Publications by authors named "Michael E Hall"

129 Publications

Sex Differences in Hypertension: Related to Genes, Jean Sizes, and Salt Sensitivity?

Hypertension 2022 01 8;79(1):47-49. Epub 2021 Dec 8.

Department of Physiology and Biophysics (M.E.H., J.E.H.), University of Mississippi Medical Center.

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http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.18425DOI Listing
January 2022

Whole Genome Sequence Analysis of the Plasma Proteome in Black Adults Provides Novel Insights into Cardiovascular Disease.

Circulation 2021 Nov 24. Epub 2021 Nov 24.

Department of Exercise Science, University of South Carolina, Columbia, SC.

Plasma proteins are critical mediators of cardiovascular processes and are the targets of many drugs. Previous efforts to characterize the genetic architecture of the plasma proteome have been limited by a focus on individuals of European descent and leveraged genotyping arrays and imputation. Here we describe whole genome sequence analysis of the plasma proteome in individuals with greater African ancestry, increasing our power to identify novel genetic determinants. Proteomic profiling of 1,301 proteins was performed in 1852 Black adults from the Jackson Heart Study using aptamer-based proteomics (SomaScan). Whole genome sequencing association analysis was ascertained for all variants with minor allele count ≥ 5. Results were validated using an alternative, antibody-based, proteomic platform (Olink) as well as replicated in the Multi-Ethnic Study of Atherosclerosis and the HERITAGE Family Study. We identify 569 genetic associations between 479 proteins and 438 unique genetic regions at a Bonferroni-adjusted significance level of 3.8 × 10. These associations include 114 novel locus-protein relationships and an additional 217 novel sentinel variant-protein relationships. Novel cardiovascular findings include new protein associations at the gene locus including ZAP70 (sentinel single nucleotide polymorphism [SNP] rs7412-T, β = 0.61±0.05, p-value = 3.27 × 10) and MMP-3 (β = -0.60±0.05, p = 1.67 × 10), as well as a completely novel pleiotropic locus at the gene, associated with nine proteins. Further, the associations suggest new mechanisms of genetically mediated cardiovascular disease linked to African ancestry; we identify a novel association between variants linked to APOL1 associated chronic kidney and heart disease and the protein CKAP2 (rs73885319-G, β = 0.34±0.04, p = 1.34 × 10) as well as an association between ATTR amyloidosis and RBP4 levels in community dwelling individuals without heart failure. Taken together, these results provide evidence for the functional importance of variants in non-European populations, and suggest new biological mechanisms for ancestry-specific determinants of lipids, coagulation and myocardial function.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.121.055117DOI Listing
November 2021

Dysglycemia and incident heart failure among blacks: The jackson heart study.

Am Heart J 2021 Nov 19;245:1-9. Epub 2021 Nov 19.

Department of Epidemiology & Prevention, Wake Forest University School of Medicine, Winston-Salem, NC.

Background: We aimed to investigate the associations of glycemic markers (hemoglobin A [HbA], fasting plasma glucose [FPG] and glycemic status [normoglycemia, prediabetes and diabetes]) with incident heart failure (HF) and its subtypes, among Blacks.

Methods: We included 2,290 community-dwelling Blacks (64% women, mean age 58 years) without prevalent HF from the Jackson Heart Study who attended the second exam (2005 - 2008). The associations between glycemic markers and incident HF (and subtypes including HF with preserved ejection fraction [HFpEF] and reduced ejection fraction [HFrEF]) were evaluated using Cox proportional hazards regression models, adjusting for risk factors and coronary heart disease.

Results: There were 119 incident HF events (48 HFpEF, 58 HFrEF, and 13 unclassified HF events) over a median follow-up of 10.5 years. Higher levels of HbA (HR per SD increment, 1.30; 95% CI 1.12, 1.51) and FPG (HR per SD increment FPG: 1.32; 95% CI: 1.17, 1.48) were associated with a higher risk of incident HF. Compared to normal glycemia, diabetes status was associated with a higher risk of incident HF (HR: 1.24; 95%CI: 1.02, 2.05). HbA was significantly associated with higher risks of HFpEF (HR per SD increment: 1.41, 95% CI: 1.18, 1.69) and HFrEF (HR per SD increment: 1.32; 95% CI: 1.12, 1.56). FPG was significantly associated with higher risk of HFpEF (HR per SD increment: 1.35, 95% CI: 1.14, 1.62) but not HFrEF (HR per SD increment: 1.12; 95% CI: 0.53, 2.35).

Conclusions: Among community-dwelling Blacks, higher levels of glycemic markers were associated with higher risk of HF subtypes.
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http://dx.doi.org/10.1016/j.ahj.2021.11.003DOI Listing
November 2021

Temporal Trends and Prognosis of Physical Examination Findings in Patients With Acute Decompensated Heart Failure: The ARIC Study Community Surveillance.

Circ Heart Fail 2021 12 27;14(12):e008403. Epub 2021 Oct 27.

Joint Department of Biomedical Engineering, University of North Carolina, North Carolina State University, Chapel Hill (M.C.C.).

Background: Bedside evaluation of congestion is a mainstay of heart failure (HF) management. Whether detected physical examination signs have changed over time as obesity prevalence has increased in HF populations, or if the associated prognosis differs for HF with reduced or preserved ejection fraction (HFrEF or HFpEF) is uncertain.

Methods: From 2005 to 2014, the ARIC study (Atherosclerosis Risk in Communities) conducted adjudicated hospital surveillance of acute decompensated HF. We analyzed trends in physical examination findings, imaging signs, and symptoms related to congestion, both over time and by obesity class, and associated 28-day mortality risks.

Results: Of 24 937 weighted hospitalizations for acute decompensated HF (mean age 75 years, 53% women, 32% Black), 47% had HFpEF. The prevalence of obesity increased from 2005 to 2014 for both HF types. With increasing obesity category, detected edema increased, while jugular venous distension decreased, and rales remained stable. Detected edema also increased over time, for both HF types. Associations between 28-day mortality and individual signs and symptoms of congestion were similar for HFpEF and HFrEF; however, the adjusted mortality risk with all 3 (edema, rales, and jugular venous distension) versus <3 physical examination findings was higher for patients with HFpEF (odds ratio, 2.41 [95% CI, 1.53-3.79]) than HFrEF (odds ratio, 1.30 [95% CI, 0.87-1.93]); for interaction by HF type =0.02.

Conclusions: In patients hospitalized with acute decompensated HF, detected physical examination findings differ both temporally and by obesity. Combined findings from the physical examination are more prognostic of 28-day mortality for patients with HFpEF than HFrEF.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.121.008403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8692393PMC
December 2021

Hypertensive Diseases in Pregnancy and Kidney Function Later in Life: The Genetic Epidemiology Network of Arteriopathy (GENOA) Study.

