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Abstract Aims Heart failure (HF) is a clinical syndrome with no definitive diagnostic tests. HF registries are often based on manual reviews of medical records of hospitalized HF patients identified using International Classification of Diseases (ICD) codes. However, most HF patients are not hospitalized, and manual review of big electronic health record (EHR) data is not practical. The US Department of Veterans Affairs (VA) has the largest integrated healthcare system in the nation, and an estimated 1.5 million patients have ICD codes for HF (HF ICD‐code universe) in their VA EHR. The objective of our study was to develop artificial intelligence (AI) models to phenotype HF in these patients. Methods and results The model development cohort (n = 20 000: training, 16 000; validation 2000; testing, 2000) included 10 000 patients with HF and 10 000 without HF who were matched by age, sex, race, inpatient/outpatient status, hospital, and encounter date (within 60 days). HF status was ascertained by manual chart reviews in VA's External Peer Review Program for HF (EPRP‐HF) and non‐HF status was ascertained by the absence of ICD codes for HF in VA EHR. Two clinicians annotated 1000 random snippets with HF‐related keywords and labelled 436 as HF, which was then used to train and test a natural language processing (NLP) model to classify HF (positive predictive value or PPV, 0.81; sensitivity, 0.77). A machine learning (ML) model using linear support vector machine architecture was trained and tested to classify HF using EPRP‐HF as cases (PPV, 0.86; sensitivity, 0.86). From the ‘HF ICD‐code universe’, we randomly selected 200 patients (gold standard cohort) and two clinicians manually adjudicated HF (gold standard HF) in 145 of those patients by chart reviews. We calculated NLP, ML, and NLP + ML scores and used weighted F scores to derive their optimal threshold values for HF classification, which resulted in PPVs of 0.83, 0.77, and 0.85 and sensitivities of 0.86, 0.88, and 0.83, respectively. HF patients classified by the NLP + ML model were characteristically and prognostically similar to those with gold standard HF. All three models performed better than ICD code approaches: one principal hospital discharge diagnosis code for HF (PPV, 0.97; sensitivity, 0.21) or two primary outpatient encounter diagnosis codes for HF (PPV, 0.88; sensitivity, 0.54). Conclusions These findings suggest that NLP and ML models are efficient AI tools to phenotype HF in big EHR data to create contemporary HF registries for clinical studies of effectiveness, quality improvement, and hypothesis generation.

Background Shared medical appointments (SMAs) in heart failure (HF) are medical visits where several patients with HF meet with multidisciplinary providers at the same time for efficient and comprehensive care. It is unknown whether HF‐SMAs can improve overall and cardiac health status for high‐risk patients with HF discharged from acute care. Methods and Results A 3‐site, open‐label, randomized‐controlled‐trial was conducted. Participants within 12 weeks of HF acute care (emergency‐room/hospitalization) requiring intravenous diuretic therapy were randomized to receive either HF‐SMA or usual HF clinical care (usual‐care) on a 1:1 ratio. The HF‐SMA team, which consisted of a nurse, nutritionist, psychologist, nurse practitioner and/or a clinical pharmacist, provided four 2‐hour session HF‐SMAs that met every other week for 8 weeks. Primary outcomes were the overall health status measured by European Quality of Life Visual Analog Scale and cardiac health status by Kansas City Cardiomyopathy Questionnaire, 180 days postrandomization. Of the 242 patients enrolled (HF‐SMA n=117, usual‐care n=125, mean age 69.3±9.4 years, 71.5% White patients, 94.6% male), 84% of participants completed the study (n=8 HF‐SMA and n=9 usual‐care patients died). After 180 days, both HF‐SMA and usual‐care participants had significant improvements from baseline in Kansas City Cardiomyopathy Questionnaire that were not statistically different. Only HF‐SMA participants had significant improvements in European Quality of Life Visual Analog Scale (mean change = 7.2±15.8 in HF‐SMA versus −0.4±19.0 points in usual‐care, P

Abstract Introduction Eight-week glecaprevir/pibrentasvir (GLE/PIB) is indicated for treatment-naïve (TN) patients with chronic hepatitis C (CHC), with or without compensated cirrhosis. Given that the Taiwanese government is committed to eliminating hepatitis C virus (HCV) by 2025, this study aimed to measure real-world evidence for TN patients using 8-week GLE/PIB in the Taiwan HCV Registry (TACR). Methods The data of patients with CHC treated with 8-week GLE/PIB were retrieved from TACR, a nationwide registry program organized by the Taiwan Association for the Study of the Liver (TASL). Treatment efficacy, defined as a sustained virologic response at posttreatment week 12 (SVR12), was assessed in the modified intention-to-treat (mITT) population, which excluded patients who were lost to follow-up or lacked SVR12 data. The safety profile of the ITT population was assessed. Results A total of 7246 (6897 without cirrhosis; 349 with cirrhosis) patients received at least one dose of GLE/PIB (ITT), 7204 of whom had SVR12 data available (mITT). The overall SVR12 rate was 98.9% (7122/7204) among all patients, 98.9% (6780/6856) and 98.3% (342/348) among patients without and with cirrhosis, respectively. For the selected subgroups, which included patients with genotype 3 infection, diabetes, chronic kidney disease, people who injected drugs, and those with human immunodeficiency virus coinfection, the SVR12 rates were 95.1% (272/286), 98.9% (1084/1096), 99.0% (1171/1183), 97.4% (566/581), and 96.1% (248/258), respectively. Overall, 14.1% (1021/7246) of the patients experienced adverse events (AEs). Twenty-two patients (0.3%) experienced serious AEs, and 15 events (0.2%) resulted in permanent drug discontinuation. Only one event was considered treatment drug related. Conclusion Eight-week GLE/PIB therapy was effective and well tolerated in all TN patients, regardless of cirrhosis status.

Abstract Fuchs endothelial corneal dystrophy (FECD) is a leading indication for corneal transplantation, but its molecular etiology remains poorly understood. We performed genome-wide association studies (GWAS) of FECD in the Million Veteran Program followed by multi-ancestry meta-analysis with the previous largest FECD GWAS, for a total of 3970 cases and 333,794 controls. We confirm the previous four loci, and identify eight novel loci: SSBP3, THSD7A, LAMB1, PIDD1, RORA, HS3ST3B1, LAMA5, and COL18A1. We further confirm the TCF4 locus in GWAS for admixed African and Hispanic/Latino ancestries and show an enrichment of European-ancestry haplotypes at TCF4 in FECD cases. Among the novel associations are low frequency missense variants in laminin genes LAMA5 and LAMB1 which, together with previously reported LAMC1, form laminin-511 (LM511). AlphaFold 2 protein modeling, validated through homology, suggests that mutations at LAMA5 and LAMB1 may destabilize LM511 by altering inter-domain interactions or extracellular matrix binding. Finally, phenome-wide association scans and colocalization analyses suggest that the TCF4 CTG18.1 trinucleotide repeat expansion leads to dysregulation of ion transport in the corneal endothelium and has pleiotropic effects on renal function.

Abstract Aims We sought to identify factors associated with right ventricular (RV) dysfunction and elevated pulmonary artery systolic pressure (PASP) and association with adverse outcomes in peripartum cardiomyopathy (PPCM). Methods and results We conducted a multi‐centre cohort study to identify subjects with PPCM with the following criteria: left ventricular ejection fraction (LVEF)

Background/Aims Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Abstract Background Cardiometabolic comorbidities have been associated with a higher risk of COVID‐19 severity and mortality, but more investigations are needed to determine which comorbidity is more detrimental. Methods Embase, Emcare, and MEDLINE were searched systematically for prospective and retrospective studies assessing the associations of cardiometabolic risk factors and COVID‐19 outcomes of hospitalization, severity, and mortality among COVID‐19‐diagnosed patients. Literature search was performed from first publication to May 19, 2021. Study quality was assessed by the Newcastle‐Ottawa Scale. Results From the literature search, 301 studies suggested that all included cardiometabolic risk factors were associated with a higher risk of COVID‐19 hospitalization, severity, and mortality, except that overweight was associated with a decreased risk of mortality (relative risk [RR] 0.88; 95% CI, 0.80–0.98). Patients with diabetes (RR 1.46; 95% CI, 1.45–1.47) were most likely to be hospitalized; patients with heart failure had the highest risk for severe COVID‐19 outcomes (RR 1.89; 95% CI, 1.71–2.09); while patients with stroke were most susceptible to overall mortality (RR 1.99; 95% CI, 1.90–2.08). In the network meta‐analysis, cerebrovascular disease had the highest impact (RR 1.69; 95% CI, 1.65–1.73) on COVID‐19 outcomes compared to other cardiometabolic risk factors. For different combinations of risk factors, cardiovascular disease and diabetes combined (RR 6.98; 95% CI, 5.28–9.22) was more detrimental than others. Conclusions Considering the high prevalence of cardiometabolic comorbidities and risk of all severe outcomes, patients with cardiometabolic comorbidities should be prioritized in vaccination and treatment development of COVID‐19.

