Vitamin D Levels and SARS-CoV-2 Infection among Medically Underserved Populations in the Minority and Rural Coronavirus Insights Study.

BACKGROUND: Extant literature presents contradictory findings on the role of vitamin D on SARS-CoV-2 infection. Our study included an examination of the relationship between vitamin D levels and SARS-CoV-2 infection among the Minority and Rural Coronavirus Insights Study (MRCIS) cohort, a diverse population of medically underserved persons presenting at five Federally qualified health centers in the United States. METHODS: We conducted a descriptive analysis to explore the relationship between vitamin D levels and SARS-CoV-2 infection among medically underserved participants. A combined molecular and serologic assessment was used to determine the prevalence of SARS-CoV-2 infection. Vitamin D was examined as both a categorical (vitamin D status: deficient, insufficient, optimal) and continuous (vitamin D level) variable. Chi-squared testing, polynomial regression models, and logistic regression models were used to assess the relationship between vitamin D and SARS-CoV-2 infection. RESULTS: The overall SARS-CoV-2 infection rate among participants was 25.9%. Most participants were either vitamin D deficient (46.5%) or insufficient (29.7%), and 23.8% had an optimal level. Vitamin D status was significantly associated with key SARS-CoV-2 infection risk factors. As mean vitamin D levels increased, the proportion of participants with SARS-CoV-2 infection decreased. For every 10 ng/mL increase in vitamin D levels the odds of SARS-CoV-2 infection decreased by 12% when adjusting for race/ethnicity and age (main effect model). Participants who identified as Hispanic/Latino or Black non-Hispanic had approximately two times increased odds of SARS-CoV-2 infection when adjusting for age and vitamin D levels compared to white non-Hispanics. However, when additional factors were added to the main effect model, the relationship between vitamin D levels and SARS-CoV-2 infection did not remain significant. CONCLUSION: Vitamin D levels were associated with an increased risk of SARS-CoV-2 infection. Hispanic/Latino and Black, non-Hispanic compared to White, non-Hispanic participants were at increased odds for infection, after adjusting for race/ethnicity and age.

Nucleocapsid and Spike Protein-Based Anti-SARS-CoV-2 Assay Performance in the Minority and Rural Coronavirus Insights Study: Characteristics of Socioeconomically Disadvantaged Populations with Health Disparities.

BACKGROUND: COVID-19 has had a devastating impact on Black, Hispanic, and other underserved, disadvantaged populations. Here anti-SARS-CoV-2 tests are characterized in disadvantaged patients to examine equivalence in US populations. METHODS: Underserved participant adults (age > 18 years) were enrolled before the availability of SARS-CoV-2 vaccines in Federal Qualified Health Centers in California, Florida, Louisiana, Illinois, and Ohio and contributed samples to the Minority and Rural Coronavirus Insights Study (MRCIS). A subset coined the MRCIS SARS-CoV-2 Antibody Cohort of 2365 participants was tested with the Roche Anti-SARS-CoV-2 assay (Cobas e601). Five hundred ninety-five of these were also tested with the Ortho Clinical Diagnostics VITROS Anti-SARS-CoV-2 IgG assay (VITROS-5600); 1770 were also tested with the Abbott ARCHITECT SARS-CoV-2 IgG assay (ARCHITECT-2000). Assay-specific cutoffs classified negative/positive results. RESULTS: Eight point four percent (199/2365) of the MRCIS SARS-CoV-2 Antibody Cohort was SARS-CoV-2 RNA positive at enrollment. Agreement between the Ortho/Roche and the Abbott/Roche antibody testing did not vary by enrollment RNA status. The Ortho (anti-spike protein) vs Roche (anti-nucleocapsid protein) comparison agreed substantially: kappa = 0.63 (95% CI: 0.57-0.69); overall agreement, 83%. However, agreement was even better for the Abbott vs Roche assays (both anti-nucleocapsid protein tests): kappa = 0.85 (95% CI: 0.81-0.87); overall agreement, 95%. Anti-SARS-CoV-2 comparisons stratified by demographic criteria demonstrated no significant variability in agreement by sex, race/ethnicity, or age. CONCLUSIONS: Analytical agreement is 96.4% for anti-spike-protein vs anti-nucleocapsid-protein comparisons. Physiologically, seroreversion of anti-nucleocapsid reactivity after infection occurred in the disadvantaged population similarly to general populations. No anti-SARS-CoV-2 assays included demonstrated a clinically significant difference due to the demographics of the disadvantaged MRCIS SARS-CoV-2 Antibody Cohort.

The Minority and Rural Coronavirus Insights Study: Design and Baseline Characteristics of a Minority Cohort.

