebo-controlled studies only. DESIGN: A meta-analysis of randomized, placebo-controlled trials. SETTING: Hospitals. PARTICIPANTS: A total of 440 patients from 6 studies were included in the analysis. INTERVENTIONS: None. The ability of fenoldopam to reduce acute kidney injury in the perioperative period when compared with placebo was investigated. MEASUREMENTS AND MAIN RESULTS: Google Scholar and PubMed were searched (updated January 1, 2012). Authors and external experts were contacted. Pooled estimates showed that fenoldopam consistently and significantly reduced the risk of acute kidney injury (odds ratio [OR] = 0.41; 95% confidence interval [CI], 0.23-0.74; p = 0.003), with a higher rate of hypotensive episodes and/or use of vasopressors (30/109 [27.5%] v 21/112 [18.8%]; OR = 2.09; 95% CI, 0.98-4.47; p = 0.06) and no effect on renal replacement therapy, survival, and length of intensive care unit or hospital stay. CONCLUSIONS: This analysis suggests that fenoldopam reduces acute kidney injury in patients undergoing cardiac surgery. Because the number of the enrolled patients was small and there was no effect on renal replacement therapy or survival, a large, multicenter, and appropriately powered trial is needed to confirm these promising results.

Percutaneous renal artery intervention versus medical therapy in patients with renal artery stenosis: a meta-analysis.

AIMS: Patients with renal artery stenosis are treated with percutaneous intervention, but randomised studies are inconclusive. We aimed to compare renal percutaneous revascularisation versus medical therapy. METHODS AND RESULTS: A systematic search for randomised controlled studies yielded three studies comparing renal angioplasty and two studies comparing renal angioplasty with stenting versus medical therapy, respectively. Six sets of data were extracted focusing on systolic and diastolic blood pressure as well as serum creatinine at follow-up. The five trials included 1,030 patients with renal artery stenosis. There was a trend toward, but no significant improvement in, systolic blood pressure (weighted mean difference [WMD] -2.76 mmHg, 95% confidence interval (CI) -5.71 to 0.18; p=0.07), diastolic blood pressure, (WMD -1.18 mmHg, 95% CI -2.69 to 0.32; p=0.12), or serum creatinine (WMD -7.26 mmol/L, 95% CI -14.99 to 0.47; p=0.07) in the patients who underwent percutaneous intervention compared to the medical therapy group. All but one trial showed at least a moderate overall bias risk. CONCLUSIONS: We did not find a significant improvement in blood pressure or renal function in patients with renal artery stenosis treated with renal artery revascularisation compared to medical therapy alone. However, trial quality was a limitation.

Intra-arterial lidocaine versus saline to reduce peri-procedural discomfort in patients undergoing percutaneous trans-radial or trans-ulnar coronary procedures.

OBJECTIVE: Trans-radial and trans-ulnar access is increasingly used for percutaneous coronary procedures, but spasm or pain may limit comfort and compliance. Intra-arterial lidocaine administration could provide a local anaesthetic effect, but its risk-benefit ratio is unclear. We aimed to compare intraarterial lidocaine versus saline to reduce peri-procedural discomfort during percutaneous trans-radial or trans-ulnar procedures. METHODS AND RESULTS: Patients undergoing percutaneous trans-radial or trans-ulnar coronary procedures were single-blinded randomly assigned to intra-arterial treatment with 20 mg lidocaine or saline. The primary end-point of the study was local pain, measured on a 10-point scale. A total of 101 patients were enrolled (50 allocated to lidocaine and 51 to saline). Trans-radial access was employed in 48 (96%) and 47 (92%), respectively, trans-ulnar access in 2 (4%) and 4 (8%), and coronary intervention was performed in 18(36%) and 11 (22%). Severity of local pain was equivalent in both groups (2.3 +/- 2.3 vs. 3.0 +/- 2.5, P= 0.167). Similar results for both groups were found also for local spasm, local access success, procedural success, and net clinical adverse events (all P > 0.05). No sustained cardiac arrhythmia or neurologic symptom developed in any patient. CONCLUSIONS: Current approaches and techniques for percutaneous trans-radial or trans-ulnar coronary procedures are associated with few local or systemic complications. Local forearm/wrist pain is relatively frequent in this setting, and is not significantly prevented by intra-arterial lidocaine.

Real-world outcome of coronary bifurcation lesions in the drug-eluting stent era: results from the 4,314-patient Italian Society of Invasive Cardiology (SICI-GISE) Italian Multicenter Registry on Bifurcations (I-BIGIS).

