Neighborhood-level social determinants of health and cardioprotective behaviors among church members in New Orleans, Louisiana.

BACKGROUND: Favorable neighborhood-level social determinants of health (SDoH) are associated with lower cardiovascular disease risk. Less is known about their influence on cardioprotective behaviors. We evaluated the associations between neighborhood-level SDoH and cardioprotective behaviors among church members in Louisiana. METHODS: Participants were surveyed between November 2021 to February 2022, and were asked about health behaviors, aspects of their neighborhood, and home address (to link to census tract and corresponding social deprivation index [SDI] data). Logistic regression models were used to assess the relation of neighborhood factors with the likelihood of engaging in cardioprotective behaviors: 1) a composite of healthy lifestyle behaviors [fruit and vegetable consumption, physical activity, and a tobacco/nicotine-free lifestyle], 2) medication adherence, and 3) receipt of routine medical care within the past year. RESULTS: Participants (n = 302, mean age: 63 years, 77% female, 99% Black) were recruited from 12 churches in New Orleans. After adjusting for demographic and clinical factors, perceived neighborhood walkability or conduciveness to exercise (odds ratio [OR]=1.25; 95% CI: 1.03, 1.53), availability of fruits and vegetables (OR=1.23; 95% CI: 1.07, 1.42), and social cohesion (OR=1.55; 95% CI: 1.22, 1.97) were positively associated with the composite of healthy lifestyle behaviors. After multivariable adjustment, SDI was in the direction of association with all three cardioprotective behavior outcomes, but associations were not statistically significant. CONCLUSIONS: In this predominantly Black, church-based population, neighborhood-level SDoH including the availability of fruits and vegetables, walkability or conduciveness to exercise, and social cohesion were associated with cardioprotective behaviors. Findings reiterate the need to address adverse neighborhood-level SDoH in the design and implementation of health interventions.

Social, Behavioral, and Metabolic Risk Factors and Racial Disparities in Cardiovascular Disease Mortality in U.S. Adults : An Observational Study.

BACKGROUND: Cardiovascular disease (CVD) mortality is persistently higher in the Black population than in other racial and ethnic groups in the United States. OBJECTIVE: To examine the degree to which social, behavioral, and metabolic risk factors are associated with CVD mortality and the extent to which racial differences in CVD mortality persist after these factors are accounted for. DESIGN: Prospective cohort study. SETTING: NHANES (National Health and Nutrition Examination Survey) 1999 to 2018. PARTICIPANTS: A nationally representative sample of 50 808 persons aged 20 years or older. MEASUREMENTS: Data on social, behavioral, and metabolic factors were collected in each NHANES survey using standard methods. Deaths from CVD were ascertained from linkage to the National Death Index with follow-up through 2019. RESULTS: Over an average of 9.4 years of follow-up, 2589 CVD deaths were confirmed. The age- and sex-standardized rates of CVD mortality were 484.7 deaths per 100 000 person-years in Black participants, 384.5 deaths per 100 000 person-years in White participants, 292.4 deaths per 100 000 person-years in Hispanic participants, and 255.1 deaths per 100 000 person-years in other race groups. In a multiple Cox regression analysis adjusted for all measured risk factors simultaneously, several social (unemployment, low family income, food insecurity, lack of home ownership, and unpartnered status), behavioral (current smoking, lack of leisure-time physical activity, and sleep <6 or >8 h/d), and metabolic (obesity, hypertension, and diabetes) risk factors were associated with a significantly higher risk for CVD death. After adjustment for these metabolic, behavioral, and social risk factors separately, hazard ratios of CVD mortality for Black compared with White participants were attenuated from 1.54 (95% CI, 1.34 to 1.77) to 1.34 (CI, 1.16 to 1.55), 1.31 (CI, 1.15 to 1.50), and 1.04 (CI, 0.90 to 1.21), respectively. LIMITATION: Causal contributions of social, behavioral, and metabolic risk factors to racial and ethnic disparities in CVD mortality could not be established. CONCLUSION: The Black-White difference in CVD mortality diminished after adjustment for behavioral and metabolic risk factors and completely dissipated with adjustment for social determinants of health in the U.S. population. PRIMARY FUNDING SOURCE: National Institutes of Health.

Weight-dependent and weight-independent effects of dulaglutide on blood pressure in patients with type 2 diabetes.

