Effects of an Intervention to Improve Evidence-Based Care for People With Diabetes and Cardiovascular Disease Across Sex, Race, and Ethnicity Subgroups: Insights From the COORDINATE-Diabetes Trial.

BACKGROUND: Results from the COORDINATE-Diabetes trial demonstrated that a multifaceted, clinic-based intervention increased prescription of evidence-based medical therapies to participants with type 2 diabetes and atherosclerotic cardiovascular disease. This secondary analysis assessed whether intervention success was consistent across sex, race, and ethnicity. METHODS: COORDINATE-Diabetes, a cluster randomized trial, recruited participants from 43 US cardiology clinics (20 randomized to intervention and 23 randomized to usual care). The primary outcome was the proportion of participants prescribed all 3 groups of evidence-based therapy (high-intensity statin, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, and sodium-glucose cotransporter-2 inhibitor or glucagon-like peptide 1 receptor agonist) at last trial assessment (6 to 12 months). In this prespecified analysis, mixed-effects logistic regression models were used to assess the outcome by self-reported sex, race, and ethnicity in the intervention and usual care groups, with adjustment for baseline characteristics, medications, comorbidities, and site location. RESULTS: Among 1045 participants with type 2 diabetes and atherosclerotic cardiovascular disease, the median age was 70 years, 32% were female, 16% were Black, and 9% were Hispanic. At the last trial assessment, there was an absolute increase in the proportion of participants prescribed all 3 groups of evidence-based therapy in women (36% versus 15%), Black participants (41% versus 18%), and Hispanic participants (46% versus 18%) with the intervention compared with usual care, with consistent benefit across sex (male versus female; Pinteraction=0.44), race (Black versus White; Pinteraction=0.59), and ethnicity (Hispanic versus Non-Hispanic; Pinteraction= 0.78). CONCLUSIONS: The COORDINATE-Diabetes intervention successfully improved delivery of evidence-based care, regardless of sex, race, or ethnicity. Widespread dissemination of this intervention could improve equitable health care quality, particularly among women and minority communities who are frequently underrepresented in clinical trials. REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT03936660.

Association of global longitudinal strain by feature tracking cardiac magnetic resonance imaging with adverse outcomes among community-dwelling adults without cardiovascular disease: The Dallas Heart Study.

AIM: Left ventricular (LV) global longitudinal strain (GLS) may detect subtle abnormalities in myocardial contractility among individuals with normal LV ejection fraction (LVEF). However, the prognostic implications of GLS among healthy, community-dwelling adults is not well-established. METHODS AND RESULTS: Overall, 2234 community-dwelling adults (56% women, 47% Black) with LVEF ≥50% without a history of cardiovascular disease (CVD) from the Dallas Heart Study who underwent cardiac magnetic resonance (CMR) with GLS assessed by feature tracking CMR (FT-CMR) were included. The association of GLS with the risk of incident major adverse cardiovascular events (MACE; composite of incident myocardial infarction, incident heart failure [HF], hospitalization for atrial fibrillation, coronary revascularization, and all-cause death), and incident HF or death were assessed with adjusted Cox proportional hazards models. A total of 309 participants (13.8%) had MACE during a median follow-up duration of 17 years. Participants with the worst GLS (Q4) were more likely male and of the Black race with a history of tobacco use and diabetes with lower LVEF, higher LV end-diastolic volume, and higher LV mass index. Cumulative incidence of MACE was higher among participants with worse (Q4 vs. Q1) GLS (20.4% vs. 9.0%). In multivariable-adjusted Cox models that included clinical characteristics, cardiac biomarkers and baseline LVEF, worse GLS (Q4 vs. Q1) was associated with a significantly higher risk of MACE (hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.07-2.24, p = 0.02) and incident HF or death (HR 1.57, 95% CI 1.03-2.38, p = 0.04). CONCLUSIONS: Impaired LV GLS assessed by FT-CMR among adults free of cardiovascular disease is associated with a higher risk of incident MACE and incident HF or death independent of cardiovascular risk factors, cardiac biomarkers and LVEF.

