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Intern Med. 2024 Apr 15; 63(8): 1043–1051.
Published online 2023 Sep 1. doi:10.2169/internalmedicine.2320-23
PMCID: PMC11081902
PMID: 37661448
Soichiro Ban,1 Kenichi Sakakura,1 Hiroyuki Jinnouchi,1 Yousuke Taniguchi,1 Takunori Tsukui,1 Masashi Hatori,1 Yusuke Watanabe,1 Kei Yamamoto,1 Masaru Seguchi,1 Hiroshi Wada,1 and Hideo Fujita1
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Associated Data
- Supplementary Materials
Abstract
Objective
Patients with acute myocardial infarction (AMI) often have peripheral artery disease (PAD). It is well known that the long-term clinical outcomes of AMI are worse in patients with a low ankle-brachial index (ABI) than in patients with a preserved ABI. Unlike ABI, the association between the inter-arm blood pressure difference (IABPD) and clinical outcomes in patients with AMI has not yet been established. This retrospective study examined whether or not the IABPD is associated with long-term clinical outcomes in patients with AMI.
Methods
We included 979 patients with AMI and divided them into a high-IABPD group (IABPD ≥10 mmHg, n=31) and a low-IABPD group (IABPD ＜10 mmHg, n=948) according to the IABPD measured during hospitalization for AMI. The primary endpoint was the all-cause mortality rate.
Results
During a median follow-up duration of 694 days (Q1, 296 days; Q3, 1,281 days), 82 all-cause deaths were observed. Kaplan-Meier curves showed that all-cause death was more frequently observed in the high-IABPD group than in the low-IABPD group (p＜0.001). A multivariate Cox hazard analysis revealed that a high IABPD was significantly associated with all-cause death (hazard ratio 2.061, 95% confidence interval 1.012-4.197, p=0.046) after controlling for multiple confounding factors.
Conclusion
A high IABPD was significantly associated with long-term all-cause mortality in patients with AMI. Our results suggest the usefulness of the IABPD as a prognostic marker for patients with AMI.
Keywords: acute myocardial infarction, inter arm blood pressure difference, clinical outcomes, all-cause death, ankle brachial index
Introduction
Acute myocardial infarction (AMI) is the leading cause of death worldwide and the most important cause of sudden cardiac death (1). In recent decades, significant reductions in morbidity and mortality have been achieved because of improvements in medical therapies and invasive strategies (2-4). However, the long-term mortality of AMI remains high (5), which suggests room for improvement in the management of patients after AMI. A possible explanation for the high long-term mortality is that we may not recognize potential high-risk groups among patients with AMI. Therefore, it is important to identify high-risk features in patients with AMI that have not yet been fully understood.
Patients with AMI often have several atherosclerotic diseases, such as peripheral artery disease (PAD). Several studies have shown that the long-term clinical outcomes of AMI are worse in patients with PAD than in those without PAD (6-9). However, these studies mainly focused on lower-extremity artery diseases; few reports have discussed upper extremity artery disease in patients with AMI.
Simultaneous blood pressure measurements of the four extremities are frequently performed to screen for PAD. The ankle brachial index (ABI) is widely recommended for the detection of lower-extremity arterial diseases (10). However, the inter-arm blood pressure difference (IABPD) may be under-recognized in clinical practice. Unlike the ABI, an association between the IABPD and clinical outcomes in patients with AMI has not yet been established.
This retrospective study examined whether or not the IABPD is associated with long-term clinical outcomes in patients with AMI.
Materials and Methods
Study design
We reviewed all AMI cases treated at our institution (Saitama Medical Center, Jichi Medical University) between January 2015 and December 2020. Patients with AMI were included, and the exclusion criteria were as follows: 1) patients without complete ABI measurement during hospitalization; 2) patients without any follow-up data after the discharge of the index admission; 3) second or more than second AMI during the study period, when a patient experienced two or more AMI incidents during the study period; 4) patients who underwent CABG during the hospitalization; and 5) patients who did not undergo percutaneous coronary intervention (PCI).
