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.

Eliminating hypertension disparities in U.S. non-Hispanic black adults: current and emerging interventions.

PURPOSE OF REVIEW: Hypertension in non-Hispanic black (NHB) adults in the United States has an earlier onset, higher prevalence, and increased severity compared with other racial/ethnic populations. Uncontrolled hypertension is responsible for the increased burden of cardiovascular disease (CVD) morbidity and mortality and decreased longevity in NHB adults. Unfortunately, eliminating the persistent hypertension-associated disparities and the white/black mortality gap, worsened by the COVID-19 pandemic, has been challenging. Overcoming the social determinants of health (SDOH), implementing therapeutic lifestyle changes (TLC), and using intensive guideline-directed medical therapy are required. Moreover, novel approaches, including community-based interventions and self-measured blood pressure (SMBP) monitoring, may mitigate U.S. disparities in hypertension. RECENT FINDINGS: In this review, we discuss recent data regarding the U.S. NHB adult disparate hypertension control and CVD morbidity and mortality. We note current approaches to address disparities, such as TLC, evidence-based pharmacotherapy, community-based interventions and SMBP. Finally, we explore future research and initiatives to seek hypertension-related health equity. SUMMARY: In the final analysis, longstanding, unacceptable hypertension and CVD morbidity and mortality in U.S. NHB adults must be addressed. Appropriate TLC and evidence-based pharmacotherapy benefit all populations, especially NHB adults. Ultimately, novel community-based interventions and SMBP may help overcome the SDOH that cause hypertension disparities.

Improving Hypertension Control in Vulnerable Populations Around the World.

PURPOSE OF REVIEW: This review aims to describe recent literature, guidelines, and approaches to reveal and reduce hypertension burden in disadvantaged populations. Hypertension is a major global health issue and the most potent risk factor for cardiovascular disease, morbidity, and mortality. It disproportionally affects vulnerable populations, including low-, middle-, and high-income countries. Specifically, the burden of hypertension is higher in US Black adults, and addressing social determinants of health is crucial for reducing disparities among vulnerable populations worldwide. RECENT FINDINGS: Multifactorial approaches, including lifestyle modifications and combination drug therapy, are essential in managing hypertension. Community-based interventions, team-based care, and telehealth strategies can also improve hypertension control. Additionally, renal nerve denervation is a potential treatment for resistant hypertension. Overall, to reduce the global hypertension burden among vulnerable populations, emphasis should be placed on equitable healthcare access and application of evidence-based medicine.

Self-management program and Black women with hypertension: Randomized controlled trial substudy.

The prevalence of hypertension (HTN) among Black women in the United States has increased over the past 10 years with a decline in levels of HTN awareness, treatment, and control. Higher death rates occur in Black women from HTN-related diseases when compared with women of other racial/ethnic groups. Although interventions aimed at self-care/self-management are vital to adults becoming the cornerstone of their own health and well-being, there is a paucity of research in Black women. This randomized controlled pilot trial substudy examined the influence of a Chronic Disease Self-Management Program (CDSMP) with tailored coaching versus the CDSMP alone on blood pressure (BP), weight, and scores on self-care questionnaires and medication adherence for Black women with HTN over 9 months. Eighty-three women who had completed the CDSMP were randomly assigned to coaching or no coaching. Median age was 54 years and the time since the HTN diagnosis was 9 years. Significant differences were noted in self-care maintenance and management over time with better self-care in the treatment group. Though not significant, both groups denoted a trend toward better medication adherence. Almost 60% of the participants in both groups showed improvements in their systolic and/or diastolic BP. However, there was no significant difference between the study groups' BP and weight variables. The CDSMP was effective in decreasing BP and improving medication adherence. Further research is needed to evaluate effective coaching strategies that motivate Black women with HTN toward self-care management.

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.

Antihyperglycemic and Blood Pressure Effects of Empagliflozin in Black Patients With Type 2 Diabetes Mellitus and Hypertension.