Mayo Clin Proc 2022 Jan 24;97(1):78-87. Epub 2021 Sep 24.

University of Mississippi Medical Center, Department of Medicine, Division of Cardiology, Jackson, MS. Electronic address:

Objective: To evaluate the relationship between hypertensive diseases in pregnancy and kidney function later in life.

Methods: We evaluated measured glomerular filtration rate (mGFR) using iothalamate urinary clearance in 725 women of the Genetic Epidemiology Network of Arteriopathy (GENOA) study. Women were classified by self-report as nulliparous (n=62), a history of normotensive pregnancies (n=544), a history of hypertensive pregnancies (n=102), or a history of pre-eclampsia (n=17). We compared adjusted associations among these four groups with mGFR using generalized estimating equations to account for familial clustering. Chronic kidney disease (CKD) was defined as mGFR of less than 60 mL/min per 1.73 m or urinary albumin-creatinine ratio (UACR) greater than or equal to 30 mg/g.

Results: Among women with kidney function measurements (mean age, 59±9 years, 52.9% African American), those with a history of hypertensive pregnancy had lower mGFR (-4.66 ml/min per 1.73 m; 95% CI, -9.12 to -0.20) compared with women with a history of normotensive pregnancies. Compared with women with a history of normotensive pregnancies, women with a history of hypertensive pregnancy also had higher odds of mGFR less than 60 ml/min per 1.73 m (odds ratio, 2.09; 95% CI, 1.21 to 3.60). Additionally, women with a history of hypertensive pregnancy had greater odds for chronic kidney disease (odds ratio, 4.89; 95% CI, 1.55 to 15.44), after adjusting for age, race, education, smoking history, hypertension, body mass index, and diabetes.

Conclusion: A history of hypertension in pregnancy is an important prognostic risk factor for kidney disease. To our knowledge, this is the first and largest investigation showing the association between hypertensive diseases in pregnancy and subsequent kidney disease using mGFR in a large biracial cohort.
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http://dx.doi.org/10.1016/j.mayocp.2021.07.018DOI Listing
January 2022

Weight-Loss Strategies for Prevention and Treatment of Hypertension: A Scientific Statement From the American Heart Association.

Hypertension 2021 11 20;78(5):e38-e50. Epub 2021 Sep 20.

Hypertension is a major risk factor for cardiovascular and renal diseases in the United States and worldwide. Obesity accounts for much of the risk for primary hypertension through several mechanisms, including neurohormonal activation, inflammation, and kidney dysfunction. As the prevalence of obesity continues to increase, hypertension and associated cardiorenal diseases will also increase unless more effective strategies to prevent and treat obesity are developed. Lifestyle modification, including diet, reduced sedentariness, and increased physical activity, is usually recommended for patients with obesity; however, the long-term success of these strategies for reducing adiposity, maintaining weight loss, and reducing blood pressure has been limited. Effective pharmacotherapeutic and procedural strategies, including metabolic surgeries, are additional options to treat obesity and prevent or attenuate obesity hypertension, target organ damage, and subsequent disease. Medications can be useful for short- and long-term obesity treatment; however, prescription of these drugs is limited. Metabolic surgery is effective for producing sustained weight loss and for treating hypertension and metabolic disorders in many patients with severe obesity. Unanswered questions remain related to the mechanisms of obesity-related diseases, long-term efficacy of different treatment and prevention strategies, and timing of these interventions to prevent obesity and hypertension-mediated target organ damage. Further investigation, including randomized controlled trials, is essential to addressing these questions, and emphasis should be placed on the prevention of obesity to reduce the burden of hypertensive cardiovascular and kidney diseases and subsequent mortality.
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http://dx.doi.org/10.1161/HYP.0000000000000202DOI Listing
November 2021

Impact of New ICD Codes on Acute MI Characteristics and Outcomes: What You Call It Matters.

J Am Coll Cardiol 2021 09;78(12):1254-1256

Division of Cardiovascular Diseases, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA.

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http://dx.doi.org/10.1016/j.jacc.2021.07.033DOI Listing
September 2021

Intrarenal modulation of NF-κB activity attenuates cardiac injury in a swine model of CKD: a renal-cardio axis.

Am J Physiol Renal Physiol 2021 10 16;321(4):F411-F423. Epub 2021 Aug 16.

Department of Neurology, University of Mississippi Medical Center, Jackson, Mississippi.

Patients with chronic kidney disease (CKD) have a high cardiovascular mortality. CKD and heart failure (HF) coexist in up to 50% of patients, and both associate with inflammation. We aimed to define the cardiac phenotype of a novel swine model of CKD and test the hypothesis that inflammation of renal origin propels the development of precursors of HF in CKD. CKD was induced in 14 pigs, which were followed for 14 wk. Renal (multidetector computed tomography) and cardiac (echocardiography) hemodynamics were quantified before and 8 wk after single intrarenal administration of placebo or a biopolymer-fused peptide inhibitor of NF-κB that blocks NF-κB activity and decreases inflammatory activity (SynB1-ELP-p50i). Blood was collected to quantify cytokines (TNF-α, monocyte chemoattractant protein-1, and interleukins), markers of inflammation (C-reactive protein), and biomarkers of HF (atrial and brain natriuretic peptides). Pigs were then euthanized, and kidneys and hearts were studied ex vivo. Normal pigs were used as time-matched controls. Renal dysfunction in CKD was accompanied by cardiac hypertrophy and fibrosis, diastolic dysfunction, increased renal and cardiac expression of TNF-α, monocyte chemoattractant protein-1, and interleukins, canonical and noncanonical mediators of NF-κB signaling, circulating inflammatory factors, and biomarkers of HF. Notably, most of these changes were improved after intrarenal SynB1-SynB1-ELP-p50i, although cardiac inflammatory signaling remained unaltered. The translational traits of this model support its use as a platform to test novel technologies to protect the kidney and heart in CKD. A targeted inhibition of renal NF-κB signaling improves renal and cardiac function, suggesting an inflammatory renal-cardio axis underlying early HF pathophysiology in CKD. Chronic kidney disease (CKD) is a progressive disorder with high cardiovascular morbidity and mortality. This work supports the role of inflammatory cytokines of renal origin in renal-cardio pathophysiology in CKD and that the heart may be a target. Furthermore, it supports the feasibility of a new strategy in a translational fashion, using targeted inhibition of renal NF-κB signaling to offset the development of cardiac injury in CKD.
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http://dx.doi.org/10.1152/ajprenal.00158.2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8560407PMC
October 2021

Gender differences in perceived stress and coping among college students.