We adopted a systolic IABPD of ≥10 mmHg as the cut-off value for a high IABPD according to the definitions of earlier studies (11-14). The final study population was divided into a low-IABPD group (IABPD ＜10 mmHg) and a high-IABPD group (IABPD ≥10 mmHg).
The primary endpoint was all-cause mortality rate. Information regarding all-cause death was acquired from the hospital records. Cardiac death was defined as death from cardiac causes, including fatal arrhythmias, myocardial infarction, heart failure, or unexplained sudden death. The day of index hospital discharge was defined as the index day (day 1). The study patients were followed up until all-cause death or until the end of the study (February 28, 2022).
This study was approved by the institutional review board of Saitama Medical Center, Jichi Medical University (S22-074), and written informed consent was waived because of the retrospective study design. Data collection and storage were performed anonymously according to the guidelines of the Japan Ministry of Health, Labour, and Welfare.
Definitions
AMI was defined according to a universal definition (15,16). Diagnostic ST elevation was defined as new ST elevation at the J point in at least 2 contiguous leads of 2 mm (0.2 mV), and patients with ST elevation were diagnosed with ST-segment elevation myocardial infarction (STEMI) (17). The definitions of hypertension, diabetes mellitus, and dyslipidemia have been described elsewhere (18-21). Laboratory data were obtained upon admission.
Since we could not measure some laboratory data, such as HbA1c or low-density lipoprotein (LDL)-cholesterol levels, during off-hours (night or holidays), we substituted the earliest HbA1c or LDL-cholesterol level from admission for the laboratory data at admission (19). The left ventricular ejection fraction (LVEF) was measured using transthoracic echocardiography during the index hospitalization and calculated using either the modified Simpson's method, Teichholz method, or eyeball estimation. The Teichholz method was adopted only when the modified Simpson's method was not available (22). An eyeball estimation was adopted only when neither the modified Simpson's method nor the Teichholz method was available (22). We also calculated the estimated glomerular filtration rate (eGFR) using the serum creatinine (Cr) level, age, weight, and sex according to the following formula: eGFR=194×Cr−1.094×age−0.287 (men), or 194×Cr−1.094×age−0.287×0.739 (women) (23). The initial and final thrombolysis in myocardial infarction (TIMI) flow grades were recorded using coronary angiography (24). We screened for moderate-to-severe Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) bleeding events during index admission (25).
Statistical analyses
Data are expressed as the mean±standard deviation (SD) or percentages. Categorical variables are presented as numbers (percentages) and were compared using Fisher's exact test. For continuous variables, the Shapiro-Wilk test was performed to determine whether or not the continuous variables were normally distributed. Normally distributed continuous variables were compared using Student's t-test. Otherwise, continuous variables were compared using the Mann-Whitney U-test. Event-free survival curves were constructed using the Kaplan-Meier method, and statistical differences between curves were assessed using the log-rank test.
We also performed a multivariate stepwise Cox hazard analysis to investigate the association between the IABPD and all-cause mortality after controlling for confounding factors. In this model, all-cause mortality was adopted as the dependent variable. Variables that were marginally different (p＜0.1) between the high- and low-IABPD groups were included as independent variables in the initial model. Variables with missing values were excluded from this model. The final independent variables were selected by likelihood ratio statistical criteria, using the backward elimination method. Variables with missing values were excluded from this model. Furthermore, similar variables were not simultaneously entered into the model to avoid multicollinearity. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated.
Statistical significance was set at p＜0.05. All analyses were performed using the SPSS 25 software program for Windows (SPSS, Chicago, USA).
Results
From January 2015 to December 2020, 1,679 cases with AMI were admitted to our medical center. After excluding 700 cases who met the exclusion criteria, the final study population consisted of 979 patients with AMI, who were divided into the high-IABPD group (n=31) and the low-IABPD group (n=948) (Fig. 1).
