High Troponin Levels After Noncardiac Surgery: Cause for Concern?

It has long been recognized that myocardial infarction (MI) after noncardiac surgery is associated with significant morbidity and mortality and that increasing age is a potent risk factor for perioperative cardiovascular complications, including MI.1, 2 With the development of increasingly sensitive and specific biomarkers for the detection of myocardial injury, coupled with the greater frequency with which biomarkers are measured after major noncardiac surgery, there has been a substantial rise in the number and proportion of older adults found to have small troponin “leaks” in the postoperative period.3, 4 These minimal troponin elevations often occur in the absence of ischemic symptoms or electrocardiographic changes, and there has been increasing concern among healthcare providers about how to interpret and manage these subclinical events. I was invited by the Editor-in-Chief of the Journal of the American Geriatrics Society to provide a commentary on this topic. Two studies recently published in JAMA and Circulation provide important insights into this issue.5, 6 In the first study, the Vascular Events in Noncardiac Surgery Patients Cohort Evaluation (VISION) investigators evaluated 15,133 individuals aged 45 and older undergoing noncardiac surgery.5 Individuals aged 65 to 74 comprised 25% of the study population and 24% of individuals were aged 75 and older; 51.5% of participants were female. Troponin T was measured 6 to 12 hours after surgery and again on postoperative Days 1, 2, and 3. Abnormal troponin T was defined as a peak value of 0.02 ng/mL or more. The primary outcome was all-cause mortality at 30 days. Overall 30-day mortality was 1.9%, and median time to death was 11 days. Troponin T was elevated in 11.9% of participants. Mortality at 30 days was 1.0%, 4.0%, 9.3%, and 16.9% in individuals with peak troponin T levels of 0.01 ng/mL or less, 0.02 ng/mL, 0.03 to 0.29 ng/mL, and 0.30 ng/mL or more, respectively. In multivariable analysis that adjusted for 24 preoperative variables, adjusted hazard ratios for 30-day mortality were 2.41, 5.00, and 10.48 for participants with peak troponin T levels of 0.02, 0.03 to 0.29, and 0.30 ng/mL or more compared with those with peak levels of 0.01 ng/mL or less. Older age was also an independent predictor of vascular and nonvascular death, but data on interactions between age, troponin T, and mortality were not reported. In the second study, the Cardiac Health After Surgery (CHASE) investigators evaluated 2,232 consecutive individuals aged 60 and older at intermediate to high risk of perioperative cardiac complications.6 The study was conducted at a single center in the Netherlands in 2011. Troponin I was measured at least once within the first 3 postoperative days in 1,627 individuals (73.4%), and high troponin I was defined as >0.06 ng/mL. The primary outcome was all-cause mortality at 30 days. The mean age of individuals with troponin I measurements was 71.0 ± 7.7; 51.9% were male. Common comorbidities were hypertension (51.0%), diabetes mellitus (17.7%), ischemic heart disease (16.2%), cerebrovascular disease (14.9%), peripheral arterial disease (11.1%), chronic obstructive pulmonary disease (10.3%), and chronic renal failure (10.2%). Elevated troponin I levels occurred in 315 individuals (19.4%), of which 51.4% occurred on the first postoperative day, 27.3% on the second day, and 21.3% on the third day. The proportion of individuals with high troponin levels increased strikingly with age: 15.6% in individuals aged 60 to 69, 20.3% in those aged 70 to 79, and 28.6% in those aged 80 and older. Fifty-six individuals (3.4%) died within 30 days of surgery, and the median time to death was 12 days. In multivariable analyses adjusted for age, sex, and preoperative variables known to predict postoperative cardiac events, troponin I levels of 0.07 to 0.59 ng/mL were associated with a 2.36 relative risk of death within 30 days compared with individuals without high troponin levels, and troponin I levels of 0.60 ng/mL and higher were associated with a relative risk of 4.19. In the fully adjusted models, high troponin levels and emergency surgery were the only independent predictors of 30-day mortality. Median hospital length of stay was 10 days in individuals with high troponin levels compared to 5 days in those without evidence of myocardial injury (P < .01). These studies, which are consistent with prior reports,7 provide compelling evidence that even seemingly trivial troponin “leaks” are not benign. Rather, any rise in troponin level is a marker of greater mortality, and there is a graded relationship between the magnitude of troponin elevation and the risk of death. These findings are particularly disturbing for the oldest individuals, given