Cardiac and noncardiac biomarkers in patients undergoing anthracycline chemotherapy - a prospective analysis.

BACKGROUND: Biomarkers represent a potential tool to identify individuals at risk for anthracycline-induced cardiotoxicity (AICT) prior to symptom onset or left ventricular dysfunction. METHODS: This study examined the levels of cardiac and noncardiac biomarkers before, after the last dose of, and 3-6 months after completion of doxorubicin chemotherapy. Cardiac biomarkers included 5th generation high-sensitivity cardiac troponin T (cTnT), N-terminal pro-brain natriuretic peptide, growth/differentiation factor-15 (GDF-15), and soluble suppression of tumorigenesis-2 (sST2). Noncardiac biomarkers included activated caspase-1 (CASP-1), activated caspase-3, C-reactive protein, tumor necrosis factor-α, myeloperoxidase (MPO), galectin-3, and 8-hydroxy-2'-deoxyguanosine. Echocardiographic data (LVEF and LVGLS) were obtained at pre- and post-chemotherapy. Subanalysis examined interval changes in biomarkers among high (cumulative doxorubicin dose ≥ 250 mg/m2) and low exposure groups. RESULTS: The cardiac biomarkers cTnT, GDF-15, and sST2 and the noncardiac biomarkers CASP-1 and MPO demonstrated significant changes over time. cTnT and GDF-15 levels increased after anthracycline exposure, while CASP-1 and MPO decreased significantly. Subanalysis by cumulative dose did not demonstrate a larger increase in any biomarker in the high-dose group. CONCLUSIONS: The results identify biomarkers with significant interval changes in response to anthracycline therapy. Further research is needed to understand the clinical utility of these novel biomarkers.

Algorithmic fairness in pandemic forecasting: lessons from COVID-19.

Racial and ethnic minorities have borne a particularly acute burden of the COVID-19 pandemic in the United States. There is a growing awareness from both researchers and public health leaders of the critical need to ensure fairness in forecast results. Without careful and deliberate bias mitigation, inequities embedded in data can be transferred to model predictions, perpetuating disparities, and exacerbating the disproportionate harms of the COVID-19 pandemic. These biases in data and forecasts can be viewed through both statistical and sociological lenses, and the challenges of both building hierarchical models with limited data availability and drawing on data that reflects structural inequities must be confronted. We present an outline of key modeling domains in which unfairness may be introduced and draw on our experience building and testing the Google-Harvard COVID-19 Public Forecasting model to illustrate these challenges and offer strategies to address them. While targeted toward pandemic forecasting, these domains of potentially biased modeling and concurrent approaches to pursuing fairness present important considerations for equitable machine-learning innovation.

Embracing Diversity, Equity, and Inclusion in the Scientific Community-Viewpoints of the Diversity, Equity, and Inclusion Committee of the North American Vascular Biology Organization.

Recent increased visibility on racial issues in the United States elicited public outcry and a collective call for action. The social justice movement has facilitated energetic discussions about race, sexual orientation, and various issues of diversity, equity, and inclusion. This article discusses issues faced by people of color that we as scientists can address, as well as challenges faced by women and internationally trained scientists in the scientific community that need immediate attention. Moreover, we highlight various ways to resolve such issues at both institutional and individual levels. Silence and incremental solutions are no longer acceptable to achieving lasting social justice and ensure prosperous societies that work for all.

The Interplay of Race/Ethnicity and Obesity on the Incidence of Venous Thromboembolism.

INTRODUCTION: Factors predisposing asymptomatic individuals within the community to venous thromboembolism are not fully understood. This study characterizes the incidence and determinants of venous thromboembolism among the Multiethnic Study of Atherosclerosis cohort with a focus on race/ethnicity and obesity. METHODS: This study (analyzed in 2020-2021) used the Multiethnic Study of Atherosclerosis cohort (2000-2017), which included participants with diverse ethnic/racial backgrounds aged 45-84 years without cardiovascular disease at baseline. The primary endpoint was time to diagnosis of venous thromboembolism defined using International Classification of Diseases codes (415, 451, 453, 126, 180, and 182). Multivariable-adjusted hazard ratios of the predictors of venous thromboembolism were calculated with a focus on the interaction between obesity and race/ethnicity categories. RESULTS: Over a median follow-up period of 14 years, 233 individuals developed venous thromboembolism. Incidence rates (per 1,000 person-years) varied across racial/ethnic groups with the highest incidence among Black (4.02) followed by White (2.98), Hispanic (2.08), and Chinese (0.79) participants. There was a stepwise increase in the incidence rate of venous thromboembolism with increasing BMI regardless of race/ethnicity: normal (1.95), overweight (2.52), obese (3.63), and morbidly obese (4.55). The association between BMI and venous thromboembolism was strongest among non-White women with the highest incidence rate for obese (4.8) compared with non-obese (1.6). The interaction among obesity, gender, and race was statistically significant (p=0.01) in non-White obese women. Risk of venous thromboembolism increased with age for all race/ethnicities. CONCLUSIONS: This study finds that obesity may confer an increased risk for venous thromboembolism among non-White women compared with other groups-White men, White women, and non-White men.