Figure 1.
Study flow chart. AMI: acute myocardial infarction, ABI: ankle brachial index, CABG: coronary artery bypass surgery, IABPD: inter-arm blood pressure difference
A comparison of the patient characteristics between the two groups is shown in Table 1. The ABI was significantly higher in the low-IABPD group than in the high-IABPD group, as were the eGFR, hemoglobin levels, and proportion of STEMI cases. Table 2 shows a comparison of the angiographic and procedural findings between the two groups. The final PCI procedure was significantly different between the two groups, and catheter size tended to be smaller in the low-IABPD group than in the high-IABPD group.
Table 1.
Comparison of Clinical Characteristics between the High IABPD Group and the Low IABPD Group.
| All (n=979) | Low IABPD (n=948) | High IABPD (n=31) | p value | |
|---|---|---|---|---|
| Age, years | 70.0 (61.0-78.0) | 70.0 (60.0-78.0) | 73.0 (67.0-81.0) | 0.064 |
| Male, n (%) | 772 (78.9) | 752 (76.8) | 20 (64.5) | 0.070 |
| BMI, (kg/m2) | 23.9 (21.8-26.2) | 23.9 (21.9-26.2) | 23.6 (21.6-27.6) | 0.812 |
| Ankle-brachial index | 1.10 (1.01-1.17) | 1.10 (1.02-1.18) | 0.96 (0.84-1.03) | <0.001 |
| IABPD, mmHg | 2.0 (1.0-4.0) | 2.0 (1.0-4.0) | 14.0 (11.0-22.0) | <0.001 |
| Comorbidities | ||||
| Hypertension, n (%) | 807 (82.4) | 780 (82.3) | 27 (87.1) | 0.634 |
| Hyperlipidemia, n (%) | 590 (60.3) | 568 (59.9) | 22 (71.0) | 0.265 |
| Diabetes mellitus, n (%) | 420 (42.9) | 404 (42.6) | 16 (51.6) | 0.359 |
| Atrial fibrillation, n (%) | 139 (14.2) | 131 (13.8) | 8 (25.8) | 0.068 |
| Chronic renal failure on peritoneal dial, n (%) | 7 (0.7) | 7 (0.7) | 0 (0) | 1.000 |
| Current smoker, n (%) | 342 (35.1) (n=974) | 333 (35.3) (n=944) | 9 (2.6) (n=30) | 0.698 |
| History of previous PCI, n (%) | 163 (16.6) | 156 (16.5) | 7 (22.6) | 0.334 |
| History of previous CABG, n (%) | 27 (2.8) | 26 (2.7) | 1 (3.2) | 0.586 |
| History of previous myocardial infarction, n (%) | 111 (11.3) | 105 (11.1) | 6 (19.4) | 0.151 |
| History of cerebral infarction, n (%) | 92 (9.4) | 87 (9.2) | 5 (16.1) | 0.203 |
| Laboratory data | ||||
| Serum creatinine, mg/dL | 0.83 (0.68-1.01) | 0.83 (0.68-1.01) | 0.97 (0.67-1.14) | 0.175 |
| eGFR, mL/min/1.73 m2 | 67.7 (52.9-81.8) | 67.9 (53.3-82.0) | 54.7 (44.6-77.1) | 0.029 |
| Hemoglobin levels, g/dL | 13.7 (12.5-14.9) | 13.8 (12.5-15.0) | 12.6 (11.3-14.5) | 0.024 |
| Brain natriuretic peptide, pg/mL | 92.7 (34.3-332.6) (n=969) | 92.1 (34.2-314.7) (n=938) | 327.0 (37.2-565.6) | 0.058 |
| Peak creatine kinase, U/L | 748.0 (231.0-2,067.0) | 755.5 (235.3-2,077.3) | 511.0 (149.0-2,067.0) | 0.514 |
