Prognosis of Myocardial Injury After Non-Cardiac Surgery in Adults Aged Younger Than 45 Years

Abstract

Background: This study compared myocardial injury after non-cardiac surgery (MINS) and mortalities between patients under and over the age of 45 years.

Methods and Results: From January 2010 and June 2019, patients with cardiac troponin measurement within 30 days after non-cardiac surgery were enrolled and divided into groups according to age: >45 (≥45 years) and <45 (<45 years). Further analyses were conducted only in patients who were diagnosed with MINS. The outcomes were MINS and 30-day mortality. Of the 35,223 patients, 31,161 (88.5%) patients were in the >45-year group and 4,062 (11.5%) were in the <45-year group. After adjustment with inverse probability of weighting, the <45-years group showed a lower incidence of MINS and cardiovascular mortality (16.6% vs. 11.7%; odds ratio, 0.77; 95% confidence interval [CI], 0.69–0.84; P<0.001 and 0.4% vs. 0.2%; hazard ratio [HR], 0.41; 95% CI, 0.19–0.88; P=0.02, respectively). In a comparison of only the <45-years group, MINS was associated with increased 30-day mortality (0.7% vs. 10.3%; HR, 10.48; 95% CI, 6.18–17.78; P<0.001), but the mortalities of patients with MINS did not differ according to age.

Conclusions: MINS has a comparable prognostic impact in patients aged under and over 45 years; therefore, future studies need to also consider patients aged <45 years regarding risk factors of MINS and screening of perioperative troponin elevation.

Age is undoubtedly one of the most basic demographic factors that affects the progression of any pathologic condition. Myocardial injury after non-cardiac surgery (MINS) has emerged as the most common postoperative condition that strongly associates with mortality.¹ The recently proposed diagnostic criteria for MINS are not only well-established on robust evidence, but also have strength in clinical application by being relatively simple; at least one value of cardiac troponin (cTn) elevation above the 99th percentile upper reference limit (URL) within 30 days after surgery, as a result of myocardial ischemia without the requirement of an ischemic symptom.^2–4 In addition, subsequently published perioperative guidelines added recommendations for the measurement of cTn level during the perioperative period.^5–7 However, the details of these recommendations differ from one study to another because the clinical impact of even basic demographic characteristics such as age has not been fully determined in MINS. Moreover, the most robust evidence for the association between MINS and mortality was established on the population of patients aged >45 years.^4,8,9 Thus, to the best of our knowledge, whether the incidence of MINS or survival after MINS could vary according to age has never been investigated. In this study, we aimed to compare the incidence and mortality of MINS between patients aged under and over 45 years.

Editorial p 2089

Methods

Study Population and Data Collection

This study is a retrospective observational study using the cohort of de-identified data curated by our institutional data warehouse. The Institutional Review Board at Samsung Medical Center waived the approval for this study and the requirement for written informed consent for access to the registry because the entire dataset was initially extracted in de-identified form (SMC 2019-08-048).

The SMC-TINCO registry (Samsung Medical Center Troponin in Noncardiac Operation, KCT0004244) is a large single-center cohort containing de-identified data of 43,019 consecutive patients who had their cTn I levels measured before or within 30 days following non-cardiac surgery between January 2010 and June 2019 in Samsung Medical Center, Seoul, Korea. The SMC-TINCO registry was generated using the “Clinical Data Warehouse Darwin-C”, which was built for investigators to search and retrieve de-identified medical records from the institutional electronic archive system. Samsung Medical Center operates a paperless electronic archive system, and the electronic archive system contains data about >4 million patients with details about >2 million surgeries, 900 million laboratory findings, and 200 million prescriptions. For mortalities outside of our institution, this system is consistently updated and validated against the National Population Registry of the Korea National Statistical Office using a unique personal identification number when available. After extracting the raw data of the preoperative evaluation sheets, the baseline characteristics of the patients were organized into a standardized form by independent investigators who were blinded to mortalities and cTn I levels.