Lifetime healthcare expenses across demographic and cardiovascular risk groups: The application of a novel modeling strategy in a large multiethnic cohort study.

Objective: To understand the burden of healthcare expenses over the lifetime of individuals and evaluate differences among those with cardiovascular risk factors and among disadvantaged groups based on race/ethnicity and sex. Methods: We linked data from the longitudinal multiethnic Dallas Heart Study, which recruited participants between 2000 and 2002, with inpatient and outpatient claims from all hospitals in the Dallas-Fort Worth metroplex through December 2018, capturing encounter expenses. Race/ethnicity and sex, as well as five risk factors, hypertension, diabetes, hyperlipidemia, smoking, and overweight/obesity, were defined at cohort enrollment. For each individual, expenses were indexed to age and cumulated between 40 and 80 years of age. Lifetime expenses across exposures were evaluated as interactions in generalized additive models. Results: A total of 2184 individuals (mean age, 45±10 years; 61% women, 53% Black) were followed between 2000 and 2018. The mean modeled lifetime cumulative healthcare expenses were $442,629 (IQR, $423,850 to $461,408). In models that included 5 risk factors, Black individuals had $21,306 higher lifetime healthcare spending compared with non-Black individuals (P < .001), and men had modestly higher expenses than women ($5987, P < .001). Across demographic groups, the presence of risk factors was associated with progressively higher lifetime expenses, with significant independent association of diabetes ($28,075, P < .001), overweight/obesity ($8816, P < .001), smoking ($3980, P = .009), and hypertension ($528, P = .02) with excess spending. Conclusion: Our study suggests Black individuals have higher lifetime healthcare expenses, exaggerated by the substantially higher prevalence of risk factors, with differences emerging in older age.

The Association of QRS Duration with Risk of Adverse Outcomes in Sex- and Race- Based Subgroups: The Dallas Heart Study.

Introduction: We explored sex and race differences in the prognostic implications of QRS prolongation among healthy adults. Methods: Participants from the Dallas Heart Study (DHS) free of cardiovascular (CV) disease who underwent ECG testing and cMRI evaluation were included. Multivariable linear regression was used to examine the cross-sectional association of QRS duration with left ventricular (LV) mass, LV ejection fraction (LVEF), and LV end diastolic volume (LVEDV). Association of QRS duration with risk of MACE was evaluated using Cox models. Interaction testing was performed between QRS duration and sex/race respectively for each outcome of interest. QRS duration was log transformed. Results: The study included 2,785 participants. Longer QRS duration was associated with higher LV mass, lower LVEF, and higher LVEDV, independent of CV risk factors ([ß: 0.21, P<0.001], [ß: - 0.13, P<0.001], [ß: 0.22, P<0.001] respectively). Men with longer QRS duration were more likely to have higher LV mass and higher LVEDV compared to women (P-int=0.012, P-int=0.01, respectively). Black participants with longer QRS duration were more likely to have higher LV mass as compared to White participants (P-int<0.001). In Cox analysis, QRS prolongation was associated with higher risk of MACE in women (HR = 6.66 [95% CI: 2.32, 19.1]) but not men. This association was attenuated after adjustment for CV risk factors, with a trend toward significance (HR = 2.45 [95% CI: 0.94, 6.39]). Longer QRS duration was not associated with risk of MACE in Black or White participants in the adjusted models. No interaction between sex/race and QRS duration for risk of MACE was observed. Discussion: In healthy adults, QRS duration is differentially associated with abnormalities in LV structure and function. These findings inform the use of QRS duration in identifying subgroups at risk for CV disease, and caution against using QRS duration cut offs uniformly for clinical decision making. What is known?: QRS prolongation in healthy adults is associated with higher risk of death, cardiovascular disease, and left ventricular hypertrophy. What the study adds?: QRS prolongation may reflect a higher degree of underlying LV hypertrophy in Blacks compared to Whites. Longer QRS interval may reflect higher risk of adverse cardiac events, driven by prevalent cardiovascular risk factors. Graphic Abstract: Risk of underlying left ventricular hypertrophy in demographic groups based on QRS prolongation.