PLoS One 2021 12;16(8):e0255634. Epub 2021 Aug 12.

Campus Recreation Department, Florida Atlantic University, Boca Raton, Florida, United States of America.

Background: Many college students register each semester for courses, leading to productive careers and fulfilled lives. During this time, the students have to manage many stressors stemming from academic, personal, and, sometimes, work lives. Students, who lack appropriate stress management skills, may find it difficult to balance these responsibilities.

Objectives: This study examined stress, coping mechanisms, and gender differences in undergraduate students towards the end of the semester.

Design And Method: University students (n = 448) enrolled in three different undergraduate exercise science courses were assessed. Two instruments, the Perceived Stress Scale and Brief Cope, were administered during the twelfth week of the semester, four weeks prior to final exams. T-tests were used to detect gender differences for the stress levels and coping strategies.

Results: Overall, females indicated higher levels of stress than their male counterparts. Gender differences were evident in both coping dimensions and individual coping strategies used. Females were found to utilize the emotion-focused coping dimension and endorsed the use of four coping strategies more often than males. These included self-distraction, emotional support, instrumental support, and venting.

Conclusions: This research adds to the existing literature by illuminating the level of perceived stress and different coping strategies used by undergraduate female and male students. In turn, students may need educational interventions to develop effective and healthy coping strategies to last a lifetime. Faculty and other university officials may want to highlight and understand these various factors to protect the students' wellbeing in their classes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255634PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360537PMC
December 2021

Prognostic value of shock index in patients admitted with non-ST-segment elevation myocardial infarction: the ARIC study community surveillance.

Eur Heart J Acute Cardiovasc Care 2021 Oct;10(8):869-877

Joint Department of Biomedical Engineering, University of North Carolina and North Carolina State University, 104 Mason Farm Rd., Chapel Hill, NC 27599, USA.

Aims: Shock index (SI), defined as the ratio of heart rate (HR) to systolic blood pressure (SBP), is easily obtained and predictive of mortality in patients with ST-segment elevation myocardial infarction. However, large-scale evaluations of SI in patients with non-ST-segment elevation myocardial infarction (NSTEMI) are lacking.

Methods And Results: Hospitalizations for acute myocardial infarction were sampled from four US areas by the Atherosclerosis Risk in Communities (ARIC) study and classified by physician review. Shock index was derived from the HR and SBP at first presentation and considered high when ≥0.7. From 2000 to 2014, 18 301 weighted hospitalizations for NSTEMI were sampled and had vitals successfully obtained. Of these, 5753 (31%) had high SI (≥0.7). Patients with high SI were more often female (46% vs. 39%) and had more prevalent chronic kidney disease (40% vs. 32%). TIMI (Thrombolysis in Myocardial Infarction) risk scores were similar between the groups (4.3 vs. 4.2), but GRACE (Global Registry of Acute Coronary Syndrome) score was higher with high SI (140 vs. 118). Angiography, revascularization, and guideline-directed medications were less often administered to patients with high SI, and the 28-day mortality was higher (13% vs. 5%). Prediction of 28-day mortality by SI as a continuous measurement [area under the curve (AUC): 0.68] was intermediate to that of the GRACE score (AUC: 0.87) and the TIMI score (AUC: 0.54). After adjustments, patients with high SI had twice the odds of 28-day mortality (odds ratio = 2.02; 95% confidence interval: 1.46-2.80).

Conclusion: The SI is easily obtainable, performs moderately well as a predictor of short-term mortality in patients hospitalized with NSTEMI, and may be useful for risk stratification in emergency settings.
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http://dx.doi.org/10.1093/ehjacc/zuab050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8557437PMC
October 2021

Regional Adiposity and Risk of Heart Failure and Mortality: The Jackson Heart Study.

J Am Heart Assoc 2021 07 9;10(14):e020920. Epub 2021 Jul 9.

Duke Clinical Research Institute Duke University School of Medicine Durham NC.

Background Visceral adipose tissue (VAT) is associated with incident heart failure (HF) and HF with preserved ejection fraction, yet it is unknown how pericardial and abdominal adiposity affect HF and mortality risks in Black individuals. We examined the associations of pericardial adipose tissue (PAT), VAT, and subcutaneous adipose tissue (SAT) with incident HF hospitalization and all-cause mortality in a large community cohort of Black participants. Methods and Results Among the 2882 Jackson Heart Study Exam 2 participants without prevalent HF who underwent body computed tomography, we used Cox proportional hazards models to examine associations between computed tomography-derived regional adiposity and incident HF hospitalization and all-cause mortality. Fully adjusted models included demographics and cardiovascular disease risk factors. Median follow-up was 10.6 years among participants with available VAT (n=2844), SAT (n=2843), and PAT (n=1386). Fully adjusted hazard ratios (95% CIs) of distinct computed tomography-derived adiposity measures (PAT per 10 cm, VAT or SAT per 100 cm) were as follows: for incident HF, PAT 1.08 (95% CI, 1.02-1.14) and VAT 1.04 (95% CI, 1.01-1.08); for HF with preserved ejection fraction, PAT 1.13 (95% CI, 1.04-1.21) and VAT 1.07 (95% CI, 1.01-1.13); for mortality, PAT 1.07 (95% CI, 1.03-1.12) and VAT 1.01 (95% CI, 0.98-1.04). SAT was not associated with either outcome. Conclusions High PAT and VAT, but not SAT, were associated with incident HF and HF with preserved ejection fraction, and only PAT was associated with mortality in the fully adjusted models in a longitudinal community cohort of Black participants. Future studies may help understand whether changes in regional adiposity improves HF, particularly HF with preserved ejection fraction, risk predictions. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00005485.
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http://dx.doi.org/10.1161/JAHA.121.020920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8483488PMC
July 2021

Physical Activity, Subclinical Myocardial Injury, and Risk of Heart Failure Subtypes in Black Adults.

JACC Heart Fail 2021 07 9;9(7):484-493. Epub 2021 Jun 9.

Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA. Electronic address:

Objectives: This study sought to evaluate the independent associations and interactions between high-sensitivity cardiac troponin I (hs-cTnI) and physical activity (PA) with risk of heart failure (HF) subtypes, HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF).

Background: Black adults are at high risk for developing HF. Physical inactivity and subclinical myocardial injury, as assessed by hs-cTnI concentration, are independent risk factors for HF.

Methods: Black adults from the Jackson Heart Study without prevalent HF who had hs-cTnI concentration and self-reported PA assessed at baseline were included. Adjusted Cox models were used to evaluate the independent and joint associations and interaction between hs-cTnI concentrations and PA with risk of HFpEF and HFrEF.