Summary: Background: Much remains unknown regarding the associations of adversities in childhood and adulthood with incident cardiovascular diseases (CVD). We aimed to examine the independent and cumulative relations of adversities in childhood and adulthood with incident CVD and whether these associations can be mitigated by adopting a healthy lifestyle later in life. Methods: We included 136,073 men and women [38–72 years at baseline] free of diagnosed CVD at baseline who responded to surveys on adversities in childhood and adulthood in the United Kingdom Biobank prospective cohort. They were recruited between 2006 and 2010 and were followed-up until 28 January 2021. Adversities included physical abuse, emotional abuse, sexual abuse, emotional neglect, and physical neglect. Participants were categorised into four groups according to the exposure periods, which were no adversity, childhood adversity only, adulthood adversity only, and cumulative adversity (both childhood and adulthood). The primary outcomes included incident fatal and non-fatal CVD events. The modifiable lifestyle factors were smoking, physical activity, diet, sleeping, social or leisure activities, and friend or family visits. Findings: We identified 16,415 (10.71/1000 person-year) incident CVD during a median follow-up of 11.8 years. Compared with participants with no adversity, CVD incidence increased by 11% in those with childhood adversity only (adjusted hazard ratio [HR]: 1.11 [95% CI 1.06–1.17], p

Abstract Background Approximately 400,000 people who smoke cigarettes survive Acute Coronary Syndrome (ACS; unstable angina, ST and non-ST elevation myocardial infarction) each year in the US. Continued smoking following ACS is an independent predictor of mortality. Depressed mood post-ACS is also predictive of mortality, and smokers with depressed mood are less likely to abstain from smoking following an ACS. A single, integrated treatment targeting depressed mood and smoking could be effective in reducing post-ACS mortality. Method/design The overall aim of the current study is to conduct a fully powered efficacy trial enrolling 324 smokers with ACS and randomizing them to 12 weeks of an integrated smoking cessation and mood management treatment [Behavioral Activation Treatment for Cardiac Smokers (BAT-CS)] or control (smoking cessation and general health education). Both groups will be offered 8 weeks of the nicotine patch if medically cleared. Counseling in both arms will be provided by tobacco treatment specialists. Follow-up assessments will be conducted at end-of-treatment (12-weeks) and 6, 9, and 12 months after hospital discharge. We will track major adverse cardiac events and all-cause mortality for 36 months post-discharge. Primary outcomes are depressed mood and biochemically validated 7-day point prevalence abstinence from smoking over 12 months. Discussion Results of this study will inform smoking cessation treatments post-ACS and provide unique data on the impact of depressed mood on success of post-ACS health behavior change attempts. Trial registration ClinicalTrials.gov, NCT03413423. Registered 29 January 2018. https://beta.clinicaltrials.gov/study/NCT03413423 .

Background/purpose: The Taiwan Association for the Study of the Liver (TASL) HCV Registry (TACR) is a nationwide registry of chronic hepatitis C patients in Taiwan. This study evaluated antiviral effectiveness of ledipasvir (LDV)/sofosbuvir (SOF) in patients in the TACR. Methods: Patients enrolled in TACR from 2017–2020 treated with LDV/SOF were eligible. The primary outcome was the proportion of patients with sustained virologic response 12 weeks after end of treatment (SVR12). Results: 5644 LDV/SOF ± ribavirin-treated patients were included (mean age: 61.4 years; 54.4% female). Dominant viral genotypes were GT1 (50.8%) and GT2 (39.3%). 1529 (27.1%) patients had liver cirrhosis, including 201 (3.6%) with liver decompensation; 686 (12.2%) had chronic kidney disease. SVR12 was achieved in 98.6% of the overall population and in 98.2% and 98.7% of patients with and without cirrhosis, respectively. SVR12 rates in patients with compensated cirrhosis treated with LDV/SOF without RBV were >98%, regardless of prior treatment experience. SVR12 was 98.6%, 98.4%, 100%, 100%, and 98.7% among those with GT1, GT2, GT4, GT5, and GT6 infections, respectively. Although patient numbers were relatively small, SVR12 rates of 100% were reported in patients infected with HCV GT2, GT5, and GT6 with decompensated cirrhosis and 98% in patients with severely compromised renal function. LDV/SOF adherence ≤60% (P

Objective: To analyze associations between adiposity and the renin-angiotensin-aldosterone system (RAAS) in a large African American (AA) cohort. Methods: Cross-sectional associations of adiposity (body mass index [BMI], waist circumference [WC], waist:height ratio, waist:hip ratio, leptin, adiponectin, leptin:adiponectin ratio [LAR], subcutaneous [SAT] and visceral adipose tissue [VAT], and liver attenuation [LA]) with aldosterone, plasma renin activity (renin), and aldosterone:renin ratio (ARR) were assessed in the Jackson Heart Study using adjusted linear regression models. Results: A 1-SD higher BMI was associated with a 4.8 % higher aldosterone, 9.4 % higher renin, and 5.0 % lower ARR (all p

Abstract Aim Heart failure (HF) outcomes are disproportionately worse in patients discharged to skilled nursing facilities (SNF) as opposed to home. We hypothesized that dementia and delirium were key factors influencing these differences. Our aim was to explore the associations of dementia and delirium with risk of hospital readmission and mortality in HF patients discharged to SNF. Methods and results The study population included Veterans hospitalized for a primary diagnosis of HF and discharged to SNFs between 2010 and 2015. Pre‐existing dementia was identified based on International Classification of Diseases‐9 codes. Delirium was determined using the Minimum Data Set 3.0 Confusion Assessment Method algorithm. Proportional hazard regression analyses were used to model outcomes and were adjusted for covariates of interest. Patients (n = 21 655) were older (77.0 ± 10.5 years) and predominantly male (96.9%). Four groups were created according to presence (+) or absence (−) of dementia and delirium. Relative to the dementia−/delirium− group, the dementia−/delirium+ group was associated with increased 30 day mortality [adjusted hazard ratio (HR) = 2.2, 95% confidence interval (CI) = 1.7, 3.0] and 365 day mortality (adjusted HR = 1.5, 95% CI = 1.3, 1.7). Readmission was highest in the dementia−/delirium+ group after 30 days (HR = 1.2, 95% CI = 1.0, 1.5). In the group with dementia (delirium−/dementia+), 30 day mortality (12.8%; HR = 0.7, 95% CI = 0.7, 0.8) and readmissions (5.3%; HR = 1.0, 95% CI = 0.8, 1.1) were not different relative to the reference group. Conclusions Delirium, independent of pre‐existing dementia, confers increased risk of hospital readmission and mortality in HF patients discharged to SNFs. Managing HF after hospitalization is a complex cognitive task and an increased focus on mental status in the acute care setting prior to discharge is needed to improve HF management and transitional care, mitigate adverse outcomes, and reduce healthcare costs.

Abstract Background Improving contractility in heart failure with reduced ejection fraction (HFrEF) has resurfaced as a potential treatment goal. Inotropic therapy is now better understood through its underlying mechanism as opposed to the observed effect of increasing contractility. Calcitropes are a subgroup of inotropes that largely depend on the stimulation of adenylyl cyclase to transform ATP into cyclic adenosine monophosphate (cAMP). At least two clinically relevant calcitropes—istaroxime and probenecid—improve contractility through an increase in systolic intracellular calcium without activating cAMP production. Probenecid, which has been safely used clinically for decades in non-cardiac conditions, has recently been identified as an agonist of the transient receptor potential vanilloid 2 channel. Translational studies have shown that it improves calcium cycling and contractility without activating noxious pathways associated with cAMP-dependent calcitropes and can improve cardiac function in patients with HFrEF. Methods The Re-Prosper-HF study (Repurposing Probenecid for the Treatment of Heart Failure with Reduced Ejection Fraction) is a three-site double-blinded randomized-controlled trial that will test the hypothesis that probenecid can improve cardiac function in patients with HFrEF. Up to 120 patients will be randomized in this double-blind, placebo-controlled study that will assess whether oral probenecid administered at 1 g orally twice per day for 180 days in patients with NYHA II-III HFrEF improves systolic function (aim 1), functional status (aim 2), and self-reported health status (aim 3). Discussion Findings from this study will provide data informing its use for improving symptomatology in patients with HFrEF as well as exploratory data for outcomes such as hospital admission rates. Trial tegistration The Re-Prosper HF Study (Re-Prosper HF) is registered on ClinicalTrials.gov with the identifier as NCT04551222. Registered on 9 September 2020.

BackgroundAtherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality worldwide. Atherosclerosis occurs due to accumulation of low-density lipoprotein cholesterol (LDL-c) in the arterial system. Thus, lipid lowering therapy is essential for both primary and secondary prevention. Proprotein convertase subtilisn/kexin type 9 (PCSK9) inhibitors (Evolocumab, Alirocumab) and small interfering RNA (siRNA) therapy (Inclisiran) have been demonstrated to lower LDL-c and ASCVD events in conjunction with maximally tolerated statin therapy. However, the degree of LDL-c reduction and the impact on reducing major adverse cardiac events, including their impact on mortality, remains unclear.ObjectiveThe purpose of this study is to examine the effects of PCSK9 inhibitors and small interfering RNA (siRNA) therapy on LDL-c reduction and major adverse cardiac events (MACE) and mortality by conducting a meta-analysis of randomized controlled trials.MethodsUsing Pubmed, Embase, Cochrane Library and clinicaltrials.gov until April 2023, we extracted randomized controlled trials (RCTs) of PCSK9 inhibitors (Evolocumab, Alirocumab) and siRNA therapy (Inclisiran) for lipid lowering and risk of MACE. Using random-effects models, we pooled the relative risks and 95% CIs and weighted least-squares mean difference in LDL-c levels. We estimated odds ratios with 95% CIs among MACE subtypes and all-cause mortality. Fixed-effect model was used, and heterogeneity was assessed using the I2 statistic.ResultsIn all, 54 studies with 87,669 participants (142,262 person-years) met criteria for inclusion. LDL-c percent change was reported in 47 studies (n = 62,634) evaluating two PCSK9 inhibitors and siRNA therapy. Of those, 21 studies (n = 41,361) included treatment with Evolocumab (140mg), 22 (n = 11,751) included Alirocumab (75mg), and 4 studies (n = 9,522) included Inclisiran (284mg and 300mg). Compared with placebo, after a median of 24 weeks (IQR 12-52), Evolocumab reduced LDL-c by -61.09% (95% CI: -64.81, -57.38, pConclusionPCSK9 inhibitors (Evolocumab, Alirocumab) and siRNA therapy (Inclisiran) significantly reduced LDL-c by >40% in high-risk individuals. Additionally, both Alirocumab and Evolocumab reduced the risk of MACE, and Alirocumab reduced cardiovascular and all-cause mortality.

BackgroundAtherosclerosis and consequent risk of cardiovascular events or mortality can be accurately assessed by quantifying coronary artery calcium score (CACS) derived from computed tomography. HMG-CoA-reductase inhibitors (statins) are the primary pharmacotherapy used to reduce cardiovascular events, yet there is growing data that support statin use may increase coronary calcification. We set out to determine the likelihood of severe CACS in the context of chronic statin therapy.MethodsWe established a retrospective, case-control study of 1,181 U.S. veterans without coronary artery disease (CAD) from a single site, the Providence VA Medical Center. Duration of statin therapy for primary prevention was divided into 5-year categorical increments. The primary outcome was CACS derived from low-dose lung cancer screening computed tomography (LCSCT), stratified by CACs severity (none = 0; mild = 1-99; moderate = 100-399; and severe ≥400 AU). Statin duration of zero served as the referent control. Ordinal logistic regression analysis determined the association between duration of statin use and CACS categories. Proportional odds assumption was tested using likelihood ratio test. Atherosclerotic cardiovascular disease (ASCVD) risk score, body mass index, and CKD (glomerular filtration rate of ResultsThe mean age of the study population was 64.7±7.2 years, and 706 (60%) patients were prescribed a statin at baseline. Duration of statin therapy was associated with greater odds of having increased CACS (>0-5 years, OR: 1.71 [CI: 1.34-2.18], p5-10 years, OR: 2.80 [CI: 2.01-3.90], p10 years, OR: 5.30 [CI: 3.23-8.70], p0-5 years, OR: 1.49 [CI: 1.16-1.92], p = 0.002; >5-10 years, OR: 2.38 [CI: 1.7-3.35], p10 years, OR: 4.48 [CI: 2.7-7.43], pConclusionsLong-term use of statins is associated with increased likelihood of severe CACS in patients with significant smoking history. The use of CACS to interpret cardiovascular event risk may require adjustment in the context of chronic statin therapy.

Abstract The study evaluated the real-world treatment outcomes of Glecaprevir/pibrentasvir (GLE/PIB) including effectiveness, safety and healthcare resource utilization based on a nation-wide registry in Taiwan. The Taiwan HCV Registry (TACR) is a nation-wide platform organized and supervised by the Taiwan Association for the Study of the Liver. Data were analyzed for patients treated with GLE/PIB, including 3144 patients who had treatment outcome available. The primary endpoint was sustained virological response (SVR12, undetectable HCV RNA throughout 12 weeks of end-of-treatment). The overall SVR12 rate was 98.9% (3110/3144), with 98.8%, 99.4% and 100% in patients receiving 8 weeks, 12 weeks, and 16 weeks of GLE/PIB respectively. The SVR12 rate in the treatment-naïve cirrhotic patients receiving 8 weeks of GLE/PIB was 98.2% (108/110). The most common AEs were fatigue (7.5%), pruritus (6.7%) and dizziness (1.5%). The mean number of outpatient visits during the GLE/PIB was 5.94 visits for patients treated with 8 weeks, significantly different from the patients treated with 12 weeks of GLE/PIB (6.90 visits). The results support the effectiveness and safety of GLE/PIB treatment in real-world clinical practice, and provide further evidence that the shorter, 8-week GLE/PIB regimen is effective and cost-saving.

Coomprhensive data on temporal trends in cardiovascular disease (CVD) risk factors and outcomes in people living with HIV are limited. Using retrospective data on 50,284 US Veterans living with HIV (VLWH) who received care in the VA from 2001 to 2019, we calculated the prevalence and incidence estimates of CVD risk factors and outcomes, as well as the average annual percent changes (AAPC) in the estimates. The mean age of the Veterans increased from 47.8 (9.1) years to 58.0 (12.4) years during the study period. The population remained predominantly (>95%) male and majority Black (∼50%). The prevalence of the CVD outcomes increased progressively over the study period: coronary artery disease (3.9%–18.7%), peripheral artery disease (2.3%, 10.3%), ischemic cerebrovascular disease (1.1%–9.9%), and heart failure (2.4%–10.5%). There was a progressive increase in risk factor burden, except for smoking which declined after 2015. The AAPC in prevalence was statistically significant for the CVD outcomes and risk factors. When adjusted for age, the predicted prevalence of CVD risk factors and outcomes showed comparable (but attenuated) trends. There was generally a comparable (but attenuated) trend in incidence of CVD outcomes, procedures, and risk factors over the study period. The use of statins increased from 10.6% (2001) to 40.8% (2019). Antiretroviral therapy usage increased from 77.7% (2001) to 85.0% (2019). In conclusion, in a retrospective analysis of large-scale VA data we found the burden and incidence of several CVD risk factors and outcomes have increased among VLWH over the past 20 years.

Abstract Aims Pre‐existing cardiovascular disease in general and related risk factors have been associated with poor coronavirus disease‐2019 (COVID‐19) outcomes. However, data on outcomes of COVID‐19 among people with pre‐existing diagnosis of heart failure (HF) have not been studied in sufficient detail. We aimed to perform detailed characterization of the association of pre‐existing HF with COVID‐19 outcomes. Methods and results A retrospective cohort study based on Veterans Health Administration (VHA) data comparing 30 day mortality and hospital admission rates after COVID‐19 diagnosis among Veterans with and without pre‐existing diagnosis of HF. Cox‐regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) with adjustment for covariates. Among 31 051 veterans (97% male) with COVID‐19, 6148 had pre‐existing diagnosis of HF. The mean (SD) age of patients with HF was 70 (13) whereas the mean (SD) age of patients without HF was 57 (17). Within the HF group with available data on left ventricular ejection fraction (EF), 1844 patients (63.4%) had an EF of >45%, and 1063 patients (36.6%) had an EF of ≤45%. Patients in the HF cohort had higher 30 day mortality (5.4% vs. 1.5%) and admission (18.5% vs. 8.4%) rates after diagnosis of COVID‐19. After adjustment for age, sex, and race, HRs (95% CIs) for 30 day mortality and for 30 day hospital admissions were 1.87 (1.61–2.17) and 1.79 (1.66–1.93), respectively. After additional adjustment for medical comorbidities, HRs for 30 day mortality and for 30 day hospital admissions were 1.37 (1.15–1.64) and 1.27 (1.16–1.38), respectively. The findings were similar among HF patients with preserved vs. reduced EF, among those taking vs. not taking angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers or angiotensin receptor neprilysin inhibitors, and among those taking vs. not taking anticoagulants. Conclusions Patients with COVID‐19 and pre‐existing diagnosis of HF had a higher risk of 30 day mortality and hospital admissions compared to those without history of HF. The findings were similar by EF categories and by angiotensin‐converting enzyme inhibitors/angiotensin receptor blocker/angiotensin receptor neprilysin inhibitors or anticoagulant use.