| Peak creatine kinase-MB, U/L | 58.0 (12.0-211.0) (n=978) | 58.0 (13.0-209.0) (n=947) | 54.0 (5.0-233.0) | 0.537 |
| Hemoglobin A1c, % | 6.2 (5.8-7.1) (n=973) | 6.2 (5.8-7.1) (n=942) | 6.2 (5.8-7.2) | 0.550 |
| Platelets (×103/μL) | 21.9 (18.1-26.6) | 21.9 (18.1-26.6) | 21.0 (18.4-26.6) | 0.847 |
| C-reactive protein, mg/μL | 0.20 (0.09-0.76) | 0.20 (0.09-0.73) | 0.27 (0.15-0.95) | 0.058 |
| Type of acute myocardial infarction | ||||
| STEMI, n (%) | 605 (61.8) | 593 (62.6) | 12 (38.7) | 0.009 |
| NSTEMI, n (%) | 374 (38.1) | 355 (37.4) | 19 (61.3) | 0.009 |
| Cardiopulmonary arrest out of hospital, n (%) | 32 (3.3) | 31 (3.3) | 1 (3.2) | 1.00 |
| Killip 1 or 2, n (%) | 833 (85.1) | 810 (85.4) | 23 (74.2) | 0.117 |
| Killip 3 or 4, n (%) | 146 (14.9) | 138 (14.6) | 8 (25.8) | 0.117 |
| Shock at admission, n (%) | 74 (7.6) | 73 (7.7) | 1 (3.2) | 0.725 |
| Vital sings | ||||
| Systolic blood pressure at admission, mmHg | 143.0 (123.0-162.0) | 143.0 (122.3-162.0) | 141.0 (123.0-167.0) | 0.730 |
| Diastolic blood pressure at admission, mmHg | 82.0 (70.0-96.0) | 82.0 (70.0-96.8) | 80.0 (63.0-92.0) | 0.359 |
| Heart rate at admission, bpm | 79.0 (66.0-95.0) | 79.0 (66.0-95.0) | 80.0 (65.0-95.0) | 0.923 |
| Left ventricular ejection fraction, % | 55.0 (44.0-63.0) | 55.0 (44.1-63.0) | 52.8 (42.0-63.2) | 0.711 |
| Moderate to severe GUSTO bleeding, n (%) | 62 (6.3) | 59 (6.2) | 3 (9.7) | 0.440 |
| Medication at admission | ||||
| Aspirin, n (%) | 250 (25.5) | 238 (25.1) | 12 (38.7) | 0.096 |
| Thienopyridine, n (%) | 125 (12.8) | 116 (12.2) | 9 (29.0) | 0.012 |
| Statin, n (%) | 305 (31.2) | 289 (30.5) | 16 (51.6) | 0.017 |
| ACE inhibitors or ARBs, n (%) | 355 (36.3) | 337 (35.5) | 18 (58.1) | 0.013 |
| Beta-blockers, n (%) | 194 (19.8) | 185 (19.5) | 9 (29.0) | 0.249 |
| Calcium channel blocker, n (%) | 351 (35.9) | 334 (35.2) | 17 (54.8) | 0.035 |
| Diuretics, n (%) | 113 (11.5) | 105 (11.1) | 8 (25.8) | 0.020 |
| Oral antidiabetic, n (%) | 21 (2.1) | 20 (2.1) | 1 (3.2) | 0.495 |
| Insulin, n (%) | 53 (5.4) | 52 (5.5) | 1 (3.2) | 1.000 |
| Direct oral anticoagulants, n (%) | 19 (2.0) | 16 (2.5) | 3 (1.0) | 0.210 |
| Warfarin, n (%) | 23 (2.3) | 22 (2.2) | 1 (3.2) | 0.527 |
| Medication at discharge | ||||
| Aspirin, n (%) | 944 (96.4) | 915 (96.5) | 29 (93.5) | 0.305 |
| Thienopyridine, n (%) | 943 (96.3) | 914 (96.4) | 29 (93.5) | 0.317 |
| Statin, n (%) | 965 (98.6) | 935 (98.6) | 30 (96.8) | 0.365 |
| ACE inhibitors or ARBs, n (%) | 942 (96.2) | 913 (96.3) | 29 (93.5) | 0.329 |
| Beta-blocker s, n (%) | 915 (93.5) | 887 (93.6) | 28 (90.3) | 0.449 |
| Calcium channel blocker, n (%) | 178 (18.2) | 170 (17.9) | 8 (25.8) | 0.224 |