BACKGROUND: Drug-eluting stents (DESs) introduction has somewhat renewed the issues of strategy and stenting technique for treatment of bifurcation lesions. In particular, concerns remain on extensive use of DESs, especially in the side branch, and on time of dual antiplatelet therapy (DAT) discontinuation, reflecting lack of pertinent long-term data. This study aimed to evaluate clinical safety and efficacy of different strategies for bifurcations treatment in a large observational real-world registry. METHODS: A multicenter, retrospective Italian study of consecutive patients undergoing bifurcation percutaneous coronary intervention between January 2002 and December 2006 was performed. The primary end point was the long-term rate of major adverse cardiac events (MACEs). The role of DAT length on outcome was also analyzed. RESULTS: A total of 4,314 patients (4,487 lesions) were enrolled at 22 independent centers. In-hospital procedural success rate was 98.7%. After median follow-up of 24 months, MACEs occurred in 17.7%, with cardiac death in 3.4%, myocardial infarction in 4.0%, target lesion revascularization in 13.2%, and stent thrombosis in 2.9%. Extensive multivariable analysis showed that MACEs were independently predicted by age, diabetes, renal failure, systolic dysfunction, multivessel disease, myocardial infarction at admission, restenotic lesion, bare-metal stent implantation, complex stenting strategy, and short duration of DAT. CONCLUSIONS: This large study based on current clinical practice in an unselected patient population presenting with bifurcation disease and submitted to percutaneous coronary intervention demonstrated favorable long-term clinical results in this challenging patient setting, especially when DESs, simple stenting strategy, and DAT for at least 6 months are used.

Thrombus aspiration in ST elevation myocardial infarction: comparative efficacy in patients treated early and late after onset of symptoms.

BACKGROUND: Restoration of myocardial perfusion is the goal of percutaneous coronary intervention (PCI) in patients with ST elevation myocardial infarction. A major predictor of no-reflow is the increasing time to treatment (TTT). Thrombus aspiration (TA) is reported to improve myocardial reperfusion as compared with standard PCI (SP). OBJECTIVE: To investigate the influence of TTT on TA efficacy. DESIGN: Pooled analysis of individual patients' data of three prospective randomised trials comparing TA and SP. PATIENTS: A total of 299 patients (150 in TA group and 149 in SP group) entered the study. The study population was divided into three subgroups according to the TTT: < or = 3 h (short TTT subgroup), >3 h to < or = 6 h (intermediate TTT subgroup), >6 h to < or = 12 h (long TTT subgroup). MAIN OUTCOME MEASURES: The goal of the study was the comparison of optimal myocardial reperfusion, defined as the combination of myocardial blush grade 2 or 3 at post-PCI angiography and ST resolution more than 70% at post-PCI ECG, between SP and TA according to TTT. RESULTS: In the SP group, increasing TTT was associated with a decreased rate of optimal reperfusion (27.4% vs 17.9% vs 10%, p for trend=0.06), whereas in the TA group the same trend was not seen (40.9% vs 33.8% vs 50%, p for trend=0.93). In a multivariate logistic regression model, a significant interaction (p=0.04) between time to treatment and thrombus aspiration was observed. CONCLUSIONS: TA limits the adverse effects of TTT prolongation on myocardial reperfusion.

Interleukin-1 blockade with anakinra to prevent adverse cardiac remodeling after acute myocardial infarction (Virginia Commonwealth University Anakinra Remodeling Trial [VCU-ART] Pilot study).

Acute myocardial infarction (AMI) initiates an intense inflammatory response in which interleukin-1 (IL-1) plays a central role. The IL-1 receptor antagonist is a naturally occurring antagonist, and anakinra is the recombinant form used to treat inflammatory diseases. The aim of the present pilot study was to test the safety and effects of IL-1 blockade with anakinra on left ventricular (LV) remodeling after AMI. Ten patients with ST-segment elevation AMI were randomized to either anakinra 100 mg/day subcutaneously for 14 days or placebo in a double-blind fashion. Two cardiac magnetic resonance (CMR) imaging and echocardiographic studies were performed during a 10- to 14-week period. The primary end point was the difference in the interval change in the LV end-systolic volume index (LVESVi) between the 2 groups on CMR imaging. The secondary end points included differences in the interval changes in the LV end-diastolic volume index, and C-reactive protein levels. A +2.0 ml/m(2) median increase (interquartile range +1.0, +11.5) in the LVESVi on CMR imaging was seen in the placebo group and a -3.2 ml/m(2) median decrease (interquartile range -4.5, -1.6) was seen in the anakinra group (p = 0.033). The median difference was 5.2 ml/m(2). On echocardiography, the median difference in the LVESVi change was 13.4 ml/m(2) (p = 0.006). Similar differences were observed in the LV end-diastolic volume index on CMR imaging (7.6 ml/m(2), p = 0.033) and echocardiography (9.4 ml/m(2), p = 0.008). The change in C-reactive protein levels between admission and 72 hours after admission correlated with the change in the LVESVi (R = +0.71, p = 0.022). In conclusion, in the present pilot study of patients with ST-segment elevation AMI, IL-1 blockade with anakinra was safe and favorably affected by LV remodeling. If confirmed in larger trials, IL-1 blockade might represent a novel therapeutic strategy to prevent heart failure after AMI.

