Anemia is a well-known predictor of a poor outcome in patients with ST-segment elevation myocardial infarction (STEMI). In contrast, data relating erythrocytosis to clinical outcomes in patients with STEMI are limited. Because erythrocytosis predisposes to a prothrombotic state, we hypothesized it would be associated with an increased risk of thrombotic complications in patients with STEMI undergoing primary percutaneous coronary intervention. We studied 1,042 consecutive patients with STEMI who underwent primary percutaneous coronary intervention and were a part of our primary percutaneous coronary intervention registry from 2001 to 2007. Patients with cardiogenic shock and late arrival were excluded. Patients were allocated into 3 groups according to their baseline hematocrit: anemia (<36% for women and <39% for men), normal, erythrocytosis (>46% for women and >47% for men). The clinical outcomes were assessed at 1, 6, and 12 months. The patients with anemia had the greatest clinical risk profile. Patients with erythrocytosis had a lower risk profile than the other 2 groups, except for greater rates of smoking. The mortality rates were greatest among the patients with anemia, followed by the patients with erythrocytosis, who in turn had greater short-term mortality than patients with normal hematocrit. Multivariate analysis, which included patients with erythrocytosis and those with normal hematocrit (excluding the patients with anemia), revealed that erythrocytosis was associated with an odds ratio of 4.3 (95% confidence interval 1.4 to 13, p = 0.01) for 1-month mortality. In conclusion, although not as strong a predictor of mortality as anemia, erythrocytosis might be associated with increased short-term mortality compared to a normal hematocrit. The measurement of hematocrit can be used as a useful prognostic marker in patients with STEMI.
In contrast to anemia, which has been clearly related to poor outcomes in various cardiac conditions, the data regarding erythrocytosis and the clinical outcomes of patients with ST-segment elevation myocardial infarction (STEMI) are limited. Sabatine et al reported that in patients with acute coronary syndromes (ACS) both high and low hemoglobin levels were associated with increased rates of mortality (for STEMI, hemoglobin levels >17 g/dl or <14 g/dl; and for non-STEMI, hemoglobin levels >16 g/dl or <11 g/dl). However, the present study consisted of patients with ACS from 16 Thrombolysis in Myocardial Infarction (TIMI) trials. The STEMI cohort included patients treated mainly with various thrombolytic drugs rather than primary percutaneous coronary intervention (PCI). Thus, data regarding patients with STEMI and relatively high hemoglobin levels, who were treated with contemporary primary PCI are lacking. Erythrocytosis and polycythemia have been associated with adverse outcomes in various populations. High hematocrit values have been related to an increased risk of development of atherosclerosis and cardiovascular disease. In addition, high hemoglobin levels were shown to increase blood viscosity, which, in turn, can cause increased coronary vascular resistance, decreased coronary blood flow, and a predisposition to thrombosis. We, therefore, hypothesized that patients with STEMI and erythrocytosis on admission, who were treated with primary PCI, would be prone to a greater risk of thrombotic complications. Accordingly, we investigated the clinical outcome of patients with STEMI and erythrocytosis on admission who underwent primary PCI.
Methods
From January 2001 to December 2007, 1,165 consecutive patients with chest pain and STEMI who underwent emergency PCI at the Rabin Medical Center, Tel Aviv, Israel, were prospectively observed and their data entered into a clinical database. Acute STEMI was defined as the presence of typical chest pain and accompanying symptoms for ≥30 minutes but <12 hours in the presence of ST-segment elevation of ≥1 mm in ≥2 contiguous leads or new or undetermined duration of left branch bundle block in association with a ≥2 times increase in cardiac enzymes (troponin I or T). The data included demographic, clinical, angiographic, and procedural data. The ethics committee of the Rabin Medical Center approved this registry. The patients were excluded from the present analysis if they presented with cardiogenic shock or arrived >12 hours after the beginning of chest pain. A total of 1,042 patients were included in the present study. They were allocated into 3 groups according to their baseline hematocrit level at admission: (1) anemia, hematocrit <36% for women and <39% for men (n = 208); (2) normal, hematocrit 36% to 46% for women and 39% to 47% for men (n = 718); and (3) erythrocytosis, hematocrit >46% for women and >47% for men (n = 116).
