The electronic frailty index and outcomes in patients with myocardial infarction.

BACKGROUND: Frailty is increasingly present in patients with acute myocardial infarction. The electronic Frailty Index (eFI) is a validated method of identifying vulnerable older patients in the community from routine primary care data. Our aim was to assess the relationship between the eFI and outcomes in older patients hospitalised with acute myocardial infarction. STUDY DESIGN AND SETTING: Retrospective cohort study using the DataLoch Heart Disease Registry comprising consecutive patients aged 65 years or over hospitalised with a myocardial infarction between October 2013 and March 2021. METHODS: Patients were classified as fit, mild, moderate, or severely frail based on their eFI score. Cox-regression analysis was used to determine the association between frailty category and all-cause mortality. RESULTS: In 4670 patients (median age 77 years [71-84], 43% female), 1865 (40%) were classified as fit, with 1699 (36%), 798 (17%) and 308 (7%) classified as mild, moderate and severely frail, respectively. In total, 1142 patients died within 12 months of which 248 (13%) and 147 (48%) were classified as fit and severely frail, respectively. After adjustment, any degree of frailty was associated with an increased risk of all-cause death with the risk greatest in the severely frail (reference = fit, adjusted hazard ratio 2.87 [95% confidence intervals 2.24 to 3.66]). CONCLUSION: The eFI identified patients at high risk of death following myocardial infarction. Automatic calculation within administrative data is feasible and could provide a low-cost method of identifying vulnerable older patients on hospital presentation.

Adoption of high-sensitivity cardiac troponin for risk stratification of patients with suspected myocardial infarction: a multicentre cohort study.

Background: Guidelines recommend high-sensitivity cardiac troponin to risk stratify patients with possible myocardial infarction and identify those eligible for discharge. Our aim was to evaluate adoption of this approach in practice and to determine whether effectiveness and safety varies by age, sex, ethnicity, or socioeconomic deprivation status. Methods: A multi-centre cohort study was conducted in 13 hospitals across the United Kingdom from November 1st, 2021, to October 31st, 2022. Routinely collected data including high-sensitivity cardiac troponin I or T measurements were linked to outcomes. The primary effectiveness and safety outcomes were the proportion discharged from the Emergency Department, and the proportion dead or with a subsequent myocardial infarction at 30 days, respectively. Patients were stratified using peak troponin concentration as low (<5 ng/L), intermediate (5 ng/L to sex-specific 99th percentile), or high-risk (>sex-specific 99th percentile). Findings: In total 137,881 patients (49% [67,709/137,881] female) were included of whom 60,707 (44%), 42,727 (31%), and 34,447 (25%) were stratified as low-, intermediate- and high-risk, respectively. Overall, 65.8% (39,918/60,707) of low-risk patients were discharged from the Emergency Department, but this varied from 26.8% [2200/8216] to 93.5% [918/982] by site. The safety outcome occurred in 0.5% (277/60,707) and 11.4% (3917/34,447) of patients classified as low- or high-risk, of whom 0.03% (18/60,707) and 1% (304/34,447) had a subsequent myocardial infarction at 30 days, respectively. A similar proportion of male and female patients were discharged (52% [36,838/70,759] versus 54% [36,113/67,109]), but discharge was more likely if patients were <70 years old (61% [58,533/95,227] versus 34% [14,428/42,654]), from areas of low socioeconomic deprivation (48% [6697/14,087] versus 43% [12,090/28,116]) or were black or asian compared to caucasian (62% [5458/8877] and 55% [10,026/18,231] versus 46% [35,138/75,820]). Interpretation: Despite high-sensitivity cardiac troponin correctly identifying half of all patients with possible myocardial infarction as being at low risk, only two-thirds of these patients were discharged. Substantial variation in the discharge of patients by age, ethnicity, socioeconomic deprivation, and site was observed identifying important opportunities to improve care. Funding: UK Research and Innovation.

