It is unknown whether the occurrence of ST-elevation myocardial infarction (STEMI) at a younger age is associated with differences in myocardial damage compared with older patients. We aimed to compare the infarct characteristics (area at risk [AAR], myocardial salvage index [MSI], infarct size [IS], microvascular obstruction [MVO]) and clinical outcome in patients aged ≤45 years and >45 years. We analyzed 795 patients with STEMI treated with primary percutaneous coronary intervention. All patients completed 12-month follow-up for the assessment of major adverse cardiac events (MACE). Left ventricular ejection fraction, AAR, MSI, IS, and MVO were determined by cardiac magnetic resonance imaging. Seventy-eight patients (9.8%) were aged 45 years or younger. Young patients were more likely to be male (p = 0.01), to be current smokers (p <0.001), and to have a family history of coronary artery disease (p = 0.05). Contrary, they had significantly lower prevalence of hypertension (p <0.001), diabetes (p <0.01), and 3-vessel disease (p <0.01). There were no significant differences in left ventricular ejection fraction (p = 0.36), AAR (p = 0.30), MSI (p = 0.34), IS (p = 0.29), or MVO (p = 0.58) between both groups. MACE rate was significantly lower in patients aged ≤45 years compared with patients aged >45 years (1.3% vs 7.5%, p = 0.04). After multivariate adjustment for clinical risk factors and cardiac magnetic resonance findings, age remained an independent predictor of MACE (hazard ratio 1.04, 95% CI 1.01 to 1.07, p = 0.03). In conclusion, infarct characteristics are not dependent on age in patients undergoing primary percutaneous coronary intervention for STEMI.
A large number of studies reported on the clinical characteristics and outcomes of young patients with ST-elevation myocardial infarction (STEMI). Most studies used a cutoff of ≤45 years to distinguish between young and nonyoung patients. These studies revealed significant differences in cardiovascular risk profiles, extent of coronary artery disease, pathophysiology of coronary artery occlusion, and clinical outcome between age groups. However, it is unknown whether these differences are also related with disparities in myocardial damage, which are known to influence prognosis. Furthermore, it has yet to be established whether the better outcome of young patients might be related to these potential differences in infarct characteristics or is attributable to a more favorable risk and co-morbidity profile compared to older patients with STEMI. Cardiac magnetic resonance (CMR) imaging has evolved as the ideal imaging technique for exact infarct sizing and tissue characterization of the jeopardized and infarcted myocardium. The present study analyzed the association between age and CMR-derived infarct characteristics (area at risk [AAR], myocardial salvage index [MSI], infarct size [IS], and microvascular obstruction [MVO]) as well as 1-year clinical outcome in consecutive patients treated with primary percutaneous coronary intervention (PPCI) who were enrolled in a CMR multicenter study.
Methods
The study protocol and principal results of the Abciximab Intracoronary versus intravenous Drug Application in ST-Elevation Myocardial Infarction trial and its CMR substudy have been previously described in detail. Briefly, Abciximab Intracoronary versus intravenous Drug Application in ST-Elevation Myocardial Infarction randomized 2,065 consecutive patients with STEMI treated with PPCI within 12 hours after symptom onset to either intracoronary or intravenous abciximab bolus. The CMR substudy recruited 795 patients with STEMI at 8 sites. Of note, there was no difference in CMR markers of myocardial damage between both abciximab groups. The clinical end point of the CMR substudy was the incidence of major adverse cardiac events (MACE), defined as a composite of all-cause death, nonfatal reinfarction, and new congestive heart failure at 12 months after infarction.
Patients underwent CMR imaging on 1.5- or 3.0-T scanners on days 1 to 10 after index event using standardized sequences. Evaluation of images was carried out using commercially available postprocessing software (cmr42; Circle Cardiovascular Imaging Inc., Calgary, Alberta, Canada). Readers blinded to study data performed the image analysis at the CMR core laboratory (University of Leipzig, Heart Center, Leipzig, Germany). The core laboratory has proved excellent reproducibility and low interobserver as well as intraobserver variability in patients with acute STEMI. Left ventricular (LV) volumes and function were determined using standard definitions. The measurements of the AAR, IS, and MVO were expressed as the percentage of LV volume (%LV). MSI was determined from AAR and IS as recently described. LV function was available for all 795 patients. Late gadolinium enhancement imaging for the determination of IS and MVO was available for 774 patients. T2-weighted imaging for the measurement of AAR was available for 695 patients.
Statistical analysis was performed using SPSS Statistics 22.0.0 (IBM, Armonk, New York). Variables are depicted as mean ± SD, median with interquartile range, or frequency with percentage as appropriate. Spearman rho correlations were calculated. Testing for differences between groups was performed with the Mann–Whitney U test or Kruskal–Wallis test for continuous variables and chi-square test for categorical variables. Outcome functions were estimated using Kaplan–Meier graphs, and age groups were compared using the log-rank test. Univariate and multivariate Cox regression analysis was performed to identify predictors for MACE. Multivariate analysis was performed using only variables with a p <0.05 in univariate analysis. All variables listed in Table 1 and all CMR findings listed in Table 2 were investigated in univariate analysis. All tests were 2-tailed, and a p ≤0.05 was considered statistically significant.
