Publications by authors named "Amil M Shah"

177 Publications

APOE Polymorphism, Cardiac Remodeling, and Heart Failure in the ARIC Study.

J Card Fail 2021 Dec 26. Epub 2021 Dec 26.

From the Division of Cardiology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA; Division of Cardiology, Department of Medicine, Brigham and Women's Hospital, Boston, MA; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD; Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA; Baylor College of Medicine, Human Genome Sequencing Center, Houston, TX, USA; Department of Medicine, University of Mississippi Medical Center, Jackson, MS. Electronic address:

Background: β-amyloid has recently been discovered in the myocardium of patients with Alzheimer's disease (AD). Whether genetic variation in APOE ɛ4, a common variant associated with AD, is associated with incident heart failure (HF), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and cardiac structure and function is unknown.

Methods: and Results: We studied 15,064 white and Black ARIC participants, relating genotype status at Visit 1 (1987-1989) to incident HF hospitalization using Cox regression. At visits 2, 4, and 5, we assessed NT-proBNP levels by genotype. At visits 3 and 5, we related Aβ peptides to incident HF. At visit 5 (2011-2013, N=6251), we assessed the relationship of genotype with prevalent HF and echocardiographic parameters. The mean age was 54.7±5.8 years, 45% were men, and 73% were white. At visit 5, there was no difference in prevalent HF by genotype. APOE ε4 carriers did not have increased risk for HF hospitalization. APOE ε4 genotype was not associated with cardiac structure and function or NT-proBNP levels. Aβ peptides were not associated with incident HF after multivariable adjustment.

Conclusions: Genetic predisposition to AD through APOE ε4 is not associated with increased HF prevalence, HF hospitalization, myocardial remodeling, or biochemical evidence of HF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cardfail.2021.12.011DOI Listing
December 2021

Impact of Chronic Obstructive Pulmonary Disease in Patients With Heart Failure With Preserved Ejection Fraction: Insights From PARAGON-HF.

J Am Heart Assoc 2021 12 19;10(23):e021494. Epub 2021 Nov 19.

BHF Glasgow Cardiovascular Research CentreUniversity of Glasgow United Kingdom.

Background Little is known about the impact of chronic obstructive pulmonary disease (COPD) in patients with heart failure with preserved ejection fraction (HFpEF). Methods and Results We examined outcomes in patients with heart failure with preserved ejection fraction, according to COPD status, in the PARAGON-HF (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in Heart Failure With Preserved Ejection Fraction) trial. The primary outcome was a composite of first and recurrent hospitalizations for heart failure and cardiovascular death. Of 4791 patients, 670 (14%) had COPD. Patients with COPD were more likely to be men (58% versus 47%; <0.001) and had worse New York Heart Association functional class (class III/IV 24% versus 19%), worse Kansas City Cardiomyopathy Questionnaire Clinical Summary Scores (69 versus 76; <0.001) and more frequent history of heart failure hospitalization (54% versus 47%; <0.001). The decrement in Kansas City Cardiomyopathy Questionnaire Clinical Summary Scores with COPD was greater than for other common comorbidities. Patients with COPD had echocardiographic right ventricular enlargement, higher serum creatinine (100 μmol/L versus 96 μmol/L) and neutrophil-to-lymphocyte ratio (2.7 versus 2.5), than those without COPD. After multivariable adjustment, COPD was associated with worse outcomes: adjusted rate ratio for the primary outcome 1.51 (95% CI, 1.25-1.83), total heart failure hospitalization 1.54 (95% CI, 1.24-1.90), cardiovascular death (adjusted hazard ratio [HR], 1.42; 95% CI, 1.10-1.82), and all-cause death (adjusted HR, 1.52; 95% CI, 1.25-1.84). COPD was associated with worse outcomes than other comorbidities and Kansas City Cardiomyopathy Questionnaire Clinical Summary Scores declined more in patients with COPD than in those without. Conclusions Approximately 1 in 7 patients with heart failure with preserved ejection fraction had concomitant COPD, which was associated with greater functional limitation and a higher risk of heart failure hospitalization and death. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01920711.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.121.021494DOI Listing
December 2021

Depressive Symptoms, Cardiac Structure and Function, and Risk of Incident Heart Failure With Preserved Ejection Fraction and Heart Failure With Reduced Ejection Fraction in Late Life.

J Am Heart Assoc 2021 12 19;10(23):e020094. Epub 2021 Nov 19.

Brigham and Women's Hospital Harvard Medical School Boston MA.