Application of the Universal Definition of Myocardial Infarction in Clinical Practice in Scotland and Sweden.

Importance: Whether the diagnostic classifications proposed by the universal definition of myocardial infarction (MI) to identify type 1 MI due to atherothrombosis and type 2 MI due to myocardial oxygen supply-demand imbalance have been applied consistently in clinical practice is unknown. Objective: To evaluate the application of the universal definition of MI in consecutive patients with possible MI across 2 health care systems. Design, Setting, and Participants: This cohort study used data from 2 prospective cohorts enrolling consecutive patients with possible MI in Scotland (2013-2016) and Sweden (2011-2014) to assess accuracy of clinical diagnosis of MI recorded in hospital records for patients with an adjudicated diagnosis of type 1 or type 2 MI. Data were analyzed from August 2022 to February 2023. Main Outcomes and Measures: The main outcome was the proportion of patients with a clinical diagnosis of MI recorded in the hospital records who had type 1 or type 2 MI, adjudicated by an independent panel according to the universal definition. Characteristics and risk of subsequent MI or cardiovascular death at 1 year were compared. Results: A total of 50 356 patients were assessed. The cohort from Scotland included 28 783 (15 562 men [54%]; mean [SD] age, 60 [17] years), and the cohort from Sweden included 21 573 (11 110 men [51%]; mean [SD] age, 56 [17] years) patients. In Scotland, a clinical diagnosis of MI was recorded in 2506 of 3187 patients with an adjudicated diagnosis of type 1 MI (79%) and 122 of 716 patients with an adjudicated diagnosis of type 2 MI (17%). Similar findings were observed in Sweden, with 970 of 1111 patients with adjudicated diagnosis of type 1 MI (87%) and 57 of 251 patients with adjudicated diagnosis of type 2 MI (23%) receiving a clinical diagnosis of MI. Patients with an adjudicated diagnosis of type 1 MI without a clinical diagnosis were more likely to be women (eg, 336 women [49%] vs 909 women [36%] in Scotland; P < .001) and older (mean [SD] age, 71 [14] v 67 [14] years in Scotland, P < .001) and, when adjusting for competing risk from noncardiovascular death, were at similar or increased risk of subsequent MI or cardiovascular death compared with patients with a clinical diagnosis of MI (eg, 29% vs 18% in Scotland; P < .001). Conclusions and Relevance: In this cohort study, the universal definition of MI was not consistently applied in clinical practice, with a minority of patients with type 2 MI identified, and type 1 MI underrecognized in women and older persons, suggesting uncertainty remains regarding the diagnostic criteria or value of the classification.

Uniform or Sex-Specific Cardiac Troponin Thresholds to Rule Out Myocardial Infarction at Presentation.

BACKGROUND: Myocardial infarction can be ruled out in patients with a single cardiac troponin measurement. Whether use of a uniform rule-out threshold has resulted in sex differences in care remains unclear. OBJECTIVES: The purpose of this study was to evaluate implementation of a uniform rule-out threshold in females and males with possible myocardial infarction, and to derive and validate sex-specific thresholds. METHODS: The implementation of a uniform rule-out threshold (<5 ng/L) with a high-sensitivity cardiac troponin I assay was evaluated in consecutive patients presenting with possible myocardial infarction. The proportion of low-risk patients discharged from the emergency department and incidence of myocardial infarction or cardiac death at 30 days were determined. Sex-specific thresholds were derived and validated, and proportion of female and male patients were stratified as low-risk compared with uniform threshold. RESULTS: In 16,792 patients (age 58 ± 17 years; 46% female) care was guided using a uniform threshold. This identified more female than male patients as low risk (73% vs 62%), but a similar proportion of low-risk patients were discharged from the emergency department (81% for both) with fewer than 5 (<0.1%) patients having a subsequent myocardial infarction or cardiac death at 30 days. Compared with a uniform threshold of <5 ng/L, use of sex-specific thresholds would increase the proportion of female (61.8% vs 65.9%) and reduce the proportion of male (54.8% vs 47.8%) patients identified as low risk. CONCLUSIONS: Implementation of a uniform rule-out threshold for myocardial infarction was safe and effective in both sexes. Sex-specific rule-out thresholds should be considered, but their impact on effectiveness and safety may be limited.