The Minority and Rural Coronavirus Insights Study (MRCIS) is an ongoing prospective cohort study examining health disparities associated with SARS-CoV-2 infection among medically underserved populations. This report describes procedures implemented to establish the MRCIS cohort and examines the factors associated with the molecular and serological assessment of SARS-CoV-2 infection status at participant enrollment. Participants were recruited from 5 geographically dispersed federally qualified health centers between November 2020 and April 2021. At baseline, participants completed a detailed demographic survey and biological samples were collected for testing. SARS-CoV-2 infection status was determined based on the combined molecular and serological test results. Chi-squared and logistic regression analyses were conducted to examine associations between sociodemographic factors, COVID-19 safety measures, existing comorbidities, and SARS-CoV-2 infection status. The final cohort included 3238 participants. The mean age of participants was 50.2 ± 15.8 years. Most participants identified as female (60.0%), heterosexual or straight (93.0%), White (47.6%), and Hispanic or Latino (49.1%). Approximately 26.1% of participants had at least one positive SARS-CoV-2 test result. The main effect model included age, sex, and race/ethnicity. Compared with adults ≥65 years, participants in all other age groups had ∼2 times increased odds of a positive SARS-CoV-2 test result. In addition, racial/ethnic minorities had ∼2 times increased odds of a positive SARS-CoV-2 infection status compared with non-Hispanic Whites. A unique cohort of a traditionally medically underserved minority population was established. Significant racial and ethnic disparities in SARS-CoV-2 infection status at baseline were discovered.

Ventricular Arrhythmias in Seniors with Heart Failure: Present Dilemmas and Therapeutic Considerations: A Systematic Review.

BACKGROUND: Heart Failure (HF) is a global public health problem, which affects over 23 million people worldwide. The prevalence of HF is higher among seniors in the USA and other developed countries. Ventricular Arrhythmias (VAs) account for 50% of deaths among patients with HF. We aim to elucidate the factors associated with VAs among seniors with HF, as well as therapies that may improve the outcomes. METHODS: PubMed, Web of Science, Scopus, Cochrane Library databases, Science Direct, and Google Scholar were searched using specific keywords. The reference lists of relevant articles were searched for additional studies related to HF and VAs among seniors as well as associated outcomes. RESULTS: The prevalence of VAs increases with worsening HF. A 24-hour Holter electrocardiogram may be useful in risk stratifying patients for device therapy if they do not meet the criterion of low ventricular ejection fraction. Implantable Cardiac Defibrillators (ICDs) are superior to anti-arrhythmic drugs in reducing mortality in patients with HF. Guideline-Directed Medical Therapy (GDMT) together with device therapy may be required to reduce symptoms. In general, the proportion of seniors on GDMT is low. A combination of ICDs and cardiac resynchronization therapy may improve outcomes in selected patients. CONCLUSION: Seniors with HF and VAs have high mortality even with the use of device therapy and GDMT. The holistic effect of device therapy on outcomes among seniors with HF is equivocal. More studies focused on seniors with advanced HF as well as therapeutic options are, therefore, required.

Refractory Heart Failure of Unknown Etiology May Be Cardiac Amyloid If Preceded by Hereditary Neurological Symptoms.

Transthyretin cardiac amyloidosis results from the deposition of transthyretin amyloid fibrils in the myocardium. This happens because of the misfolding of genetically normal (wild type - ATTR) or mutant (hereditary ATTR) transthyretin. The clinical presentation of hereditary ATTR cardiac amyloidosis is dependent on the exact site of the amino acid substitution. The V122I gene mutation is most common among people of African descent and usually manifests with cardiomyopathy. The mutations are transmitted in an autosomal dominant manner with variable penetrance and associated with clinical features occurring most commonly after the age of 40. The symptoms of heart failure (HF) may be preceded by several years of vague neurological symptoms which is more concerning if there is no clear explanation. A high index of suspicion is therefore crucial in ensuring prompt diagnosis and therapy, as this may favorably alter the gloomy prognosis associated with cardiac amyloidosis.

DISCOVERY: prevalence of transthyretin (TTR) mutations in a US-centric patient population suspected of having cardiac amyloidosis.

BACKGROUND: Hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) is a multisystem disease that presents with polyneuropathy and/or cardiomyopathy. METHODS: DISCOVERY, a multicenter screening study, enrolled patients with clinically suspected cardiac amyloidosis to determine the frequency of transthyretin (TTR) mutations and assess disease characteristics. RESULTS: Of 1007 patients, the majority were from the US (84%), Black/African American (56%), male (63%), and with a mean (standard deviation) age of 65 (13) years. Among 1001 patients with genotyping results, 74 (7%) had a pathogenic TTR mutation (71/836 [8%] from the US). Val122Ile was the most common mutation, found in 11% of Black/African American patients overall; Black/African American ethnicity was an independent predictor of having a pathogenic TTR mutation. Additional independent predictors of such mutations in the total population and Black/African American group were interventricular septum thickness, low electrocardiogram voltage, and age. CONCLUSIONS: Pathogenic TTR mutations occurred in 8% of US patients with suspected cardiac amyloidosis. Most mutations were Val122Ile, almost exclusively found in Black/African American patients. Disease often remains undetected until advanced and difficult to treat, therefore, clinicians should assess at-risk patients for hATTR amyloidosis as early as possible.

