Clearing the Air to Address Pollution's Cardiovascular Health Crisis.

Air pollution is a critical global health issue that significantly impacts cardiovascular health. The air pollutant PM2.5 (particulate matter with a diameter of 2.5 micrometres or less) has been positioned as a leading environmental risk factor for morbidity and mortality, especially from cardiovascular diseases (CVDs). Using data from the World Health Organization (WHO), Global Health Observatory, and the United Nations Environment Programme, we explored global trends in air pollution, with a focus on PM2.5 levels, the implications for cardiovascular health, and the policy measures aimed at reducing their impact. Despite progress in reducing pollution levels in high-income countries, global trends show a limited annual reduction in PM2.5 concentration. The analysis highlights disparities between regions, with low- and middle-income countries bearing the brunt of air pollution-related CVDs. In 2019 alone, ambient air pollution was responsible for approximately 4.2 million deaths worldwide. Of these, 70% were caused by CVDs, with approximately 1.9 million deaths from ischemic heart disease and 900,000 deaths from stroke. Policy gaps remain a challenge, with many countries lacking adequate legally binding air quality standards. We recommend the adoption of WHO air quality guidelines, enhanced monitoring of air pollution levels, and increased investment in interdisciplinary research to understand the full scope of air pollution's effects on cardiovascular health. Addressing the global cardiovascular crisis linked to air pollution will require coordinated efforts from policymakers, healthcare systems, and global health organisations.

Prognostic significance of troponin in patients with malignancy (NIHR Health Informatics Collaborative TROP-MALIGNANCY study).

BACKGROUND: Cardiac troponin is commonly raised in patients presenting with malignancy. The prognostic significance of raised troponin in these patients is unclear. OBJECTIVES: We sought to investigate the relation between troponin and mortality in a large, well characterised cohort of patients with a routinely measured troponin and a primary diagnosis of malignancy. METHODS: We used the National Institute for Health Research (NIHR) Health Informatics Collaborative data of 5571 patients, who had troponin levels measured at 5 UK cardiac centres between 2010 and 2017 and had a primary diagnosis of malignancy. Patients were classified into solid tumour or haematological malignancy subgroups. Peak troponin levels were standardised as a multiple of each laboratory's 99th -percentile upper limit of normal (xULN). RESULTS: 4649 patients were diagnosed with solid tumours and 922 patients with haematological malignancies. Raised troponin was an independent predictor of mortality in all patients (Troponin > 10 vs. <1 adjusted HR 2.01, 95% CI 1.73 to 2.34), in solid tumours (HR 1.84, 95% CI 1.55 to 2.19), and in haematological malignancy (HR 2.72, 95% CI 1.99 to 3.72). There was a significant trend in increasing mortality risk across troponin categories in all three subgroups (p < 0.001). CONCLUSION: Raised troponin level is associated with increased mortality in patients with a primary diagnosis of malignancy regardless of cancer subtype. Mortality risk is stable for patients with a troponin level below the ULN but increases as troponin level increases above the ULN in the absence of acute coronary syndrome.

HIV-Associated Cardiovascular Disease Pathogenesis: An Emerging Understanding Through Imaging and Immunology.

Cardiac abnormalities were identified early in the epidemic of AIDS, predating the isolation and characterization of the etiologic agent, HIV. Several decades later, the causation and pathogenesis of cardiovascular disease (CVD) linked to HIV infection continue to be the focus of intense speculation. Before the widespread use of antiretroviral therapy, HIV-associated CVD was primarily characterized by HIV-associated cardiomyopathy linked to profound immunodeficiency. With increasing antiretroviral therapy use, viral load suppression, and establishment of immune competency, the effects of HIV on the cardiovascular system are more subtle. Yet, people living with HIV still face an increased incidence of cardiovascular pathology. Advances in cardiac imaging modalities and immunology have deepened our understanding of the pathogenesis of HIV-associated CVD. This review provides an overview of the pathogenesis of HIV-associated CVD integrating data from imaging and immunologic studies with particular relevance to the HIV population originating from high-endemic regions, such as sub-Saharan Africa. The review highlights key evidence gaps in the field and suggests future directions for research to better understand the complex HIV-CVD interactions.

Diagnostic and prognostic value of an ejection fraction adjusted for myocardial remodeling.