Multiple Cardiac Biomarkers to Improve Prediction of Cardiovascular Events: Findings from the Generation Scotland Scottish Family Health Study.

BACKGROUND: Many studies have investigated whether single cardiac biomarkers improve cardiovascular risk prediction for primary prevention but whether a combined approach could further improve risk prediction is unclear. We aimed to test a sex-specific, combined cardiac biomarker approach for cardiovascular risk prediction. METHODS: In the Generation Scotland Scottish Family Health Study, N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor-15 (GDF-15), cardiac troponin I (cTnI), cardiac troponin T (cTnT), and C-reactive protein (CRP) were measured in stored serum using automated immunoassays. Sex-specific Cox models that included SCORE2 risk factors evaluated addition of single and combined biomarkers for prediction of major adverse cardiovascular events (MACE). Combined biomarker models were compared to a baseline model that included SCORE2 risk factors. RESULTS: The study population comprised 18 383 individuals (58.9% women, median age of 48 years [25th-75th percentile, 35-58 years]). During the median follow up of 11.6 (25th-75th percentile, 10.8-13.0) years, MACE occurred in 942 (5.1%) individuals. The greatest increase in discrimination with addition of individual biomarkers to the base model was for women GDF-15 and for men NT-proBNP (change in c-index: + 0.010 for women and +0.005 for men). For women, combined biomarker models that included GDF-15 and NT-proBNP (+0.012) or GDF-15 and cTnI (+0.013), but not CRP or cTnT, further improved discrimination. For men, combined biomarker models that included NT-proBNP and GDF-15 (+0.007), NT-proBNP and cTnI (+0.006), or NT-proBNP and CRP (+0.008), but not cTnT, further improved discrimination. CONCLUSIONS: A combined biomarker approach, particularly the use of GDF-15, NT-proBNP and cTnI, further refined cardiovascular risk estimates.

Implementation of a high sensitivity cardiac troponin I assay and risk of myocardial infarction or death at five years: observational analysis of a stepped wedge, cluster randomised controlled trial.

OBJECTIVE: To evaluate the impact of implementing a high sensitivity assay for cardiac troponin I on long term outcomes in patients with suspected acute coronary syndrome. DESIGN: Secondary observational analysis of a stepped wedge, cluster randomised controlled trial. SETTING: 10 secondary and tertiary care centres in Scotland, UK. PARTICIPANTS: 48 282 consecutive patients with suspected acute coronary syndrome. Myocardial injury was defined as any high sensitivity assay result for cardiac troponin I >99th centile of 16 ng/L in women and 34 ng/L in men. INTERVENTION: Hospital sites were randomly allocated to either early (n=5 hospitals) or late (n=5 hospitals) implementation of a high sensitivity cardiac troponin I assay with sex specific diagnostic thresholds. MAIN OUTCOME MEASURE: The main outcome was myocardial infarction or death at five years. RESULTS: 10 360 patients had cardiac troponin concentrations greater than the 99th centile, of whom 1771 (17.1%) were reclassified by the high sensitivity assay. The five year incidence of subsequent myocardial infarction or death before and after implementation of the high sensitivity assay was 29.4% (5588/18 978) v 25.9% (7591/29 304), respectively, in all patients (adjusted hazard ratio 0.97, 95% confidence interval 0.93 to 1.01), and 63.0% (456/720) v 53.9% (567/1051), respectively, in those reclassified by the high sensitivity assay (0.82, 0.72 to 0.94). After implementation of the high sensitivity assay, a reduction in subsequent myocardial infarction or death was observed in patients with non-ischaemic myocardial injury (0.83, 0.75 to 0.91) but not in those with type 1 or type 2 myocardial infarction (0.92, 0.83 to 1.01 and 0.98, 0.84 to 1.14). CONCLUSIONS: Implementation of a high sensitivity cardiac troponin I assay in the assessment of patients with suspected acute coronary syndrome was associated with a reduced risk of subsequent myocardial infarction or death at five years in those reclassified by the high sensitivity assay. Improvements in outcome were greatest in patients with non-ischaemic myocardial injury, suggesting a broader benefit beyond the identification of myocardial infarction. TRIAL REGISTRATION: ClinicalTrials.gov NCT01852123.