Results: Among 3,959 participants, 25.1% had subclinical myocardial injury (hs-cTnI ≥4 and ≥6 ng/l in women and men, respectively), and 48.2% were inactive (moderate-to-vigorous PA = 0 min/week). Over 12.0 years of follow-up, 163 and 150 participants had an incident HFpEF and HFrEF event, respectively. In adjusted analysis, higher hs-cTnI concentration (per 1-U log increase) was associated with higher risk of HFpEF (hazard ratio [HR]: 1.47; 95% confidence interval [CI]: 1.25 to 1.72]) and HFrEF (HR: 1.57; 95% CI: 1.35 to 1.83]). In contrast, higher PA (per 1-U log increase) was associated with a lower risk of HFpEF (HR: 0.93; 95% CI: 0.88 to 0.99]) but not HFrEF. There was a significant interaction between hs-cTnI and PA for risk of HFpEF (p interaction = 0.04) such that inactive participants with subclinical myocardial injury were at higher risk of HFpEF but active participants were not.

Conclusions: Among Black adults with subclinical myocardial injury, higher levels of PA were associated with attenuated risk of HFpEF.
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http://dx.doi.org/10.1016/j.jchf.2021.04.003DOI Listing
July 2021

HuR brings the heat: linking adipose tissue to cardiac dysfunction.

Am J Physiol Heart Circ Physiol 2021 07 11;321(1):H214-H216. Epub 2021 Jun 11.

Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi.

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http://dx.doi.org/10.1152/ajpheart.00305.2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321811PMC
July 2021

Insights From MESA (Multi-Ethnic Study of Atherosclerosis): Into the Crypts of Fat.

J Am Coll Cardiol 2021 06;77(21):2653-2655

Division of Cardiovascular Diseases, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA.

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http://dx.doi.org/10.1016/j.jacc.2021.04.007DOI Listing
June 2021

Multiomic Profiling in Black and White Populations Reveals Novel Candidate Pathways in Left Ventricular Hypertrophy and Incident Heart Failure Specific to Black Adults.

Circ Genom Precis Med 2021 06 21;14(3):e003191. Epub 2021 May 21.

Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA (D.H.K., U.A.T., D.N., M.D.B., X.S., M.J.K., D.S., M.H., J.M.R., Z.-Z.C., D.E.C., B.P., J.G.W., R.E.G.).

Background: Increased left ventricular (LV) mass is associated with adverse cardiovascular events including heart failure (HF). Both increased LV mass and HF disproportionately affect Black individuals. To understand the underlying mechanisms, we undertook a proteomic screen in a Black cohort and compared the findings to results from a White cohort.

Methods: We measured 1305 plasma proteins using the SomaScan platform in 1772 Black participants (mean age, 56 years; 62% women) in JHS (Jackson Heart Study) with LV mass assessed by 2-dimensional echocardiography. Incident HF was assessed in 1600 participants. We then compared protein associations in JHS to those observed in White participants from FHS (Framingham Heart Study; mean age, 54 years; 56% women).

Results: In JHS, there were 110 proteins associated with LV mass and 13 proteins associated with incident HF hospitalization with false discovery rate <5% after multivariable adjustment. Several proteins showed expected associations with both LV mass and HF, including NT-proBNP (N-terminal pro-B-type natriuretic peptide; β=0.04; =2×10; hazard ratio, 1.48; =0.0001). The strongest association with LV mass was novel: LKHA4 (leukotriene-A4 hydrolase; β=0.05; =5×10). This association was confirmed on an alternate proteomics platform and further supported by related metabolomic data. Fractalkine/CX3CL1 (C-X3-C Motif Chemokine Ligand 1) showed a novel association with incident HF (hazard ratio, 1.32; =0.0002). While established biomarkers such as cystatin C and NT-proBNP showed consistent associations in Black and White individuals, LKHA4 and fractalkine were significantly different between the two groups.

Conclusions: We identified several novel biological pathways specific to Black adults hypothesized to contribute to the pathophysiologic cascade of LV hypertrophy and incident HF including LKHA4 and fractalkine.
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http://dx.doi.org/10.1161/CIRCGEN.120.003191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497179PMC
June 2021

Diagnosis, Education, and Care of Patients with -Associated Nephropathy: A Delphi Consensus and Systematic Review.

J Am Soc Nephrol 2021 Apr 14. Epub 2021 Apr 14.

Department of Bioethics and Humanities, University of Washington, Seattle, Washington.

Background: variants contribute to the markedly higher incidence of ESKD in Blacks compared with Whites. Genetic testing for these variants in patients with African ancestry who have nephropathy is uncommon, and no specific treatment or management protocol for -associated nephropathy currently exists.

Methods: A multidisciplinary, racially diverse group of 14 experts and patient advocates participated in a Delphi consensus process to establish practical guidance for clinicians caring for patients who may have -associated nephropathy. Consensus group members took part in three anonymous voting rounds to develop consensus statements relating to the following: () counseling, genotyping, and diagnosis; () disease awareness and education; and () a vision for management of -associated nephropathy in a future when treatment is available. A systematic literature search of the MEDLINE and Embase databases was conducted to identify relevant evidence published from January 1, 2009 to July 14, 2020.

Results: The consensus group agreed on 55 consensus statements covering such topics as demographic and clinical factors that suggest a patient has -associated nephropathy, as well as key considerations for counseling, testing, and diagnosis in current clinical practice. They achieved consensus on the need to increase awareness among key stakeholders of racial health disparities in kidney disease and of -associated nephropathy and on features of a successful education program to raise awareness among the patient community. The group also highlighted the unmet need for a specific treatment and agreed on best practice for management of these patients should a treatment become available.

Conclusions: A multidisciplinary group of experts and patient advocates defined consensus-based guidance on the care of patients who may have -associated nephropathy.
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http://dx.doi.org/10.1681/ASN.2020101399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425659PMC
April 2021

Development and Validation of Machine Learning-Based Race-Specific Models to Predict 10-Year Risk of Heart Failure: A Multicohort Analysis.

Circulation 2021 06 13;143(24):2370-2383. Epub 2021 Apr 13.

Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas (M.W.S., K.V.P., A.C., C.A., S.R., J.A.d.L., A.P.).

Background: Heart failure (HF) risk and the underlying risk factors vary by race. Traditional models for HF risk prediction treat race as a covariate in risk prediction and do not account for significant parameters such as cardiac biomarkers. Machine learning (ML) may offer advantages over traditional modeling techniques to develop race-specific HF risk prediction models and to elucidate important contributors of HF development across races.