All patients were treated with aspirin 325 mg before PCI and clopidogrel 300 to 600 mg either before PCI or immediately after PCI. Unfractionated heparin (70 U/kg loading) was given before PCI and adjusted to achieve an activated clotting time of 200 to 250 seconds during the procedure. Glycoprotein IIb/IIIa inhibitors were used at the discretion of the operator. Coronary angiography was performed through the femoral route. The selection of stent type, predilation with undersized balloons, and postdilation with larger balloons were also left to the operator’s discretion. All stents were implanted using a moderate to high deployment pressure (12 to 16 atm). All patients were prescribed lifelong aspirin and clopidogrel (75 mg/day) for 3 to 12 months, depending on the stent type. The baseline clinical characteristics, angiographic details, and clinical outcomes were collected.
Coronary angiograms were recorded at baseline and after PCI. They were analyzed by experienced cardiologists at our angiography core laboratory using the MDView QA System (Medcon Telemedicine Technology, Tel-Aviv, Israel). The cardiologists were unaware of the group allocation of the patients. Analysis was performed using automated edge-detection techniques. The contrast-filled guiding catheter (6F or 7F) was used for calibration. Standard morphologic criteria were used to identify the lesion location, lumen diameter, presence of thrombus, Thrombolysis in Myocardial Infarction flow grade, and no reflow. On the basis of these measurements, the percentage of diameter stenosis was determined before and after PCI.
The immediate and in-hospital events were recorded from the hospital charts. For each patient, a standardized questionnaire was completed either by telephone or in the outpatient clinic at the 1-, 6-, and 12-month follow-up visits. Mortality was confirmed from the records of the Interior Ministry of Israel. Repeated revascularization procedures and episodes of reinfarction were confirmed using the hospital and affiliated hospital databases. These databases were searched for all patients in the study to gather information regarding repeated events. The follow-up data were complete for 100% of the patients at 1 month. At 12 months, mortality data were available for 100% of the patients, and revascularization and reinfarction data were available for 94% of the patients. Procedural success was defined as angiographic residual stenosis of <20% by visual estimate or quantitative coronary angiography. The diagnosis of reinfarction was determined from recurrent chest pain suggestive of acute myocardial infarction accompanied by repeated increases in cardiac enzymes to ≥2 times the upper limit of normal ≥48 hours after PCI and/or new ST elevation or pathologic Q waves. Target vessel revascularization was defined as any revascularization that involved the target vessel. Stent thrombosis was defined according to the Academic Research Consortium definitions as definite in the context of ACS and/or reinfarction in the culprit coronary territory with angiographically proven thrombosis (thrombus or occlusion) of the previously implanted stent. Major adverse cardiac events at 12 months included cardiac death, nonfatal myocardial infarction, or target vessel revascularization (without repetition). All events were further adjudicated by an experienced cardiologist from our research team.
Continuous variables are presented as the mean ± SD, and categorical variables, as frequencies (percentages). Comparisons were performed among the 3 study groups and separately between the erythrocytosis and normal groups. Continuous variables were compared using unpaired Student’s t tests. Categorical variables were compared using chi-square statistics or Fischer’s exact test, as appropriate. Multivariate logistic regression analysis was performed to determine the significance of variables related to 1-month mortality among all 3 groups and, separately, among patients with erythrocytosis and a normal hematocrit (excluding patients with anemia). The model included all clinical variables with p <0.1 on univariate analysis. Analyses were performed using Statisca software (StatSoft, Tulsa, Oklahoma), and p <0.05 was considered significant.