From the registry, we excluded the following patients for this study: (1) patients who were aged <18 years at the time of surgery; (2) patients without postoperative cTn I; and (3) patients who had cardiac massage before the surgery. The eligible patients were divided into 2 groups according to age: patients aged <45 years as the under 45-year group and patients aged ≥45 years old as the >45-year group. The entire population was further stratified into 4 groups according to age and MINS (<45 years without MINS, <45 years with MINS, >45 years without MINS, and >45 years with MINS), and an additional analysis was performed after selecting only those patients who were diagnosed with MINS.

Outcome Measures and Definitions

The primary outcome was MINS, defined as an elevation of cTn I level above the 99th percentile URL within 30 days after surgery,² but an elevation with an evidence of non-ischemic etiology such as sepsis, pulmonary embolus, atrial fibrillation, cardioversion, or chronic elevation was not regarded as MINS.^3,4 The secondary outcomes included 30-day and in-hospital mortalities, and mortality was classified into cardiovascular and non-cardiovascular mortalities. Cardiovascular mortality was death related to myocardial infarction, cardiac arrhythmia, heart failure, stroke, or vascular causes, and non-cardiovascular mortality was defined as death from a cause other than cardiovascular conditions. All deaths without an undisputed non-cardiovascular cause were considered as cardiovascular deaths.¹⁰ Active cancer was defined as a histologic diagnosis of cancer within the previous 6 months.¹¹ High-risk surgery was defined as a procedure with reported mortality risk >5% according to the 2014 European Society of Cardiology/Anesthesiology guidelines.⁶

Perioperative cTn I Measurement and Management

Perioperative cTn I measurement was not performed in all patients, but was recommended for the patients with at least one of the major cardiovascular risk factors such as history of ischemic heart disease, heart failure, stroke including transient ischemic attack, diabetes mellitus on insulin therapy, or chronic kidney disease or for those undergoing intermediate- to high-risk surgery according to the guideline.⁶ It was also measured in patients with mild risk at the discretion or request of an attending clinician. An automated analyzer (Advia Centaur XP; Siemens Healthcare Diagnostics, Erlangen, Germany) with immunoassay was used. The lowest limit of detection was 6 ng/L. The 99th percentile URL was 40 ng/L, as provided by the manufacturer.¹² Patients with an elevated cTn level were referred to cardiologists for further evaluation and proper management by an attending clinician. Other perioperative management followed the institutional protocols, which were based on current guidelines.

Statistical Analysis

For continuous data, differences were compared by using the t-test or the Mann-Whitney U-test, as applicable, and presented as mean±standard deviation (SD) or median with interquartile range (IQR). Categorical data were presented as number (%) and compared using the chi-squared or Fisher’s exact test. Kaplan-Meier estimates were used to construct survival curves and compared with the log-rank test. Logistic regression was used to compare MINS and Cox proportional hazards model for mortality. To further reduce selection bias while maintaining balanced confounding variables between the 2 groups, we used weighted regression models with inverse probability of weighting (IPW) on all measured variables.¹³ The inverse probability weights in this technique were defined as the reciprocal of propensity scores, and standardized mean difference of <10% was deemed as well-balanced covariates between the groups. MINS was compared using a stratified logistic regression model and was reported as adjusted odds ratio (OR) with 95% confidence intervals (CI), and the mortalities were compared with Cox proportional hazards model and was reported as an adjusted hazard ratio (HR). For secondary outcomes, we adopted a post-hoc Bonferroni’s correction. Regarding the sample size, power of the analysis was computed before the formal analysis based on the OR for the occurrence of MINS using Spearman’s rank correlation and the powerSurvEpi package.¹⁴ The expected power ranged 0.71, 0.97 and >0.99 when the OR was 0.9, 0.85, 0.8.

For sensitivity analysis, the observed association was separately evaluated according to sex and former and latter cases of surgeries. A subgroup analysis was also performed to reveal hidden interaction with relevant covariates and presented in a forest plot. To compare the impact of age on MINS with other variables, we calculated the attributable fraction (AF) for variables based on the results of the Cox proportional hazards model. This measure represents the proportional reduction of MINS within a population that would occur if the incidence of the variable was reduced to zero. Statistical analyses were performed with R 3.5.3 (Vienna, Austria; http://www.R-project.org/). All tests were 2-tailed, and P<0.05 was considered statistically significant.