SARS-CoV-2 has caused symptomatic COVID-19 and widespread death across the globe. We sought to determine genetic variants contributing to COVID-19 susceptibility and hospitalization in a large biobank linked to a national United States health system. We identified 19,168 (3.7%) lab-confirmed COVID-19 cases among Million Veteran Program participants between March 1, 2020, and February 2, 2021, including 11,778 Whites, 4,893 Blacks, and 2,497 Hispanics. A multi-population genome-wide association study (GWAS) for COVID-19 outcomes identified four independent genetic variants (rs8176719, rs73062389, rs60870724, and rs73910904) contributing to COVID-19 positivity, including one novel locus found exclusively among Hispanics. We replicated eight of nine previously reported genetic associations at an alpha of 0.05 in at least one population-specific or the multi-population meta-analysis for one of the four MVP COVID-19 outcomes. We used rs8176719 and three additional variants to accurately infer ABO blood types. We found that A, AB, and B blood types were associated with testing positive for COVID-19 compared with O blood type with the highest risk for the A blood group. We did not observe any genome-wide significant associations for COVID-19 severity outcomes among those testing positive. Our study replicates prior GWAS findings associated with testing positive for COVID-19 among mostly White samples and extends findings at three loci to Black and Hispanic individuals. We also report a new locus among Hispanics requiring further investigation. These findings may aid in the identification of novel therapeutic agents to decrease the morbidity and mortality of COVID-19 across all major ancestral populations.

The relationship between particulate matter with a diameter of 2.5 micrometers or less (PM2.5) and heart failure (HF) hospitalizations and mortality in the US is unclear. Prior studies are limited to studying the effects of daily PM2.5 exposure on HF hospitalizations in specific geographic regions. Because PM2.5 can vary by geography, this study examines the effects of annual ambient PM2.5 exposure on HF hospitalizations and mortality at a county-level across the US. A cross-sectional analysis of county-level ambient PM2.5 concentration, HF hospitalizations, and HF mortality across 3135 US counties nationwide was performed, adjusting for county-level demographics, socioeconomic factors, comorbidities, and healthcare-associated behaviors. There was a moderate correlation between county PM2.5 and HF hospitalization among Medicare beneficiaries (r = 0.41) and a weak correlation between county PM2.5 and HF mortality (r = 0.08) (p-values < 0.01). After adjustment for various county level covariates, every 1 ug/m3 increase in annual PM2.5 concentration was associated with an increase of 0.51 HF Hospitalizations/1,000 Medicare Beneficiaries and 0.74 HF deaths/100,000 residents (p-values < 0.05). In addition, the relationship between PM2.5 and HF hospitalizations was similar when factoring in metropolitan status of the counties. In conclusion, increased ambient PM2.5 concentration level was associated with increased incidence of HF hospitalizations and mortality at the county level across the US. This calls for future studies exploring policies that reduce ambient particulate matter pollution and their downstream effects on potentially improving HF outcomes.

BackgroundPatients with acute coronary syndrome (ACS) with depressed mood demonstrate poor cardiovascular behavioral risk profiles and elevated risk for recurrent ACS and mortality. Behavioral Activation (BA) offers an intervention framework for an integrated treatment targeting both depression and critical health behaviors post-ACS. Behavioral Activation for Health and Depression (BA-HD) was developed and pilot tested in a multiphase iterative process.MethodsFirst, an initial treatment manual was conceptualized based on the team's prior work, as well as the extant literature. Second, qualitative interviews were conducted with target patients and target providers on the proposed BA-HD treatment rationale, content, and structure. Framework matrix analyses were used to summarize and aggregate responses. Third, an expert panel was convened to elicit additional manual refinements. Finally, patients with post-ACS depression and health behavior non-adherence were recruited to complete an open pilot trial to evaluate acceptability (Client Satisfaction Questionnaire [CSQ], exit interview) and treatment engagement (number of sessions attended; treatment completion was considered completion of 8 out of 10 possible sessions).ResultsThe initial BA-HD treatment manual expanded an existing treatment manual for post-ACS BA-based mood management and smoking cessation to target four health behaviors relevant to post-ACS patients (e.g., smoking cessation, medication adherence, physical activity, and diet). After the initial conceptualization, ten post-ACS patients and eight cardiac rehabilitation professionals completed qualitative interviews. Patients endorsed bi-directional interactions between mood and health behaviors post-ACS. Both patients and providers expressed general support of the proposed treatment rationale and values-guided, collaborative goal-setting approach. Patients, providers, and experts provided feedback that shaped the iterative manual development. After the BA-HD manual was finalized, eight participants were enrolled in a single-arm pilot trial. The mean CSQ score was 30.57 ± 2.23, indicating high satisfaction. Seven out of eight (88%) completed treatment. Pre- to post treatment improvements in depressed mood and health behaviors were promising.ConclusionsBA-HD treatment is an acceptable approach to target both mood and health behaviors in post-ACS patients with depression. A future larger, controlled trial is needed to evaluate the efficacy of the BA-HD treatment.Trial registrationClinicalTrials.gov Identifier: NCT04158219.

Shared medical appointments (SMAs) offer a means for providing knowledge and skills needed for chronic disease management to patients. However, SMAs require a time and attention investment from health care providers, who must understand the goals and potential benefits of SMAs from the perspective of patients and providers. To better understand how to gain provider engagement and inform future SMA implementation, qualitative inquiry of provider experience based on a knowledge-attitude-practice model was explored. Semi-structured interviews were conducted with 24 health care providers leading SMAs for heart failure at three Veterans Administration Medical Centers. Rapid matrix analysis process techniques including team-based qualitative inquiry followed by stakeholder validation was employed. The interview guide followed a knowledge-attitude-practice model with a priori domains of knowledge of SMA structure and content (understanding of how SMAs were structured), SMA attitude/beliefs (general expectations about SMA use), attitudes regarding how leading SMAs affected patients, and providers. Data regarding the patient referral process (organizational processes for referring patients to SMAs) and suggested improvements were collected to further inform the development of SMA implementation best practices. Providers from all three sites reported similar knowledge, attitude and beliefs of SMAs. In general, providers reported that the multi-disciplinary structure of SMAs was an effective strategy towards improving clinical outcomes for patients. Emergent themes regarding experiences with SMAs included improved self-efficacy gained from real-time collaboration with providers from multiple disciplines, perceived decrease in patient re-hospitalizations, and promotion of self-management skills for patients with HF. Most providers reported that the SMA-setting facilitated patient learning by providing opportunities for the sharing of experiences and knowledge. This was associated with the perception of increased comradery and support among patients. Future research is needed to test suggested improvements and to develop best practices for training additional sites to implement HF SMA.

ObjectiveTo study the relationship between county-level COVID-19 outcomes (incidence and mortality) and county-level median household income and status of Medicaid expansion of US counties.MethodsRetrospective analysis of 3142 US counties was conducted to study the relationship between County-level median-household-income and COVID-19 incidence and mortality per 100,000 people in US counties, January-20th-2021 through December-6th-2021. County median-household-income was log-transformed and stratified by quartiles. Multilevel-mixed-effects-generalized-linear-modeling adjusted for county socio-demographic and comorbidities and tested for Medicaid-expansion-times-income-quartile interaction on COVID-19 outcomes.ResultsThere was no significant difference in COVID-19 incidence-rate across counties by income quartiles or by Medicaid expansion status. Conversely, for non-Medicaid-expansion states, counties in the lowest income quartile had a 41% increase in COVID-19 mortality-rate compared to counties in the highest income quartile. Mortality-rate was not related to income in counties from Medicaid-expansion states.ConclusionsMedian-household-income was not related to COVID-19 incidence-rate but negatively related to COVID-19 mortality-rate in US counties of states without Medicaid-expansion.

Abstract Background Kidney transplantation (KT) correlates with an increased risk of developing several malignancies; however, the risk of colorectal cancer (CRC) after KT remains debatable and has been marginally explored. Hence, in this nationwide, retrospective, population-based cohort study, we aimed to examine the correlation between KT and CRC in a large-scale population-based Chinese cohort. Methods We identified a total of 3739 regular hemodialysis patients undergoing KT (exposed cohort) and 42,324 hemodialysis patients not undergoing KT (non-exposed cohort) between 2000 and 2008 from Taiwan’s National Health Insurance Research Database (NHIRD). Both cohorts were followed up from January 1, 2000, to the date of CRC diagnosis, death, or the end of 2013. Using Kaplan–Meier method, we measured the cumulative incidence of CRC in each cohort. Furthermore, Cox proportional hazards models were used to compute hazards ratios (HRs) and 95% confidence intervals (CIs) to estimate the correlation between KT and CRC in hemodialysis patients. Results The Kaplan–Meier analysis revealed that the cumulative incidence of CRC was significantly higher in the exposed cohort than in the non-exposed cohort (log-rank test, P

Background Studies have reported that people living with HIV have higher burden of subclinical cardiovascular disease, but the data are not adequately synthesized. We performed meta‐analyses of studies of coronary artery calcium and coronary plaque in people living with HIV. Methods and Results We performed systematic search in electronic databases, and data were abstracted in standardized forms. Study‐specific estimates were pooled using meta‐analysis. 43 reports representing 27 unique studies and involving 10 867 participants (6699 HIV positive, 4168 HIV negative, mean age 52 years, 86% men, 32% Black) were included. The HIV‐positive participants were younger (mean age 49 versus 57 years) and had lower Framingham Risk Score (mean score 6 versus 18) compared with the HIV‐negative participants. The pooled estimate of percentage with coronary artery calcium >0 was 45% (95% CI, 43%–47%) for HIV‐positive participants, and 52% (50%–53%) for HIV‐negative participants. This difference was no longer significant after adjusting for difference in Framingham Risk Score between the 2 groups. The odds ratio of coronary artery calcium progression for HIV‐positive versus ‐negative participants was 1.64 (95% CI, 0.91–2.37). The pooled estimate for prevalence of noncalcified plaque was 49% (95% CI, 47%–52%) versus 20% (95% CI, 17%–23%) for HIV‐positive versus HIV‐negative participants, respectively. Odds ratio for noncalcified plaque for HIV‐positive versus ‐negative participants was 1.23 (95% CI, 1.08–1.38). There was significant heterogeneity that was only partially explained by available study‐level characteristics. Conclusions People living with HIV have higher prevalence of noncalcified coronary plaques and similar prevalence of coronary artery calcium, compared with HIV‐negative individuals. Future studies on coronary artery calcium and plaque progression can further elucidate subclinical atherosclerosis in people living with HIV.