| Diuretics, n (%) | 313 (32.0) | 301 (31.8) | 12 (38.7) | 0.436 |
| Oral antidiabetic, n (%) | 315 (32.2) | 303 (32.0) | 12 (38.7) | 0.438 |
| Insulin, n (%) | 71 (7.3) | 70 (7.4) | 1 (3.2) | 0.721 |
| Direct oral anticoagulants, n (%) | 78 (8.0) | 75 (7.9) | 3 (9.7) | 0.731 |
| Warfarin, n (%) | 38 (3.9) | 38 (4.0) | 0 (0) | 0.628 |
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Data were expressed as mean±SD or numbers (percentages). A Student’s t-test was used for normally distributed continuous variables, and Mann–Whitney U test was used for abnormally distributed continuous variables. Fischer’s exact test was used for categorical variables. IABPD: inter arm blood pressure difference, BMI: body mass index, GUSTO: Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries Trial, PCI: percutaneous coronary intervention, CABG: coronary artery-bypass grafting, eGFR: estimated glomerular filtration rate, STEMI: ST elevation myocardial infarction, NSTEMI: non-ST-segment elevation myocardial infarction, ACE inhibitors: angiotensin-converting enzyme inhibitors, ARB: angiotensin receptor blockers
Table 2.
Comparison of Lesion and Procedural Characteristics between the High IABPD Group and the Low IABPD Group.
| All (n=979) | Low IABPD (n=948) | High IABPD (n=31) | p value | |
|---|---|---|---|---|
| Number of narrowed coronary arteries | 0.063 | |||
| Single, n (%) | 440 (44.9) | 432 (45.5) | 8 (25.8) | |
| Double, n (%) | 319 (32.6) | 304 (32.1) | 15 (48.4) | |
| Triple, n (%) | 220 (22.5) | 212 (22.4) | 8 (25.8) | |
| Infarct-related artery | 0.156 | |||
| Left main-left anterior descending artery, n (%) | 493 (50.4) | 479 (50.5) | 14 (45.2) | |
| Right coronary artery, n (%) | 326 (33.3) | 314 (33.1) | 12 (38.7) | |
| Left circumflex artery, n (%) | 143 (14.6) | 140 (14.8) | 3 (9.7) | |
| Graft, n (%) | 5 (0.5) | 5 (0.5) | 0 (0) | |
| Not determined, n (%) | 12 (1.2) | 10 (1.1) | 2 (6.5) | |
| ≥ 50% stenosis at left main coronary trunk, n (%) | 89 (9.1) | 85 (9.0) | 4 (12.9) | 0.518 |
| First TIMI flow (0, 1, 2, 3) | 0.788 | |||
| 0, n (%) | 391 (39.9) | 381 (38.9) | 10 (32.3) | |
| 1, n (%) | 77 (7.9) | 75 (7.9) | 2 (6.5) | |
| 2, n (%) | 167 (17.1) | 161 (17.0) | 6 (19.4) | |
| 3, n (%) | 344 (35.1) | 331 (34.9) | 13 (41.9) | |
| Final TIMI flow (0, 1, 2, 3) | 0.745 | |||
| 0, n (%) | 6 (0.6) | 6 (0.6) | 0 (0.0) | |
| 1, n (%) | 6 (0.6) | 6 (0.6) | 0 (0.0) | |
| 2, n (%) | 35 (3.6) | 35 (3.7) | 0 (0.0) | |
| 3, n (%) | 932 (95.2) | 901 (95.0) | 31 (100) | |
| Chronic total occlusion in non-culprit arteries, n (%) | 124 (12.7) | 120 (12.7) | 4 (12.9) | 1.00 |