BACKGROUND: Empagliflozin, a sodium-glucose cotransporter 2 inhibitor indicated for type 2 diabetes mellitus (T2DM), can lower blood pressure (BP) and reduce cardiovascular mortality in patients with T2DM and preexisting cardiovascular disease. Its effects in blacks have been understudied. METHODS: In this 24-week study, 150 blacks with T2DM and hypertension had glycohemoglobin (primary end point), office and 24-hour ambulatory BP, body weight, and safety assessments. After a 2-week, open-label, placebo run-in, patients were randomly assigned to once daily empagliflozin (10 mg for the first 4 weeks, then force-titrated to 25 mg until week 24) or placebo. A mixed-effects model for repeated measures was performed on the primary and 2 key secondary end points, and an analysis of covariance for nonrepeated measures with last observation carried forward was performed for 2 other key secondary end points. Hierarchical testing was applied for these end points. RESULTS: Overall, 52.7% of participants were men, mean (SD) age, 56.8 (9.3) years; mean duration of T2DM, 9.3 (7.1) years. The baseline values of key parameters (mean [SD]) were as follows: glycohemoglobin, 8.59 (1.02)%; ambulatory systolic BP, 146.3 (11.0) mm Hg; and ambulatory diastolic BP, 89.4 (8.1) mm Hg. By week 24, the mean (standard error) change in glycohemoglobin in the empagliflozin group was -0.77 (0.15%) in comparison with an increase of 0.07 (0.16%) in the placebo group; placebo-corrected difference, -0.78% (95% CI, -1.18 to -0.38; P=0.0002). Reductions in body weight by week 24 were -2.38 (0.38) empagliflozin and -0.80 (0.47) placebo; the placebo-corrected difference was -1.23 kg (95% CI, -2.39 to -0.07; P=0.0382). Empagliflozin significantly reduced 24-hour ambulatory systolic BP versus placebo by weeks 12 and 24 (placebo-corrected difference, -5.21 mm Hg [95% CI, -9.24 to -1.18; P=0.0117] and -8.39 mm Hg [95% CI, -13.74 to -3.04; P=0.0025], respectively). Diastolic BP was also reduced. CONCLUSIONS: In blacks with T2DM, empagliflozin reduced glycohemoglobin, body weight, and BP. The effect of empagliflozin on BP increased from 12 to 24 weeks, suggesting a full antihypertensive effect takes ≥6 months to be fully realized. At week 24, the placebo-subtracted BP effect was similar to standard antihypertensive monotherapies, suggesting that empagliflozin may be beneficial for this high-risk population. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02182830.

Efficacy and Safety of Firibastat, A First-in-Class Brain Aminopeptidase A Inhibitor, in Hypertensive Overweight Patients of Multiple Ethnic Origins.

BACKGROUND: Despite existing therapy, successful control of hypertension in the United States is estimated at less than 50%. In blacks, hypertension occurs earlier, is more severe, controlled less often and has a higher morbidity and mortality than in whites. Blacks are also less responsive to monotherapy with angiotensin-I converting enzyme inhibitors or angiotensin-II receptor type 1 blockers. Obesity, higher salt-sensitivity and low plasma renin activity are possible reasons of this poor blood pressure (BP) control, especially in blacks. The aim of the study was to assess efficacy and safety of firibastat, a first-in-class aminopeptidase A inhibitor preventing conversion of brain angiotensin-II into angiotensin-III, in BP lowering in a high-risk diverse hypertensive population. METHODS: Two hundred fifty-six overweight or obese hypertensive patients, including 54% black and Hispanic individuals, were enrolled in a multicenter, open-label, phase II study. After a 2-week wash-out period, subjects received firibastat for 8 weeks (250 mg BID orally for 2 weeks, then 500 mg BID if automated office blood pressure (AOBP) >140/90 mm Hg; hydrochlorothiazide 25 mg QD was added after 1 month if AOBP ≥160/110 mm Hg). The primary end point was change from baseline in systolic AOBP after 8 weeks of treatment, and secondary end points include diastolic AOBP, 24-hour mean ambulatory BP and safety. RESULTS: Firibastat lowered systolic AOBP by 9.5 mm Hg ( P<0.0001) and diastolic AOBP by 4.2 mm Hg ( P<0.0001). 85% of the subjects did not receive hydrochlorothiazide and were treated with firibastat alone. Significant BP reduction was found across all subgroups regardless age, sex, body mass index, or race. Systolic AOBP decreased by 10.2 mm Hg ( P<0.0001) in obese patients, by 10.5 mm Hg ( P<0.0001) in blacks, and 8.9 mm Hg ( P<0.0001) in nonblacks. Most frequent adverse events were headaches (4%) and skin reactions (3%). No angioedema was reported. No change in potassium, sodium, and creatinine blood level were observed. CONCLUSIONS: Our results demonstrate the efficacy of firibastat in lowering BP in a high-risk diverse population where monotherapy with angiotensin-I converting enzyme inhibitors or angiotensin-II receptor type 1 blockers may be less effective and support the strategy to further investigate firibastat in subjects with difficult-to-treat or potentially resistant hypertension. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique Identifier: NCT03198793.

Association of cardiac biomarkers and comorbidities with increased mortality, severity, and cardiac injury in COVID-19 patients: A meta-regression and decision tree analysis.

BACKGROUND: Coronavirus disease-2019 (COVID-19) has a deleterious effect on several systems, including the cardiovascular system. We aim to systematically explore the association of COVID-19 severity and mortality rate with the history of cardiovascular diseases and/or other comorbidities and cardiac injury laboratory markers. METHODS: The standardized mean difference (SMD) or odds ratio (OR) and 95% confidence intervals (CIs) were applied to estimate pooled results from the 56 studies. The prognostic performance of cardiac markers for predicting adverse outcomes and to select the best cutoff threshold was estimated by receiver operating characteristic curve analysis. Decision tree analysis by combining cardiac markers with demographic and clinical features was applied to predict mortality and severity in patients with COVID-19. RESULTS: A meta-analysis of 17 794 patients showed patients with high cardiac troponin I (OR = 5.22, 95% CI = 3.73-7.31, P < .001) and aspartate aminotransferase (AST) levels (OR = 3.64, 95% CI = 2.84-4.66, P < .001) were more likely to develop adverse outcomes. High troponin I more than 13.75 ng/L combined with either advanced age more than 60 years or elevated AST level more than 27.72 U/L was the best model to predict poor outcomes. CONCLUSIONS: COVID-19 severity and mortality are complicated by myocardial injury. Assessment of cardiac injury biomarkers may improve the identification of those patients at the highest risk and potentially lead to improved therapeutic approaches.