Much remains unknown about the role of added sugar in relation to cardiovascular disease (CVD) and the relative contributions of sugar-sweetened beverages (SSB) or artificially sweetened beverages (ASB) to CVD risk. Among the 109,034 women who participated in Women’s Health Initiative, we assessed average intakes of added sugar, SSB and ASB, and conducted Cox regression to estimate the hazard ratios (HRs) and their 95% confidence intervals for CVD risk. The consistency of findings was compared to a network meta-analysis of all available cohorts. During an average of 17.4 years of follow-up, 11,597 cases of total CVD (nonfatal myocardial infarction, coronary heart disease (CHD) death, stroke, coronary revascularization, and/or incident heart failure) were confirmed. Added sugar as % energy intake daily (%EAS) at ≥15.0% was positively associated with total CVD (HR = 1.08 [1.01, 1.15]) and CHD (HR = 1.20 [1.09, 1.32]). There was also a higher risk of total CVD associated with ≥1 serving of SSB intake per day (HR = 1.29 [1.17, 1.42]), CHD (1.35 [1.16, 1.57]), and total stroke (1.30 [1.10, 1.53]). Similarly, ASB intake was associated with an increased risk of CVD (1.14 [1.03, 1.26]) and stroke (1.24 [1.04, 1.48]). According to the network meta-analysis, there was a large amount of heterogeneity across studies, showing no consistent pattern implicating added sugar, ASB, or SSB in CVD outcomes. A diet containing %EAS ≥15.0% and consuming ≥1 serving of SSB or ASB may be associated with a higher CVD incidence. The relative contribution of added sugar, SSB, and ASB to CVD risk warrants further investigation.

The high cost and time for developing a new drug or repositioning a partially-developed drug has fueled interest in “repurposing” drugs. Drug repurposing is particularly of interest for Alzheimer’s disease (AD) or AD-related dementias (ADRD) because there are no unrestricted disease-modifying treatments for ADRD. We have designed and pilot tested a 3-Step Medication-Wide Association Study Plus (MWAS+) approach to rigorously accelerate the identification of drugs with a high potential to be repurposed for delaying and preventing AD/ADRD: Step 1 is a hypothesis-free exploration; Step 2 is mechanistic filtering; And Step 3 is hypothesis testing using observational data and prospective cohort design. Our results demonstrated the feasibility of the MWAS+ approach. The Step 1 analysis identified potential candidate drugs including atorvastatin and GLP1. The literature search in Step 2 found evidence supporting the mechanistic plausibility of the statin-ADRD association. Finally, Step 3 confirmed our hypothesis that statin may lower the risk of incident ADRD, which was statistically significant using a target trial design that emulated randomized controlled trials.

Background Although HIV is associated with increased risk of heart failure (HF), it is not known if people living with HIV develop HF at a younger age compared with individuals without HIV. Crude comparisons of age at diagnosis of HF between individuals with and without HIV does not account for differences in underlying age structures between the populations. Methods and Results We used Veterans Health Administration data to compare the age at HF diagnosis between veterans with and without HIV, with adjustment for difference in population age structure. Statistical weights, calculated for each 1‐year strata of veterans with HIV in each calendar year from 2000 to 2018, were applied to the veterans without HIV to standardize the age structure. We identified 5093 veterans with HIV (98% men, 34% White) with first HF episode recorded after HIV diagnosis (median age at incidence of HF, 58 years), and 1 425 987 veterans without HIV (98% men, 78% White) with HF (corresponding age, 72 years), with an absolute difference of 14 years. After accounting for difference in age structure, the adjusted median age at HF diagnosis for veterans without HIV was 63 years, 5 years difference with veterans with HIV (P

Background: Increasing evidence points to cardiac injury (CI) as a common coronavirus disease 2019 (COVID-19) related complication. The characteristics of early CI (occurred within 72 h of admission) and late CI (occurred after 72 h of admission) and its association with mortality in COVID-19 patients is unknown.Methods: This retrospective study analyzed patients confirmed with COVID-19 in Union Hospital (Wuhan, China) from Jan 29th to Mar 15th, 2020. Clinical outcomes (discharge, or death) were monitored to April 15, 2020, the latest date of follow-up. Demographic, clinical, laboratory, as well as treatment and prognosis were collected and analyzed in patients with early, late CI and without CI.Results: A total of 196 COVID-19 patients were included for analysis. The median age was 65 years [interquartile range (IQR) 56–73 years], and 112 (57.1%) were male. Of the 196 COVID-19 patients, 49 (25.0%) patients had early and 20 (10.2%) patients had late CI, 56.6% developed Acute-Respiratory-Distress-Syndrome (ARDS) and 43 (21.9%) patients died. Patients with any CI were more likely to have developed ARDS (87.0 vs. 40.2%) and had a higher in-hospital mortality than those without (52.2 vs. 5.5%, P < 0.001). Among CI subtypes, a significantly higher risk of in-hospital death was found in patients with early CI with recurrence [19/49 patients, adjusted odds ratio (OR) = 7.184, 95% CI 1.472–35.071] and patients with late CI (adjusted OR = 5.019, 95% CI 1.125–22.388) compared to patients with early CI but no recurrence.Conclusions: CI can occur early on or late after, the initial 72 h of admission and is associated with ARDS and an increased risk of in-hospital mortality. Both late CI and recurrent CI after the initial episode were associated with worse outcomes than patients with early CI alone. This study highlights the importance of early examination and periodical monitoring of cardiac biomarkers, especially for patients with early CI or at risk of clinical deterioration.

Background Although sub‐Saharan Africa has a high prevalence of cardiovascular diseases (CVDs), there remains a lack of systematic and comprehensive assessment of risk factors and early CVD outcomes in adults in sub‐Saharan Africa. Methods and Results Using a stratified multistage random sampling method, we recruited 1106 men and women, aged >18 years, from the general population in Ghana to participate in a national health survey from 2016 to 2017. In Ghanaian adults, the age‐standardized prevalence of known CVD risk factors was 15.1% (95% CI, 12.9%–17.3%) for obesity, 6.8% (95% CI, 5.1%–8.5%) for diabetes mellitus, 26.1% (95% CI, 22.9%–29.4%) for hypertension, and 9.3% (95% CI, 7.1%–11.5%) for hyperuricemia. In addition, 10.1% (95% CI, 7.0%–13.2%) of adults had peripheral artery disease, 8.3% (95% CI, 6.7%–10.0%) had carotid thickening, 4.1% (95% CI, 2.9%–5.2%) had left ventricular hypertrophy, and 2.5% (95% CI, 1.5%–3.4%) had chronic kidney disease. Three CVD risk factors appeared to play prominent roles in the development of target organ damage, including obesity for peripheral artery disease (odds ratio [OR], 2.22; 95% CI, 1.35–3.63), hypertension for carotid thickening (OR, 1.92; 95% CI, 1.22–3.08), and left ventricular hypertrophy (OR, 5.28; 95% CI, 2.55–12.11) and hyperuricemia for chronic kidney disease (OR, 5.49; 95% CI, 2.84–10.65). Conclusions This comprehensive health survey characterized the baseline conditions of a national cohort of adults while confirming the prevalence of CVD risk factors, and early CVD outcomes have reached epidemic proportions in Ghana. The distinct patterns of risk factors in the development of target organ damage present important challenges and opportunities for interventions to improve cardiometabolic health among adults in Ghana.