Methods: We performed a retrospective analysis of 4 large, community cohort studies (ARIC [Atherosclerosis Risk in Communities], DHS [Dallas Heart Study], JHS [Jackson Heart Study], and MESA [Multi-Ethnic Study of Atherosclerosis]) with adjudicated HF events. The study included participants who were >40 years of age and free of HF at baseline. Race-specific ML models for HF risk prediction were developed in the JHS cohort (for Black race-specific model) and White adults from ARIC (for White race-specific model). The models included 39 candidate variables across demographic, anthropometric, medical history, laboratory, and electrocardiographic domains. The ML models were externally validated and compared with prior established traditional and non-race-specific ML models in race-specific subgroups of the pooled MESA/DHS cohort and Black participants of ARIC. The Harrell C-index and Greenwood-Nam-D'Agostino χ tests were used to assess discrimination and calibration, respectively.

Results: The ML models had excellent discrimination in the derivation cohorts for Black (n=4141 in JHS, C-index=0.88) and White (n=7858 in ARIC, C-index=0.89) participants. In the external validation cohorts, the race-specific ML model demonstrated adequate calibration and superior discrimination (Black individuals, C-index=0.80-0.83; White individuals, C-index=0.82) compared with established HF risk models or with non-race-specific ML models derived with race included as a covariate. Among the risk factors, natriuretic peptide levels were the most important predictor of HF risk across both races, followed by troponin levels in Black and ECG-based Cornell voltage in White individuals. Other key predictors of HF risk among Black individuals were glycemic parameters and socioeconomic factors. In contrast, prevalent cardiovascular disease and traditional cardiovascular risk factors were stronger predictors of HF risk in White adults.

Conclusions: Race-specific and ML-based HF risk models that integrate clinical, laboratory, and biomarker data demonstrated superior performance compared with traditional HF risk and non-race-specific ML models. This approach identifies distinct race-specific contributors of HF.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.053134DOI Listing
June 2021

Cigarette Smoking, Incident Coronary Heart Disease, and Coronary Artery Calcification in Black Adults: The Jackson Heart Study.

J Am Heart Assoc 2021 04 23;10(7):e017320. Epub 2021 Mar 23.

Department of Medicine University of Mississippi Medical Center Jackson MS.

Background Although Black adults are more likely to die from coronary heart disease (CHD) compared with White adults, few studies have examined the relationship between cigarette smoking and CHD risk among Black adults. We evaluated the relationship between cigarette smoking, incident CHD, and coronary artery calcification in the JHS (Jackson Heart Study). Methods and Results We classified JHS participants without a history of CHD (n=4432) by self-reported baseline smoking status into current, former (smoked at least 400 cigarettes/life) or never smokers at baseline (2000-2004). We further classified current smokers by smoking intensity (number of cigarettes smoked per day [1-19 or ≥20]) and followed for incident CHD (through 2016). Hazard ratios (HR) for incident CHD for each smoking group compared with never smokers were estimated with adjusted Cox proportional hazard regression models. At baseline, there were 548 (12.4%) current, 782 (17.6%) former, and 3102 (70%) never smokers. During follow-up (median, 13.8 years), 254 participants developed CHD. After risk factor adjustment, CHD risk was significantly higher in current smokers compared with never smokers (HR, 2.11; 95% CI, 1.39-3.18); the difference between former smokers and never smokers (HR, 1.37; 95% CI, 1.0-1.90) did not achieve statistical significance. Among current smokers, we did not observe a dose-response effect for CHD risk. Additionally, in multivariable logistic regression models with a subset of our analytic cohort, current smokers had greater odds of coronary artery calcification score >0 compared with never smokers (odds ratio, 2.63; 95% CI, 1.88-3.68). Conclusions In a large prospective cohort of Black adults, current smoking was associated with a >2-fold increased risk of CHD over a median follow-up of greater than a decade.
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http://dx.doi.org/10.1161/JAHA.120.017320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174312PMC
April 2021

Direct Cardiac Actions of the Sodium Glucose Co-Transporter 2 Inhibitor Empagliflozin Improve Myocardial Oxidative Phosphorylation and Attenuate Pressure-Overload Heart Failure.

J Am Heart Assoc 2021 03 13;10(6):e018298. Epub 2021 Mar 13.

Department of Physiology and Biophysics Mississippi Center for Obesity ResearchMississippi Center for Heart ResearchUniversity of Mississippi Medical Center Jackson MS.

Background We determined if the sodium glucose co-transporter 2 inhibitor empagliflozin attenuates pressure overload-induced heart failure in non-diabetic mellitus mice by direct cardiac effects and the mechanisms involved. Methods and Results Male C57BL/6J mice (4-6 months of age) were subjected to sham surgeries or transverse aortic constriction to produce cardiac pressure overload. Two weeks after transverse aortic constriction, empagliflozin (10 mg/kg per day) or vehicle was administered daily for 4 weeks. Empagliflozin increased survival rate and significantly attenuated adverse left ventricle remodeling and cardiac fibrosis after transverse aortic constriction. Empagliflozin also attenuated left ventricular systolic and diastolic dysfunction, evaluated by echocardiography, and increased exercise endurance by 36% in mice with transverse aortic constriction-induced heart failure. Empagliflozin significantly increased glucose and fatty acid oxidation in failing hearts, while reducing glycolysis. These beneficial cardiac effects of empagliflozin occurred despite no significant changes in fasting blood glucose, body weight, or daily urine volume. In vitro experiments in isolated cardiomyocytes indicated that empagliflozin had direct effects to improve cardiomyocyte contractility and calcium transients. Importantly, molecular docking analysis and isolated perfused heart experiments indicated that empagliflozin can bind cardiac glucose transporters to reduce glycolysis, restore activation of adenosine monophosphate-activated protein kinase and inhibit activation of the mammalian target of rapamycin complex 1 pathway. Conclusions Our study demonstrates that empagliflozin may directly bind glucose transporters to reduce glycolysis, rebalance coupling between glycolysis and oxidative phosphorylation, and regulate the adenosine monophosphate-activated protein kinase mammalian target of rapamycin complex 1 pathway to attenuate adverse cardiac remodeling and progression of heart failure induced by pressure-overload in non-diabetic mellitus mice.
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http://dx.doi.org/10.1161/JAHA.120.018298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174202PMC
March 2021

Physical Activity, Inflammation, Coronary Artery Calcification, and Incident Coronary Heart Disease in African Americans: Insights From the Jackson Heart Study.

Mayo Clin Proc 2021 04 10;96(4):901-911. Epub 2021 Mar 10.

Department of Medicine, University of Mississippi Medical Center, Jackson; Department of Physiology and Biophysics, Mississippi Center for Obesity Research, University of Mississippi Medical Center, Jackson.

Objective: To examine associations between physical activity (PA), inflammation, coronary artery calcification (CAC), and incident coronary heart disease (CHD) in African Americans.