BACKGROUND: Patients with type 2 diabetes (T2D) treated with glucagon-like peptide-1 receptor agonists may experience reductions in weight and blood pressure. The primary objective of the current study was to determine the weight-dependent and weight-independent effects of ~ 6 months treatment with dulaglutide 1.5 mg treatment in participants with T2D. METHODS: Mediation analysis was conducted for five randomized, placebo-controlled trials of dulaglutide 1.5 mg to estimate the weight-dependent (i.e., mediated by weight) and weight-independent effects from dulaglutide vs. placebo on change from baseline for systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure. A random-effects meta-analysis combined these results. To investigate a dose response between dulaglutide 4.5 mg and placebo, mediation analysis was first conducted in AWARD-11 to estimate the weight-dependent and weight-independent effects of dulaglutide 4.5 mg vs. 1.5 mg, followed by an indirect comparison with the mediation result for dulaglutide 1.5 mg vs. placebo. RESULTS: Baseline characteristics were largely similar across the trials. In the mediation meta-analysis of placebo-controlled trials, the total treatment effect of dulaglutide 1.5 mg after placebo-adjustment on SBP was - 2.6 mmHg (95% CI - 3.8, - 1.5; p < 0.001) and was attributed to both a weight-dependent effect (- 0.9 mmHg; 95% CI: - 1.4, - 0.5; p < 0.001) and a weight-independent effect (- 1.5 mmHg; 95% CI: - 2.6, - 0.3; p = 0.01), accounting for 36% and 64% of the total effect, respectively. For pulse pressure, the total treatment effect of dulaglutide (- 2.5 mmHg; 95% CI: - 3.5, - 1.5; p < 0.001) was 14% weight-dependent and 86% weight-independent. For DBP there was limited impact of dulaglutide treatment, with only a small weight-mediated effect. Dulaglutide 4.5 mg demonstrated an effect on reduction in SBP and pulse pressure beyond that of dulaglutide 1.5 mg which was primarily weight mediated. CONCLUSIONS: Dulaglutide 1.5 mg reduced SBP and pulse pressure in people with T2D across the placebo-controlled trials in the AWARD program. While up to one third of the effect of dulaglutide 1.5 mg on SBP and pulse pressure was due to weight reduction, the majority was independent of weight. A greater understanding of the pleotropic effects of GLP-1 RA that contribute to reduction in blood pressure could support developing future approaches for treating hypertension. Trial registrations (clinicaltrials.gov) NCT01064687, NCT00734474, NCT01769378, NCT02597049, NCT01149421, NCT03495102.

Perceived Religious Influence on Health Is Associated with Beneficial Health Behaviors in Members of Predominantly Black Churches.

Background: Cardiovascular disease is the leading cause of death in the United States, and Black populations are disproportionately affected. Black populations also have high rates of religiosity, which may be an important health motivator, but mechanisms are unclear. Objective: We examined the relationship between perceived religious influence on health and cardiovascular health behaviors, risk factors, and confidence participating in medical care in Black church congregants. Methods: We surveyed 302 members of 13 churches with predominantly Black congregations in New Orleans, Louisiana. Participants reported if religious beliefs had an influence on their health and if they avoided harmful behaviors because of religion. Fruit and vegetable intake, physical activity, smoking status, confidence asking questions to health care providers, understanding treatment plans and self-reported hypertension, hypercholesterolemia, and diabetes were assessed. Logistic regression was used adjusting for age, sex, and education. Results: Survey respondents were 77% female with a median age of 66 years, and 72%, 56%, and 37% reported hypertension, hypercholesterolemia, and diabetes, respectively. Perceived religious influence on health was positively associated with fruit and vegetable intake, physical activity, and confidence asking questions to health care providers. Avoiding harmful behaviors because of religion was positively associated with physical activity. There was no association between perceived religious influence on health and smoking, hypertension, hypercholesterolemia, or diabetes. Conclusion: Perceived religious influence on health was associated with beneficial cardiovascular health behaviors and confidence participating in medical care. These findings can inform the design and delivery of interventions to reduce cardiovascular disease among Black religious communities.

A systematic review of racial/ethnic disparities in pharmacotherapy and surgical treatment outcomes in peripheral arterial disease among African American/non-Hispanic Black, non-Hispanic White and Hispanic patients.