Proceedings From a National Heart, Lung, and Blood Institute and the Centers for Disease Control and Prevention Workshop to Control Hypertension.

Hypertension treatment and control prevent more cardiovascular events than management of other modifiable risk factors. Although the age-adjusted proportion of US adults with controlled blood pressure (BP) defined as <140/90 mm Hg, improved from 31.8% in 1999-2000 to 48.5% in 2007-2008, it remained stable through 2013-2014 and declined to 43.7% in 2017-2018. To address the rapid decline in hypertension control, the National Heart, Lung, and Blood Institute and the Division for Heart Disease and Stroke Prevention of the Centers for Disease Control and Prevention convened a virtual workshop with multidisciplinary national experts. Also, the group sought to identify opportunities to reverse the adverse trend and further improve hypertension control. The workshop immediately preceded the Surgeon General's Call to Action to Control Hypertension, which recognized a stagnation in progress with hypertension control. The presentations and discussions included potential reasons for the decline and challenges in hypertension control, possible "big ideas," and multisector approaches that could reverse the current trend while addressing knowledge gaps and research priorities. The broad set of "big ideas" was comprised of various activities that may improve hypertension control, including: interventions to engage patients, promotion of self-measured BP monitoring with clinical support, supporting team-based care, implementing telehealth, enhancing community-clinical linkages, advancing precision population health, developing tailored public health messaging, simplifying hypertension treatment, using process and outcomes quality metrics to foster accountability and efficiency, improving access to high-quality health care, addressing social determinants of health, supporting cardiovascular public health and research, and lowering financial barriers to hypertension control.

Increasing Equity While Improving the Quality of Care: JACC Focus Seminar 9/9.

This review summarizes racial and ethnic disparities in the quality of cardiovascular care-a challenge given the fragmented nature of the health care delivery system and measurement. Health equity for all racial and ethnic groups will not be achieved without a substantially different approach to quality measurement and improvement. The authors adapt a tool frequently used in quality improvement work-the driver diagram-to chart likely areas for diagnosing root causes of disparities and developing and testing interventions. This approach prioritizes equity in quality improvement. The authors demonstrate how this approach can be used to create interventions that reduce systemic racism within the institutions and professions that deliver health care; attends more aggressively to social factors related to race and ethnicity that affect health outcomes; and examines how hospitals, health systems, and insurers can generate effective partnerships with the communities they serve to achieve equitable cardiovascular outcomes.

Understanding myocardial infarction trends during the early COVID-19 pandemic: an infodemiology study.

During the first months of the coronavirus disease 2019 (COVID-19) pandemic in early 2020, Google Trends data in the United States showed a strong increase in search query frequency for chest pain symptoms despite a concurrent decrease in search interest for myocardial infarction. This suggests a reduced attention to acute coronary syndrome (ACS) and chest pain as its main symptom during this time period. These observations could help explain why cardiovascular mortality rose dramatically despite a strong decrease in hospitalisation rates for ACS.

Addressing the Disproportionate Impact of COVID-19 on Communities of Color.

With Black and Hispanic communities across the USA experiencing more detrimental negative effects from the COVID-19 pandemic as compared with other demographic groups, the virus has exposed the racial and ethnic disparities in treatment and care that public health experts have been grappling with for years. This paper explains how the systematic collection of racial and ethnic data gleaned from COVID-19 testing in underserved communities can be used to better understand this pandemic and inform measures within our control to prevent the spread of disease in the future.

Declining interest in clinical imaging during the COVID-19 pandemic: An analysis of Google Trends data.