Results

Total Population

We excluded 1,154 patients who were aged <18 years, 6,596 patients without postoperative cTn I, and 46 patients who had cardiac massage prior to the surgery. In total, 35,223 patients were left for analysis and were divided as follows: 31,161 (88.5%) patients in the >45-year group and 4,062 (11.5%) patients in the <45-year group. The mean ages of the 2 groups were 65.4 (±10.2) years and 35.4 (±7.0) years, respectively. The baseline characteristics of the entire population are summarized in Table 1. Patients in the <45-year group were less likely to be male and showed lower incidence of pre-existing conditions such as hypertension, diabetes, ischemic heart disease, stroke, arrhythmia, and active cancer. In contrast, they were more frequently current smokers or alcohol users and more frequently on preoperative treatment such as in the intensive care unit, on continuous renal replacement therapy, or on a ventilator. For operative variables, the <45-year group also showed higher frequencies of emergency operations, general anesthesia, and requirement for inotropic infusions with longer operative duration, but the incidence of high-risk surgery was lower. The median durations of follow up for primary outcome were 30 (30–30) days in all groups. The types of surgery for each group are summarized in Supplementary Table 1.

Table 1. Baseline Characteristics of the Entire Population

	Entire population				IPW
	>45 years (N=31,161)	<45 years (N=4,062)	P value	SMD	>45 years (N=31,202.6)	<45 years (N=3,879.3)	P value	SMD
Male	17,043 (54.7)	1,968 (48.4)	<0.001	12.5	16,852.1 (54.0)	2,193.6 (56.5)	0.07	5.1
Diabetes	15,695 (50.4)	1,668 (41.1)	<0.001	18.8	15,369.0 (49.3)	1,819.4 (46.9)	0.11	4.7
Hypertension	18,833 (60.4)	823 (20.3)	<0.001	89.8	17,386.2 (55.7)	2,096.8 (54.1)	0.22	3.4
Current smoking	2,735 (8.8)	622 (15.3)	<0.001	20.2	2,988.8 (9.6)	454.4 (11.7)	0.01	6.9
Current alcohol	5,638 (18.1)	1,207 (29.7)	<0.001	27.5	6,068.2 (19.4)	770.1 (19.9)	0.68	1
Chronic kidney disease	1,668 (5.4)	216 (5.3)	0.96	0.2	1,686.8 (5.4)	232.8 (6.0)	0.42	2.6
History of coronary artery disease	5,099 (16.4)	133 (3.3)	<0.001	45.1	4,627.4 (14.8)	510.1 (13.1)	0.29	4.8
History of heart failure	858 (2.8)	126 (3.1)	0.22	2.1	870.9 (2.8)	115.7 (3.0)	0.74	1.1
History of stroke	2,153 (6.9)	128 (3.2)	<0.001	17.3	2,016.6 (6.5)	237.8 (6.1)	0.71	1.4
History of arrhythmia	2,257 (7.2)	57 (1.4)	<0.001	29	2,047.3 (6.6)	264.0 (6.8)	0.85	1
History of heart valve disease	406 (1.3)	63 (1.6)	0.22	2.1	420.2 (1.3)	72.7 (1.9)	0.09	4.2
Active cancer	14,043 (45.1)	1,445 (35.6)	<0.001	19.4	13,691.0 (43.9)	1,562.4 (40.3)	0.02	7.3
Preoperative care
Intensive care unit	1,053 (3.4)	200 (4.9)	<0.001	7.7	1,122.1 (3.6)	189.9 (4.9)	0.08	6.4
ECMO	0	1 (0.0)	0.23	2.2	0	0.1 (0.0)	0.01	0.8
Continuous renal replacement therapy	60 (0.2)	20 (0.5)	<0.001	5.1	68.4 (0.2)	20.2 (0.5)	0.16	5
Ventilator	171 (0.5)	52 (1.3)	<0.001	7.7	198.7 (0.6)	27.7 (0.7)	0.58	1
Operative variables
ESC/ESA surgical high risk	6,198 (19.9)	517 (12.7)	<0.001	19.5	5,943.3 (19.0)	826.7 (21.3)	0.1	5.6
Emergency surgery	4,011 (12.9)	792 (19.5)	<0.001	18.1	4,290.9 (13.8)	613.1 (15.8)	0.02	5.8
General anesthesia	27,110 (87.0)	3762 (92.6)	<0.001	18.6	27,355.2 (87.7)	3,431.8 (88.5)	0.45	2.5
Operation duration, h	3.07 (±2.16)	3.45 (±2.41)	<0.001	16.7	3.12 (±2.24)	3.20 (±2.20)	0.16	3.7
Continuous infusion of inotropics	8,461 (27.2)	1,418 (34.9)	<0.001	16.8	8,775.3 (28.1)	1,177.1 (30.3)	0.07	4.9
RBC transfusion	2,370 (7.6)	295 (7.3)	0.46	1.3	2,365.9 (7.6)	311.3 (8.0)	0.51	1.6