Supranormal Left Ventricular Ejection Fraction, Stroke Volume, and Cardiovascular Risk: Findings From Population-Based Cohort Studies.

BACKGROUND: Supranormal ejection fraction by echocardiography in clinically referred patient populations has been associated with an increased risk of cardiovascular disease (CVD). The prognostic implication of supranormal left ventricular ejection fraction (LVEF)-assessed by cardiac magnetic resonance (CMR)-in healthy, community-dwelling individuals is unknown. OBJECTIVES: The purpose of this study is to investigate the prognostic implication of supranormal LVEF as assessed by CMR and its inter-relationship with stroke volume among community-dwelling adults without CVD. METHODS: Participants from the MESA (Multi-Ethnic Study of Atherosclerosis) and DHS (Dallas Heart Study) cohorts free of CVD who underwent CMR with LVEF above the normal CMR cutoff (≥57%) were included. The association between cohort-specific LVEF categories and risk of clinically adjudicated major adverse cardiovascular events (MACE) was assessed using adjusted Cox models. Subgroup analysis was also performed to evaluate the association of LVEF and risk of MACE among individuals stratified by left ventricular stroke volume index. RESULTS: The study included 4,703 participants from MESA and 2,287 from DHS with 727 and 151 MACE events, respectively. In adjusted Cox models, the risk of MACE was highest among individuals in LVEF Q4 (vs Q1) in both cohorts after accounting for potential confounders (MESA: HR = 1.27 [95% CI: 1.01-1.60], P = 0.04; DHS: HR = 1.72 [95% CI: 1.05-2.79], P = 0.03). A significant interaction was found between the continuous measures of LVEF and left ventricular stroke volume index (P interaction = 0.02) such that higher LVEF was significantly associated with an increased risk of MACE among individuals with low but not high stroke volume. CONCLUSIONS: Among community-dwelling adults without CVD, LVEF in the supranormal range is associated with a higher risk of adverse cardiovascular outcomes, particularly in those with lower stroke volume.

Diabetes Status Modifies the Association Between Different Measures of Obesity and Heart Failure Risk Among Older Adults: A Pooled Analysis of Community-Based NHLBI Cohorts.

BACKGROUND: Obesity and diabetes are associated with a higher risk of heart failure (HF). The interrelationships between different measures of adiposity-overall obesity, central obesity, fat mass (FM)-and diabetes status for HF risk are not well-established. METHODS: Participant-level data from the ARIC study (Atherosclerosis Risk in Communities; visit 5) and the CHS (Cardiovascular Health Study; visit 1) cohorts were obtained from the National Heart, Lung, and Blood Institute Biologic Specimen and Data Repository Information Coordinating Center, harmonized, and pooled for the present analysis, excluding individuals with prevalent HF. FM was estimated in all participants using established anthropometric prediction equations additionally validated using the bioelectrical impedance-based FM in the ARIC subgroup. Incident HF events on follow-up were captured across both cohorts using similar adjudication methods. Multivariable-adjusted Fine-Gray models were created to evaluate the associations of body mass index (BMI), waist circumference (WC), and FM with risk of HF in the overall cohort as well as among those with versus without diabetes at baseline. The population attributable risk of overall obesity (BMI≥30 kg/m2), abdominal obesity (WC>88 and 102 cm in women and men, respectively), and high FM (above sex-specific median) for incident HF was evaluated among participants with and without diabetes. RESULTS: The study included 10 387 participants (52.9% ARIC; 25.1% diabetes; median age, 74 years). The correlation between predicted and bioelectrical impedance-based FM was high (R2=0.90; n=5038). During a 5-year follow-up, 447 participants developed HF (4.3%). Higher levels of each adiposity measure were significantly associated with higher HF risk (hazard ratio [95% CI] per 1 SD higher BMI=1.15 [1.05, 1.27], WC=1.22 [1.10, 1.36]; FM=1.13 [1.02, 1.25]). A significant interaction was noted between diabetes status and measures of BMI (P interaction=0.04) and WC (P interaction=0.004) for the risk of HF. In stratified analysis, higher measures of each adiposity parameter were significantly associated with higher HF risk in individuals with diabetes (hazard ratio [95% CI] per 1 SD higher BMI=1.29 [1.14-1.47]; WC=1.48 [1.29-1.70]; FM=1.25 [1.09-1.43]) but not those without diabetes, including participants with prediabetes and euglycemia. The population attributable risk percentage of overall obesity, abdominal obesity, and high FM for incident HF was higher among participants with diabetes (12.8%, 29.9%, and 13.7%, respectively) versus those without diabetes (≤1% for each). CONCLUSIONS: Higher BMI, WC, and FM are strongly associated with greater risk of HF among older adults, particularly among those with prevalent diabetes.