Background Adiponectin is a polypeptide hormone related to obesity, and a known modulator of pulmonary vascular remodeling. Association between plasma adiponectin levels and pulmonary hypertension (PH) has not been studied in African Americans (AAs) who are disproportionately affected by obesity. The relationship between adiponectin and heart failure (HF) and mortality, outcomes associated with PH, is unclear. Methods We performed cross-sectional and longitudinal analysis to examine if there is an association between plasma adiponectin and PH and associated clinical outcomes, in participants of Jackson Heart Study (JHS). JHS is a prospective observational cohort study of heart disease in AAs from Jackson, Mississippi. Results Of the 3161 participants included in the study, mean age (SD) was 56.38 (12.61) years, 1028 were men (32.5%), and mean (SD) BMI was 31.42 (7.05) kg/m 2 . Median (IQR) adiponectin was 4516.82 (2799.32–7065.85) ng/mL. After adjusting for potential confounders including BMI, higher adiponectin levels were associated with increased odds of PH (adjusted odds ratio per log increment in adiponectin, (1.81; 95% CI, 1.41–2.32). High adiponectin levels were also associated with associated HF admissions (adjusted hazard ratio [HR] per log increment in adiponectin, 1.63, 95% CI, 1.24–2.14) and mortality (adjusted HR per log increment in adiponectin, 1.20; 95% CI 1.02–1.41). Conclusions Elevated plasma adiponectin levels are associated with PH, HF admissions and mortality risk in AAs. High adiponectin levels may help identify an at-risk population that could be evaluated for targeted prevention and management strategies in future studies

To clarify the predictive factors of significant platelet count improvement in thrombocytopenic chronic hepatitis C (CHC) patients. CHC patients with baseline platelet counts of 3/μL receiving direct-acting antiviral (DAA) therapy with at least 12-weeks post-treatment follow-up (PTW12) were enrolled. Significant platelet count improvement was defined as a ≥10% increase in platelet counts at PTW12 from baseline. Platelet count evolution at treatment week 4, end-of-treatment, PTW12, and PTW48 was evaluated. This study included 4922 patients. Sustained virologic response after 12 weeks post-treatment was achieved in 98.7% of patients. Platelet counts from baseline, treatment week 4, and end-of-treatment to PTW12 were 108.8 ± 30.2, 121.9 ± 41.1, 123.1 ± 43.0, and 121.1 ± 40.8 × 103/μL, respectively. Overall, 2230 patients (45.3%) showed significant platelet count improvement. Multivariable analysis revealed that age (odds ratio (OR) = 0.99, 95% confidence interval (CI): 0.99–1.00, p = 0.01), diabetes mellitus (DM) (OR = 1.20, 95% CI: 1.06–1.38, p = 0.007), cirrhosis (OR = 0.66, 95% CI: 0.58–0.75, p < 0.0001), baseline platelet counts (OR = 0.99, 95% CI: 0.98–0.99, p < 0.0001), and baseline total bilirubin level (OR = 0.80, 95% CI: 0.71–0.91, p = 0.0003) were independent predictive factors of significant platelet count improvement. Subgroup analyses showed that patients with significant platelet count improvement and sustained virologic responses, regardless of advanced fibrosis, had a significant increase in platelet counts from baseline to treatment week 4, end-of-treatment, PTW12, and PTW48. Young age, presence of DM, absence of cirrhosis, reduced baseline platelet counts, and reduced baseline total bilirubin levels were associated with significant platelet count improvement after DAA therapy in thrombocytopenic CHC patients.

Background Palliative care supports quality of life, symptom control, and goal setting in heart failure (HF) patients. Unlike hospice, palliative care does not restrict life‐prolonging therapy. This study examined the association between palliative care during hospitalization for HF on the subsequent transitions and procedures. Methods and Results Veterans admitted to hospitals with HF from 2010 to 2015 were randomly selected for the Veterans Administration External Peer Review Program. Variables pertaining to demographic, clinical, laboratory, and usage were captured from Veterans Administration electronic records. Patients receiving hospice services before admission were excluded. Patients who received palliative care were propensity matched to those who did not. The primary outcomes were whether the patient experienced transitions or procedures in the 6 months after admission. Transitions included multiple readmissions (≥2) or intensive care admissions and procedures included mechanical ventilation, pacemaker implantation, or defibrillator implantation. Among 57 182 hospitalized HF patients, 1431 received palliative care, and were well matched to 1431 without (standardized mean differences ≤ ±0.05 on all matched variables). Palliative care was associated with significantly fewer multiple rehospitalizations (30.9% versus 40.3%, P

Background Women represent a large proportion of the growing heart failure (HF) epidemic, yet data are lacking regarding optimal dietary and lifestyle prevention strategies for them. Specifically, the association between magnesium intake and HF in a multiracial cohort of women is uncertain. Methods and Results We included 97 725 postmenopausal women from the WHI (Women's Health Initiative) observational studies and placebo arms of the hormone trial. Magnesium intake was measured at baseline by a 122‐item validated food‐frequency questionnaire and stratified into quartiles based on diet only, total intake (diet with supplements), and residual intake (calibration by total energy). Incident hospitalized HF (2153 events, median follow‐up 8.1 years) was adjudicated by medical record abstraction. In Cox proportional hazards models, we evaluated the association between magnesium intake and HF adjusting for potential confounders. Analyses were repeated on a subcohort (n=18 745; median‐follow‐up, 13.2 years) for whom HF cases were subclassified into preserved ejection fraction (526 events), reduced ejection fraction (291 events) or unknown (168 events). Most women were white (85%) with a mean age of 63. Compared with the highest quartile of magnesium intake, women in the lowest quartile had an increased risk of incident HF, with adjusted hazard ratios of 1.32 (95% CI, 1.02–1.71) for diet only (P trend=0.03), 1.26 (95% CI, 1.03–1.56) for total intake, and 1.31 (95% CI, 1.02–1.67) for residual intake. Results did not significantly vary by race. Subcohort analyses showed low residual magnesium intake was associated with HF with reduced ejection fraction (hazard ratio, 1.81, lowest versus highest quartile; 95% CI, 1.08–3.05) but not HF with preserved ejection fraction. Conclusions Low magnesium intake in a multiracial cohort of postmenopausal women was associated with a higher risk of incident HF, especially HF with reduced ejection fraction.

Objective: To determine whether insulin resistance (IR) measured by homeostasis model of insulin resistance (HOMA-IR) can further stratify diabetes risk in African Americans (AAs) beyond obesity and identify obese, low risk and non-obese, high risk individuals. Methods: Using the Jackson Heart Study cohort, we categorized participants without diabetes into four phenotypes: non-obese/insulin-sensitive, non-obese/IR, obese/insulin-sensitive and obese/IR. Obesity was defined as BMI ≥ 30 or BMI 25–30 plus an increased waist circumference. IR was defined as HOMA-IR ≥ 2. We used modified Poisson regression models to estimate the incident risk-ratios (IRR) of diabetes across these phenotypes adjusting for potential confounders and HbA1c. Results: Among 3219 AAs without diabetes, 14.0% were non-obese/insulin-sensitive, 24.6% non-obese/IR, 6.2% obese/insulin-sensitive, and 55.3% obese/IR. The overall crude incidence rate of diabetes was 29.91 cases/1000 person-years. In fully-adjusted models, compared to the non-obese/insulin-sensitive group, the relative risk of diabetes was highest in obese/IR (IRR = 2.35; 95% CI: 1.53, 3.60), followed by non-obese/IR (IRR = 1.59; 95% CI: 1.02, 2.46), and non-significant for the obese/insulin-sensitive (IRR = 1.70; 95% CI: 0.97, 2.99) group. Conclusions: HOMA-IR can further stratify diabetes risk in AA adults beyond obesity, identifying non-obese high-risk and lower-risk obese individuals. However, diabetes risk should still be carefully monitored in obese populations despite insulin sensitivity. Keywords: Overweight, Adiposity, Insulin sensitivity, Diabetes mellitus, Black race

IntroductionExercise modalities offered as part of traditional pulmonary rehabilitation (PR) do not always translate to successful performance of Activities of Daily Living (ADL) and may hinder gains in patient's sense of well-being. Data is lacking on the efficacy of incorporation of ADL-focused training in PR. The aim of this study was to determine the impact of incorporation of ADL simulation and energy-conservation training in PR as part of a quality-initiative on health-related-quality-of-life (HRQOL), dyspnea, fatigue, and six-minute-walk-test among PR patients.MethodsRetrospective study where medical records of consecutive patients with chronic respiratory diseases who completed PR from 2016 to 2018 were reviewed. ADL-focused energy-conservation training was added to traditional PR in September 2017 by replacing three monthly sessions of traditional PR with energy-conservation training as a quality-improvement-initiative. The change from baseline on HRQOL measured by COPD assessment test (CAT), six-minute-walk-test, MMRC dyspnea score and CRQ-dyspnea and CRQ-fatigue questionnaires, were compared between patients who received traditional PR versus energy-conservation PR. Within and between group differences were calculated via repeated-measures ANOVA.ResultsThe baseline characteristics of 91 patients who participated in traditional PR versus energy-conservation PR (n = 85) were similar (mean age = 68.6±10.4 years, 49% men). While improvement from baseline was similar and significant for both groups for MMRC, CRQ-dyspnea and CRQ-fatigue scores, and six-minute walk test, patients who participated in energy-conservation PR had significantly higher improvement in HRQOL CAT scores (p = 0.01) than those who completed traditional PR.ConclusionTailoring patient's training programs to include energy-conservation training exercises specific to ADL in PR improved HRQOL over traditional PR in patients with chronic respiratory diseases despite no significant change in functional status. Future randomized-controlled trials will be needed to confirm these initial findings.