Increasing Diversity in Clinical Trials: Overcoming Critical Barriers.

Clinical trial results provide the critical evidence base for evaluating the safety and efficacy of new medicines and medical products. Efficacy and safety may differ among population subgroups depending on intrinsic/extrinsic factors, including sex, age, race, ethnicity, lifestyle, and genetic background. Racial and ethnic minorities continue to be underrepresented in cardiovascular and other clinical trials. Although barriers to diversity in trials are well recognized, sustainable solutions for overcoming them have proved elusive. We investigated barriers impacting minority patients' willingness to participate in trials and-based on literature review and evaluation, and input from key stakeholders, including minority patients, referring physicians, investigators who were minority-serving physicians, and trial coordinators-formulated potential solutions and tested them across stakeholder groups. We identified key themes from solutions that resonated with stakeholders using a transtheoretical model of behavior change and created a communications message map to support a multistakeholder approach for overcoming critical participant barriers.

Fixed-Dose Versus Off-Label Combination of Isosorbide Dinitrate Plus Hydralazine Hydrochloride: Retrospective Propensity-Matched Analysis in Black Medicare Patients with Heart Failure.

INTRODUCTION: Based upon the findings of the African-American Heart Failure Trial, the US Food and Drug Administration approved the fixed-dose combination of isosorbide dinitrate (ISDN) and hydralazine hydrochloride (HYD) (FDC-ISDN/HYD) as a new drug for treatment of heart failure (HF) in self-identified African Americans. According to the FDA, FDC-ISDN/HYD has no therapeutic equivalent. However, off-label combinations of the separate generic drugs ISDN and HYD (OLC-ISDN+HYD) or isosorbide mononitrate (ISMN) and HYD (OLC-ISMN+HYD) are routinely substituted without any supporting outcome data. We conducted an exploratory retrospective propensity-matched cohort study using Medicare data to determine whether a survival difference exists between these treatments in medication-adherent patients. METHODS: Black Medicare beneficiaries with HF were matched with Medicare Part D data to identify patients with prescriptions to FDC-ISDN/HYD or the off-label combinations. Only patients with 1-year adherence levels ≥80% were included in the analysis. Propensity-matched scoring created two sets of matched cohort pairs on a 1:1 basis, each set comparing FDC-ISDN/HYD with one of the off-label combinations. Kaplan-Meier (KM) survival curves with the log-rank test were then calculated for each pair for the year of medication adherence. RESULTS: The analysis population was relatively older (77 years) and mainly female (66.7%), with a high burden of comorbid disease. The KM estimates of 1-year survival were 87.9% (95% CI 85.6-89.9%) and 83.0% (95% CI 80.3-85.3%) (log rank p = 0.0024), respectively, for the matched cohorts FDC-ISDN/HYD and OLC-ISDN+HYD (n = 886 in each group) and 88.2% (95% CI 85.9-90.2%) and 84.8% (95% CI 82.2-87.0%) (log rank p = 0.0320), respectively, for the matched cohorts FDC-ISDN/HYD and OLC-ISMN+HYD (n = 868 in each group). CONCLUSION: The 1-year survival advantage for FDC-ISDN/HYD compared with off-label combinations in adherent black Medicare beneficiaries with HF suggests a genuine difference between these medications and warrants prospective investigation.

2014 hypertension recommendations from the eighth joint national committee panel members raise concerns for elderly black and female populations.

A report from panel members appointed to the Eighth Joint National Committee titled "2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults" has garnered much attention due to its major change in recommendations for hypertension treatment for patients ≥60 years of age and for their treatment goal. In response, certain groups have opposed the decision to initiate pharmacologic treatment to lower blood pressure (BP) at systolic BP ≥150 mm Hg and treat to a goal systolic BP of <150 mm Hg in the general population age ≥60 years. This paper contains 3 sections-an introduction followed by the opinions of 2 writing groups-outlining objections to or support of maintaining this proposed strategy in certain at-risk populations, namely African Americans, women, and the elderly. Several authors argue for maintaining current targets, as opposed to adopting the new recommendations, to allow for optimal treatment for older women and African Americans, helping to close sex and race/ethnicity gaps in cardiovascular disease morbidity and mortality.