High-Sensitivity Cardiac Troponin for Risk Assessment in Patients With Chronic Coronary Artery Disease.

BACKGROUND: Cardiac troponin is used for risk stratification of patients with acute coronary syndromes; however, the role of testing in other settings remains unclear. OBJECTIVES: The aim of this study was to evaluate whether cardiac troponin testing could enhance risk stratification in patients with chronic coronary artery disease independent of disease severity and conventional risk measures. METHODS: In a prospective cohort of consecutive patients with symptoms suggestive of stable angina attending for outpatient coronary angiography, high-sensitivity cardiac troponin I was measured before angiography, and clinicians were blinded to the results. The primary outcome was myocardial infarction or cardiovascular death during follow-up. RESULTS: In 4,240 patients (age 66 years [IQR: 59-73 years], 33% female), coronary artery disease was identified in 3,888 (92%) who had 255 (6%) primary outcome events during a median follow-up of 2.4 years (IQR: 1.3-3.6 years). In patients with coronary artery disease, troponin concentrations were 2-fold higher in those with an event compared with those without (6.7 ng/L [IQR: 3.2-14.2 ng/L] vs 3.3 ng/L [IQR: 1.7-6.6 ng/L]; P < 0.001). Troponin concentrations were associated with the primary outcome after adjusting for cardiovascular risk factors and coronary artery disease severity (adjusted HR: 2.3; 95% CI: 1.7-3.0, log10 troponin; P < 0.001). A troponin concentration >10 ng/L identified patients with a 50% increase in the risk of myocardial infarction or cardiovascular death. CONCLUSIONS: In patients with chronic coronary artery disease, cardiac troponin predicts risk of myocardial infarction or cardiovascular death independent of cardiovascular risk factors and disease severity. Further studies are required to evaluate whether routine testing could inform the selection of high-risk patients for treatment intensification. (Myocardial Injury in Patients Referred for Coronary Angiography [MICA]; ISRCTN15620297).

Depression and Malnutrition for Prediction of Mortality after Transcatheter Aortic Valve Replacement: A Registry Study of a Tertiary Referral Hospital.

Moderate to severe frailty is a predictor of a poor outcome after transcatheter aortic valve replacement (TAVR), but little is known about the prognostic importance of different geriatric frailty markers in an overall fit or pre-frail geriatric population undergoing TAVR. This retrospective study aimed to examine the incremental value of adding patient frailty markers to conventional surgical risk score to predict all-cause mortality in relatively fit elderly patients undergoing TAVR. Overall patient frailty was assessed using the comprehensive geriatric assessment frailty index (CGA-FI). Multivariable Cox regression models were used to evaluate relationships of different geriatric frailty markers with all-cause mortality and single and combined frailty models were compared to a baseline model that included EuroSCORE II factors. One hundred relatively fit geriatric patients (84 ± 4 years old, mean CGA-FI 0.14 ± 0.05) were included, and 28% died during a median follow-up of 24 months. After adjustment, risk of depression (geriatric depression scale 15 (GDS-15)) and malnutrition remained significantly associated with all-cause mortality (HR 4.381, 95% CI 1.787-10.743; p = 0.001 and HR 3.076, 95% CI 1.151-8.217; p = 0.025, respectively). A combined frailty marker model including both GDS-15 and malnutrition on top of EuroSCORE II improved the discriminative ability to predict all-cause mortality (change in c-index: + 0.044). Screening for those frailty markers on top of the traditionally used EuroSCORE II may improve risk stratification and prognosis in relatively fit geriatric patients undergoing TAVR.