Hypertension and race/ethnicity.

PURPOSE OF REVIEW: United States racial/ethnic minorities may experience disproportionate hypertension (HTN) morbidity and mortality. This review discusses recent literature regarding the differential impact of HTN, especially among African Americans and Hispanics. RECENT FINDINGS: Although disparities in HTN prevalence, control, and outcomes persist in racial/ethnic minorities relative to non-Hispanic Whites, racial/ethnic minorities are frequently underrepresented in genetic and clinical studies. Genomics have improved our understanding of HTN, but with no clinically useful application, the role of social determinants of health in HTN disparities is increasingly recognized. Team-based approaches with targeted, multilevel interventions may overcome barriers that uniquely impact racial/ethnic minorities. SUMMARY: Despite extensive epidemiological research, racial/ethnic minorities remain at higher risk HTN-related morbidity and mortality. Translational efforts may address the differential impact of HTN in racial/ethnic minorities. This review highlights recent research and concepts related to HTN and race/ethnicity.

Socioeconomic Status and Cardiovascular Outcomes: Challenges and Interventions.

Socioeconomic status (SES) has a measurable and significant effect on cardiovascular health. Biological, behavioral, and psychosocial risk factors prevalent in disadvantaged individuals accentuate the link between SES and cardiovascular disease (CVD). Four measures have been consistently associated with CVD in high-income countries: income level, educational attainment, employment status, and neighborhood socioeconomic factors. In addition, disparities based on sex have been shown in several studies. Interventions targeting patients with low SES have predominantly focused on modification of traditional CVD risk factors. Promising approaches are emerging that can be implemented on an individual, community, or population basis to reduce disparities in outcomes. Structured physical activity has demonstrated effectiveness in low-SES populations, and geomapping may be used to identify targets for large-scale programs. Task shifting, the redistribution of healthcare management from physician to nonphysician providers in an effort to improve access to health care, may have a role in select areas. Integration of SES into the traditional CVD risk prediction models may allow improved management of individuals with high risk, but cultural and regional differences in SES make generalized implementation challenging. Future research is required to better understand the underlying mechanisms of CVD risk that affect individuals of low SES and to determine effective interventions for patients with high risk. We review the current state of knowledge on the impact of SES on the incidence, treatment, and outcomes of CVD in high-income societies and suggest future research directions aimed at the elimination of these adverse factors, and the integration of measures of SES into the customization of cardiovascular treatment.

Real-world opportunity of empagliflozin to improve blood pressure control in African American patients with type 2 diabetes: A National Cardiovascular Data Registry "research-to-practice" project from the diabetes collaborative registry.

The 1245.29 Trial recently showed that empaglifozin improved both blood pressure and glucose control in African American (AA) patients with type 2 diabetes (T2D) and hypertension. Using the Diabetes Collaborative Registry, a large-scale US registry of outpatients with diabetes recruited from primary care, cardiology and endocrinology practices, we sought to understand the potential impact of these observations in routine clinical practice. Among 74 290 AA patients with T2D from 368 US clinics, 60.4% had hypertension, of whom 34.5% had systolic blood pressure ≥ 140 mm Hg (20.8% of the total AA T2D population). Only 1.7% of this eligible population had been prescribed a sodium-glucose co-transporter two inhibitor. The mean estimated 5-year risk of cardiovascular death was 7.7%, which could be reduced to 6.2% when modelling the antihypertensive effect of empagliflozin across the eligible population (based on an 8-mm Hg blood pressure reduction). These findings may represent a potential opportunity for better management of cardiovascular risk factors and improved outcomes in this vulnerable cohort.

Community Outreach to African-Americans: Implementations for Controlling Hypertension.

PURPOSE OF REVIEW: The purpose of this review is to examine the impact and effectiveness of community interventions for controlling hypertension in African-Americans. The questions addressed are as follows: Which salient prior and current community efforts focus on African-Americans and are most effective in controlling hypertension and patient-related outcomes? How are these efforts implemented and possibly sustained? RECENT FINDINGS: The integration of out-of-office blood pressure measurements, novel hypertension control centers (i.e., barbershops), and community health workers improve hypertension control and may reduce the excess hypertension-related complications in African-Americans. Several community-based interventions may assist effectiveness of clinical care teams, decrease care barriers, and improve adherence. A multifaceted, tailored, multidisciplinary community-based approach may effectively reduce barriers to blood pressure control among African-Americans. Future research should evaluate the long-term benefits of community health workers, barbershops as control centers, and out-of-office blood pressure monitoring upon control and eventually on morbidity and mortality.

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.