Physical Activity and Cardiorespiratory Fitness: Vital Signs for Cardiovascular Risk Assessment.

PURPOSE OF REVIEW: Current risk prediction tools do not include physical activity (PA) or cardiorespiratory fitness (CRF), despite their robust association with adverse cardiovascular disease (CVD) events and their potential as targets for preventive interventions. RECENT FINDINGS: PA and CRF are each associated with cardiovascular (CV) morbidity and mortality, independent of traditional risk factors. Improvement in CRF is associated with reduced risk of atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF). Risk prediction tools have been developed for ASCVD, and more recently for HF, to refine CVD risk assessment and inform CVD prevention strategies. Attempts have been made to incorporate PA and CRF into available CVD risk prediction models. Inclusion of PA and CRF into established CVD risk assessment models improves CVD risk prediction incremental to established CVD risk prediction tools, suggesting PA and CRF are markers of CVD risk and targets for CVD prevention.

Regional adiposity, cardiorespiratory fitness, and left ventricular strain: an analysis from the Dallas Heart Study.

BACKGROUND: Low cardiorespiratory fitness (CRF), high body mass index, and excess visceral adiposity are each associated with impairment in left ventricular (LV) peak circumferential strain (Ecc), an intermediate phenotype that precedes the development of clinical heart failure (HF). However, the association of regional fat distribution and CRF with Ecc independent of each other and other potential confounders is not known. METHODS: Participants from the Dallas Heart Study Phase 2 who underwent dual energy X-ray absorptiometry assessment of regional fat distribution, CRF assessment by submaximal treadmill test, and Ecc quantification by tissue-tagged cardiovascular magnetic resonance were included in the analysis. The cross-sectional associations of measures of regional adiposity, namely visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and lower-body fat (LBF) with Ecc after adjustment for CRF and other potential confounders (independent variables) were assessed using multivariable linear regression analysis. RESULTS: The study included 1089 participants (55% female, 39% black). In the unadjusted analysis, higher VAT was associated with greater impairment in Ecc. After adjustment for baseline risk factors, CRF, parameters of LV structure and function, and other fat depots such as SAT and LBF, higher VAT remained associated with greater impairment in Ecc (ß: 0.19, P = 0.002). SAT and LBF were not significantly associated with Ecc, however, CRF remained associated with Ecc in the fully adjusted model including all fat depots (ß: - 0.15, P < 0.001). CONCLUSIONS: VAT and CRF are each independently associated with impairment in Ecc, suggesting that higher VAT burden and low CRF mediate pathological cardiac remodeling through distinct mechanisms.

Running away from cardiovascular disease at the right speed: The impact of aerobic physical activity and cardiorespiratory fitness on cardiovascular disease risk and associated subclinical phenotypes.