Background: Lower extremity peripheral arterial disease (PAD) is associated with significant morbidity and mortality in racial/ethnic diverse populations. However, limited data exist on treatment outcome disparities in racial/ethnic diverse populations, particularly in AA/NHB populations. Objective: The aim of this systematic review is to analyze disparities in the outcomes of PAD treatments, particularly pharmacotherapy and surgery, among racial/ethnic groups in the US. Methods: A comprehensive search of original investigations pertaining to PAD treatments between 2015 and 2021 was performed. Quality assessment of the studies was also completed. Results: Fourteen studies were included. Thirteen studies reported differences in treatment outcomes for surgical intervention, and one study reported differences for concurrent surgical and pharmacotherapy. NHB and Hispanic/Latinx ethnicities were associated with decreased overall and perioperative mortality in four studies. Six studies noted increased amputation risk among racial/ethnic diverse populations. Only one study noted significant survival benefit by race/ethnicity. Three studies noted increased risk of major adverse limb events and post-operative complications. One study noted increased limb patency after intervention in racial/ethnic cohorts. Overall, all studies reported high methodological quality with adequate assessment of outcomes and follow-up of cohort. Conclusion: In this analysis, the predominant intervention reported is surgical. Overall, racial/ethnic populations are less likely to experience PAD-associated mortality but are more likely to experience adverse events. Further studies are necessary to include all racial/ethnic diverse populations in assessing PAD therapeutic intervention outcomes. Moreover, targeted public health efforts are necessary to increase PAD educational awareness, community-driven risk modification, and patient-centered care planning.

Ten things to know about ten cardiovascular disease risk factors.

Given rapid advancements in medical science, it is often challenging for the busy clinician to remain up-to-date on the fundamental and multifaceted aspects of preventive cardiology and maintain awareness of the latest guidelines applicable to cardiovascular disease (CVD) risk factors. The "American Society for Preventive Cardiology (ASPC) Top Ten CVD Risk Factors 2021 Update" is a summary document (updated yearly) regarding CVD risk factors. This "ASPC Top Ten CVD Risk Factors 2021 Update" summary document reflects the perspective of the section authors regarding ten things to know about ten sentinel CVD risk factors. It also includes quick access to sentinel references (applicable guidelines and select reviews) for each CVD risk factor section. The ten CVD risk factors include unhealthful nutrition, physical inactivity, dyslipidemia, hyperglycemia, high blood pressure, obesity, considerations of select populations (older age, race/ethnicity, and sex differences), thrombosis/smoking, kidney dysfunction and genetics/familial hypercholesterolemia. For the individual patient, other CVD risk factors may be relevant, beyond the CVD risk factors discussed here. However, it is the intent of the "ASPC Top Ten CVD Risk Factors 2021 Update" to provide a succinct overview of things to know about ten common CVD risk factors applicable to preventive cardiology.

Global interventions in hypertension: new and emerging concepts.

PURPOSE OF REVIEW: Hypertension (HTN) is the most prevalent risk factor for cardiovascular disease (CVD) worldwide, affecting 1.39 billion people. This review discusses recent literature regarding the global burden of HTN and emerging concepts in prevalence, treatment, and control in different regions around the globe. RECENT FINDINGS: Community-based interventions and telemedicine may be useful in increasing access to care and identifying/assisting patients with HTN, especially in populations with geographical and economic barriers to healthcare. Home blood pressure monitoring is beneficial for HTN control in diverse regions. Polypills have proven benefits to decrease HTN and CVD risk. Continuation of treatment with angiotensin-converting-enzyme inhibitors and angiotensin-receptor blockers in high risk COVID-19 patients appears appropriate. SUMMARY: Extensive research demonstrates that early screening/treatment, lifestyle modification, and pharmacotherapy are essential to control HTN worldwide. This review highlights recent research and novel concepts on effective interventions being used globally.

Sociodemographic Determinants of Life's Simple 7: Implications for Achieving Cardiovascular Health and Health Equity Goals.