OBJECTIVE: Current evidence suggests a decrease in elective diagnostic imaging procedures during the COVID-19 pandemic with potentially severe long-term consequences. The aim of this study was to quantify recent trends in public interest and related online search behavior for a range of imaging modalities, and "nowcast" future scenarios with respect to imaging use. METHODS: We used Google Trends, a publicly available database to access search query data in systematic and quantitative fashion, to search for key terms related to clinical imaging. We queried the search volume for multiple imaging modalities, identified the most common terms, extracted data for the United States over the time range from August 1, 2016 to August 1, 2020. Results were given in relative terms, using the Google metric 'search volume index'. RESULTS: We report a decrease in public interest across all imaging modalities since March 2020 with a subsequent slow increase starting in May 2020. Mean relative search volume (RSV) has changed by -19.4%, -38.3%, and -51.0% for the search terms "Computed tomography", "Magnetic resonance imaging", and "Mammography", respectively, and comparing the two months prior to and following March 1, 2020. RSV has since steadily recuperated reaching all-year highs. CONCLUSION: Decrease in public interest coupled with delays and deferrals of diagnostic imaging will likely result in a high demand for healthcare in the coming months. To respond to this challenge, measures such as risk-stratification algorithms must be developed to allocate resources and avoid the risk of overstraining the healthcare system.

Prognostic value of coronary artery calcium score, area, and density among individuals on statin therapy vs. non-users: The coronary artery calcium consortium.

BACKGROUND AND AIMS: Statins do not decrease coronary artery calcium (CAC) and may increase existing calcification or its density. Therefore, we examined the prognostic significance of CAC among statin users at the time of CAC scanning. METHODS: We included 28,025 patients (6151 statin-users) aged 40-75 years from the CAC Consortium. Cox regression models were used to assess the association of CAC with coronary heart disease (CHD) and cardiovascular disease (CVD) mortality. Models were adjusted for traditional CVD risk factors. Additionally, we examined the predictive performance of CAC components including CAC area, volume, and density using an age- and sex-adjusted Cox regression model. RESULTS: Participants (mean age 53.9 ± 10.3 years, 65.0% male) were followed for median 11.2 years. There were 395 CVD and 182 CHD deaths. One unit increase in log CAC score was associated with increased risk of CVD mortality (hazard ratio (HR), 1.2; 95% CI = 1.1-1.3) and CHD mortality (HR, 1.2; 95% CI = 1.1-1.4)) among statin users. There was a small but significant negative interaction between CAC score and statin use for the prediction of CHD (p-value = 0.036) and CVD mortality (p-value = 0.025). The volume score and CAC area were similarly associated with outcomes in statin users and non-users. Density was associated with CVD and CHD mortality in statin naïve patients, but with neither in statin users. CONCLUSION: CAC scoring retains robust risk prediction in statin users, and the changing relationship of CAC density with outcomes may explain the slightly weaker relationship of CAC with outcomes in statin users.

Using Mobile Health Tools to Assess Physical Activity Guideline Adherence and Smoking Urges: Secondary Analysis of mActive-Smoke.

BACKGROUND: Rates of cigarette smoking are decreasing because of public health initiatives, pharmacological aids, and clinician focus on smoking cessation. However, a sedentary lifestyle increases cardiovascular risk, and therefore, inactive smokers have a particularly enhanced risk of cardiovascular disease. OBJECTIVE: In this secondary analysis of mActive-Smoke, a 12-week observational study, we investigated adherence to guideline-recommended moderate-to-vigorous physical activity (MVPA) in smokers and its association with the urge to smoke. METHODS: We enrolled 60 active smokers (≥3 cigarettes per day) and recorded continuous step counts with the Fitbit Charge HR. MVPA was defined as a cadence of greater than or equal to 100 steps per minute. Participants were prompted to report instantaneous smoking urges via text message 3 times a day on a Likert scale from 1 to 9. We used a mixed effects linear model for repeated measures, controlling for demographics and baseline activity level, to investigate the association between MVPA and urge. RESULTS: A total of 53 participants (mean age 40 [SD 12] years, 57% [30/53] women, 49% [26/53] nonwhite, and 38% [20/53] obese) recorded 6 to 12 weeks of data. Data from 3633 person-days were analyzed, with a mean of 69 days per participant. Among all participants, median daily MVPA was 6 min (IQR 2-13), which differed by sex (12 min [IQR 3-20] for men vs 3.5 min [IQR 1-9] for women; P=.004) and BMI (2.5 min [IQR 1-8.3] for obese vs 10 min [IQR 3-15] for nonobese; P=.04). The median total MVPA minutes per week was 80 (IQR 31-162). Only 10% (5/51; 95% CI 4% to 22%) of participants met national guidelines of 150 min per week of MVPA on at least 50% of weeks. Adjusted models showed no association between the number of MVPA minutes per day and mean daily smoking urge (P=.72). CONCLUSIONS: The prevalence of MVPA was low in adult smokers who rarely met national guidelines for MVPA. Given the poor physical activity attainment in smokers, more work is required to enhance physical activity in this population.