Acute heart failure in the African American patient.

BACKGROUND: African Americans (AAs) are disproportionately affected by acute heart failure (AHF) compared with other racial/ethnic groups. Disparities in AHF risk factors among AAs are attributed to higher rates of hypertension and diabetes mellitus, lower socioeconomic status, higher dietary caloric and salt intake, and biologic/genetic differences. However, AAs are frequently underrepresented in AHF clinical trials, and race-related differences in risks and clinical outcomes are not well understood. OBJECTIVE: The aim of this work was to review published data on AHF in the AA population, including management strategies that may differ based on race and common barriers to optimal care. METHODS: Publications were identified in Pubmed (through June 10, 2013) with the use of the search strategy terms (acute heart failure) AND (black OR African American OR racial). RESULTS: Racial disparities in the quality of AHF care are relatively uncommon; however, racial differences in pathophysiology have resulted in differing pharmacologic recommendations (eg, isosorbide dinitrate plus hydralazine is indicated only in AAs). Various socioeconomic factors influence disease progression, treatment compliance, and hospitalization/rehospitalization rates. CONCLUSIONS: Further research would enhance understanding of pathophysiologic heart failure differences between racial groups. Programs are needed that incorporate known clinical and cultural differences to improve quality of care and reduce the disease burden of AHF for all patients.

Comparison of mental stress-induced myocardial ischemia in coronary artery disease patients with versus without left ventricular dysfunction.

To examine the susceptibility to myocardial ischemia with mental stress in patients who have coronary artery disease and normal left ventricular (LV) function versus those who have impaired LV function, we examined 58 patients who had coronary artery disease, including 22 who had normal LV function (ejection fraction >/=50%), 16 who had mild to moderate LV dysfunction (ejection fraction 30% to 50%), and 20 who had severe LV dysfunction (ejection fraction 3. At comparable double products across the 3 groups, ischemia was induced with mental stress more frequently in patients who had severe LV dysfunction (50%) than in those who had normal LV function (9%; p <0.01). The frequency of exercise-induced ischemia was different only between those who had mild/moderate LV dysfunction and those who had normal LV function (56% vs 18%, respectively, p <0.05). The pattern of mental stress versus exercise ischemia differed between groups (p <0.02): there was a higher prevalence of mental stress ischemia versus exercise ischemia in patients who had severe LV dysfunction (p = 0.06), a marginally higher prevalence of exercise versus mental stress ischemia in those who had moderate LV dysfunction (p = 0.07), and no difference in mental stress versus exercise ischemia in those who had normal LV function. Thus, at comparable double products during mental stress and similar extent of coronary artery disease, ischemia with mental stress was induced more frequently in patients who had severe LV dysfunction than in those who had normal LV function. These data suggest that mental stress ischemia may be of particular clinical importance in patients who have coronary artery disease and LV dysfunction.

Left ventricular mass measured by myocardial perfusion gated SPECT. Relation to three-dimensional echocardiography.

PURPOSE: The purpose of this investigation was to determine whether left ventricular mass (LVM) assessed from myocardial perfusion gated SPECT (GSPECT) data corresponds with echocardiographic estimates, and whether mass accuracy decreases as relative myocardial wall thickness increases. MATERIALS AND METHODS: Myocardial perfusion tomograms were selected retrospectively for 37 patients, of whom 18 had Tl-201 and 19 had Tc-99m sestamibi GSPECT poststress data collections, which were subsequently processed using quantitative gated SPECT software (Cedars Sinai Medical Center, Los Angeles, CA). These patients also had clinically indicated echocardiograms for assessment of wall thickness and possible valvular involvement. In addition, LV internal diameter and posterior wall thickness were measured at end-diastole by two-dimensional guided M-mode echocardiography to assess relative myocardial wall thickness, and LVM was measured by three-dimensional echocardiography using an acoustic spatial locator device. RESULTS: LVM values were not significantly different between GSPECT and three-dimensional echocardiography (153 +/- 39 g versus 146 +/- 35 g, respectively; P = NS). GSPECT correlated significantly (r = 0.63, P < 0.0001) with three-dimensional echocardiography, with a mean difference of 7 +/- 32 g but a substantial root mean squared error of 31 g. Results were similar for similar mass ranges when subgrouped by isotope and by the presence of significant myocardial perfusion defects. Results were independent of relative myocardial wall thickness determined by two-dimensional echocardiography. The two methods yielded similar results in the highest mass range of 400 to 500 g. CONCLUSIONS: GSPECT and three-dimensional echo LVM correlated significantly, but given the large spread of statistical errors, these two techniques should not be considered interchangeable. Because gamma camera resolution is limited, GSPECT LVM should be viewed as an approximation.