ObjectivePoor housing conditions have been linked with worse health outcomes and infectious disease spread. Since the relationship of poor housing conditions with incidence and mortality of COVID-19 is unknown, we investigated the association between poor housing condition and COVID-19 incidence and mortality in US counties.MethodsWe conducted cross-sectional analysis of county-level data from the US Centers for Disease Control, US Census Bureau and John Hopkins Coronavirus Resource Center for 3135 US counties. The exposure of interest was percentage of households with poor housing conditions (one or greater of: overcrowding, high housing cost, incomplete kitchen facilities, or incomplete plumbing facilities). Outcomes were incidence rate ratios (IRR) and mortality rate ratios (MRR) of COVID-19 across US counties through 4/21/2020. Multilevel generalized linear modeling (with total population of each county as a denominator) was utilized to estimate relative risk of incidence and mortality related to poor housing conditions with adjustment for population density and county characteristics including demographics, income, education, prevalence of medical comorbidities, access to healthcare insurance and emergency rooms, and state-level COVID-19 test density. We report incidence rate ratios (IRRs) and mortality ratios (MRRs) for a 5% increase in prevalence in households with poor housing conditions.ResultsAcross 3135 US counties, the mean percentage of households with poor housing conditions was 14.2% (range 2.7% to 60.2%). On April 21st, the mean (SD) number of cases and deaths of COVID-19 were 255.68 (2877.03) cases and 13.90 (272.22) deaths per county, respectively. In the adjusted models standardized by county population, with each 5% increase in percent households with poor housing conditions, there was a 50% higher risk of COVID-19 incidence (IRR 1.50, 95% CI: 1.38-1.62) and a 42% higher risk of COVID-19 mortality (MRR 1.42, 95% CI: 1.25-1.61). Results remained similar using earlier timepoints (3/31/2020 and 4/10/2020).Conclusions and relevanceCounties with a higher percentage of households with poor housing had higher incidence of, and mortality associated with, COVID-19. These findings suggest targeted health policies to support individuals living in poor housing conditions should be considered in further efforts to mitigate adverse outcomes associated with COVID-19.

Background Pulmonary hypertension is prevalent in black individuals, especially women. Elevated pulmonary artery systolic pressure (PASP) is associated with significant morbidity and mortality. Methods and Results We developed linear and proportional hazards models to examine potential gender‐related differences in risk factors for elevated PASP (estimated by transthoracic echocardiography) and PASP‐associated clinical outcomes (incident heart failure admissions and mortality) in JHS (Jackson Heart Study) participants. JHS is a prospective observational cohort study of heart disease in blacks from the Jackson, Mississippi, metropolitan area. The study cohort included participants with measurable transtricuspid gradients (n=3286) at the time of first/baseline examination, 2000–2004. The median age (interquartile range) of patients at baseline was 57.8 years (18.6 years) with 67.5% being women. The median PASP at baseline was higher in women (men: 26 mm Hg [interquartile range 8], women: 27 mm Hg [interquartile range 9]. In multivariate linear regression analyses with PASP, significant gender interactions were noted for age, chronic lung disease, pulse pressure, and obstructive spirometry. In exploratory analyses stratified by gender, body mass index, and obstructive and restrictive spirometry patterns were associated with PASP in women, and chronic lung disease was associated with PASP in men. Age and pulse pressure had stronger associations with PASP in women compared with men. There was a significant interaction between gender and PASP for heart failure admissions but not mortality. Conclusions Specific cardiopulmonary risk factors are associated with elevated PASP in women and men. Women with elevated PASP have a higher risk of incident heart failure admissions. Future research is needed to understand associated gender‐specific mechanisms that can help identify targeted prevention and management strategies for patients with elevated PASP.

Abstract Background Diabetes shared medical appointments (SMAs) and reciprocal peer support programs have been found in efficacy trials to help adults with diabetes improve their self-management and achieve short-term gains in clinical and patient-centered outcomes. In order to translate this evidence to system-level interventions, there is a need for large-scale, pragmatic trials that examine the effectiveness, implementation, and costs of SMAs and reciprocal peer support across diverse settings. Methods The Shared Health Appointments and Reciprocal Enhanced Support (SHARES) study is a multisite, cluster randomized trial that is evaluating the effectiveness and implementation of SMAs with and without an additional reciprocal Peer-to-Peer (P2P) support program, when compared to usual care. The P2P program comprises periodic peer support group sessions and telephone contact between SMA participant pairs to promote more effective diabetes self-management. We will examine outcomes across three different treatment groups: (1) SMAs, (2) SMAs plus P2P, and (3) usual care. We will collect and analyze data over a 2.5-year implementation period at five geographically diverse Veterans Affairs (VA) health systems. The primary outcome is the relative change in hemoglobin A1c over time. Secondary outcomes are changes in systolic blood pressure, antihypertensive medication use, statin use, and insulin initiation over the study period. The unit of analysis is the individual, adjusted by the individual’s SMA group (the cluster). We will use mixed methods to rigorously evaluate processes and costs of implementing these programs in each of the clinic settings. Discussion We hypothesize that patients will experience improved outcomes immediately following participation in SMAs and that augmenting SMAs with reciprocal peer support will help to maintain these gains over time. The results of this study will be among the first to examine the effects of diabetes SMAs alone and in conjunction with P2P in a range of real-life clinical settings. In addition, the study will provide important information on contextual factors associated with successful program implementation. Trial registration ClinicalTrials.gov, ID: NCT02132676 . Registered on 21 August 2013.

Background There is significant geographical variation in heart failure (HF) mortality across the United States. County socioeconomic factors that influence these outcomes are unknown. We studied the association between county socioeconomic factors and HF mortality and compared it with coronary heart disease (CHD) mortality. Methods and Results This is a cross‐sectional analysis of socioeconomic factors and mortality in HF and CHD across 3135 US counties from 2010 to 2015. County‐level poverty, education, income, unemployment, health insurance status, and cause‐specific mortality rates were collected from the Centers for Disease Control and Prevention and US Census Bureau databases. Poverty had the strongest correlation with both HF and CHD mortality, disproportionately higher for HF (r=0.48) than CHD (r=0.24). HF mortality increased by 5.2 deaths/100 000 for each percentage increase in county poverty prevalence in a frequency‐weighted, demographic‐adjusted, multivariate regression model. The greatest attenuation in the poverty regression coefficient (66.4%) was seen after adjustment for prevalence of diabetes mellitus and obesity. Subgroup analysis by census region showed that this relationship was the strongest in the South and weakest in the Northeast (6.1 versus 1.4 deaths/100 000 per 1% increase in county poverty in a demographics‐adjusted model). Conclusions County poverty is the strongest socioeconomic factor associated with HF and CHD mortality, an association that is stronger with HF than with CHD and varied by census region. Over half of the association was explained by differences in the prevalence of diabetes mellitus and obesity across the counties. Health policies targeting improvement in these risk factors may address and possibly minimize health disparities caused by socioeconomic factors.

Background Center‐based cardiac rehabilitation (CBCR) has been shown to improve outcomes in patients with heart failure (HF). Home‐based cardiac rehabilitation (HBCR) can be an alternative to increase access for patients who cannot participate in CBCR. Hybrid cardiac rehabilitation (CR) combines short‐term CBCR with HBCR, potentially allowing both flexibility and rigor. However, recent data comparing these initiatives have not been synthesized. Methods and Results We performed a meta‐analysis to compare functional capacity and health‐related quality of life (hr‐QOL) outcomes in HF for (1) HBCR and usual care, (2) hybrid CR and usual care, and (3) HBCR and CBCR. A systematic search in 5 standard databases for randomized controlled trials was performed through January 31, 2019. Summary estimates were pooled using fixed‐ or random‐effects (when I2>50%) meta‐analyses. Standardized mean differences (95% CI) were used for distinct hr‐QOL tools. We identified 31 randomized controlled trials with a total of 1791 HF participants. Among 18 studies that compared HBCR and usual care, participants in HBCR had improvement of peak oxygen uptake (2.39 mL/kg per minute; 95% CI, 0.28–4.49) and hr‐QOL (16 studies; standardized mean difference: 0.38; 95% CI, 0.19–0.57). Nine RCTs that compared hybrid CR with usual care showed that hybrid CR had greater improvements in peak oxygen uptake (9.72 mL/kg per minute; 95% CI, 5.12–14.33) but not in hr‐QOL (2 studies; standardized mean difference: 0.67; 95% CI, −0.20 to 1.54). Five studies comparing HBCR with CBCR showed similar improvements in functional capacity (0.0 mL/kg per minute; 95% CI, −1.93 to 1.92) and hr‐QOL (4 studies; standardized mean difference: 0.11; 95% CI, −0.12 to 0.34). Conclusions HBCR and hybrid CR significantly improved functional capacity, but only HBCR improved hr‐QOL over usual care. However, both are potential alternatives for patients who are not suitable for CBCR.