| Use of aspiration catheter, n (%) | 155 (15.8) | 150 (15.8) | 5 (16.1) | 1.00 |
| Final percutaneous coronary intervention procedure | 0.031 | |||
| Plain old balloon angioplasty, n (%) | 29 (3.0) | 29 (3.1) | 0 (0.0) | |
| Drug-coated balloon, n (%) | 40 (4.1) | 36 (3.8) | 4 (12.9) | |
| Bare metal stent, n (%) | 14 (1.4) | 14 (1.5) | 0 (0.0) | |
| Drug eluting stent, n (%) | 879 (89.8) | 854 (90.1) | 25 (80.6) | |
| POBA and thrombectomy, n (%) | 6 (0.6) | 6 (0.6) | 0 (0.0) | |
| Aspiration only, n (%) | 5 (0.5) | 5 (0.5) | 1 (3.2) | |
| Wire did not cross the lesion, n (%) | 5 (0.5) | 4 (0.4) | 1 (3.2) | |
| Approach site | 0.209 | |||
| Radial, n (%) | 734 (75.0) | 713 (75.2) | 21 (67.7) | |
| Brachial, n (%) | 9 (0.9) | 8 (0.8) | 1 (3.2) | |
| Femoral, n (%) | 236 (24.1) | 227 (23.9) | 9 (29.0) | |
| Catheter size (Fr) | 0.015 | |||
| 6Fr, n (%) | 699 (71.4) | 684 (72.2) | 15 (48.4) | |
| 7Fr, n (%) | 270 (27.6) | 254 (26.8) | 16 (51.6) | |
| 8Fr, n (%) | 10 (1.0) | 10 (1.1) | 0 (0.0) |
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Data were expressed as mean±SD or numbers (percentages). A Student’s t-test was used for normally distributed continuous variables, and Mann-Whitney U test was used for abnormally distributed continuous variables. Fischer’s exact test was used for categorical variables. IABPD: inter arm blood pressure difference, TIMI: thrombolysis in myocardial infarction, POBA: plain old balloon angioplasty
Fig. 2 shows the Kaplan-Meier curves for all-cause death between the two groups. The median follow-up duration was 694 days (Q1, 296 days; Q3, 1,281 days). A total of 82 all-cause deaths were observed during the follow-up period. The incidence of all-cause death was significantly higher in the high-IABPD group than in the low-IABPD group. Table 3 shows a comparison of the clinical outcomes between the two groups. Cardiac and all-cause deaths were more frequently observed in the high-IABPD group than in the low-IABPD group. An univariate Cox hazard analysis is presented in Supplementary material. A multivariate stepwise Cox hazard analysis is presented in Table 4. The initial model included the IABPD, age, sex, eGFR, atrial fibrillation, ABI, hemoglobin levels, C-reactive protein, STEMI, aspirin at admission, thienopyridine at admission, statin at admission, angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) at admission, calcium channel blockers at admission, diuretics at admission, number of narrowed coronary arteries, catheter size, and the final PCI procedure. A high IABPD was significantly associated with all-cause death (HR 2.061, 95% CI 1.012-4.197, p=0.046).
Table 3.