Data are presented as n (%) or mean (±standard deviation). ECMO, extracorporeal membranous oxygenation; ESA, European Society of Anaesthesiology; ESC, European Society of Cardiology; IPW, inverse probability weighting; RBC, red blood cell; SMD, standardized mean difference.

Of the 5,829 patients with postoperative cTn elevation, 196 patients with non-ischemic etiology were regarded as not suffering MINS. After an adjustment with IPW, MINS consistently showed a significantly lower incidence in patients aged <45 years (16.6% vs. 11.7%; OR, 0.77; 95% CI, 0.69–0.84; P<0.001). Cardiovascular mortality was also consistently lower in the <45-year group (0.4% vs. 0.2%; HR, 0.41; 95% CI, 0.19–0.88; P=0.02) (Table 2, Figure 1). This association was consistently significant in both sex, and former and latter cases of surgeries (Supplementary Table 2). In subgroup analysis, significant interactions with diabetes, high-risk surgery, and general anesthesia were observed (P for interaction; <0.001 for all subgroups). The lower incidence of MINS in the <45-year group was limited to patients with diabetes, undergoing high-risk surgery, or under general anesthesia (Supplementary Figure 1).

Table 2. Clinical Outcomes of the Entire Population

	Univariate analysis				Multivariable analysis		IPW analysis
	>45 years (N=31,161)	<45 years (N=4,062)	Unadjusted OR/HR (95% CI)	P value	Adjusted OR/HR (95% CI)	P value	Adjusted OR/HR (95% CI)	P value
Myocardial injury after non-cardiac surgery†	5,158 (16.6)	475 (11.7)	0.67 (0.60–0.74)	<0.001	0.77 (0.69–0.86)	<0.001	0.77 (0.69–0.84)	<0.001
30-day mortality	540 (1.7)	75 (1.8)	1.07 (0.84–1.36)	0.6	1.10 (0.70–1.17)	0.45	1.30 (1.04–1.63)	0.02
Cardiovascular death	138 (0.4)	8 (0.2)	0.45 (0.22–0.91)	0.03	0.42 (0.20–0.87)	0.02	0.41 (0.19–0.88)	0.02
Non-cardiovascular death	402 (1.3)	67 (1.6)	1.28 (0.99–1.66)	0.06	1.05 (0.80–1.39)	0.71	1.61 (1.26–2.05)	<0.001
In-hospital mortality	667 (2.1)	101 (2.5)	0.89 (0.72–1.10)	0.3	0.87 (0.70–1.09)	0.23	1.09 (0.89–1.33)	0.42

Data are presented as n (%). CI, confidence interval; HR, hazard ratio; IPW, inverse probability weighting; OR, odds ratio. Multivariable analysis included sex, hypertension, diabetes mellitus, smoking, alcohol, stroke, coronary artery disease, arrhythmia, active cancer, operative risk, operative duration, general anesthesia, emergency operation, and intraoperative continuous infusion of inotropics. ^†Presented as odds ratio.

Figure 1.

Kaplan-Meier curves for (A) in-hospital, (B) overall, (C) cardiovascular, and (D) non-cardiovascular mortalities.