Methods: Among Jackson Heart Study participants without prevalent CHD at baseline (n=4295), we examined the relationships between PA and high-sensitivity C-reactive protein, the presence of CAC (Agatston score ≥100), and incident CHD. Based on the American Heart Association's Life's Simple 7 metrics, participants were classified as having poor, intermediate, or ideal PA.

Results: After adjustment for possible confounding factors, ideal PA was associated with lower high-sensitivity C-reactive protein levels (β, -0.15; 95% CI, -0.15 to -0.002) and a lower prevalence of CAC (odds ratio, 0.70; 95% CI, 0.51-0.96) compared with poor PA. During a median of 12.8 years of follow-up, there were 164 incident CHD events (3.3/1000 person-years). Ideal PA was associated with a lower rate of incident CHD compared with poor PA (hazard ratio, 0.55; 95% CI, 0.31-0.98).

Conclusion: In a large community-based African American cohort, ideal PA was associated with lower inflammation levels, a lower prevalence of CAC, and a lower rate of incident CHD. These findings suggest that promotion of ideal PA may be an important way to reduce the risk of subclinical and future clinical CHD in African Americans.
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http://dx.doi.org/10.1016/j.mayocp.2020.09.042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026689PMC
April 2021

Interaction of Obesity and Hypertension on Cardiac Metabolic Remodeling and Survival Following Myocardial Infarction.

J Am Heart Assoc 2021 03 5;10(6):e018212. Epub 2021 Mar 5.

Department of Physiology and Biophysics University of Mississippi Medical Center Jackson MS.

Background Obesity and hypertension are risk factors for myocardial infarction (MI); however, their potential interactions on post-MI outcomes are unclear. We examined interactions of obesity and hypertensionon post-MI function, remodeling, metabolic changes, and recovery. Methods and Results Male and female C57BL/6J mice were provided standard chow or high-fat/fructose diet for 8 weeks and then infused with angiotensin II for 2 weeks to induce hypertension. MI was then induced by surgical ligation of the left coronary artery for 7 days. Obesity alone did not cause cardiac injury or exacerbate hypertension-induced cardiac dysfunction. After MI, however, obese-normotensive mice had lower survival rates compared with chow-fed mice (56% versus 89% males; 54% versus 75% females), which were further decreased by hypertension (29% males; and 35% females). Surviving obese-normotensive males displayed less left ventricular dilation and pulmonary congestion compared with chow-fed males after MI; hypertension reversed left ventricular dilation because of high-fat/fructose diet and promoted significant pulmonary congestion compared with chow-fed controls. Obese-normotensive males displayed higher left ventricular α-MHC (alpha-myosin heavy chain) protein, phosphorylated Akt (protein kinase B) and AMPK (adenosine-monophosphate activated kinase), PPAR-γ (peroxisome proliferator activated receptor gamma), and plasma adiponectin levels after MI, indicating favorable contractile and metabolic changes. However, these favorable contractile and metabolic changes were attenuated by hypertension. Obese-hypertensive males also had lower levels of collagen in the infarcted region, indicating decreased ability to promote an adaptive wound healing response to MI. Conclusions Obesity reduces post-MI survival but is associated with improved post-MI cardiac function and metabolism in surviving normotensive mice. When hypertension accompanies obesity, favorable metabolic pathways associated with obesity are attenuated and post-MI cardiac function and remodeling are adversely impacted.
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http://dx.doi.org/10.1161/JAHA.120.018212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174210PMC
March 2021

Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program.

Nature 2021 02 10;590(7845):290-299. Epub 2021 Feb 10.

The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

The Trans-Omics for Precision Medicine (TOPMed) programme seeks to elucidate the genetic architecture and biology of heart, lung, blood and sleep disorders, with the ultimate goal of improving diagnosis, treatment and prevention of these diseases. The initial phases of the programme focused on whole-genome sequencing of individuals with rich phenotypic data and diverse backgrounds. Here we describe the TOPMed goals and design as well as the available resources and early insights obtained from the sequence data. The resources include a variant browser, a genotype imputation server, and genomic and phenotypic data that are available through dbGaP (Database of Genotypes and Phenotypes). In the first 53,831 TOPMed samples, we detected more than 400 million single-nucleotide and insertion or deletion variants after alignment with the reference genome. Additional previously undescribed variants were detected through assembly of unmapped reads and customized analysis in highly variable loci. Among the more than 400 million detected variants, 97% have frequencies of less than 1% and 46% are singletons that are present in only one individual (53% among unrelated individuals). These rare variants provide insights into mutational processes and recent human evolutionary history. The extensive catalogue of genetic variation in TOPMed studies provides unique opportunities for exploring the contributions of rare and noncoding sequence variants to phenotypic variation. Furthermore, combining TOPMed haplotypes with modern imputation methods improves the power and reach of genome-wide association studies to include variants down to a frequency of approximately 0.01%.
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http://dx.doi.org/10.1038/s41586-021-03205-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875770PMC
February 2021

A Wavelet Approach to the Estimation of Left Ventricular Early Filling Wave Propagation Velocity from Color M-Mode Echocardiograms.

Ultrasound Med Biol 2021 05 2;47(5):1397-1407. Epub 2021 Feb 2.

School of Mechanical Engineering, Purdue University, West Lafayette, Indiana, USA. Electronic address:

A new approach to calculating left ventricular (LV) early filling propagation velocity (VP) from color M-mode echocardiograms using wavelet analysis is described. Current methods for measuring VP do not account for the spatiotemporal variation in VP. They are confined by empirical assumptions and user inputs that hinder the accuracy of VP, limiting its clinical utility. We evaluated three methods for measuring LV early filling: conventional VP, the strength of propagation (VS) and wavelet propagation velocity (VW) determined from the most energetically significant wave (peak VW). Group A comprised 125 patients (n = 50 normal filling, n = 25 impaired relaxation, n = 25 pseudonormal filling and n = 25 restrictive filling), and group B comprised 69 patients (n = 32 normal, n = 15 dilated and n = 22 hypertrophic). Peak VW most accurately distinguished normal from diseased patients. For group A, the area under the receiver operating characteristic curve was 0.92 for peak VW versus 0.62 for VP, 0.63 for VS and 0.58 for intraventricular pressure difference. These correspond to a 50%-70% improvement in classification ability. Similar improvements were measured in group B. Peak VW may provide a more accurate evaluation of diastolic function than standard methods and enable better diagnostic classification of patients with diastolic dysfunction.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2021.01.009DOI Listing
May 2021

Metabolomic Profiles and Heart Failure Risk in Black Adults: Insights From the Jackson Heart Study.

Circ Heart Fail 2021 01 19;14(1):e007275. Epub 2021 Jan 19.

Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (U.A.T., D.H.K., T.Z., D.N., D.E.C., J.M.R., Z.-Z.C., B.P., M.D.B., X.S., C.S., J.G.W., R.E.G.).

Background: Heart failure (HF) is a heterogeneous disease characterized by significant metabolic disturbances; however, the breadth of metabolic dysfunction before the onset of overt disease is not well understood. The purpose of this study was to determine the association of circulating metabolites with incident HF to uncover novel metabolic pathways to disease.

Methods: We performed targeted plasma metabolomic profiling in a deeply phenotyped group of Black adults from the JHS (Jackson Heart Study; n=2199). We related metabolites associated with incident HF to established etiological mechanisms, including increased left ventricular mass index and incident coronary heart disease. Furthermore, we evaluated differential associations of metabolites with HF with preserved ejection fraction versus HF with reduced ejection fraction.

Results: Metabolites associated with incident HF included products of posttranscriptional modifications of RNA, as well as polyamine and nitric oxide metabolism. A subset of metabolite-HF associations was independent of well-established HF pathways such as increased left ventricular mass index and incident coronary heart disease and included homoarginine (per 1 SD increase in metabolite level, hazard ratio, 0.77; =1.2×10), diacetylspermine (hazard ratio, 1.34; =3.4×10), and uridine (hazard ratio, 0.79; , 3×10). Furthermore, metabolites involved in pyrimidine metabolism (orotic acid) and collagen turnover (-methylproline) among others were part of a distinct metabolic signature that differentiated individuals with HF with preserved ejection fraction versus HF with reduced ejection fraction.

Conclusions: The integration of clinical phenotyping with plasma metabolomic profiling uncovered novel metabolic processes in nontraditional disease pathways underlying the heterogeneity of HF development in Black adults.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.007275DOI Listing
January 2021

Joint modelling of longitudinal lipids and time to coronary heart disease in the Jackson Heart Study.

BMC Med Res Methodol 2020 12 3;20(1):294. Epub 2020 Dec 3.

Department of Medicine, University of Mississippi Medical Center, 2500 N State St, Jackson, 39216, MS, USA.

Background: Multiple longitudinal responses together with time-to-event outcome are common in biomedical studies. There are several instances where the longitudinal responses are correlated with each other and at the same time each longitudinal response is associated with the survival outcome. The main purpose of this study is to present and explore a joint modeling approach for multiple correlated longitudinal responses and a survival outcome. The method will be illustrated using the Jackson Heart Study (JHS), which is one of the largest cardiovascular studies among African Americans.

Methods: Four longitudinal responses, i.e., total cholesterol (TC), high density lipoprotein (HDL) cholesterol, triglyceride (TG) and inflammation measured by high-sensitivity C-reactive protein (hsCRP); and time-to-coronary heart disease (CHD) were considered from the JHS. The repeated lipid and hsCRP measurements from a given subject overtime are likely correlated with each other and could influence the subject's risk for CHD. A joint modeling framework is considered. To deal with the high dimensionality due to the multiple longitudinal profiles, we use a pairwise bivariate model fitting approach that was developed in the context of multivariate Gaussian random effects models. The method is further explored through simulations.

Results: The proposed model performed well in terms of bias and relative efficiency. The JHS data analysis showed that lipid and hsCRP trajectories could exhibit interdependence in their joint evolution and have impact on CHD risk.

Conclusions: We applied a unified and flexible joint modeling approach to analyze multiple correlated longitudinal responses and survival outcome. The method accounts for the correlation among the longitudinal responses as well as the association between each longitudinal response and the survival outcome at once. This helps to explore how the combination of multiple longitudinal trajectories could be related to the survival process.
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http://dx.doi.org/10.1186/s12874-020-01177-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713018PMC
December 2020

Consensus-Based Technical Recommendations for Clinical Translation of Renal Phase Contrast MRI.

J Magn Reson Imaging 2022 Feb 2;55(2):323-335. Epub 2020 Nov 2.

Department of Bioengineering, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy.

Background: Phase-contrast (PC) MRI is a feasible and valid noninvasive technique to measure renal artery blood flow, showing potential to support diagnosis and monitoring of renal diseases. However, the variability in measured renal blood flow values across studies is large, most likely due to differences in PC-MRI acquisition and processing. Standardized acquisition and processing protocols are therefore needed to minimize this variability and maximize the potential of renal PC-MRI as a clinically useful tool.

Purpose: To build technical recommendations for the acquisition, processing, and analysis of renal 2D PC-MRI data in human subjects to promote standardization of renal blood flow measurements and facilitate the comparability of results across scanners and in multicenter clinical studies.

Study Type: Systematic consensus process using a modified Delphi method.

Population: Not applicable.

Sequence Field/strength: Renal fast gradient echo-based 2D PC-MRI.

Assessment: An international panel of 27 experts from Europe, the USA, Australia, and Japan with 6 (interquartile range 4-10) years of experience in 2D PC-MRI formulated consensus statements on renal 2D PC-MRI in two rounds of surveys. Starting from a recently published systematic review article, literature-based and data-driven statements regarding patient preparation, hardware, acquisition protocol, analysis steps, and data reporting were formulated.

Statistical Tests: Consensus was defined as ≥75% unanimity in response, and a clear preference was defined as 60-74% agreement among the experts.

Results: Among 60 statements, 57 (95%) achieved consensus after the second-round survey, while the remaining three showed a clear preference. Consensus statements resulted in specific recommendations for subject preparation, 2D renal PC-MRI data acquisition, processing, and reporting.

Data Conclusion: These recommendations might promote a widespread adoption of renal PC-MRI, and may help foster the set-up of multicenter studies aimed at defining reference values and building larger and more definitive evidence, and will facilitate clinical translation of PC-MRI.

Level Of Evidence: 1 TECHNICAL EFFICACY STAGE: 1.
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http://dx.doi.org/10.1002/jmri.27419DOI Listing
February 2022

Recurrent Admissions for Acute Decompensated Heart Failure Among Patients With and Without Peripheral Artery Disease: The ARIC Study.

J Am Heart Assoc 2020 11 26;9(21):e017174. Epub 2020 Oct 26.

Joint Department of Biomedical Engineering University of North Carolina and North Carolina State University Chapel Hill NC.