Trajectories of cardiac troponin in the decades before cardiovascular death: a longitudinal cohort study.

BACKGROUND: High-sensitivity cardiac troponin testing is a promising tool for cardiovascular risk prediction, but whether serial testing can dynamically predict risk is uncertain. We evaluated the trajectory of cardiac troponin I in the years prior to a cardiovascular event in the general population, and determine whether serial measurements could track risk within individuals. METHODS: In the Whitehall II cohort, high-sensitivity cardiac troponin I concentrations were measured on three occasions over a 15-year period. Time trajectories of troponin were constructed in those who died from cardiovascular disease compared to those who survived or died from other causes during follow up and these were externally validated in the HUNT Study. A joint model that adjusts for cardiovascular risk factors was used to estimate risk of cardiovascular death using serial troponin measurements. RESULTS: In 7,293 individuals (mean 58 ± 7 years, 29.4% women) cardiovascular and non-cardiovascular death occurred in 281 (3.9%) and 914 (12.5%) individuals (median follow-up 21.4 years), respectively. Troponin concentrations increased in those dying from cardiovascular disease with a steeper trajectory compared to those surviving or dying from other causes in Whitehall and HUNT (Pinteraction < 0.05 for both). The joint model demonstrated an independent association between temporal evolution of troponin and risk of cardiovascular death (HR per doubling, 1.45, 95% CI,1.33-1.75). CONCLUSIONS: Cardiac troponin I concentrations increased in those dying from cardiovascular disease compared to those surviving or dying from other causes over the preceding decades. Serial cardiac troponin testing in the general population has potential to track future cardiovascular risk.

Troponin in early presenters to rule out myocardial infarction.

AIMS: Whether a single cardiac troponin measurement can safely rule out myocardial infarction in patients presenting within a few hours of symptom onset is uncertain. The study aim was to assess the performance of troponin in early presenters. METHODS AND RESULTS: In patients with possible myocardial infarction, the diagnostic performance of a single measurement of high-sensitivity cardiac troponin I at presentation was evaluated and externally validated in those tested ≤3, 4-12, and >12 h from symptom onset. The limit-of-detection (2 ng/L), rule-out (5 ng/L), and sex-specific 99th centile (16 ng/L in women; 34 ng/L in men) thresholds were compared. In 41 103 consecutive patients [60 (17) years, 46% women], 12 595 (31%) presented within 3 h, and 3728 (9%) had myocardial infarction. In those presenting ≤3 h, a threshold of 2 ng/L had greater sensitivity and negative predictive value [99.4% (95% confidence interval 99.2%-99.5%) and 99.7% (99.6%-99.8%)] compared with 5 ng/L [96.5% (96.2%-96.8%) and 99.3% (99.1%-99.4%)]. In those presenting ≥3 h, the sensitivity and negative predictive value were similar for both thresholds. The sensitivity of the 99th centile was low in early and late presenters at 71.4% (70.6%-72.2%) and 92.5% (92.0%-93.0%), respectively. Findings were consistent in an external validation cohort of 7088 patients. CONCLUSION: In early presenters, a single measurement of high-sensitivity cardiac troponin I below the limit of detection may facilitate the safe rule out of myocardial infarction. The 99th centile should not be used to rule out myocardial infarction at presentation even in those presenting later following symptom onset.

Patterns of Cardiac Troponin I Concentrations as Risk Predictors of Cardiovascular Disease and Death: The Trøndelag Health Study.