Background Image reconstruction thickness may impact quantitative coronary artery calcium scoring (CACS) from lung cancer screening computed tomography (LCSCT), limiting its application in practice. Methods and Results We evaluated Agatston‐based quantitative CACS from 1.25‐mm LCSCT and cardiac computed tomography for agreement in 87 patients. We then evaluated Agatston‐based quantitative CACS from 1.25‐, 2.5‐, and 5.0‐mm slice thickness LCSCT for agreement in 258 patients. Secondary analysis included the impact of slice thickness on predictive value of 4‐year outcomes. Median age of patients who underwent 1.25‐mm LCSCT and cardiac computed tomography was 63 years (interquartile interval, 57, 68). CACS from 1.25‐mm LCSCT and cardiac computed tomography demonstrated a strong Pearson correlation, R=0.9770 (0.965, 0.985), with good agreement. The receiver operating characteristic curve areas under the curve for cardiac computed tomography and LCSCT were comparable at 0.8364 (0.6628, 1.01) and 0.8208 (0.6431, 0.9985), respectively (P=0.733). Median age of patients who underwent LCSCT with 3 slice thicknesses was 66 years (interquartile interval, 63, 73). Compared with CACS from 1.25‐mm scans, CACS from 2.5‐ and 5.0‐mm scans demonstrated strong Pearson correlations, R=0.9949 (0.9935, 0.996) and R=0.9478 (0.9338, 0.959), respectively, though bias was largely negative for 5.0‐mm scans. Receiver operating characteristic curve areas under the curve for 1.25‐, 2.5‐, and 5.0‐mm scans were comparable at 0.7040 (0.6307, 0.7772), 0.7063 (0.6327, 0.7799), and 0.7194 (0.6407, 0.7887), respectively (P=0.6487). When using individualized high‐risk thresholds derived from respective receiver operating characteristic curves, all slice thicknesses demonstrated similar prognostic value. Conclusions Slice thickness is an important consideration when interpreting Agatston CACS from LCSCTs. Despite the absence of ECG gating, it appears reasonable to report CACS from either 1.25‐ or 2.5‐mm slice thickness LCSCT to help stratify cardiovascular risk. Conversely, 5.0‐mm scans largely underidentify calcium, limiting practical use within the established CACS values used to categorize cardiovascular risk.

Background: This study investigated the correlation between epicardial adipose tissue (EAT), a measure of central obesity, and sexual function in males with vasculogenic erectile dysfunction (ED). Materials and Methods: The study was a cross-sectional study of selected males with ED aged

The effectiveness and costs associated with addition of pharmacist-led group medical visits to standard care for patients with Type-2 Diabetes Mellitus (T2DM) is unknown.Randomized-controlled-trial in three US Veteran Health Administration (VHA) Hospitals, where 250 patients with T2DM, HbA1c >7% and either hypertension, active smoking or hyperlipidemia were randomized to either (1) addition of pharmacist-led group-medical-visits or (2) standard care alone for 13 months. Group (4-6 patients) visits consisted of 2-hour, education and comprehensive medication management sessions once weekly for 4 weeks, followed by quarterly visits. Change from baseline in cardiovascular risk estimated by the UKPDS-risk-score, health-related quality-of-life (SF36v) and institutional healthcare costs were compared between study arms.After 13 months, both groups had similar and significant improvements from baseline in UKPDS-risk-score (-0.02 ±0.09 and -0.04 ±0.09, group visit and standard care respectively, adjusted p

Background: Shared medical appointments (SMAs) are clinical visits in which several patients meet with 1 or more providers at the same time. Objective: To describe the outcomes of an interdisciplinary SMA for veterans recently discharged for heart failure (HF). Methods: A retrospective chart review for patients’ readmission rates, survival, medication adherence, and medication-related problems. For qualitative outcomes, we performed semistructured interviews on 12 patients who had undergone HF SMAs and their respective caregivers focusing on care satisfaction, HF knowledge, disease self-care, medication reconciliation, and peer support. Results: The cohort comprised 70 patients—49% had left ventricular function 10 medications. Medication-related problems occurred in 60% of patients. Interviews revealed overall satisfaction with HF-SMA, but patients felt overwhelmed with HF instructions, perceived lack of peer support and self-efficacy, and feelings of hopelessness related to HF. Conclusion: Shared medical appointments are well-perceived. Medication problems and need for medication management are prevalent along with patient’s lack of self-efficacy in HF care. Multiple HF-SMA visits may be needed to reinforce concepts, reduce confusion, and garner peer support.

Background: Recently, the number of patients diagnosed with end-stage renal disease (ESRD) in Taiwan has been rising. ESRD is known to typically develop from chronic kidney disease (CKD). The objectives of the study were to describe the prevalence of CKD and to evaluate the associated factors among military aircrews. Materials and Methods: In this study, military aircrews that received physical examinations in four military hospitals between 2004 and 2010 were selected. The abbreviated modification of diet in renal disease (aMDRD) formula was used to calculate glomerular filtration rates (GFRs). Urine protein, urine red blood cells, and urine pH values were used to define whether patients had CKD. This study analyzed 1317 cases. Results: The prevalence of CKD was 10.4% in the military aircrews. The risk of CKD was statistically significant higher in positive urine occult blood, high bilirubin, hyperuricemia, high total cholesterol, and each additional 1-year of age with odds ratio (95% confidence interval): 6.53 (3.86-11.06), 2.62 (1.28-5.37), 1.95 (1.11-3.42), 1.76 (1.05-2.95), and 1.03 (1.00-1.07), respectively. Conclusions: The majority of the participants diagnosed with CKD were in the early stages of the disease. The aMDRD formula could be calculated from annual physical examination results for using to understand GFRs and increase awareness of the kidney function, thereby delaying disease progression.

BackgroundMore than 60% of patients decline participation in cardiac rehabilitation after a myocardial infarction. Options to improve physical activity (PA) and other risk factors in these high‐risk individuals are limited. We conducted a phase 2 randomized controlled trial to determine feasibility, safety, acceptability, and estimates of effect of tai chi on PA, fitness, weight, and quality of life. Methods and ResultsPatients with coronary heart disease declining cardiac rehabilitation enrollment were randomized to a “LITE” (2 sessions/week for 12 weeks) or to a “PLUS” (3 sessions/week for 12 weeks, then maintenance classes for 12 additional weeks) condition. PA (accelerometry), weight, and quality of life (Health Survey Short Form) were measured at baseline and 3, 6, and 9 months after baseline; aerobic fitness (stress test) was measured at 3 months. Twenty‐nine participants (13 PLUS and 16 LITE) were enrolled. Retention at 9 months was 90% (LITE) and 88% (PLUS). No serious tai chi–related adverse events occurred. Significant mean between group differences in favor of the PLUS group were observed at 3 and 6 months for moderate‐to‐vigorous PA (100.33 min/week [95% confidence interval, 15.70–184.95 min/week] and 111.62 min/week; [95% confidence interval, 26.17–197.07 min/week], respectively, with a trend toward significance at 9 months), percentage change in weight, and quality of life. No changes in aerobic fitness were observed within and between groups. ConclusionsIn this community sample of patients with coronary heart disease declining enrollment in cardiac rehabilitation, a 6‐month tai chi program was safe and improved PA, weight, and quality of life compared with a 3‐month intervention. Tai chi could be an effective option to improve PA in this high‐risk population. Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT02165254.

BackgroundGiven high rates of obesity, hypertension, and diabetes mellitus, black persons are at risk to develop heart failure. The association of moderate to vigorous physical activity (MVPA) and heart failure in black adults is underresearched. The purpose of this study was to explore whether greater MVPA was associated with lower risk of heart failure hospitalizations (HFHs) among black adults with normal ejection fractions. Methods and ResultsWe performed a prospective analysis of 4066 black adults who participated in the Jackson Heart Study and who had physical activity measured, had normal ejection fraction on 2‐dimensional echocardiograms, and were followed for 7 years for incident HFH. We used Cox proportional regression analyses adjusted for age, sex, body mass index, smoking status, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, coronary heart disease, atrial fibrillation, and chronic kidney disease and examined effect modification by sex and body mass index. Of the eligible population, 1925 participants, according to the duration of MVPA, had poor health (0 minutes/week), 1332 had intermediate health (1–149 minutes/week), and 809 had ideal health (≥150 minutes/week). There were 168 incident HFHs. MVPA for intermediate and ideal health was associated with decreasing risk of incident HFH (hazard ratio: 0.70 [95% confidence interval, 49–1.00] and 0.35 [95% confidence interval, 0.19–0.64], respectively; Ptrend=0.003). The full model revealed hazard ratios of 0.74 [95% confidence interval, 0.52–1.07] and 0.41 [95% confidence interval, 0.22–0.74], respectively. There was no effect modification between MVPA and body mass index or sex on incident HFH. ConclusionsA dose‐response relationship between increasing levels of MVPA and protection from incident HFH was found in black men and women with normal ejection fractions.