The Comparison of Clinical Outcomes between the High IABPD Group and the IABPD Group.
| All (n=979) | Low IABPD (n=948) | High IABPD (n=31) | p value | |
|---|---|---|---|---|
| All-cause death, n (%) | 82 (8.4) | 73 (7.7) | 9 (29.0) | <0.001 |
| Cardiac death, n (%) | 27 (2.8) | 23 (2.4) | 4 (12.9) | 0.009 |
| Non-cardiac death, n (%) | 42 (4.3) | 39 (4.1) | 3 (9.7) | 0.144 |
| Death of unknown causes, n (%) | 13 (1.3) | 11 (1.2) | 2 (6.5) | 0.061 |
| No-fatal myocardial infarction, n (%) | 70 (7.2) | 65 (6.9) | 5 (16.1) | 0.064 |
| Re-admission for heart failure, n (%) | 87 (8.9) | 82 (8.6) | 5 (16.1) | 0.186 |
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Data were expressed percentages. A Fischer’s exact test was used for categorical variables. IABPD: inter arm blood pressure difference
Table 4.
Multivariate Stepwise Cox Hazard Analysis to Predict All-cause Death.
| Dependent variable: all-cause death | |||
|---|---|---|---|
| Independent variables | Hazard ratio | 95% confidence interval | p value |
| High IABPD | 2.061 | 1.012-4.197 | 0.046 |
| Ankle-brachial index | 0.228 | 0.077-0.677 | 0.008 |
| STEMI | 1.599 | 1.010-2.513 | 0.045 |
| Hemoglobin levels (every 1 g/dL increase) | 0.872 | 0.788-0.965 | 0.008 |
| Age | 1.046 | 1.020-1.072 | <0.001 |
| Catheter size 6Fr (versus others) | 1.616 | 1.023-2.552 | 0.040 |
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Initial model included age, male, eGFR, atrial fibrillation, ankle-brachial index, hemoglobin levels, C-reactive protein, STEMI, aspirin at admission, thienopyridine at admission, statin at admission, ACE inhibitors or ARBs at admission, calcium channel blocker at admission, diuretics at admission, number of narrowed coronary arteries, catheter size and final percutaneous coronary intervention procedure.
Analysis was performed by stepwise method (backward elimination and likelihood ratio) and eleventh step was final.
IABPD: inter arm blood pressure difference, STEMI: ST elevation myocardial infarction
Figure 2.
Kaplan-Meier curves for the all-cause death event-free survival between the low- and high-IABPD groups. A log-rank test was used.
Discussion
We included 979 patients with AMI and divided them into high- (n=31) and low- (n=948) IABPD groups. We followed up patients for a median duration of 694 days. All-cause death was observed more frequently in the high-IABPD group than in the low-IABPD group. A multivariate Cox hazard analysis revealed that a high IABPD was significantly associated with all-cause death (HR 2.061, 95% CI 1.012-4.197, p=0.046). Our results support routine IABPD measurement to identify high-risk groups among patients with AMI.
IABPD are associated with cardiovascular death or all-cause death in various clinical settings, such as hypertension, diabetes, cerebrovascular disease, and coronary artery disease (11-13,26-29). The differences between the present and previous studies should be clarified. Kilic et al. investigated the association between the IABPD and all-cause death in 532 patients with acute coronary syndrome (30) and found no significant association between these item at two-year follow-up. The age was younger in their study (mean, 60.1 years old) than in our study (median, 70 years old), but the median follow-up duration was comparable between their study (23.2 months) and our study [694 days (23.1 months)]. Hsu et al. also investigated the association between an IABPD ≥10 mmHg and all-cause death but did not find a significant association between the IABPD and all-cause death among 200 patients with AMI (31). The age was younger in their study (mean, 66 years old) than in our study (median, 70 years old), but the median follow-up duration was longer in their study (64 months) than in our study (23.1 months). The prevalence of hypertension, dyslipidemia, and diabetes mellitus was lower in their study (41.0%, 31.0%, and 28.5%, respectively) than in our study (82.4%, 60.3%, and 42.9%, respectively). Our results differ from those of previous studies regarding the association between the IABPD and all-cause death in patients with AMI or acute coronary syndrome. The number of study patients (n=979) was greater in our study than in these 2 studies (n=200, n=532). Notably, those studies might have had too little power to detect a significant association between the IABPD and all-cause mortality. Furthermore, the study population was younger in these two studies than in our study, which is also a possible explanation for why the IABPD was not found to be associated with all-cause mortality in either of the two previous studies.