Higher levels of physical activity (PA) and cardiorespiratory fitness (CRF) are associated with lower risk of incident cardiovascular disease (CVD). However, the relationship of aerobic PA and CRF with risk of atherosclerotic CVD outcomes and heart failure (HF) seem to be distinct. Furthermore, recent studies have raised concerns of potential toxicity associated with extreme levels of aerobic exercise, with higher levels of coronary artery calcium and incident atrial fibrillation noted among individuals with very high PA levels. In contrast, the relationship between PA levels and measures of left ventricular structure and function and risk of HF is more linear. Thus, personalizing exercise levels to optimal doses may be key to achieving beneficial outcomes and preventing adverse CVD events among high risk individuals. In this report, we provide a comprehensive review of the literature on the associations of aerobic PA and CRF levels with risk of adverse CVD outcomes and the preceding subclinical cardiac phenotypes to better characterize the optimal exercise dose needed to favorably modify CVD risk.

Temporal Trends in Heart Failure Incidence Among Medicare Beneficiaries Across Risk Factor Strata, 2011 to 2016.

Importance: Heart failure (HF) incidence is declining among Medicare beneficiaries. However, the epidemiological mechanisms underlying this decline are not well understood. Objective: To evaluate trends in HF incidence across risk factor strata. Design, Setting, and Participants: Retrospective, national cohort study of 5% of all fee-for-service Medicare beneficiaries with no prior HF followed up from 2011 to 2016. The study examined annual trends in HF incidence among groups with and without primary HF risk factors (hypertension, diabetes, and obesity) and predisposing cardiovascular conditions (acute myocardial infarction [MI] and atrial fibrillation [AF]). Exposures: The presence of comorbid HF risk factors including hypertension, diabetes, obesity, acute MI, and AF identified by International Classification of Diseases, Ninth Revision, Clinical Modification codes and International Statistical Classification of Diseases, Tenth Revision, Clinical Modification codes. Main Outcomes and Measures: Incident HF, defined using at least 1 inpatient HF claim or at least 2 outpatient HF claims among those without a previous diagnosis of HF. Results: Of 1 799 027 unique Medicare beneficiaries at risk for HF (median age, 73 years [interquartile range, 68-79 years]; 56% female [805 060-796 253 participants during the study period]), 249 832 had a new diagnosis of HF. The prevalence of all 5 risk factors increased over time (0.8% mean increase in hypertension per year, 1.9% increase in diabetes, 2.9% increase in obesity, 0.2% increase in acute MI, and 0.4% increase in AF). Heart failure incidence declined from 35.7 cases per 1000 beneficiaries in 2011 to 26.5 cases per 1000 beneficiaries in 2016, consistent across subgroups based on sex and race/ethnicity. A greater decline in HF incidence was observed among patients with prevalent hypertension (relative excess decline, 12%), diabetes (relative excess decline, 3%), and obesity (relative excess decline, 16%) compared with those without corresponding risk factors. In contrast, there was a relative increase in HF incidence among individuals with acute MI (26% vs no acute MI) and AF (22% vs no AF). Conclusions and Relevance: Findings of this study suggest that the temporal decline in HF incidence among Medicare beneficiaries reflects a decrease in HF incidence among those with primary HF risk factors. The increase in HF incidence among those with acute MI and those with AF highlights potential targets for future HF prevention strategies.

Prevalence of Apparent Treatment-Resistant Hypertension in the United States According to the 2017 High Blood Pressure Guideline.

OBJECTIVE: To evaluate the prevalence of apparent treatment-resistant hypertension (aTR-hypertension) in US adults with treated hypertension by using the nationally representative National Health and Nutrition Examination Survey (NHANES). PATIENTS AND METHODS: Nonpregnant US adults older than 20 years with a self-reported history of treated hypertension who had blood pressure measured in NHANES cycles 2007 to 2014 were included in this study. Study participants were stratified into 4 groups according to average blood pressure and antihypertensive medication use: well-controlled hypertension, undertreated hypertension, aTR-hypertension by the 2017 guideline, and aTR-hypertension by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) guideline. National Health and Nutrition Examination Survey sample weights were used to estimate the national prevalence. RESULTS: From 2007 to 2014, 5512 participants with treated hypertension representing 46.7 million people nationally were included. Compared with JNC 7 guideline criteria, application of the 2017 high blood pressure guideline criteria increased the prevalence of aTR-hypertension in US adults with treated hypertension from 12.0% to 15.95%, identifying an additional 1.85 million individuals with aTR-hypertension nationally. Individuals newly reclassified as having aTR-hypertension were younger. However, the prevalence of thiazide diuretic use remained less than 70%, and that of mineralocorticoid antagonist use remained less than 10% regardless of the guideline definition. CONCLUSION: On the basis of the 2017 high blood pressure guideline, the prevalence of aTR-hypertension is 15.95% in US adults with treated hypertension. This represents an absolute increase of 4% (1.85 million additional individuals nationally) compared with the JNC 7 guideline definition, with a consistent increase across all subpopulations with treated hypertension.