that advanced age is a preoperative risk factor for major perioperative complications (including cardiac, pulmonary, renal, neurological, and cognitive disorders), as well as a risk factor for myocardial injury, as manifested by elevated troponin levels in the postoperative period.1, 2, 6 An important limitation of both of these studies5, 6 is that baseline renal function and change in renal function during the periprocedural period were not adequately accounted for in the multivariable models. Several questions arise concerning translation of these findings into clinical practice. First, are interventions available that reduce the risk of myocardial injury during and after surgery, thereby improving clinical outcomes? Beta-blockers are recommended for individuals with known coronary artery disease or other conditions associated with high risk of ischemic complications (e.g., vascular surgery in older adults with multiple cardiac risk factors),8 but routine use of beta-blockers in the perioperative period is controversial because data from various studies are conflicting.9, 10 In the largest randomized trial to date, which enrolled more than 8,300 subjects with a mean age of 69, perioperative treatment with extended-release metoprolol succinate was associated with 16% lower cardiovascular death, nonfatal MI, or nonfatal cardiac arrest (P = .04). However, all-cause mortality and incident stroke were significantly higher in the metoprolol group.11 Detailed analyses of outcomes according to age were not reported, but the adjusted odds ratio for all-cause mortality was 1.65 in individuals aged 70 and older compared with those younger than 70.11 Although current guidelines also recommend preoperative stress testing in selected high-risk individuals before major noncardiac surgery,8 there is no convincing evidence that intensified medical therapy or coronary revascularization improves short- or long- term outcomes in individuals with abnormal stress tests.8, 12 Another important question is how to manage individuals with elevated postoperative troponin levels. In individuals with markedly increased troponin levels accompanied by ischemic chest pain, electrocardiographic changes, or hemodynamic instability, it seems reasonable to take an aggressive approach, including early coronary angiography and revascularization if feasible, but data to support this strategy are limited, and there is potential for procedural complications, especially bleeding and acute kidney injury, with the oldest individuals being at highest risk. Use of aspirin and statins has been associated with better outcomes in individuals with perioperative myocardial injury,13 but additional data are needed. In a small randomized trial of 70 older adults with high troponin levels after orthopedic surgery, cardiology care was not associated with better 1-year survival than standard management.14 Finally, the VISION and CHASE investigators raised the question of whether routine measurement of troponin levels is warranted after noncardiac surgery in individuals at moderate to high risk of perioperative complications, a large proportion of whom are older adults.5, 6 This is a difficult issue, because there is no evidence that any intervention improves outcomes in individuals with high but asymptomatic troponin levels, and there is potential for harm from additional testing. Conversely, a high troponin level may serve as a signal that more-vigilant care is indicated, and it may aid in subsequent decision-making, including reassessment of goals of care and desire for future interventions. Based on available data, I do not believe that the potential benefits of routine troponin monitoring outweigh the potential risks; rather, I support selective troponin testing in cases in which there is a clinical suspicion of myocardial ischemia. In summary, there is a strong body of evidence indicating that postoperative troponin leaks are clinically significant and portend risk of early mortality, but additional research is needed to develop strategies for preventing postoperative myocardial injury and for determining optimal management of individuals with high postoperative troponin levels. Furthermore, as in most areas of geriatrics, it is highly unlikely that a one-size-fits-all approach will be optimal. Therefore, it is crucial that any new management strategies be undertaken in the context of the older adult's overall health status and goals of care. The author thanks Mathew S. Maurer, MD, for critical review of the manuscript. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the author and has determined that the author has no financial or any other kind of personal conflicts with this paper. Author Contributions: Michael W. Rich is responsible for the entire content of this paper. Sponsor's Role: None.