Results
A total of 1,042 patients with STEMI, who were treated with primary PCI, were included in the present study. According to their baseline (admission) hematocrit values, 208 (20%) had anemia, 116 (11%) had erythrocytosis, and 718 (69%) had normal hematocrit values. The baseline clinical characteristics are presented in Table 1 . Patients with anemia had the greatest risk profile—they were older; were more likely to be women; were more likely to have diabetes, renal insufficiency, hypertension, peripheral vascular disease, and previous stroke; and were more likely to present with Killip class >1 and a high Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) score. Overall, the patients with erythrocytosis had a lower risk profile than those in the other 2 groups. When compared with the “normal” group, patients with erythrocytosis were younger and less likely to be women or to have diabetes, hypertension (trend), or previous stroke. The only exception was a greater rate of current smokers among patients with erythrocytosis compared to the other 2 groups. Previous medical treatment and the intervals from the onset of chest pain to arrival at the emergency department and performance of PCI were similar among the 3 groups ( Table 2 ). The angiographic and procedural characteristics were also similar among the 3 groups ( Table 3 ), apart for a lower rate of glycoprotein IIb/IIIa inhibitor use among patients with anemia and a greater likelihood of multivessel disease among patients with erythrocytosis than in patients with a normal hematocrit.
| Variable | Hematocrit <39% or <36% (n = 208) | Normal (n = 718) | Hematocrit >47% (n = 116) | p Value | |
|---|---|---|---|---|---|
| 3 Group Comparison | Normal vs Hematocrit >47% | ||||
| Age (years) | 66 ± 13 | 60 ± 12 | 55 ± 12 | 0.0001 | 0.001 |
| Women | 53 (26%) | 133 (19%) | 4 (3.5%) | 0.0001 | <0.0001 |
| Diabetes mellitus | 69 (33%) | 179 (25%) | 19 (16%) | 0.001 | 0.04 |
| Renal insufficiency ⁎ | 58 (28%) | 72 (10%) | 11 (9.5%) | 0.001 | 0.9 |
| Hypertension | 124 (60%) | 302 (42%) | 39 (34%) | 0.0001 | 0.08 |
| Current smoker | 58 (28%) | 337 (47%) | 72 (62%) | 0.0001 | 0.002 |
| Previous myocardial infarction | 24 (12%) | 86 (12%) | 12 (10.5%) | 0.9 | 0.6 |
| Previous coronary intervention | 33 (16%) | 93 (13%) | 9 (8%) | 0.1 | 0.1 |
| Previous coronary bypass grafting | 8 (3.9%) | 14 (2.0%) | 4 (3.5%) | 0.2 | 0.3 |
| Previous peripheral vascular disease | 16 (7.8%) | 27 (3.8%) | 7 (6.1%) | 0.05 | 0.25 |
| Previous stroke | 20 (9.8%) | 29 (4.0%) | 0 | 0.0001 | 0.03 |
| Ejection fraction <40% | 85 (41%) | 302 (42%) | 55 (47%) | 0.6 | 0.3 |
| Anterior wall myocardial infarction | 94 (45%) | 337 (47%) | 62 (53%) | 0.6 | 0.2 |