Coronary artery calcium scoring in low risk patients with family history of coronary heart disease: Validation of the SCCT guideline approach in the coronary artery calcium consortium.

BACKGROUND: The Society of Cardiovascular Computed Tomography (SCCT) recommends consideration of coronary artery calcium (CAC) scoring among individuals with a family history (FH) of coronary heart disease (CHD) and atherosclerotic cardiovascular disease (ASCVD) risk <5%. No dedicated study has examined the prognostic significance of CAC scoring among this population. METHODS: The CAC Consortium is a multi-center observational cohort study from four clinical centers linked to long-term follow-up for cause-specific mortality. All CAC scans were physician referred and performed in patients without a history of CHD. Our analysis includes 14,169 patients with ASCVD scores <5% and self-reported FH of CHD. RESULTS: This cohort had a mean age of 48.1 (SD 7.4), was 91.3% white, 47.4% female, had an average ASCVD score of 2.3% (SD 1.3), and 59.4% had a CAC = 0. The event rate for all-cause mortality was 1.2 per 1000 person-years, 0.3 per 1000 person-years for CVD-specific mortality, and 0.2 per 1000 person-years for CHD-specific mortality. In multivariable Cox proportional hazard models, those with CAC>100 had a 2.2 (95% CI 1.5-3.3) higher risk of all-cause mortality, 4.3 (95% CI 1.9-9.5) times higher risk of CVD-specific mortality, and a 10.4 (95% CI 3.2-33.7) times higher risk of CHD-specific mortality compared to individuals with CAC = 0. The NNS to detect CAC >100 in this sample was 9. CONCLUSION: In otherwise low risk patients with FH of CHD, CAC>100 were associated with increased risk of all-cause and CHD mortality with event rates in a range that may benefit with preventive pharmacotherapy. These data strongly support new SCCT recommendations regarding testing of patients with a family history of CHD.

The association between left main coronary artery calcium and cardiovascular-specific and total mortality: The Coronary Artery Calcium Consortium.

BACKGROUND AND AIMS: Left main (LM) coronary artery disease is associated with greater myocardial infarction-related mortality, however, coronary artery calcium (CAC) scoring does not account for disease location. We explored whether LM CAC predicts excess mortality in asymptomatic adults. METHODS: Cause-specific cardiovascular and all-cause mortality was studied in 28,147 asymptomatic patients with non-zero CAC scores in the CAC Consortium. Multivariate regression was performed to evaluate if the presence and burden of LM CAC predict mortality after adjustment for clinical risk factors and the Agatston CAC score. We further analyzed the per-unit hazard associated with LM CAC in comparison to CAC in other arteries. RESULTS: The study population had mean age of 58.3 ±â€¯10 years and CAC score of 301 ±â€¯631. LM CAC was present in 21.7% of the cases. During 312,398 patient-years of follow-up, 1,907 deaths were observed. LM CAC was associated with an increased burden of clinical risk factors and total CAC, and was independently predictive of increased hazard for all-cause (HR 1.2 [1.1, 1.3]) and cardiovascular disease death (HR 1.3 [1.1, 1.5]). The hazard for death increased proportionate to the percentage of CAC localized to the LM. On a per-100 Agatston unit basis, LM CAC was associated with a 6-9% incremental hazard for death beyond knowledge of CAC in other arteries. CONCLUSIONS: The presence and high burden of left main CAC are independently associated with a 20-30% greater hazard for cardiovascular and total mortality in asymptomatic adults, arguing that LM CAC should be routinely noted in CAC score reports when present.

Role of Coronary Artery Calcium for Stratifying Cardiovascular Risk in Adults With Hypertension.

We examined the utility of coronary artery calcium (CAC) for cardiovascular risk stratification among hypertensive adults, including those fitting eligibility for SPRINT (Systolic Blood Pressure Intervention Trial). Additionally, we used CAC to identify hypertensive adults with cardiovascular disease (CVD) mortality rates equivalent to those observed in SPRINT who may, therefore, benefit from the most intensive blood pressure therapy. Our study population included 16 167 hypertensive patients from the CAC Consortium, among whom 6375 constituted a "SPRINT-like" population. We compared multivariable-adjusted hazard ratios of coronary heart disease and CVD deaths by CAC category (0, 1-99, 100-399, ≥400). Additionally, we generated a CAC-CVD mortality curve for patients aged >50 years to determine what CAC scores were associated with CVD death rates observed in SPRINT. Mean age was 58.1±10.6 years. During a mean follow-up of 11.6±3.6 years, there were 409 CVD deaths and 207 coronary heart disease deaths. Increasing CAC scores were associated with increased coronary heart disease and CVD mortality (coronary heart disease-CAC 100-399: hazard ratio [95% CI] 1.88 [1.04-3.40], CAC ≥400: 4.16 [2.34-7.39]; CVD-CAC 100-399: 1.93 [1.31-2.83], CAC ≥400: 3.51 [2.40-5.13]). A similar increased risk was observed across 10-year atherosclerotic CVD risk categories and in the SPRINT-like population. A CAC score of 220 (confidence range, 165-270) was associated with the CVD mortality rate observed in SPRINT. CAC risk stratifies adults with hypertension, including those who are SPRINT eligible. A CAC score of 220 can identify hypertensive adults with SPRINT-level CVD mortality risk and, therefore, may be reasonable for identifying candidates for aggressive blood pressure therapy.