We further stratified the entire population into 4 groups according to both age and the occurrence of MINS (<45 years without MINS [3,587, 10.2%], <45 years with MINS [475, 1.3%], >45 years without MINS [26,003, 73.8%], and >45 years with MINS [5,158, 14.6%]) and compared mortalities using the set of patients aged <45 years without MINS as a reference group. The baseline characteristics of the 4 groups are summarized in Supplementary Table 3. In a comparison to the patients aged <45 years without MINS, the multivariable analysis showed that the 30-day mortality of patients with MINS was enormously increased regardless of age (0.7% vs. 10.3%; HR, 10.48; 95% CI, 6.18–17.78; P<0.001 for the <45-year group with MINS and 0.7% vs. 7.1%; OR, 8.76; 95% CI, 5.80–13.22; P<0.001 for the >45-year group with MINS) (Figure 2, Table 3), and MINS was independently associated with mortality also in patients aged <45 years. The AFs of variables on MINS are presented in Supplementary Table 4. The AF of age <45 years was significant and was estimated as −2.9%.

Figure 2.

Kaplan-Meier curves of 30-day mortality for 4 groups, stratified by age and myocardial injury after non-cardiac surgery (MINS) diagnosis. Yellow line: <45 years without MINS; Red line: <45 years with MINS; Green line: ≥45 years without MINS; and Blue line: ≥45 years with MINS.

Table 3. Clinical Outcomes of the 4 Groups According to Age and MINS

	<45 years without MINS (N=3,587)	<45 years with MINS (N=475)	>45 years without MINS (N=26,003)	>45 years with MINS (N=5,158)
30-day mortality	26 (0.7)	49 (10.3)	174 (0.7)	366 (7.1)
Unadjusted HR (95% CI)	1 [Ref.]	15.05 (9.36–24.22)	0.92 (0.61–1.39)	10.13 (6.81–15.08)
P value		<0.001	0.7	<0.001
Adjusted HR (95% CI)		10.48 (6.18–17.78)	1.70 (1.12–2.59)	8.76 (5.80–13.22)
P value		<0.001	0.01	<0.001
Cardiovascular death	1 (0.0)	7 (1.5)	42 (0.2)	96 (1.9)
Unadjusted HR (95% CI)	1 [Ref.]	55.58 (6.84–451.8)	5.79 (0.80–42.1)	68.62 (9.57–492.1)
P value		<0.001	0.08	<0.001
Adjusted HR (95% CI)		58.43 (7.18–475.60)	9.84 (1.34–72.21)	40.72 (5.59–296.78)
P value		<0.001	0.02	<0.001
Non-cardiovascular death	25 (0.7)	42 (8.8)	132 (0.5)	270 (5.2)
Unadjusted HR (95% CI)	1 [Ref.]	13.42 (8.18–22.03)	0.73 (0.48–1.12)	7.79 (5.17–11.73)
P value		<0.001	0.15	<0.001
Adjusted HR (95% CI)		9.10 (5.24–15.80)	1.38 (0.89–2.13)	7.52 (4.91–11.50)
P value		<0.001	0.15	<0.001
In-hospital mortality	34 (0.9)	67 (14.1)	210 (0.8)	457 (8.9)
Unadjusted HR (95% CI)	1 [Ref.]	6.64 (4.30–10.24)	1.29 (0.89–1.86)	5.46 (3.83–7.79)
P value		<0.001	0.18	<0.001
Adjusted HR (95% CI)		6.32 (4.06–9.84)	1.95 (1.34–2.83)	5.32 (3.70–7.66)
P value		<0.001	<0.001	0.03

CI, confidence interval; HR, hazard ratio; MINS, myocardial injury after non-cardiac surgery. Multivariable analysis included sex, hypertension, diabetes mellitus, smoking, alcohol, stroke, coronary artery disease, arrhythmia, active cancer, operative risk, operative duration, general anesthesia, emergency operation, and intraoperative continuous infusion of inotropics.

MINS Patients

After selecting the 5,633 patients who were diagnosed with MINS, 5,158 (91.6%) patients were in the >45-year group with MINS and 475 (8.4%) patients in the <45-year group with MINS. Most baseline characteristics showed similar tendencies, and the difference in the incidence of high-risk surgery became non-significant (Supplementary Table 5). Although 30-day mortality was numerically higher in the <45-year group with MINS, the difference was not significant after an adjustment, and all other mortalities similarly showed inconsistent or non-significant results (Table 4, Supplementary Figure 2).