| Hemoglobin (g/dl) | 11.5 ± 1.0 | 14.1 ± 0.9 | 16.3 ± 0.7 | 0.0001 | 0.001 |
| White blood cell count (1,000/μl) | 11.2 ± 4.0 | 12.2 ± 4.1 | 14.5 ± 10.0 | 0.0001 | 0.005 |
| Platelet count (1,000/μl) | 270 ± 104 | 258 ± 67 | 260 ± 71 | 0.2 | 0.6 |
| Peak creatine kinase (×10 3 U/L) | 1.8 ± 1.8 | 2.0 ± 1.9 | 2.5 ± 2.4 | 0.009 | 0.03 |
| Killip class >1 | 42 (20%) | 93 (13%) | 20 (17%) | 0.03 | 0.2 |
| CADILLAC score | 6.9 ± 3.8 | 3.6 ± 3.2 | 3.6 ± 3.3 | 0.001 | 0.9 |
| Variable | Hematocrit <39% or <36% (n = 208) | Normal (n = 718) | Hematocrit >47% (n = 116) | p Value |
|---|---|---|---|---|
| Medications | ||||
| Aspirin | 185 (89%) | 668 (93%) | 110 (95%) | 0.1 |
| Clopidogrel pretreatment | 87 (42%) | 337 (47%) | 52 (45%) | 0.6 |
| β Blockers | 23 (11%) | 101 (14%) | 14 (12%) | 0.6 |
| Angiotensin-converting enzyme inhibitors/Angiotensin receptor blockers | 21 (10%) | 79 (11%) | 6 (5.6%) | 0.2 |
| Statins | 83 (40%) | 237 (33%) | 39 (29%) | 0.2 |
| Intervals | ||||
| Symptom onset to emergency department (hours) | 2.2 ± 2.5 | 2 ± 2.4 | 2 ± 2.5 | 0.5 |
| Emergency department to coronary intervention (hours) | 1.4 ± 1.5 | 1.2 ± 1.5 | 1.4 ± 1.4 | 0.6 |
| Variable | Hematocrit <39% or <36% (n = 208) | Normal (n = 718) | Hematocrit >47% (n = 116) | p Value | |
|---|---|---|---|---|---|
| 3 Group Comparison | Normal vs Hematocrit >47% | ||||
| Culprit artery | |||||
| Left anterior descending | 90 (43%) | 323 (45%) | 62 (53%) | 0.2 | 0.1 |
| Left circumflex | 23 (11%) | 100 (14%) | 21 (18%) | 0.2 | 0.25 |
| Right coronary | 87 (42%) | 259 (36%) | 30 (26%) | 0.2 | 0.1 |
| Multivessel disease | 135 (65%) | 388 (54%) | 74 (64%) | 0.25 | 0.05 |
| Preintervention Thrombolysis in Myocardial Infarction flow 0-1 | 139 (67%) | 452 (63%) | 73 (63%) | 0.7 | 1 |
| Postintervention Thrombolysis in Myocardial Infarction flow 3 | 195 (94%) | 689 (96%) | 108 (93%) | 0.6 | 0.2 |
| Preintervention culprit stenosis | 96 ± 9% | 96 ± 7% | 96 ± 7% | 0.8 | 1 |
| Postintervention culprit stenosis | 4 ± 4% | 4 ± 3% | 5 ± 4% | 0.5 | 0.4 |
| Preintervention reference diameter (mm) | 3.1 ± 0.5 | 3.1 ± 0.5 | 3.1 ± 0.6 | 0.8 | 0.9 |
| Postprocedure minimal lumen diameter (mm) | 3 ± 0.7 | 3.1 ± 0.6 | 3.1 ± 0.8 | 0.3 | 0.9 |
| No reflow | 14 (6.5%) | 42 (5.8%) | 6 (5.4%) | 0.9 | 0.8 |
| Glycoprotein IIb/IIIa inhibitors | 131 (63%) | 574 (80%) | 96 (83%) | 0.0001 | 0.5 |
| Visible thrombus | 177 (85%) | 610 (85%) | 100 (86%) | 0.9 | 0.7 |
| Thrombectomy devices | 19 (9.3%) | 40 (5.6%) | 4 (3.5%) | 0.2 | 0.3 |
| Drug-eluting stents | 27 (13%) | 122 (17%) | 21 (18%) | 0.5 | 0.8 |
| Mean stent width (mm) | 3.1 ± 0.4 | 3.1 ± 0.5 | 3.2 ± 0.4 | 0.2 | 0.5 |
| Procedural success | 195 (94%) | 689 (96%) | 111 (93%) | 0.5 | 0.9 |
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