Where we live: The impact of neighborhoods and community factors on cardiovascular health in the United States.

While the prevalence of cardiovascular risk factors has decreased in the United States in recent years, cardiovascular disparities by sex and race persist. Among the factors contributing to these disparities is the physical environment in which individuals live. Neighborhood characteristics, ranging from air pollution exposure to residential segregation, have been found to be related to cardiovascular health (CVH) and stroke risk. Through the use of cross-sectional, longitudinal, and analytic regression modeling, we are gaining clarity about the relationship between an individual's external environment and CVH. Moreover, differences in CVH vary by sex and/or race within the same neighborhood. The mechanism by which these disparities exist is still being explored. In this review, we examine the literature that has accumulated regarding how external environments and community factors affect individuals and populations by race and sex.

mActive-Smoke: A Prospective Observational Study Using Mobile Health Tools to Assess the Association of Physical Activity With Smoking Urges.

BACKGROUND: Evidence that physical activity can curb smoking urges is limited in scope to acute effects and largely reliant on retrospective self-reported measures. Mobile health technologies offer novel mechanisms for capturing real-time data of behaviors in the natural environment. OBJECTIVE: This study aimed to explore this in a real-world longitudinal setting by leveraging mobile health tools to assess the association between objectively measured physical activity and concurrent smoking urges in a 12-week prospective observational study. METHODS: We enrolled 60 active smokers (≥3 cigarettes per day) and recorded baseline demographics, physical activity, and smoking behaviors using a Web-based questionnaire. Step counts were measured continuously using the Fitbit Charge HR. Participants reported instantaneous smoking urges via text message using a Likert scale ranging from 1 to 9. On study completion, participants reported follow-up smoking behaviors in an online exit survey. RESULTS: A total of 53 participants (aged 40 [SD 12] years, 57% [30/53] women, 49% [26/53] nonwhite) recorded at least 6 weeks of data and were thus included in the analysis. We recorded 15,365 urge messages throughout the study, with a mean of 290 (SD 62) messages per participant. Mean urge over the course of the study was positively associated with daily cigarette consumption at follow-up (Pearson r=.33; P=.02). No association existed between daily steps and mean daily urge (beta=-6.95×10-3 per 1000 steps; P=.30). Regression models of acute effects, however, did reveal modest inverse associations between steps within 30-, 60-, and 120-min time windows of a reported urge (beta=-.0191 per 100 steps, P<.001). Moreover, 6 individuals (approximately 10% of the study population) exhibited a stronger and consistent inverse association between steps and urge at both the day level (mean individualized beta=-.153 per 1000 steps) and 30-min level (mean individualized beta=-1.66 per 1000 steps). CONCLUSIONS: Although there was no association between objectively measured daily physical activity and concurrently self-reported smoking urges, there was a modest inverse relationship between recent step counts (30-120 min) and urge. Approximately 10% of the individuals appeared to have a stronger and consistent inverse association between physical activity and urge, a provocative finding warranting further study.

Racial/Ethnic Disparities in Quality of Care for Cardiovascular Disease in Ambulatory Settings: A Review.

Racial and ethnic disparities in cardiovascular disease (CVD) outcomes are widely reported, but research has largely focused on differences in quality of inpatient and urgent care to explain these disparate outcomes. The objective of this review is to synthesize recent evidence on racial and ethnic disparities in management of CVD in the ambulatory setting. Database searches yielded 550 articles of which 25 studies met the inclusion criteria. Reviewed studies were categorized into non-interventional studies examining the association between race and receipt of ambulatory CVD services with observational designs, and interventional studies evaluating specific clinical courses of action intended to ameliorate disparities. Based on the Donabedian framework, this review demonstrates that significant racial/ethnic disparities persist in process and outcome measures of quality of ambulatory CVD care. Multimodal interventions were most effective in reducing disparities in CVD outcomes.