A Study of Population and Sex-specific Troponin Cutoffs for Ruling Out Acute Myocardial Infarction

Acute myocardial infarction (MI) is defined as a rise and/or fall in cardiac troponins (cTn) with at least one value above the 99th percentile upper reference limit (URL) in the context of symptoms or clinical evidence of myocardial ischemia. The URL is based on measurements in a healthy reference population. Currently, a sex-uniform manufacturer-provided 99th percentile URL of troponin is utilised at Danish hospitals as a diagnostic cutoff for acute MI for both men and women. Reportedly, healthy men have twofold the troponin level compared to healthy women, suggesting that the use of a uniform URL for troponins may lead to the under-diagnostication of acute MI in women and potentially over-diagnostication in men. The purpose of the DANSPOT study is to evaluate the clinical effect on diagnosis, treatment and outcomes in men and women presenting with acute MI of implementing international guidelines recommendations of sex-specific 99th percentile URLs for troponin into clinical practice. First, to determine the sex-specific 99th percentile URLs of troponins based on a healthy Danish reference population, blood samples from Danish blood donors were analysed using one troponin T assay and four troponin I assays. Second, the DANSPOT study is a nationwide cluster-randomised trial with a "stepped-wedge" design, with participation of all 22 Danish hospital laboratories and associated departments of cardiology. With one-month intervals, each of the 22 centres is randomised to shift from the presently applied uniform 99th percentile URL of troponin to our newly determined population- and sex-specific 99th percentile URL. Each patient is followed up for 12 months after their first troponin measurement during the index admission. The hypothesis of the DANSPOT study is that implementation of population- and sex-specific 99th percentile URLs for troponin will ensure that the right patients receive the right treatment. The investigators expect to detect significantly more women with acute MI, theoretically resulting in a more accurate diagnosis and treatment of women and men with acute MI.

Inclusion criteria for the primary cohort: The primary cohort will include the women and men who are expected to be most significantly impacted by the intervention, and this group is specifically defined by 1. Presenting complaints suggestive of ACS 2. At least one cTn measurement within 24 hours of admission 3. A peak cTn value between the current sex-uniform manufacturer-derived 99th percentile URL and the novel sex-and population-specific 99th percentile URLs for women and men. Presenting complaints suggestive of ACS will be identified in hospital records by the following presenting complaints of "chest pain" (DR074), "angina pectoris" (DI20), "observation due to suspicion of myocardial infarction" (Z034), "myocardial infarction" (DI21), "abdominal and pelvic pain" (DR10), "pain in the throat and chest" (DR07), "dyspnea" (DR060), "reflux" (DK21), "ischemic heart disease" (DI22-DI25) and "observation due to suspicion of another cardiovascular disorder" (DZ035). Study participants are included at their index admission, and subsequent admissions are evaluated in follow up analyses. Exclusion criteria: * Age \< 18 years * Patients with discharge diagnoses with conditions like pericarditis, myocarditis, endocarditis, cardiomyopathy, valve disease, arrhythmia, heart failure, pulmonary embolism, respiratory diseases, infectious diseases, digestive system diseases excluding reflux, digestive system diseases, diseases of the urinary and reproductive organs, and diseases of bones, muscles, and connective tissue, and do not have a discharge diagnosis of myocardial infarction or angina pectoris The initial month following the implementation of the new sex-specific 99th percentile URLs will be excluded from consideration, as it will be seen as an adjustment period. Consequently, the intervention period will be extended by one month.