| Variable | All Patients (n=795) | ≤45 Years (n=78) | >45 Years (n=717) | p Value |
|---|---|---|---|---|
| Age (years) | 62 [51-71] | 42 [40-44] | 64 [54-72] | <0.001 |
| Men | 603 (76%) | 68 (87%) | 535 (75%) | 0.01 |
| Body mass index (kg/m 2 ) | 27 [25-30] | 27 [25-30] | 27 [25-30] | 0.98 |
| Cardiovascular risk factors | ||||
| Current smoking | 339/727 (43%) | 64/76 (82%) | 275/651 (38%) | <0.001 |
| Hypertension ∗ | 540/792 (68%) | 34 (44%) | 506/714 (71%) | <0.001 |
| Hypercholesterolemia † | 304/787 (38%) | 22/76 (28%) | 282/771 (39%) | 0.07 |
| Diabetes mellitus | 160/792 (20%) | 7 (9%) | 153/714 (21%) | <0.01 |
| Family history for coronary artery disease | 270/614 (34%) | 37/67 (47%) | 233/547 (33%) | 0.05 |
| Systolic blood pressure (mmHg) | 130 [117-147] | 130 [116-150] | 130 [117-147] | 0.73 |
| Diastolic blood pressure (mmHg) | 80 [70-88] | 80 [70-90] | 80 [70-87] | 0.33 |
| Heart rate (beats/min) | 76 [67-87] | 77 [70-84] | 76 [67-87] | 0.91 |
| Pain-to-balloon time (min) | 180 [109–310] | 182 [109-324] | 159 [106-313] | 0.27 |
| Previous infarction | 48/794 (6%) | 4 (5%) | 44/716 (6%) | 0.72 |
| Previous percutaneous coronary intervention | 67 (8%) | 3 (4%) | 64 (9%) | 0.13 |
| Previous coronary artery bypass grafting | 11 (1%) | 1 (1%) | 10 (1%) | 0.94 |
| Anterior infarction | 395/768 (50) | 37/76 (47) | 324/682 (45) | 0.53 |
| Killip-class on admission | 0.14 ‡ | |||
| 1 | 699 (88%) | 72 (92%) | 627 (87%) | |
| 2 | 59 (7%) | 5 (6%) | 54 (8%) | |
| 3 | 20 (3%) | 0 (0%) | 20 (3%) | |
| 4 | 17 (2%) | 1 (1%) | 16 (2%) | |
| Number of narrowed coronary artries | <0.01 § | |||
| 1 | 422 (53%) | 51 (65%) | 371 (52%) | |
| 2 | 224 (28%) | 21 (27%) | 203 (28%) | |
| 3 | 147 (19%) | 6 (8%) | 141 (20%) | |
| Infarct related artery | 0.89 | |||
| Left anterior descending | 347 (44%) | 36 (46%) | 311 (43%) | |
| Right coronary artery | 344 (43%) | 34 (44%) | 310 (43%) | |
| Left circumflex | 97 (12%) | 8 (10%) | 89 (12%) | |
| Left main | 5 (1%) | 0 (0%) | 5 (1%) | |
| Bypass graft | 2(0%) | 0 (0%) | 2 (0%) | |
| TIMI-risk score | 3 [2-5] | 2 [1-3] | 4 [2-5] | <0.001 |
| TIMI-flow before percutaneous coronary intervention | 0.34 | |||
| 0 | 445 (56%) | 43 (55%) | 402 (56%) | |
| 1 | 104 (13%) | 15 (19%) | 89 (12%) | |
| 2 | 129 (16%) | 10 (13%) | 119 (17%) | |
| 3 | 117 (15%) | 10 (13%) | 107 (15%) | |
| TIMI-flow after percutaneous coronary intervention | 0.67 ¶ | |||
| 0 | 12 (2%) | 2 (3%) | 10 (1%) | |
| 1 | 19 (2%) | 4 (5%) | 15 (2%) | |
| 2 | 62 (8%) | 2 (3%) | 60 (8%) | |
| 3 | 701 (88%) | 70 (90%) | 631 (88%) | |
| Drug-eluting stent | 335 (42%) | 38 (49%) | 297 (41%) | 0.22 |
| Bare-metal stent | 469 (59%) | 38 (49%) | 431 (60%) | 0.05 |
| Thrombectomy | 190 (24%) | 27 (35%) | 163 (23%) | 0.02 |
| Concomitant medications | ||||
| Aspirin | 793 (100%) | 77 (100%) | 716 (100%) | 1.0 |
| ß-blockers | 759 (96%) | 75 (96%) | 684 (95%) | 0.44 |
| ACE-I/ARB | 755 (95%) | 73 (94%) | 682 (95%) | 0.86 |
| Statin | 752 (95%) | 75 (96%) | 677 (94%) | 0.28 |
| Aldosterone antagonist | 91 (11%) | 9 (12%) | 82 (11%) | 0.95 |
| Gp-IIb/IIIa-inhibitor (abciximab) | 748 (94%) | 74 (95%) | 674 (94%) | 0.79 |
∗ Hypertension was diagnosed if patients were on antihypertensive treatment or had ≥3 systolic blood pressure values >140 mm Hg on at least 2 different days.
† Hypercholesterolemia was diagnosed if patients were on cholesterol-lowering medication or their serum total cholesterol was ≥200 mg/dl.
‡ Killip’ s class I to II versus III to IV.
§ Number of diseased vessels 1 to 2 versus 3.
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