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The relationship between aortic calcification and hard outcomes suggests that chest x-ray examination may be a good candidate for risk stratification for ACS patients due to its widespread availability, ready feasibility, and easy interpretability. Furthermore, calcification in aortic arch is more reliably detected than aorta in a thoracic or abdominal portion in chest x-ray examination, which was often obscured by other intrathoracic and intra-abdominal organs. The connection between AAC and clinical outcomes in ACS patients was incompletely investigated. Our study aimed to examine the epidemiology, coronary characteristics as well as clinical outcomes of ACS patients with AAC and clarify whether AAC plays a prognostic role in ACS patients.
Patients admitted to the coronary care unit of Taipei Veterans General Hospital under the impression of acute coronary syndrome, including STEMI, NSTEMI, and UA, were recruited retrospectively between January 1 and December 31, 2013. The definitions of STEMI, NSTEMI, and UA followed the ACCF/AHA guidelines. The data collection, processing, analysis, and interpretation were approved by the committee of the Institutional Review Board of Taipei Veterans General Hospital (IRB number 2014-11-003 AC). The underlying systemic disorders, anginal symptoms, electrocardiography, chest plain film, laboratory investigations, coronary artery angiography, the course of hospitalization, in-hospital events, and discharge follow-up (if available) of each patient were thoroughly scrutinized. The image interpretation, including electrocardiography, chest plain film (Figure 1), coronary artery angiography, were separately performed twice by two experienced cardiologists blinded to clinical conditions. If discrepancy existed between two cardiologists in the same patient, a third experienced cardiologist would join reviewing examinations. The primary outcome was the composite endpoint of long-term major adverse cardiovascular events (MACE) comprising of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, the definition of which followed the universal agreement of consensus. The secondary outcomes were 30-day and long-term all-cause mortality. The baseline characteristics were shown in Table 1.
During the mean follow-up of 165 ± 140 days (maximally 492 days), there were 47 all-cause deaths, 46 cardiovascular deaths, 37 non-fatal myocardial infarctions and 5 non-fatal strokes (Figure 2A). ACS patients with AAC had significantly higher incidence of cardiovascular death (27.6% vs. 11.2%, Log-Rank p = 0.002, Figure 2B) and all-cause death (28.3% vs. 11.2%, Log-Rank p = 0.001, Figure 2C) as compared to those without. As regarding the long-term composite endpoint of non-fatal MI, non-fatal stroke, and cardiovascular death, the calcification group had a significantly higher risk as compared to the non-calcification group (39.4% vs. 24.6%, Log-Rank p=0.011, Figure 2D).
Subgroup analysis focusing on primary endpoints demonstrated clinical outcomes in favor of patients without AAC, as compared with those with AAC, in every aspect of grouping, especially in those with hypertension, without diabetes mellitus, and male (Figure 3).
The all-cause mortality rate during follow-up escalated grossly with the AAC grade, though the survival differences did not reach statistical significance between grade 0 and 1, and between grade 2 and 3 (Figure 4A). Thirty-six (28.3%) mortalities occurred among AAC (+) group and 11 (11.2%) among AAC (-) group. Among AAC (+) mortalities, 35 (97.2%) were cardiovascular death, including fatal MI, heart failure, and sudden cardiac death. The only one non-CV death (2.8%) was cancer-related, which occurred on the 27th day of index ACS episode. All 11 AAC (-) mortalities were cardiovascular death. The major adverse cardiovascular event rate significantly escalated with AAC grade (Figure 4B) (p for trend <0.001).
In multivariate analysis, the presence of AAC was associated with statistically elevated risk of long-term MACE, all-cause mortality, cardiovascular death and 30-day mortality. After being adjusted for age, gender, type 2 diabetes mellitus, and hypertension, the presence of AAC still conferred statistically significant increase of risks.
In conclusion, aortic arch calcification from chest x-ray examination in patients with ACS provides valuable prognostic information on clinical outcomes. Studies with larger patient numbers would be needed to confirm this observation and delineate the detail picture of clinical outcomes in 4 AAC grade groups. Different principles of management for ACS patients with aortic arch calcification might also be needed and tested in subsequent studies.