Table 4. Clinical Outcomes of Patients With Myocardial Injury After Non-Cardiac Surgery

	Univariate analysis				Multivariable analysis		IPW analysis
	>45 years (N=5,158)	<45 years (N=475)	Unadjusted HR (95% CI)	P value	Adjusted HR (95% CI)	P value	Adjusted HR (95% CI)	P value
30-day mortality	366 (7.1)	49 (10.3)	1.49 (1.11–2.01)	0.01	1.08 (0.79–1.49)	0.62	1.18 (0.83–1.67)	0.35
Cardiovascular death	96 (1.9)	7 (1.5)	0.81 (0.37–1.74)	0.59	0.71 (0.32–1.60)	0.41	0.52 (0.20–1.39)	0.19
Non-cardiovascular death	270 (5.2)	42 (8.8)	1.73 (1.25–2.40)	<0.001	1.18 (0.85–1.67)	0.36	1.42 (0.98–2.06)	0.07
In-hospital mortality	457 (8.9)	67 (14.1)	1.21 (0.93–1.56)	0.15	1.15 (0.87–1.50)	0.33	1.14 (0.86–1.53)	0.36

CI, confidence interval; HR, hazard ratio; IPW, inverse probability weighting. Multivariable analysis included sex, hypertension, diabetes mellitus, smoking, alcohol, stroke, coronary artery disease, arrhythmia, active cancer, operative risk, operative duration, general anesthesia, emergency operation, and intraoperative continuous infusion of inotropics.

Discussion

The main findings of this study are as follows: (1) the incidence of MINS was significantly lower in patients aged <45 years, as was the 30-day cardiovascular mortality; (2) in a multiple group comparison regarding both MINS and age, short-term mortalities were dependent on the occurrence of MINS rather than on age; and (3) in patients who were diagnosed with MINS, short-term mortalities were not different according to age. Together, these findings suggest that MINS consistently has prognostic impact in patients aged <45 years as well as in older patients.

MINS has recently been accepted as a strong predictor of postoperative mortality.^15,16 It is estimated to occur in 5–25% of the over 200 million non-cardiac surgical patients every year, making it the most common condition associated with death during the first 30 days following surgery.^17,18 These previous findings about MINS were initially identified through the landmark analysis of the VISION (Vascular Events in Noncardiac Surgery Patients Cohort Evaluation) study, which prospectively recruited more than 15,000 patients from several countries, but only those who were aged >45 years.^4,8,9 Therefore, it was previously recommended as an expert opinion to measure perioperative cTn in patients aged >45 years;¹⁹ the age-difference in the incidence and mortality of MINS has not been fully investigated.

In our study, the incidence of MINS was significantly lower in the group aged <45 years. This can be well explained by the limits that the 99th percentile URL inherently possess. According to the current recommendation by the International Federation of Clinical Chemistry and Laboratory Medicine Task Force on Clinical Applications of Bio-Markers, the 99th percentile URL of the cTn assay can be calculated using apparently healthy 300 men and 300 women.²⁰ Although it is well known that the 99th percentile URL can vary by age, sex, or race,^21,22 a single universal value of the URL has been usually applied by convention in clinical practice without taking into account any demographic features. In older patients, a trend towards a higher 99th percentile URL was reported in numerous studies.^23–25 If a higher URL had been applied for older patients, this gap in the incidence of MINS between younger and older patients might have been reduced. There may be a need for different MINS thresholds according to age, but this requires further investigation and is beyond the scope of this study. Another possibility is that younger patients may be more tolerant to the perioperative events that lead to the occurrence of MINS. Reportedly, aging has been related to vulnerability to myocardial ischemia by compromising restoration with reduced coronary perfusion.^26,27 Our subgroup analysis also demonstrated that the lower incidence of MINS in younger patients was limited to the ones with particular perioperative risk factors such as diabetes, higher surgical risk, or general anesthesia. In addition, although younger age showed a significant AF on MINS, the number was relatively low compared with other variables.

Considering the insurmountable differences by age in the long-term follow up, we compared mortalities for the short-term follow up. A notable finding was that only the cardiovascular mortality of the <45-year group was consistently lower following the incidence of MINS. This may be related to the etiology of MINS. The main mechanism of MINS is oxygen supply/demand mismatch ischemia, either related to coronary or a non-coronary cause.³ However, fatal cases of perioperative myocardial ischemia have reportedly been related to acute coronary syndrome with coronary plaque rupture;^28,29 therefore, the incidence of MINS might have been more remarkably affected by the younger age in cases directly related to coronary issues, as shown in previous studies.³⁰ However, this difference in mortality according to age vanished to the level of insignificance after selecting only the patients who were diagnosed with MINS.