Background: Life's Simple 7 (LS7; nutrition, physical activity, cigarette use, body mass index, blood pressure, cholesterol, glucose) predicts cardiovascular health. The principal objective of our study was to define demographic and socioeconomic factors associated with LS7 to better inform programs addressing cardiovascular health and health equity. Methods: National Health and Nutrition Examination Surveys 1999-2016 data were analyzed on non-Hispanic White [NHW], NH Black [NHB], and Hispanic adults aged ≥20 years without cardiovascular disease. Each LS7 variable was assigned 0, 1, or 2 points for poor, intermediate, and ideal levels, respectively. Composite LS7 scores were grouped as poor (0-4 points), intermediate (5-9), and ideal (10-14). Results: 32,803 adults were included. Mean composite LS7 scores were below ideal across race/ethnicity groups. After adjusting for confounders, NHBs were less likely to have optimal LS7 scores than NHW (multivariable odds ratios (OR .44; 95% CI .37-.53), whereas Hispanics tended to have better scores (1.18; .96-1.44). Hispanics had more ideal LS7 scores than NHBs, although Hispanics had lower incomes and less education, which were independently associated with fewer ideal LS7 scores. Adults aged ≥45 years were less likely to have ideal LS7 scores (.11; .09-.12) than adults aged <45 years. Conclusions: NHBs were the least likely to have optimal scores, despite higher incomes and more education than Hispanics, consistent with structural racism and Hispanic paradox. Programs to optimize lifestyle should begin in childhood to mitigate precipitous age-related declines in LS7 scores, especially in at-risk groups. Promoting higher education and reducing poverty are also important.

Racial disparity in atherosclerotic cardiovascular disease in hospitalized patients with diabetes 2005-2015: Potential warning signs for future U.S. public health.

INTRODUCTION: The pattern of atherosclerotic cardiovascular disease (ASCVD) and diabetes driven hospitalizations in the United States (U.S.) is unclear. We attempted to identify the disparate outcome in race related ASCVD hospitalizations with comorbid diabetes. METHODS: Adults aged ≥40 years old with ASCVD (acute coronary syndrome (ACS), coronary artery disease (CAD), stroke, or peripheral arterial disease (PAD)) as the first-listed diagnosis with comorbid diabetes as a secondary diagnosis were determined using the U.S. 2005-2015 National (Nationwide) Inpatient Sample (NIS) data. The incidence of other modifiable cardiovascular risk factors (hypertension, dyslipidemia, smoking/substance abuse, obesity, and renal failure), in hospital procedures and outcomes was estimated. Complex samples multivariate regression was used to determine the odds ratio (OR) with 95% confidence Interval (CI) of risk associations and to determine patient comorbidity adjusted ASCVD related in-hospital mortality rate. RESULTS: The rate of total ASCVD hospitalizations with comorbid diabetes adjusted to the U.S. census population increased by 5.7% for black men compared to 4% for black women. There was a higher odd of an ASCVD hospitalization if there was comorbid hypertension (Odds Ratio (OR 1.29; 95% CI 95% 1.28-1.31), dyslipidemia (OR 2.03; 95% CI 2.01-2.05), renal failure (OR 1.84; 95% CI 1.82-1.86), and smoking/substance use disorder (OR 1.31; 95% CI 1.29-1.33). White Women had the highest risk-adjusted incidence of ASCVD related in-hospital mortality (4.2%) relative to black women (3.9%), compared to white men (3.6%) and black men (3.5%) respectively. CONCLUSIONS: Despite improving treatment options for ASCVD in the diabetic population, blacks with diabetes continue to have a higher hospitalization burden with a concomitant disparity in comorbid presentation and outcome. Further evaluation is the need to understand these associations.

Treatment effect of alirocumab according to age group, smoking status, and hypertension: Pooled analysis from 10 randomized ODYSSEY studies.

BACKGROUND: Age, smoking, hypercholesterolemia, and hypertension are major risk factors for atherosclerotic cardiovascular disease. OBJECTIVE: We examined whether the effects of alirocumab on low-density lipoprotein cholesterol (LDL-C) differed according to age, hypertension, or smoking status. METHODS: Data were pooled from 10 Phase 3 ODYSSEY randomized trials (24-104 weeks' duration) in 4983 people with heterozygous familial hypercholesterolemia (FH) or non-familial hypercholesterolemia (3188 on alirocumab, 1795 on control [620 on ezetimibe and 1175 on placebo]). Most participants received concomitant maximum tolerated statin therapy. In 8 trials, the alirocumab dose was increased from 75 mg every 2 weeks (Q2W) to 150 mg Q2W at Week 12 if predefined risk-based LDL-C goals were not achieved at Week 8 (≥70 mg/dL in very high cardiovascular risk; ≥100 mg/dL in moderate or high cardiovascular risk). Two trials compared alirocumab 150 mg Q2W vs placebo. The efficacy and safety of alirocumab were assessed post hoc in subgroups stratified by age (<65, ≥65 to <75, ≥75 years) and baseline hypertension or smoking status. RESULTS: Alirocumab reduced LDL-C by 23.7% (75/150 mg vs ezetimibe + statin) to 65.4% (150 mg vs placebo + statin) from baseline to Week 24 vs control. Subgroup analyses confirmed no significant interactions in response to alirocumab between age group, hypertension, or smoking status. Overall rates of treatment-emergent adverse events were similar between alirocumab and control groups. CONCLUSIONS: In this pooled analysis from 10 trials, alirocumab led to substantial LDL-C reductions vs control in every age group and regardless of hypertension or smoking status. Alirocumab was well tolerated in all subgroups.