We should discuss why a high IABPD was associated with long-term all-cause mortality in patients with AMI. First, the IABPD is directly associated with subclavian artery stenosis (12,32). The presence of subclavian artery stenosis increases the risk of all-cause and cardiovascular deaths (33) and may additionally suggest advanced systemic atherosclerosis. Advanced systemic atherosclerosis, including carotid artery stenosis, is associated with poor clinical outcomes (34-36). Furthermore, a possible cause of subclavian artery stenosis is inflammatory diseases, such as Takayasu arteritis (37). Undiagnosed inflammatory diseases might be a cause of all-cause death in patients with an IABPD ≥10 mmHg. However, since the details of the causes of death were not available in this study, we lack direct evidence to support the above speculation.
Therefore, the clinical implications of this study should be noted. Since a high IABPD in patients with AMI was associated with long-term all-cause death, our results support the routine measurement of the IABPD in patients with AMI. If the IABPD is high in patients with AMI, high-risk patients should be carefully followed up by cardiologists. Compared to other risk markers, such as carotid intima-media thickness or computed tomography coronary calcium (38,39), the IABPD is simpler and less invasive to measure. However, it is difficult to measure the IABPD during hospitalization in patients with AMI. Furthermore, a high IABPD may be associated with subclavian steal syndrome, which causes neurological deficits due to central nervous system ischemia (40). Recognizing a high IABPD in patients with AMI may increase the opportunity to consult neurologists or neurosurgeons to prevent future neurological events.
Several limitations associated with the present study warrant mention. Since this was a single-center, retrospective study, there was potential selection bias. The IABPD was derived from ABI measurements. We did not check the reproducibility of the IABPD during the study period. Because the IABPD was measured in the physiological laboratory, the most severely ill patients who could not move to the physiological laboratory did not undergo this measurement, which is also a source of selection bias. The IABPD values during AMI hospitalization may not represent the patient's real IABPD values, as approximately 75% of the study patients underwent trans-radial or trans-brachial PCI. Information regarding the endpoints was acquired from hospital records. There is a possibility that some cardiac deaths might have been judged as non-cardiac deaths by physicians in other hospitals. Therefore, we selected all-cause death rather than cardiac death as the primary endpoint. The lack of supporting evidence for causal inference is also a limitation of this study. In the multivariate Cox regression model, the backward stepwise method was applied. The objective of the backward stepwise method was to simplify the model by retaining only the most statistically significant variables. During this process, clinically meaningful variables that did not meet the prespecified statistical criteria might have been omitted from the final model. The proportion of STEMI/non-ST-segment elevation myocardial infarction (NSTEMI) cases was significantly different between the two groups. Although we included STEMI as an independent variable in the multivariate Cox hazard analysis, the different proportions of STEMI/NSTEMI between the two groups would also represent a potential source of bias.
Conclusion
A high IABPD was significantly associated with long-term all-cause mortality in patients with AMI. Our results suggest the usefulness of the IABPD as a prognostic marker for patients with AMI.
Author's disclosure of potential Conflicts of Interest (COI).
Kenichi Sakakura: Honoraria, Abbott Vascular, Boston Scientific, Medtronic Cardiovascular, Terumo, OrbusNeich, Japan Lifeline, Kaneka and NIPRO. Hiroyuki Jinnouchi: Honoraria, Abbott Vascular. Hideo Fujita: Consultant, Mehergen Group Holdings.
Supplementary Material
Supplemental Table 1. Univariable Cox regression analysis to predict all-cause death
Results of univariable Cox analysis.
Click here to view.(74K, pdf)
Acknowledgement
The authors thank all staff in the catheter laboratory, cardiology units, and emergency and critical care units at Saitama Medical Center, Jichi Medical University for their technical support in this study.
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