Background Depressive symptoms are associated with heightened risk of heart failure (HF), but their association with cardiac function and with HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) in late life is unclear. We aimed to determine the prevalence of depression in HFpEF and in HFrEF in late life, and the association of depressive symptoms with cardiac function and incident HFpEF and HFrEF. Methods and Results We studied 6025 participants (age, 75.3±5.1 years; 59% women; 20% Black race) in the ARIC (Atherosclerosis Risk in Communities) study at visit 5 who underwent echocardiography and completed the Center for Epidemiologic Studies Depression Scale questionnaire. Among HF-free participants (n=5086), associations of Center for Epidemiologic Studies Depression Scale score with echocardiography and incident adjudicated HFpEF and HFrEF were assessed using multivariable linear and Cox proportional hazards regression. Prevalent HFpEF, but not HFrEF, was associated with a higher prevalence of depression compared with HF-free participants (<0.001 and =0.59, respectively). Among HF-free participants, Center for Epidemiologic Studies Depression Scale score was not associated with cardiac structure and function after adjusting for demographics and comorbidities (all >0.05). Over 5.5-year follow-up, higher Center for Epidemiologic Studies Depression Scale score was associated with heightened risk of incident HFpEF (hazard ratio [HR] [95% CI], 1.06 [1.04-1.12]; =0.02), but not HFrEF (HR [95% CI], 1.02 [0.96-1.08]; =0.54), independent of echocardiographic measures, NT-proBNP (N-terminal pro-B-type natriuretic peptide), troponin, and hs-CRP (high-sensitivity C-reactive protein) (HR [95% CI], 1.06 [1.00-1.12]; =0.04). Conclusions Worse depressive symptoms predict incident HFpEF in late life, independent of common comorbidities, cardiac structure and function, and prognostic biomarkers. Further studies are necessary to understand the mechanisms linking depression to risk of HFpEF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.120.020094DOI Listing
December 2021

Differences in Left Atrial Size and Function and Supraventricular Ectopy Between Black and White Participants in the ARIC Study.

J Am Heart Assoc 2021 11 29;10(21):e021723. Epub 2021 Oct 29.

Cardiovascular Division Department of Medicine University of Minnesota Medical School Minneapolis MN.

Background Black Americans have more atrial fibrillation risk factors but lower atrial fibrillation risk than White Americans. Left atrial (LA) enlargement and/or dysfunction, frequent atrial tachycardia (AT), and premature atrial contractions (PAC) are associated with increased atrial fibrillation risk. Racial differences in these factors may exist that could explain the difference in atrial fibrillation risk. Methods and Results We included 2133 ARIC (Atherosclerosis Risk in Communities) study participants (aged 74±4.5 years[mean±SD], 59% women, 27% Black participants) who had echocardiograms in 2011 to 2013 and wore the Zio XT Patch (a 2-week continuous heart monitor) in 2016 to 2017. Linear regression was used to analyze (1) differences in AT/day or PAC/hour between Black and White participants, (2) differences in LA measures between Black and White participants, and (3) racial differences in the association of LA measures with AT or PAC frequency. Compared with White participants, Black participants had a higher prevalence of cardiovascular risk factors and disease, lower AT frequency, greater LA size, and lower LA function. After multivariable adjustments, Black participants had 37% (95% CI, 24%-47%) fewer AT runs/day than White participants. No difference in PAC between races was noted. Greater LA size and reduced LA function are associated with more AT and PAC runs; however, no race interaction was present. Conclusions Differences in LA measures are unlikely to explain the difference in atrial fibrillation risk between Black and White individuals. Despite more cardiovascular risk factors and greater atrial remodeling, Black participants have lower AT frequency than White participants. Future research is needed to elucidate the protective mechanisms that confer resilience to atrial arrhythmias in Black individuals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.121.021723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8751819PMC
November 2021

Association of Hyper-Polypharmacy With Clinical Outcomes in Heart Failure With Preserved Ejection Fraction.

Circ Heart Fail 2021 11 22;14(11):e008293. Epub 2021 Oct 22.

Minneapolis VA Center for Care Delivery and Outcomes Research and University of Minnesota Medical School (O.V.).

Background: Polypharmacy is associated with a poor prognosis in the elderly, however, information on the association of polypharmacy with cardiovascular outcomes in heart failure with preserved ejection fraction is sparse. This study sought to investigate the relationship between polypharmacy and adverse cardiovascular events in patients with heart failure with preserved ejection fraction.

Methods: Baseline total number of medications was determined in 1758 patients with heart failure with preserved ejection fraction enrolled in the Americas regions of the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist), by 3 categories: nonpolypharmacy (<5 medications), polypharmacy (5-9), and hyper-polypharmacy (≥10). We examined the relationship of polypharmacy status with the primary outcome (cardiovascular death, HF hospitalization, or aborted cardiac arrest), hospitalizations for any reason, and serious adverse events.

Results: The proportion of patients taking 5 or more medications was 92.5% (inclusive of polypharmacy [38.7%] and hyper-polypharmacy [53.8%]). Over a 2.9-year median follow-up, compared with patients with polypharmacy, hyper-polypharmacy was associated with an increased risk for the primary outcome, hospitalization for any reason and any serious adverse events in the univariable analysis, but not significantly associated with mortality. After multivariable adjustment for demographic and comorbidities, hyper-polypharmacy remained significantly associated with an increased risk for hospitalization for any reason (hazard ratio, 1.22 [95% CI, 1.05-1.41]; =0.009) and any serious adverse events (hazard ratio, 1.23 [95% CI, 1.07-1.42]; =0.005), whereas the primary outcome was no longer statistically significant.