Introduction: Ejection fraction (EF) is widely used to evaluate heart function during heart failure (HF) due to its simplicity compared but it may misrepresent cardiac function during ventricular hypertrophy, especially in heart failure with preserved EF (HFpEF). To resolve this shortcoming, we evaluate a correction factor to EF, which is equivalent to computing EF at the mid-wall layer (without the need for mid-layer identification) rather than at the endocardial surface, and thus better complements other complex metrics. Method: The retrospective cohort data was studied, consisting of 2,752 individuals (56.5% male, age 69.3 ± 16.4 years) admitted with a request of a troponin test and undergoing echocardiography as part of their clinical assessment across three centres. Cox-proportional regression models were constructed to compare the adjusted EF (EFa) to EF in evaluating risk of heart failure admissions. Result: Comparing HFpEF patients to non-HF cases, there was no significant difference in EF (62.3 ± 7.6% vs. 64.2 ± 6.2%, p = 0.79), but there was a significant difference in EFa (56.6 ± 6.4% vs. 61.8 ± 9.9%, p = 0.0007). Both low EF and low EFa were associated with a high HF readmission risk. However, in the cohort with a normal EF (EF ≥ 50%), models using EFa were significantly more associative with HF readmissions within 3 years, where the leave one out cross validation ROC analysis showed a 18.6% reduction in errors, and Net Classification Index (NRI) analysis showed that risk increment classification of events increased by 12.2%, while risk decrement classification of non-events decreased by 16.6%. Conclusion: EFa is associated with HF readmission in patients with a normal EF.

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.

The burden and natural history of cardiac pathology at TB diagnosis in a high-HIV prevalence district in Zambia: protocol for the TB-Heart study.

BACKGROUND: Tuberculosis (TB) continues to be a major cause of death across sub-Saharan Africa (SSA). In parallel, non-communicable disease and especially cardiovascular disease (CVD) burden has increased substantially in the region. Cardiac manifestations of TB are well-recognised but the extent to which they co-exist with pulmonary TB (PTB) has not been systematically evaluated. The aim of this study is to improve understanding of the burden of cardiac pathology in PTB in those living with and without HIV in a high-burden setting. METHODS: This is a cross-sectional and natural history study to evaluate the burden and natural history of cardiac pathology in participants with PTB in Lusaka, Zambia, a high burden setting for TB and HIV. Participants with PTB, with and without HIV will be consecutively recruited alongside age- and sex-matched TB-uninfected comparators on a 2:1 basis. Participants will undergo baseline assessments to collect clinical, socio-demographic, functional, laboratory and TB disease impact data followed by point-of-care and standard echocardiography. Participants with PTB will undergo further repeat clinical and functional examination at two- and six months follow-up. Those with cardiac pathology at baseline will undergo repeat echocardiography at six months. DISCUSSION: The outcomes of the study are to a) determine the burden of cardiac pathology at TB diagnosis, b) describe its association with patient-defining risk factors and biochemical markers of cardiac injury and stretch and c) describe the natural history of cardiac pathology during the course of TB treatment.

Could paramedics use the HEART Pathway to identify patients at low-risk of myocardial infarction in the prehospital setting?

In the Emergency Department, patients with suspected myocardial infarction can be risk stratified using the HEART pathway, which has recently been amended for prehospital use and modified for the incorporation of a high-sensitivity cardiac troponin test. In a prospective analysis, the performance of both HEART pathways in the prehospital setting, with a high-sensitivity cardiac troponin test using 3 different thresholds, was evaluated for major adverse cardiac events at 30 days. We found that both low-risk HEART pathways, when using the most conservative cardiac troponin thresholds, approached but did not reach accepted rule-out performance in the Emergency Department.

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.

Kidney replacement therapy: trends in incidence, treatment, and outcomes of myocardial infarction and stroke in a nationwide Scottish study.

BACKGROUND AND AIMS: Patients with kidney failure have a higher risk of cardiovascular disease compared with the general population. Whilst temporal trends of myocardial infarction and stroke are declining in the general population, these have not been evaluated in patients with kidney failure. This study aimed to describe national trends in the incidence, treatment, and outcomes of myocardial infarction and stroke in patients with kidney failure (i.e. on dialysis or with a kidney transplant) over a 20-year period, stratified by age and sex. METHODS: In this retrospective national data linkage study, all patients with kidney failure in Scotland (UK) receiving kidney replacement therapy between January 1996 and December 2016 were linked to national hospitalization, prescribing, and death records. The primary outcomes were the incidence of myocardial infarction and stroke, and subsequent cardiovascular death. Generalized additive models were constructed to estimate age-standardized, sex-stratified incidence rates and trends in cardiovascular and all-cause death. RESULTS: Amongst 16 050 patients with kidney failure [52 (SD 15) years; 41.5% women], there were 1992 [66 (SD 12) years; 34.8% women] and 996 [65 (SD 13) years; 45.1% women] incident myocardial infarctions and strokes, respectively, between January 1996 and December 2016. During this period, the age-standardized incidence of myocardial infarction per 100 000 decreased in men {from 4376 [95% confidence interval (CI) 3998-4785] to 1835 (95% CI 1692-1988)} and women [from 3268 (95% CI 2982-3593) to 1369 (95% CI 1257-1491)]. Similarly, the age-standardized incidence of stroke per 100 000 also decreased in men [from 1978 (95% CI 1795-2175) to 799 (95% CI 729-875)] and women [from 2234 (95% CI 2031-2468) to 903 (95% CI 824-990)]. Compared with the general population, the incidence of myocardial infarction was four- to eight-fold higher in patients with kidney failure, whilst for stroke it was two- to four-fold higher. The use of evidence-based cardioprotective treatment increased over the study period, and the predicted probability of cardiovascular death within 1 year of myocardial infarction for a 66-year-old patient with kidney failure (mean age of the cohort) fell in men (76.6% to 38.6%) and women (76.8% to 38.8%), and also decreased in both sexes following stroke (men, from 63.5% to 41.4%; women, from 67.6% to 45.8%). CONCLUSIONS: The incidence of myocardial infarction and stroke has halved in patients with kidney failure over the past 20 years but remains significantly higher than in the general population. Despite improvements in treatment and outcomes, the prognosis of these patients following myocardial infarction and stroke remains poor.