BACKGROUND: Concentrations of cardiac troponin predict risk of cardiovascular disease and death in the general population. There is limited evidence on changing patterns of cardiac troponin in the years preceding cardiovascular events. METHODS: We analyzed cardiac troponin I (cTnI) with a high-sensitivity assay in 3272 participants in the Trøndelag Health (HUNT) Study at study visit 4 (2017-2019). Of these, 3198 had measurement of cTnI at study visit 2 (1995-1997), 2661 at study visit 3, and 2587 at all 3 study visits. We assessed the trajectories of cTnI concentrations in the years prior to cardiovascular events using a generalized linear mixed model, with adjustment for age, sex, cardiovascular risk factors, and comorbidities. RESULTS: At HUNT4 baseline, median age was 64.8 (range 39.4-101.3) years, and 55% were women. Study participants who were admitted because of heart failure or died from cardiovascular cause on follow-up had a steeper increase in cTnI compared with study participants with no events (P < .001). The average yearly change in cTnI was 0.235 (95% confidence interval, 0.192-0.289) ng/L for study participants with heart failure or cardiovascular death, and -0.022 (95% confidence interval, -0.022 to -0.023) ng/L for study participants with no events. Study participants who experienced myocardial infarction, ischemic stroke, or noncardiovascular mortality exhibited similar cTnI patterns. CONCLUSIONS: Fatal and nonfatal cardiovascular events are preceded by slowly increasing concentrations of cardiac troponin, independently of established cardiovascular risk factors. Our results support the use of cTnI measurements to identify at-risk subjects who progress to subclinical and later overt cardiovascular disease.

Sex Differences in Cardiac Troponin Trajectories Over the Life Course.

BACKGROUND: Cardiac troponin concentrations are lower in women than men. We examined whether age- and risk factor-related changes in cardiac troponin over the life course differ by sex and if the trajectory of cardiac troponin was informative in respect of cardiovascular outcomes in women and men in the general population. METHODS: In the Whitehall II cohort, high-sensitivity cardiac troponin I concentrations were measured on 3 occasions over a 15-year period. Using linear mixed-effects models, the sex-specific trajectories of cardiac troponin were evaluated, and the relationship with conventional cardiovascular risk factors determined. Using multistate joint models, the association between sex-specific trajectories of cardiac troponin and a composite outcome of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death was evaluated. RESULTS: In 2142 women and 5151 men (mean, 58±7 and 57±7 years of age, respectively), there were 177 (8.3%) and 520 (10.1%) outcome events, respectively, during a median follow-up of 20.9 (25th to 75th percentile, 15.8-21.3) years. Cardiac troponin concentrations were persistently lower in women than in men (median baseline concentration: 2.4 [25th to 75th percentile, 1.7-3.6] ng/L versus 3.7 [25th to 75th percentile, 2.6-5.8] ng/L, respectively, P<0.001), with women exhibiting a relatively larger increase with advancing age as compared with men (Pinteraction<0.001). Apart from age, a significant and divergent interaction with sex was found for the association between cardiac troponin and body mass index (BMI) (Pinteraction=0.008) and diabetes (Pinteraction=0.003). During follow-up, cardiac troponin concentrations were associated to the outcome in both women and men (adjusted hazard ratio per 2-fold difference [95% CI, 1.34 (1.17-1.52) and 1.30 (1.21-1.40), respectively], Pinteraction=0.752). The slope of cardiac troponin was significantly associated with the outcome in women, but not in men (adjusted hazard ratio [95% CI, 2.70 (1.01-7.33) and 1.31 (0.62-2.75), respectively], Pinteraction=0.250). CONCLUSIONS: Trajectories of cardiac troponin differ between women and men in the general population, with differing associations to conventional risk factors and cardiovascular outcomes. Our findings highlight the importance of a sex-specific approach when serial cardiac troponin testing is applied for cardiovascular risk prediction.

Improving Risk Stratification for Patients With Type 2 Myocardial Infarction.

