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

Prevalence, determinants, and clinical associations of high-sensitivity cardiac troponin in patients attending emergency departments

Background: High-sensitivity cardiac troponin assays may improve the diagnosis of myocardial infarction but increase the detection of elevated cardiac troponin in patients without acute coronary syndrome. Methods: In a prospective cohort study, we evaluated the prevalence, determinants, and outcome of patients with elevated cardiac troponin attending the emergency department without suspected acute coronary syndrome. We measured high-sensitivity cardiac troponin in 918 consecutive patients attending the emergency department without suspected acute coronary syndrome who had blood sampling performed by the attending clinician. Elevated high-sensitivity cardiac troponin I was defined as concentrations above the sex-specific 99th percentile threshold. Clinical demographics, physiological measures, and all-cause mortality at 1 year associated with elevated high-sensitivity cardiac troponin concentrations were recorded. Results: Elevated cardiac troponin concentration occurred in 114 (12.4%) patients, of whom 2 (0.2%), 3 (0.3%), and 109 (11.9%) were adjudicated as type 1 myocardial infarction, type 2 myocardial infarction, and myocardial injury, respectively. Elevated troponin concentrations were associated with increasing age, worsening renal function, multimorbidity, and adverse physiology. Across a total of 912 patient-years follow-up, cardiac troponin concentration was a strong predictor of death (hazard ratio [HR] 1.26 per 2-fold increase, 95% confidence interval [CI] 1.06 to 1.49) independent of age, sex, multimorbidity, and adverse physiology. Conclusions: High-sensitivity cardiac troponin concentrations were elevated in 1 in 8 consecutive patients without suspected acute coronary syndrome attending the emergency department and were associated with increasing age, multimorbidity, adverse physiology, and death. Elevated cardiac troponin in unselected patients predominantly reflects myocardial injury rather than myocardial infarction

Performance of a prehospital HEART score in patients with possible myocardial infarction: a prospective evaluation

Introduction The History, Electrocardiogram (ECG), Age, Risk Factors and Troponin (HEART) score is commonly used to risk stratify patients with possible myocardial infarction as low risk or high risk in the Emergency Department (ED). Whether the HEART score can be used by paramedics to guide care were high-sensitivity cardiac troponin testing available in a prehospital setting is uncertain. Methods In a prespecified secondary analysis of a prospective cohort study where paramedics enrolled patients with suspected myocardial infarction, a paramedic Heart, ECG, Age, Risk Factors (HEAR) score was recorded contemporaneously, and a prehospital blood sample was obtained for subsequent cardiac troponin testing. HEART and modified HEART scores were derived using laboratory contemporary and high-sensitivity cardiac troponin I assays. HEART and modified HEART scores of ≤3 and ≥7 were applied to define low-risk and high-risk patients, and performance was evaluated for an outcome of major adverse cardiac events (MACEs) at 30 days. Results Between November 2014 and April 2018, 1054 patients were recruited, of whom 960 (mean 64 (SD 15) years, 42% women) were eligible for analysis and 255 (26%) experienced a MACE at 30 days. A HEART score of ≤3 identified 279 (29%) as low risk with a negative predictive value of 93.5% (95% CI 90.0% to 95.9%) for the contemporary assay and 91.4% (95% CI 87.5% to 94.2%) for the high-sensitivity assay. A modified HEART score of ≤3 using the limit of detection of the high-sensitivity assay identified 194 (20%) patients as low risk with a negative predictive value of 95.9% (95% CI 92.1% to 97.9%). A HEART score of ≥7 using either assay gave a lower positive predictive value than using the upper reference limit of either cardiac troponin assay alone. Conclusions A HEART score derived by paramedics in the prehospital setting, even when modified to harness the precision of a high-sensitivity assay, does not allow safe rule-out of myocardial infarction or enhanced rule-in compared with cardiac troponin testing alone. https://emj.bmj.com/content/40/7/474 This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0