Impact of Residential Social Deprivation on Prediction of Heart Failure in Patients With Type 2 Diabetes: External Validation and Recalibration of the WATCH-DM Score Using Real World Data.

BACKGROUND: Patients with type 2 diabetes are at risk of heart failure hospitalization. As social determinants of health are rarely included in risk models, we validated and recalibrated the WATCH-DM score in a diverse patient-group using their social deprivation index (SDI). METHODS: We identified US Veterans with type 2 diabetes without heart failure that received outpatient care during 2010 at Veterans Affairs medical centers nationwide, linked them to their SDI using residential ZIP codes and grouped them as SDI <20%, 21% to 40%, 41% to 60%, 61% to 80%, and >80% (higher values represent increased deprivation). Accounting for all-cause mortality, we obtained the incidence for heart failure hospitalization at 5 years follow-up; overall and in each SDI group. We evaluated the WATCH-DM score using the C statistic, the Greenwood Nam D'Agostino test χ2 test and calibration plots and further recalibrated the WATCH-DM score for each SDI group using a statistical correction factor. RESULTS: In 1 065 691 studied patients (mean age 67 years, 25% Black and 6% Hispanic patients), the 5-year incidence of heart failure hospitalization was 5.39%. In SDI group 1 (least deprived) and 5 (most deprived), the 5-year heart failure hospitalization was 3.18% and 11%, respectively. The score C statistic was 0.62; WATCH-DM systematically overestimated heart failure risk in SDI groups 1 to 2 (expected/observed ratios, 1.38 and 1.36, respectively) and underestimated the heart failure risk in groups 4 to 5 (expected/observed ratios, 0.95 and 0.80, respectively). Graphical evaluation demonstrated that the recalibration of WATCH-DM using an SDI group-based correction factor improved predictive capabilities as supported by reduction in the χ2 test results (801-27 in SDI groups I; 623-23 in SDI group V). CONCLUSIONS: Including social determinants of health to recalibrate the WATCH-DM score improved risk prediction highlighting the importance of including social determinants in future clinical risk prediction models.

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.

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.

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.

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.

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.

National Trends in Coronary Artery Disease Imaging: Associations With Health Care Outcomes and Costs.

BACKGROUND: In 2016, the National Institute for Health and Care Excellence Clinical Guideline Number 95 ("Chest pain of recent onset") (CG95) recommended coronary computed tomography angiography (CCTA) as the first-line test for possible angina. OBJECTIVES: The purpose of this study was to determine the impact of temporal trends in imaging use on outcomes for coronary artery disease (CAD) following the CG95 recommendations. METHODS: Investigations from 2012 to 2018 were extracted from a national database and linked to hospital admission and mortality registries. Growth rates were adjusted for population size, with image modality use, cardiovascular hospital admissions, and mortality compared using Kendall's rank correlation. The impact of CG95 was assessed using an interrupted time-series analysis. RESULTS: A total of 1,909,314 investigations for CAD were performed, with an annualized per capita growth of 4.8%. Costs were £0.35 million/100,000 population/year with an increase of 2.8%/year mirroring inflation (2.5%/year). CG95 was associated with a rise in CCTA (exp[ß]: 1.10; 95% CI: 1.03-1.18), no change in myocardial perfusion imaging, and a potential modest fall (exp[ß]: 0.997; 95% CI: 0.993-1.00]) in invasive coronary angiography. There was an apparent trend between computed tomography angiography growth and invasive catheter angiography reduction across regions (Kendall Tau: -0.19; P = 0.08). CCTA growth was associated with a reduction in cardiovascular mortality (Kendall Tau: -0.21; P = 0.045), and ischemic heart disease deaths (Kendall Tau: -0.22; P = 0.042), with an apparent trend with reduced all-cause mortality (Kendall Tau: -0.19; P = 0.07). CONCLUSIONS: Imaging investigations for CAD are increasing. Greater regional increases in CCTA were associated with fewer hospitalizations for myocardial infarction and a more rapid decline in CAD mortality.