In a further analysis, after stratifying the study patients into 4 groups according to both age and MINS, the mortality was enormously increased in patients with MINS regardless of age. MINS was independently associated with increased mortality also in patients aged <45 years, and the increase of cardiovascular mortality appeared to be even more pronounced in those aged <45 years. These findings could be related to the fact that the <45-year group had a relatively higher risk, but the mortality in only those patients with MINS did not show a difference according to age, suggesting a comparable prognostic impact of MINS in patients younger and older than age 45 years. These results underscore the fact that the occurrence of MINS should not be ignored, even in younger patients undergoing non-cardiac surgery and suggest that younger patients who are at risk may need to be selected for perioperative cTn screening.

In the recent perioperative guidelines, a recommendation for perioperative cTn investigation to screen for MINS has been included, but the details vary. The guidelines from the American College of Cardiology/American Heart Association and the European Society of Cardiology/Anesthesiology give recommendations for routine cTn measurement for patients with ischemic symptoms or those at high risk for cardiovascular events.^5,6 The more recent Canadian Cardiovascular Society guideline adds a strong recommendation for obtaining daily cTn measurements for 2–3 days following surgery in patients with a >5% cardiovascular risk, based on the finding that the vast majority of clinically important MINS may be undetected otherwise.^7,9 Our results provide a clue that the current guidelines may also need to be applied to the younger population, and a future study involving the younger population in a prospective setting seems necessary. Of note, the present guidelines are supported by the cost benefit of perioperative cTn screening,³¹ so this may also need to be investigated for younger patients.

Our study has several limitations. First, as is common with a single-center, observational study, the results might have been affected by selection bias or unmeasured confounding factors. Also, because our institutional patients were mostly Asians, ethnic differences could not be considered. Second, although perioperative cTn was measured for a particular group of patients according to the institutional protocol, it could also be measured at the discretion of a clinician. And also, given that patients with a high cardiovascular risk usually underwent the test, our results may have been exaggerated. Third, a detailed preoperative cardiac evaluation, including results such as left ventricular ejection fraction or coronary artery angiograms, was not available for all patients. Additionally, functional capacity may be different according to age, but it could not be included in the analysis owing the retrospective nature. Despite these limitations, this is the first study to compare the incidence and relevant outcomes of MINS in patients under and over age 45 years. Our results may be used to reinforce evidence for future guidelines regarding perioperative cTn screening.

Conclusions

MINS has comparable prognostic impact in patients under and over age 45 years; therefore, a future study involving patients <45 years following guidelines to address risk factors of MINS and screening for perioperative troponin elevation needs to be considered.

Authors’ Contributions

Substantial contributions to the conception or design of the work: J.P., J.-h.K., S.-H.L. Acquisition, analysis: J.P., J.-h.K., A.R.O., J.K., K.Y. Interpretation of data for the work: J.P., J.-h.K., S.-H.L., J.-H.L., J.J.M., S.-C.L., H.-C.G., K.K., J.A. Drafting the work: J.P., J.-h.K. Revising it critically for important intellectual content: S.-H.L., J.-h.C., H.-C.G. Final approval of the version to be published: All authors.

Sources of Funding

The authors received no specific funding for this work.

Disclosures

The authors have declared that no competing interests.

IRB Information

The present study was approved by the Institutional Review Board at Samsung Medical Center. Reference number: SMC 2019-08-048. Trial Registration: KCT0004244.

Data Availability

The data we used for this study was curated using CDW (Clinical data Warehouse), which pseudonymized the data from our institutional electronic medical records. Therefore, our data is deidentified by eliminating all identifiable variables such as name, social security number, hospital number, etc. However, it is illegal to make these data available to the public without restriction.

Regarding the availability of our data, please contact [e-mail], the head of our institutional data security department.

Supplementary Files

Please find supplementary file(s);

http://dx.doi.org/10.1253/circj.CJ-21-0106

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