Improved identification of secondary hypertension: use of a systematic protocol.

BACKGROUND: The accurate identification and diagnosis of secondary hypertension is critical, especially while atherosclerotic cardiovascular heart disease continues to be the leading cause of death in the industrialized world. Nevertheless, despite the existence of diagnostic tools, there are significant variations of the estimated prevalence of secondary hypertension, due to multiple etiologies and suboptimal recognition. This study demonstrates the results of using a systematic and protocolled approach to improve recognition of the presence of secondary hypertension. In the future, this questionnaire can be a quick and effective tool to unveil secondary hypertension in a broad array of clinical settings. METHODS: A total of 28,633 consecutive patients from January 1, 2007 to January 1, 2017 were diagnosed as having primary or secondary hypertension, utilizing the International Code of Diseases. Patients were located at the Center of Hypertension, Institute of Cardiology at Austral University Hospital, Buenos Aires, Argentina and were then further classified as having TRH, or non-resistant hypertension, to which a systematic protocol was employed in search for secondary hypertension. The confirmation of secondary hypertension was subsequently confirmed by diagnostic laboratory and imaging techniques in a hospital setting. RESULTS: A final population of 12,284 patients with treatment resistant hypertension (TRH) and non-treatment resistant hypertension (NTRH) were included in this study, where an etiology of secondary hypertension was identified in 50.9% and 36% of patients in each treatment group, respectively. Physicians used confirmatory laboratory testing and imaging of patients who were identified as having a cause for their secondary hypertension, with no significant differences in sex, age and body mass index (BMI) among study groups. CONCLUSIONS: These results illustrate the prevalence and distribution of the causes of secondary hypertension using a systematic, protocolled approach, which revealed a higher percentage of secondary hypertension than previously reported. This tool may be used by healthcare providers to ensure the appropriate recognition of secondary causes of hypertension in a wider range of patients with high blood pressure beyond resistant hypertension, changing the diagnostic paradigm of this condition.

Opportunities for improving cardiovascular health outcomes in adults younger than 65 years with guideline-recommended statin therapy.

The impact of age, race/ethnicity, healthcare insurance, and selected clinical variables on statin-preventable ASCVD were quantified in adults aged 21 to 79 years from National Health and Nutrition Examination Surveys 2007-2012 using the 2013 American College of Cardiology/American Heart Association guideline on the treatment of cholesterol. Among ≈42.4 million statin-eligible, untreated adults, 52.6% were hypertensive and 71% were younger than 65 years. Of ≈232 000 statin-preventable ASCVD events annually, most occur in individuals younger than 65 years, with higher proportions in blacks and Hispanics than whites (73.0% and 69.2% vs 56.9%, respectively; P<.01). Among adults younger than 65 years, the ratio of statin-eligible but untreated to statin-treated adults was higher in blacks and Hispanics than whites (3.0 and 2.9 vs 1.3, respectively; P<.01), and blacks, men, hypertensives, and cigarette smokers were more likely to be statin eligible than their statin-ineligible counterparts by multivariable logistic regression. Two thirds of untreated statin-eligible adults had two or more healthcare visits per year. Identifying and treating more statin-eligible adults in the healthcare system could improve cardiovascular health equity.

Improving Medication Adherence in Cardiometabolic Disease: Practical and Regulatory Implications.