Systematic review and meta-analysis of currently available clinical evidence on migraine and patent foramen ovale percutaneous closure: much ado about nothing?

OBJECTIVES: To investigate the role of transcatheter closure of patent foramen ovale on the occurrence of migraine. BACKGROUND: In recent years, a potential relationship between, migraine, stroke, and patent foramen ovale (PFO) has emerged. METHODS: BioMedCentral, Google Scholar, and PubMed from January 2000 to December 2008 were systematically searched for pertinent clinical studies. Secondary sources were also used. Secondary prevention studies of transcatheter closure for patent foramen ovale were required to include at least more than 10 patients followed for more than 6 months. The primary end-point was the rate of cured or significantly improved migraine after percutaneous PFO closure. RESULTS: After excluding 637 citations, we finally included a total of 11 studies for a total of 1,306 patients. Forty percent of the subjects included suffered from migraine, while most had a previous history of transient ischemic attack/stroke and were investigated retrospectively. Quantitative synthesis showed that complete cure of migraine in 46% (95% C.I.25-67%), while resolution or significant improvement of migraine occurred in 83% (95% C.I. 78-88%) of cases. CONCLUSIONS: Notwithstanding the limitations inherent in the primary studies, this systematic review suggests that a significant group of subjects with migraine, in particular if treated after a neurological event, may benefit from percutaneous closure of their patent foramen ovale. However, many questions remain unsolved.

Impact of routine angiographic follow-up after percutaneous coronary drug-eluting stenting for unprotected left main disease: the Turin Registry.

BACKGROUND: Most cardiologists performing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) for unprotected left main disease (ULM) mandate mid-term angiographic follow-up, yet there are few data supporting this approach. We aimed to retrospectively compare the outcome of patients with ULM treated with DES according to their follow-up management strategy. METHODS: Patients with ULM stenosis undergoing PCI with DES and surviving up to 6 months were retrospectively identified from our ongoing database. We distinguished those undergoing clinical follow-up only, those with clinically driven angiographic follow-up, and those with routine angiographic follow-up. The primary end-point was the long-term rate of major adverse cardiac events (MACE, i.e., death, myocardial infarction, bypass surgery, or repeat ULM PCI). RESULTS: A total of 198 patients were included: 55 (28%) in the clinical follow-up group, 64 (32%) in the clinically driven angiographic follow-up group, and 79 (40%) in the routine angiographic follow-up group. After 37.0 +/- 15.7 months, mortality was similar in the 3 groups (respectively 7.3, 4.7, and 5.9%, p = 0.27). However, MACE were significantly more common in the clinically driven angiographic follow-up group (42.2 vs. 7.3 and 26.1%, p = 0.02), mainly due to the expected increase in repeat revascularization in those undergoing angiographic follow-up (23.4 vs. 1.8 and 13.14%). Notably, there were no differences in the rate of stent thrombosis across the three groups, with rates of 3.1 vs. 1.8 and 2.5% (p = 0.35). CONCLUSIONS: An expectant management can be safely adopted in most patients with ULM treated percutaneously, as long as a low threshold for control coronary angiography is maintained.

Epidural analgesia improves outcome in cardiac surgery: a meta-analysis of randomized controlled trials.