Sex-differences in oral anticoagulation therapy in patients hospitalized with atrial fibrillation:a nationwide cohort study

Background Important disparities in the treatment and outcomes of women and men with atrial fibrillation (AF) are well recognized. Whether introduction of direct oral anticoagulants has reduced disparities in treatment is uncertain. Methods and Results All patients who had an incident hospitalization from 2010 to 2019 with nonvalvular AF in Scotland were included in the present cohort study. Community drug dispensing data were used to determine prescribed oral anticoagulation therapy and comorbidity status. Logistic regression modeling was used to evaluate patient factors associated with treatment with vitamin K antagonists and direct oral anticoagulants. A total of 172 989 patients (48% women [82 833 of 172 989]) had an incident hospitalization with nonvalvular AF in Scotland between 2010 and 2019. By 2019, factor Xa inhibitors accounted for 83.6% of all oral anticoagulants prescribed, while treatment with vitamin K antagonists and direct thrombin inhibitors declined to 15.9% and 0.6%, respectively. Women were less likely to be prescribed any oral anticoagulation therapy compared with men (adjusted odds ratio [aOR], 0.68 [95% CI, 0.67–0.70]). This disparity was mainly attributed to vitamin K antagonists (aOR, 0.68 [95% CI, 0.66–0.70]), while there was less disparity in the use of factor Xa inhibitors between women and men (aOR, 0.92 [95% CI, 0.90–0.95]). Conclusions Women with nonvalvular AF were significantly less likely to be prescribed vitamin K antagonists compared with men. Most patients admitted to the hospital in Scotland with incident nonvalvular AF are now treated with factor Xa inhibitors and this is associated with fewer treatment disparities between women and men

Use of High-Sensitivity Cardiac Troponin in Patients With Kidney Impairment: A Randomized Clinical Trial.

Research Letter - No abstract available

Differences in relative and absolute effectiveness of oral P2Y12 inhibition in men and women: a meta-analysis and modelling study

ObjectiveTo estimate the absolute treatment effects of newer P2Y12 inhibitors (ticagrelor and prasugrel) compared to clopidogrel in men and women with acute coronary syndrome (ACS).MethodsWe searched Ovid MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) for randomised controlled trials of oral P2Y12 inhibitors for acute stroke or ACS. Age and sex-specific mortality was obtained for all patients admitted to hospital with myocardial infarction in Scotland from 2006 to 2010 (prior to introduction of prasugrel or ticagrelor).ResultsFrom 9,277 articles, 9 fulfilled our inclusion criteria. Three trials compared newer P2Y12 inhibitors to clopidogrel in ACS, in which the treatment rate ratio (RR) for major adverse cardiovascular events in men was 0.80 (95% CI 0.69 to 0.93). For the same outcome, across all 9 trials the sex-treatment interaction RR was 1.08 (95% CI 0.98 to 1.19). Combining these estimates yielded a treatment RR in women of 0.86 (95% CI 0.72 to 1.04). 17,842 women and 27,818 men were admitted to hospital with myocardial infarction. Mortality was higher for women than men for all-cause (5708, 32.0% versus 5891,21.2%), cardiovascular(4032, 22.6% versus 4117, 14.8%) and bleeding (193, 1.1% versus 228, 0.8%) deaths. On applying the sex-specific RRs to this population, the absolute risk reduction for mortality at 1- year was similar for women and men for all-cause (2.30% (95% CI -0.92 to 5.22) versus 2.47% (95% CI 0.62 to 4.10)), cardiovascular (2.70% (95% CI -0.63 to 5.74)) versus 2.72% (95% CI 0.92 to 4.35)) and bleeding (-0.27% (95% CI -1.06 to 0.30) versus -0.18% (95% CI -0.71 to 0.24)) deaths.ConclusionNewer P2Y12 inhibitors may be slightly less efficacious in women than men, but the absolute risk reduction is similar in both sexes

Serial troponin measurements to monitor risk and response to endothelin A antagonism in chronic kidney disease.

Research Lette