Medication nonadherence, a major problem in cardiovascular disease (CVD), contributes yearly to approximately 125,000 preventable deaths, which is partly attributable to only about one-half of CVD patients consistently taking prescribed life-saving medications. Current interest has focused on how labeling and education influence adherence. This paper summarizes the scope of CVD nonadherence, describes key U.S. Food and Drug Administration initiatives, and identifies potential targets for improvement. We describe key adherence factors, methods, and technological applications for simplifying regimens and enhancing adherence, and 4 areas where additional collaborative research and implementation involving the regulatory system and clinical community could substantially reduce nonadherence: 1) identifying monitoring methods; 2) improving the evidence base to better understand adherence; 3) developing patient/health provider team-based engagement strategies; and 4) alleviating health disparities. Alignment of U.S. Food and Drug Administration approaches to dissemination of information about appropriate use with clinical practice could improve adherence, and thereby reduce CVD death and disability.

Cardiovascular safety for once-weekly dulaglutide in type 2 diabetes: a pre-specified meta-analysis of prospectively adjudicated cardiovascular events.

BACKGROUND: Patients with type 2 diabetes (T2D) have a substantial increased risk for cardiovascular (CV) disease and associated mortality than those without diabetes. Dulaglutide is a once-weekly glucagon-like peptide-1 receptor agonist that is approved for treatment of T2D. METHODS: This meta-analysis evaluates the CV risk in patients with T2D treated with dulaglutide in 9 randomized safety and efficacy trials. Mean (median) treatment duration was 333 (358) days. Reported CV events were independently adjudicated by a treatment-blinded clinical endpoint committee. The primary measure was a 4-component major adverse CV event (4-component MACE) composite endpoint of death due to CV causes, nonfatal myocardial infarction (MI), nonfatal stroke, or hospitalization for unstable angina. Additional pre-specified endpoints included adjudicated coronary revascularizations, hospitalization for heart failure, and all-cause mortality. A Cox proportional hazards regression model (stratified by study) was used to estimate the hazard ratio (HR) and confidence interval (CI). Tests of treatment effects for the primary endpoint were conducted at a 2-sided alpha level of 0.0198 and a corresponding 98.02 % CI was calculated. Statistical heterogeneity between the strata (studies) was tested by including in the Cox model an interaction term between treatment and strata. RESULTS: The analysis included 6010 randomized patients [dulaglutide: 3885; comparator therapy (active or placebo): 2125]; cumulative exposure to dulaglutide or comparator therapy was 3941 and 2223 patient-years, respectively. The demographic and baseline CV disease characteristics were similar across groups. Twenty-six (0.67 %) patients in the dulaglutide group versus 25 (1.18 %) in the comparator group experienced a primary 4-component MACE (HR 0.57; adjusted 98.02 % CI 0.30, 1.10). Results for the 3-component MACE (composite endpoint of death due to CV causes, nonfatal MI or stroke), 6-component MACE (composite endpoint of death due to CV causes, nonfatal MI or stroke, hospitalization for unstable angina or heart failure, or coronary revascularizations) and all-cause mortality were consistent with the primary analysis (HR < 1.0 for all). CONCLUSIONS: These results suggest that dulaglutide does not increase the risk of major CV events in T2D patients. The ongoing CV outcomes study, Researching CV Events with a Weekly Incretin in Diabetes (REWIND), will further assess CV safety of dulaglutide.

Polypharmacy in Older Adults With Hypertension: A Comprehensive Review.

Older adults are more likely to take more than two medications for medical conditions, and polypharmacy is associated with increased risk of adverse events (fall injury, hyperkalemia and hypokalemia, heart failure, and blood pressure exacerbation), polypharmacy mismanagement, drug-drug interaction, and increased costs. Knowledge of drugs that interact with known antihypertensive agents is paramount to avoiding or reducing adverse events, hospitalizations, and health care dollars. Innovative approaches such as use of a fixed-dose combination pill, ingestible sensor system, electronic reminder system, medical audits, and the integration of a pharmacist in the care of patients should be implemented to avoid polypharmacy mismanagement.

Ticagrelor Versus Clopidogrel in Black Patients With Stable Coronary Artery Disease: Prospective, Randomized, Open-Label, Multiple-Dose, Crossover Pilot Study.