BACKGROUND: Despite poor cardiovascular outcomes, there are no dedicated, validated risk stratification tools to guide investigation or treatment in type 2 myocardial infarction. OBJECTIVES: The goal of this study was to derive and validate a risk stratification tool for the prediction of death or future myocardial infarction in patients with type 2 myocardial infarction. METHODS: The T2-risk score was developed in a prospective multicenter cohort of consecutive patients with type 2 myocardial infarction. Cox proportional hazards models were constructed for the primary outcome of myocardial infarction or death at 1 year using variables selected a priori based on clinical importance. Discrimination was assessed by area under the receiving-operating characteristic curve (AUC). Calibration was investigated graphically. The tool was validated in a single-center cohort of consecutive patients and in a multicenter cohort study from sites across Europe. RESULTS: There were 1,121, 250, and 253 patients in the derivation, single-center, and multicenter validation cohorts, with the primary outcome occurring in 27% (297 of 1,121), 26% (66 of 250), and 14% (35 of 253) of patients, respectively. The T2-risk score incorporating age, ischemic heart disease, heart failure, diabetes mellitus, myocardial ischemia on electrocardiogram, heart rate, anemia, estimated glomerular filtration rate, and maximal cardiac troponin concentration had good discrimination (AUC: 0.76; 95% CI: 0.73-0.79) for the primary outcome and was well calibrated. Discrimination was similar in the consecutive patient (AUC: 0.83; 95% CI: 0.77-0.88) and multicenter (AUC: 0.74; 95% CI: 0.64-0.83) cohorts. T2-risk provided improved discrimination over the Global Registry of Acute Coronary Events 2.0 risk score in all cohorts. CONCLUSIONS: The T2-risk score performed well in different health care settings and could help clinicians to prognosticate, as well as target investigation and preventative therapies more effectively. (High-Sensitivity Troponin in the Evaluation of Patients With Suspected Acute Coronary Syndrome [High-STEACS]; NCT01852123).

Influence of Age on the Diagnosis of Myocardial Infarction.

BACKGROUND: The 99th centile of cardiac troponin, derived from a healthy reference population, is recommended as the diagnostic threshold for myocardial infarction, but troponin concentrations are strongly influenced by age. Our aim was to assess the diagnostic performance of cardiac troponin in older patients presenting with suspected myocardial infarction. METHODS: In a secondary analysis of a multicenter trial of consecutive patients with suspected myocardial infarction, we assessed the diagnostic accuracy of high-sensitivity cardiac troponin I at presentation for the diagnosis of type 1, type 2, or type 4b myocardial infarction across 3 age groups (<50, 50-74, and ≥75 years) using guideline-recommended sex-specific and age-adjusted 99th centile thresholds. RESULTS: In 46 435 consecutive patients aged 18 to 108 years (mean, 61±17 years), 5216 (11%) had a diagnosis of myocardial infarction. In patients <50 (n=12 379), 50 to 74 (n=22 380), and ≥75 (n=11 676) years, the sensitivity of the guideline-recommended threshold was similar at 79.2% (95% CI, 75.5-82.9), 80.6% (95% CI, 79.2-82.1), and 81.6% (95% CI, 79.8-83.2), respectively. The specificity decreased with advancing age from 98.3% (95% CI, 98.1-98.5) to 95.5% (95% CI, 95.2-95.8), and 82.6% (95% CI, 81.9-83.4). The use of age-adjusted 99th centile thresholds improved the specificity (91.3% [90.8%-91.9%] versus 82.6% [95% CI, 81.9%-83.4%]) and positive predictive value (59.3% [57.0%-61.5%] versus 51.5% [49.9%-53.3%]) for myocardial infarction in patients ≥75 years but failed to prevent the decrease in either parameter with increasing age and resulted in a marked reduction in sensitivity compared with the use of the guideline-recommended threshold (55.9% [53.6%-57.9%] versus 81.6% [79.8%-83.3%]. CONCLUSIONS: Age alters the diagnostic performance of cardiac troponin, with reduced specificity and positive predictive value in older patients when applying the guideline-recommended or age-adjusted 99th centiles. Individualized diagnostic approaches rather than the adjustment of binary thresholds are needed in an aging population.