Association Between Regional Adipose Tissue Distribution and Risk of Heart Failure Among Blacks.

BACKGROUND: Obesity is highly prevalent among blacks and is associated with a greater risk of heart failure (HF). However, the contribution of regional adiposity depots such as visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue toward risk of HF in blacks is unknown. METHODS AND RESULTS: We included 2602 participants (mean age: 59 years, 35% men) from the Jackson Heart Study without prevalent HF who underwent computed tomography quantification of VAT and subcutaneous adipose tissue during the second visit (2005-2009). The associations between different adiposity measures and HF were evaluated using adjusted Cox models. There were 122 incident HF events over a median follow-up of 7.1 years. Higher amounts of VAT were associated with greater risk of HF in age- and sex-adjusted analyses (hazard ratio [95% CI] per 1-SD higher VAT: 1.29 [1.09-1.52]). This association was attenuated and not significant after additional adjustment for traditional HF risk factors and body mass index. Overall obesity, represented by body mass index, was associated with higher risk of HF independent of risk factors and VAT (hazard ratio [95% CI] per 1-kg/m2 higher body mass index: 1.06 [1.02-1.11]). Subcutaneous adipose tissue was not associated with risk of HF in adjusted analyses. CONCLUSIONS: In a community-dwelling black population, higher amounts of overall and visceral adiposity are associated with higher risk of HF. The association between VAT and HF risk in blacks may reflect differences in traditional HF risk factor burden. Future studies are needed to confirm this observation and clarify the independent role of different measures of adiposity on HF outcomes.

Exercise Training for Prevention and Treatment of Heart Failure.

Heart failure (HF) results in high healthcare costs and burdens for the United States in respects to hospitalizations, therapies, and associated disability. The relative proportion of HF with preserved ejection fraction (HFpEF) compared with HF with reduced ejection fraction (HFrEF) is on the rise; HFpEF has already become the dominant form of HF and it continues to increase. The serious implications of these trends are compounded by a dearth of effective HFpEF therapies. While low physical activity, low cardiorespiratory fitness (CRF), and obesity, are risk factors for HF in general, they particularly predispose to HFpEF. Thus, weight loss and exercise that leads to improved CRF may constitute important opportunities for effective intervention. In this review, we discuss the interplay between physical inactivity, CRF, and obesity in the development of HF, particularly HFpEF, and highlight the current evidence on weight loss and exercise as preventive and therapeutic opportunities.

Marcellus Shale Drilling's Impact on the Dairy Industry in Pennsylvania: A Descriptive Report.

Unconventional natural gas drilling in Pennsylvania has accelerated over the past five years, and is unlikely to abate soon. Dairy farming is a large component of Pennsylvania's agricultural economy. This study compares milk production, number of cows, and production per cow in counties with significant unconventional drilling activity to that in neighboring counties with less unconventional drilling activity, from 1996 through 2011. Milk production and milk cows decreased in most counties since 1996, with larger decreases occurring from 2007 through 2011 (when unconventional drilling increased substantially) in five counties with the most wells drilled compared to six adjacent counties with fewer than 100 wells drilled. While this descriptive study cannot draw a causal association between well drilling and decline in cows or milk production, given the importance of Pennsylvania's dairy industry and the projected increase in unconventional natural gas drilling, further research to prevent unintended economic and public health consequences is imperative.