BACKGROUND: The burden of coronary artery disease (CAD) is high in blacks, highlighting the need for clinical research of antiplatelet agents in this population. We sought to evaluate platelet reactivity during loading and maintenance dosing of ticagrelor versus clopidogrel, and the pharmacokinetic profile of ticagrelor and its metabolite AR-C124910XX, in black patients with stable CAD taking low-dose aspirin (acetylsalicylic acid). METHODS AND RESULTS: In a multicenter, randomized, open-label, crossover study, 34 blacks with stable CAD receiving acetylsalicylic acid 75 to 100 mg/d were randomized to clopidogrel (600 mg, then 75 mg QD for 7-9 days) or ticagrelor (180 mg, then 90 mg BID for 7-9 days). After washout 10 to 14 days, patients switched regimens. The primary end point was platelet reactivity 2 hours post loading dose (P2Y12 reactivity units [PRU] measured by the VerifyNow assay). Least-squares mean PRU at 2 hours post loading dose was lower with ticagrelor (27.6) versus clopidogrel (211.2); least-squares mean difference was -183.6 (95% confidence interval, -213.9 to -153.3; P<0.001). At all time points, the least-squares mean PRU was significantly lower, and the percent reduction in PRU from baseline was statistically greater, with ticagrelor versus clopidogrel. At 2 hours post dose, the prevalence of high on-treatment platelet reactivity (≥208 PRU) was lower with ticagrelor (0%) than with clopidogrel (57.1%). Pharmacokinetic profiles of ticagrelor and AR-C124910XX were consistent with previous reports in stable CAD populations. CONCLUSIONS: In black patients with stable CAD receiving low-dose acetylsalicylic acid, ticagrelor provided a faster onset and greater degree of platelet inhibition than clopidogrel. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01523392.

Effects of the once-weekly glucagon-like peptide-1 receptor agonist dulaglutide on ambulatory blood pressure and heart rate in patients with type 2 diabetes mellitus.

Glucagon-like peptide-1 receptor agonists, used to treat type 2 diabetes mellitus, are associated with small reductions in systolic blood pressure (SBP) and increases in heart rate. However, findings based on clinic measurements do not adequately assess a drug's 24-hour pharmacodynamic profile. The effects of dulaglutide, a once-weekly glucagon-like peptide-1 receptor agonist, on BP and heart rate were investigated using ambulatory BP monitoring. Patients (n=755; 56±10 years; 81% white; 48% women), with type 2 diabetes mellitus, taking ≥1 oral antihyperglycemic medication, with a clinic BP between 90/60 and 140/90 mm Hg were randomized to dulaglutide (1.5 or 0.75 mg) or placebo subcutaneously for 26 weeks. Ambulatory BP monitoring was performed at baseline and at 4, 16, and 26 weeks. The primary end point was change from baseline to week 16 in mean 24-hour SBP, a tree gatekeeping strategy compared the effects of dulaglutide to placebo. Both doses of dulaglutide were noninferior to placebo for changes in 24-hour SBP and diastolic blood pressure, and dulaglutide 1.5 mg significantly reduced SBP (least squares mean difference [95% confidence interval]), -2.8 mm Hg [-4.6, -1.0]; P≤0.001). Dulaglutide 0.75 mg was noninferior to placebo (1.6 bpm; [0.3, 2.9]; P≤0.02) for 24-hour heart rate (least squares mean difference [95% confidence interval]), but dulaglutide 1.5 mg was not (2.8 bpm [1.5, 4.2]). Dulaglutide 1.5 mg was associated with a reduction in 24-hour SBP and an increase in 24-hour heart rate. The mechanisms responsible for the observed effects remain to be clarified.

Cardiorenal metabolic syndrome and cardiometabolic risks in minority populations.

Cardiovascular disease (CVD), including heart disease and stroke, is the leading cause of death in the USA, regardless of self-determined race/ethnicity, and largely driven by cardiometabolic risk (CMR) and cardiorenal metabolic syndrome (CRS). The primary drivers of increased CMR include obesity, hypertension, insulin resistance, hyperglycemia, dyslipidemia, chronic kidney disease as well as associated adverse behaviors of physical inactivity, smoking, and unhealthy eating habits. Given the importance of CRS for public health, multiple stakeholders, including the National Minority Quality Forum (the Forum), the American Association of Clinical Endocrinologists (AACE), the American College of Cardiology (ACC), and the Association of Black Cardiologists (ABC), have developed this review to inform clinicians and other health professionals of the unique aspects of CMR in racial/ethnic minorities and of potential means to improve CMR factor control, to reduce CRS and CVD in diverse populations, and to provide more effective, coordinated care. This paper highlights CRS and CMR as sources of significant morbidity and mortality (particularly in racial/ethnic minorities), associated health-care costs, and an evolving index tool for cardiometabolic disease to determine geographical and environmental factors. Finally, this work provides a few examples of interventions potentially successful at reducing disparities in cardiometabolic health.