Background Peripheral artery disease (PAD) is both a common comorbidity and a contributing factor to heart failure. Whether PAD is associated with hospitalization for recurrent decompensation among patients with established heart failure is uncertain. Methods and Results Since 2005, the ARIC (Atherosclerosis Risk in Communities) study has conducted active surveillance of hospitalized acute decompensated heart failure (ADHF), with events verified by physician review. From 2005 to 2016, 1481 patients were hospitalized with ADHF and discharged alive (mean age, 78 years; 69% White). Of these, 207 (14%) had diagnosis of PAD. Those with PAD were more often men (55% versus 44%) and smokers (17% versus 8%), with a greater prevalence of coronary artery disease (72% versus 52%). Patients with PAD had an increased risk of at least 1 ADHF readmission, both within 30 days (11% versus 7%) and 1 year (39% versus 28%) of discharge from the index hospitalization. After adjustments, PAD was associated with twice the hazard of ADHF readmission within 30 days (HR, 2.02; 95% CI, 1.14-3.60) and a 60% higher hazard of ADHF readmission within 1 year (HR, 1.60; 95% CI, 1.25-2.05). The 1-year hazard of ADHF readmission associated with PAD was stronger with heart failure with reduced ejection fraction (HR, 2.01; 95% CI, 1.29-3.13) than preserved ejection fraction (HR, 1.04; 95% CI, 0.69-1.56); for interaction=0.05. Conclusions Patients with ADHF and concomitant PAD have a higher likelihood of ADHF readmission. Strategies to prevent ADHF readmissions in this high-risk group are warranted.
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http://dx.doi.org/10.1161/JAHA.120.017174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763414PMC
November 2020

Relation of Low Normal Left Ventricular Ejection Fraction to Heart Failure Hospitalization in Blacks (From the Jackson Heart Study).

Am J Cardiol 2020 12 8;136:100-106. Epub 2020 Sep 8.

Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi.

There is no clear consensus on a lower cutoff value for normal left ventricular ejection fraction (EF) and the prognostic implications of low normal EF (LNEF) are poorly understood, particularly in Blacks. Therefore, we investigated the association of LNEF and incident heart failure (HF) in a community-based cohort of Blacks. We studied 3,669 participants (mean age 54 years, 63% women) of the Jackson Heart Study without prevalent HF or coronary heart disease (CHD). Participants were divided into three groups: (1) Reduced EF (<50%), (2) LNEF (≥50%, <55%), and (3) Normal EF (≥55%). There were 197 cases of incident HF hospitalizations over a median follow-up of 10 years (interquartile range 9.4 to 10). After adjustment for conventional risk factors and incident CHD, the LNEF group had a higher rate of incident HF hospitalization than the Normal EF group (HR 1.58, 95% CI 1.04 to 2.38, p<0.05). Furthermore, this relation remained statistically significant after additionally adjusting for LV mass index but was not significant after adjusting for LV diastolic dysfunction grade. In participants with LNEF with incident HF, 63% developed HF with reduced EF and 37% developed HF with preserved EF. In conclusion, LNEF is associated with higher risk of incident HF hospitalization in comparison with normal EF in a community-based cohort of Blacks. In those with LNEF who went on to develop HF, most cases were HF with reduced EF. These findings suggest that strategies are needed for risk stratification and management to improve outcomes in patients with LNEF.
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http://dx.doi.org/10.1016/j.amjcard.2020.08.025DOI Listing
December 2020

Clinical Associations of Vascular Stiffness, Microvascular Dysfunction, and Prevalent Cardiovascular Disease in a Black Cohort: The Jackson Heart Study.

J Am Heart Assoc 2020 09 2;9(18):e017018. Epub 2020 Sep 2.

Department of Medicine Division of Cardiovascular Diseases University of Mississippi Medical Center Jackson MS.

Background Measures of vascular dysfunction are related to adverse cardiovascular disease (CVD) outcomes in non-Hispanic, White populations; however, data from Black individuals are limited. We aimed to investigate the associations between novel hemodynamic measures and prevalent CVD in a sample of Black individuals. Methods and Results Among older Black participants of the Jackson Heart Study, we assessed noninvasive vascular hemodynamic measures using arterial tonometry and Doppler ultrasound. We assessed 5 measures of aortic stiffness and wave reflection (carotid-femoral pulse wave velocity, pulse wave velocity ratio, forward pressure wave amplitude, central pulse pressure, and augmentation index), and 2 measures of microvascular function (baseline and hyperemic brachial flow velocity). Using multivariable logistic regression models, we examined the relations between vascular hemodynamic measures and prevalent CVD. In models adjusted for traditional CVD risk factors, higher carotid-femoral pulse wave velocity (odds ratio [OR],1.25; 95% CI, 1.01-1.55; =0.04), lower augmentation index (OR, 0.84; 95% CI, 0.70-0.99; =0.05), and lower hyperemic brachial flow velocity (OR, 0.77; 95% CI, 0.65-0.90; =0.001) were associated with higher odds of CVD. After further adjustment for hypertension treatment, lower augmentation index (OR, 0.84; 95% CI, 0.70-0.99; =0.04) and hyperemic brachial flow velocity (OR, 0.79; 95% CI, 0.67-0.94; =0.006), but not carotid-femoral pulse wave velocity (OR, 1.23; 95% CI, 0.99-1.051; =0.06), were associated with higher odds of CVD. Conclusions In a sample of older Black individuals, more severe microvascular damage and aortic stiffness were associated with prevalent CVD. Further research on hemodynamic mechanisms that contribute to cardiovascular risk among older Black individuals is merited.
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http://dx.doi.org/10.1161/JAHA.120.017018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726980PMC
September 2020

Systolic overload-induced pulmonary inflammation, fibrosis, oxidative stress and heart failure progression through interleukin-1β.

J Mol Cell Cardiol 2020 09 24;146:84-94. Epub 2020 Jul 24.

Lillehei Heart Institute and Cardiovascular Division, University of Minnesota Medical School, Minneapolis, MN 55455, USA; Department of Physiology & Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA.

Chronic heart failure is associated with increased interleukin-1β (IL-1β), leukocyte infiltration, and fibrosis in the heart and lungs. Here we further studied the role of IL-1β in the transition from left heart failure to pulmonary hypertension and right ventricular hypertrophy in mice with existing left heart failure produced by transverse aortic constriction. We demonstrated that transverse aortic constriction-induced heart failure was associated with increased lung inflammation and cleaved IL-1β, and inhibition of IL-1β signaling using blocking antibodies of clone B122 effectively attenuated further decrease of left ventricular systolic function in mice with existing heart failure. We found that inhibition of IL-1β attenuated lung inflammation, inflammasome activation, fibrosis, oxidative stress, and right ventricular hypertrophy. IL-1β blocking antibodies of clone B122 also significantly attenuated lung T cell activation. Together, these data indicate that IL-1β signaling exerts a causal role for heart failure progression, or the transition from left heart failure to lung remodeling and right heart hypertrophy.
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http://dx.doi.org/10.1016/j.yjmcc.2020.07.008DOI Listing
September 2020
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