OBJECTIVE: The authors conducted a review of randomized studies to determine whether there were any advantages for clinically relevant outcomes by adding epidural analgesia in patients undergoing cardiac surgery under general anesthesia. DESIGN: Meta-analysis. SETTING: Hospitals. PARTICIPANTS: A total of 2366 patients from 33 randomized trials. INTERVENTIONS: None. DATA SOURCES AND STUDY SELECTION: PubMed, BioMedCentral, CENTRAL, EMBASE, Cochrane Central Register of Controlled Trials, and conference proceedings were searched (updated January 2008) for randomized trials that compared general anesthesia with an anesthetic plan including general anesthesia and epidural analgesia in cardiac surgery. Two independent reviewers appraised study quality, with divergences resolved by consensus. Overall analysis showed that epidural analgesia reduced the risk of the composite endpoint mortality and myocardial infarction (30/1125 [2.7%] in the epidural group v 64/1241 [5.2%] in the control arm, odds ratio [OR] = 0.61 [0.40-0.95], p = 0.03 number needed to treat [NNT] = 40), the risk of acute renal failure (35/590 [5.9%] in the epidural group v 54/618 [8.7%] in the control arm, OR = 0.56 [0.34-0.93], p = 0.02, NNT = 36), and the time of mechanical ventilation (weighted mean differences = -2.48 hours [-2.64, -2.32], p < 0.001). CONCLUSIONS: This analysis suggested that epidural analgesia on top of general anesthesia reduced the incidence of perioperative acute renal failure, the time on mechanical ventilation, and the composite endpoint of mortality and myocardial infarction in patients undergoing cardiac surgery.

Meta-analysis of randomized controlled trials of statins versus placebo in patients with heart failure.

Although statins have been shown to improve outcomes in retrospective analyses of patients with heart failure (HF), recent randomized placebo-controlled trials have shown mixed results. The goal of this study was to systematically review randomized trials comparing statins to placebo for HF and compare the impact of different statins. CENTRAL, mRCT, and PubMed were searched for eligible studies that prospectively randomized patients with HF to statins or placebo. Primary end points were all-cause mortality, cardiovascular mortality, hospitalization for worsening HF, adverse drug events, and changes in left ventricular ejection fraction (LVEF). Pooling was performed with random effect methods with summary effect estimates (95% confidence intervals). Ten studies (10,192 patients) with follow-up from 3 to 47 months were included. Three trials randomized patients to rosuvastatin, 1 to simvastatin, and 6 to atorvastatin. Overall, statins did not affect all-cause or cardiovascular mortality but did significantly decrease hospitalization for worsening HF during follow-up (odds ratio [OR] 0.67, p = 0.008). Patients randomized to statins had a significant 4.2% increase in LVEF at follow-up (95% confidence interval 1.3 to 7.1, p = 0.004). Furthermore, post hoc analyses showed heterogeneity among different statins and demonstrated that randomization to atorvastatin significantly decreased all-cause mortality (OR 0.39, p = 0.004), decreased hospitalization for worsening HF (OR 0.30, p <0.000 01), and randomization to atorvastatin and simvastatin led to a significant improvement in LVEF, whereas these benefits were not observed in patients randomized to rosuvastatin. In conclusion, meta-analysis of randomized controlled trials demonstrated that statins are safe and improve LVEF and decrease hospitalization for worsening HF.

Hemoglobin levels predict exercise performance, ST-segment depression, and outcome in patients referred for routine exercise treadmill testing.

BACKGROUND: While the role of hemoglobin in heart failure and renal disease has been investigated, little is known about its effect on clinical exercise test performance and mortality in patients referred for routine exercise treadmill testing (ETT). HYPOTHESIS: Patients with low hemoglobin will have poor exercise capacity and would be at increased risk of mortality and cardiovascular (CV) events. METHODS: Clinical variables, laboratory values, and exercise treadmill data were obtained for 1,799 patients referred for routine ETT from 1997 to 2004. All-cause mortality was obtained from the United States Social Security death index and autopsy reports or clinical notes were used to determine CV events and mortality. P values < 0.05 were considered significant. RESULTS: Our population had a mean age of 58 +/- 12 years, 16% had diabetes, 53% had hypertension, 35% had hypercholesterolemia, and 67% had a history of smoking. During follow-up, 10.3% of patients died, 3.9% of patients died of CV causes, and 11.6% had cardiovascular events. Anemic patients (hemoglobin [Hgb] < 13 g/dL) achieved lower metabolic equivalents (METs) than nonanemic patients and had more ST-segment depression (15.5% versus 8.6%, p < 0.004). Proportional hazard analysis demonstrated that hemoglobin was significantly associated with all-cause mortality (p < 0.0007), CV mortality (p < 0.009), and CV events (p < 0.01). Kaplan-Meier survival analysis demonstrated that anemic patients had significantly higher mortality and CV events. CONCLUSION: Hemoglobin is significantly associated with exercise performance, ST-segment depression during ETT, mortality, and cardiovascular events. The incorporation of hemoglobin may add diagnostic and prognostic information to ETT.