Association of troponin level and age with mortality in 250 000 patients: cohort study across five UK acute care centres

Abstract

Objective: To determine the relation between age and troponin level and its prognostic implication.

Design: Retrospective cohort study.

Setting: Five cardiovascular centres in the UK National Institute for Health Research Health Informatics Collaborative (UK-NIHR HIC).

Participants: 257 948 consecutive patients undergoing troponin testing for any clinical reason between 2010 and 2017.

Main outcome measure: All cause mortality.

Results: 257 948 patients had troponin measured during the study period. Analyses on troponin were performed using the peak troponin level, which was the highest troponin level measured during the patient's hospital stay. Troponin levels were standardised as a multiple of each laboratory's 99th centile of the upper limit of normal (ULN). During a median follow-up of 1198 days (interquartile range 514-1866 days), 55 850 (21.7%) deaths occurred. A positive troponin result (that is, higher than the upper limit of normal) signified a 3.2 higher mortality hazard (95% confidence interval 3.1 to 3.2) over three years. Mortality varied noticeably with age, with a hazard ratio of 10.6 (8.5 to 13.3) in 18-29 year olds and 1.5 (1.4 to 1.6) in those older than 90. A positive troponin result was associated with an approximately 15 percentage points higher absolute three year mortality across all age groups. The excess mortality with a positive troponin result was heavily concentrated in the first few weeks. Results were analysed using multivariable adjusted restricted cubic spline Cox regression. A direct relation was seen between troponin level and mortality in patients without acute coronary syndrome (ACS, n=120 049), whereas an inverted U shaped relation was found in patients with ACS (n=14 468), with a paradoxical decline in mortality at peak troponin levels >70×ULN. In the group with ACS, the inverted U shaped relation persisted after multivariable adjustment in those who were managed invasively; however, a direct positive relation was found between troponin level and mortality in patients managed non-invasively.

Conclusions: A positive troponin result was associated with a clinically important increased mortality, regardless of age, even if the level was only slightly above normal. The excess mortality with a raised troponin was heavily concentrated in the first few weeks.

Study registration: ClinicalTrials.gov NCT03507309.

Fig 1

Flow of study cohort. Patients were eligible for inclusion based on the first troponin measurement during the study period. ICD-10=international classification of diseases (10th revision)

Fig 2

Age distribution and three year estimated mortality rate in study population; age distribution of UK population; ratio of study to UK age distribution; and percentage of patients with raised troponin level across age groups

Fig 3

Hazard ratios for troponin positive versus troponin negative groups across different age bands for all patients and Kaplan-Meier mortality curves by troponin positivity in 18-39, 40-79, and ≥80 years age bands. Error bars denote upper 95% confidence interval

Fig 4

Three year Kaplan-Meier cumulative mortality by troponin level for all patients, and deaths per 100 patients undergoing troponin testing during several time periods

Fig 5

Unadjusted association between peak troponin level and the hazard ratio for mortality for all patients admitted to hospital. The shaded area around the spline curve represents the 95% confidence interval. The probability distribution of troponin in all patients (pale purple) is displayed below the x axis. The reference for the hazard ratio was set at 1. ULN=upper limit of normal

Fig 6

Multivariable adjusted spline of association between peak troponin level and the hazard ratio for all cause mortality in subgroups with acute coronary syndrome (ACS) and those without ACS. Adjusted for patient age; sex; haemoglobin level; creatinine level; C reactive protein level; white cell count; platelet count; number of troponin tests during the index hospital admission; family history of cardiovascular disease; current smoker; diabetes mellitus; hypertension; hypercholesterolaemia; heart failure; previous ischaemic heart disease; atrial fibrillation; aortic stenosis; chronic kidney disease; neoplasm; and obstructive lung disease. The shaded area around the spline curves represents the 95% confidence interval. Both curves arise from a single restricted cubic spline analysis using ACS diagnosis as a stratifier. The reference for the hazard ratio was set at 1 in both subgroups. The probability distribution of troponin level in patients with or without ACS is displayed below the x axes. ACS=acute coronary syndrome; ULN=upper limit of normal

Fig 7

Proportion of patients with acute coronary syndrome (ACS) undergoing invasive management according to troponin level; multivariable adjusted spline of association between peak troponin level and the hazard ratio for all cause mortality in patients with ACS stratified by invasive versus non-invasive management. Adjusted for patient age; sex; haemoglobin level; creatinine level; C reactive protein level; white cell count; platelet count; number of troponin tests during the index hospital admission; family history of cardiovascular disease; current smoker; diabetes mellitus; hypertension; hypercholesterolaemia; heart failure; previous ischaemic heart disease; atrial fibrillation; aortic stenosis; chronic kidney disease; neoplasm; and obstructive lung disease. The grey shaded area around the spline curves represents the 95% confidence interval. Both curves arise from a single restricted cubic spline analysis using invasive management as a stratifier. The reference for the hazard ratio was set at 1 in the group with ACS who did or did not undergo invasive management. The probability distribution of troponin level in patients invasively managed (orange) and non-invasively managed (purple) is displayed below the x axis of the bottom panel. ACS=acute coronary syndrome; ULN=upper limit of normal