Conclusions: Hyper-polypharmacy was common and associated with an elevated risk of hospitalization for any reason and any serious adverse events in patients with heart failure with preserved ejection fraction. There were no significant associations between polypharmacy status and mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.008293DOI Listing
November 2021

Associations of the Dietary Approaches to Stop Hypertension dietary pattern with cardiac structure and function.

Nutr Metab Cardiovasc Dis 2021 Nov 9;31(12):3345-3351. Epub 2021 Sep 9.

Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, USA.

Background And Aims: Various food groups have been associated with measures of left ventricular geometry and function. Whether the Dietary Approaches to Stop Hypertension (DASH) dietary pattern in mid-life is associated with a favorable cardiac structure and function later in life is unknown.

Methods And Results: The study population consisted of the Atherosclerosis Risk in Communities study participants free of cardiovascular disease at study visit 3 in 1993-1995. Dietary intake was assessed by food frequency questionnaire at study visits 1 (1987-1989) and 3 (1993-1995). Participants who underwent transthoracic echocardiograms at the Jackson field center at visit 3 (n = 1974) and at all field centers at study visit 5 (2011-2013; n = 4651) were included in this study. General linear regression was used to evaluate associations between dietary intake and markers of cardiac structure and function adjusting for potential confounders. Higher DASH score was associated with lower left ventricle mean wall thickness and higher absolute value of longitudinal strain at visit 5 (p = 0.004 and < 0.001, respectively).

Conclusion: The DASH dietary pattern in midlife was favorably associated with left ventricle structure and systolic function later in life. These results emphasize the importance of adhering to a healthy eating plan as one lifestyle measure to preserve cardiac structure and function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.numecd.2021.08.050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8605993PMC
November 2021

Resistance to antihypertensive treatment and long-term risk: The Atherosclerosis Risk in Communities study.

J Clin Hypertens (Greenwich) 2021 10 21;23(10):1887-1896. Epub 2021 Sep 21.

Minneapolis VA Health Care System and University of Minnesota, Minneapolis, MN, USA.

More stringent blood pressure (BP) goals have led to greater prevalence of apparent resistant hypertension (ARH), yet the long-term prognostic impact of ARH diagnosed according to these goals in the general population remains unknown. We assessed the prognostic impact of ARH according to contemporary BP goals in 9612 participants of the Atherosclerosis Risk in Communities (ARIC) study without previous cardiovascular disease. ARH, defined as BP above goal (traditional goal <140/90 mmHg, more stringent goal <130/80 mmHg) despite the use of ≥3 antihypertensive drug classes or any BP with ≥4 antihypertensive drug classes (one of which was required to be a diuretic) was compared with controlled hypertension (BP at goal with 1-3 antihypertensive drug classes). Cox regression models were adjusted for age, sex, race, study center, BMI, heart rate, smoking, eGFR, LDL, HDL, triglycerides, and diabetes. Using the traditional BP goal, 133 participants (3.8% of the treated) had ARH. If the more stringent BP goal was instead applied, 785 participants (22.6% of the treated) were reclassified from controlled hypertension to uncontrolled hypertension (n = 725) or to ARH (n = 60). Over a median follow-up time of 19 years, ARH was associated with increased risk for a composite end point (all-cause mortality, hospitalization for myocardial infarction, stroke, or heart failure) regardless of whether traditional (adjusted HR 1.50, 95% CI: 1.23-1.82) or more stringent (adjusted HR 1.43, 95% CI: 1.20-1.70) blood pressure goals were applied. We conclude that in patients free from cardiovascular disease, ARH predicted long-term risk regardless of whether traditional or more stringent BP criteria were applied.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jch.14269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8678845PMC
October 2021

Prognostic Value of Minimal Left Atrial Volume in Heart Failure With Preserved Ejection Fraction.

J Am Heart Assoc 2021 08 30;10(15):e019545. Epub 2021 Jul 30.

Cardiovascular Division Brigham and Women's Hospital and Harvard Medical School Boston MA.

Background Maximal left atrial (LA) volume is reported by most echocardiography laboratories and is associated with clinical outcomes in patients with heart failure (HF). Recent studies suggest that minimal LA volume may better reflect left ventricular filling pressure and may be more prognostic than maximal LA volume. This study assessed the prognostic value of indexed minimal LA volume (LAVImin) in patients with HF with preserved ejection fraction. Methods and Results We assessed the relationship of LAVImin with a primary composite end point of cardiovascular death, aborted cardiac death, or HF hospitalization in 347 patients with HF with preserved ejection fraction enrolled from the Americas region in TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial). We compared LAVImin with indexed maximal LA volume with respect to their prognostic values. In addition, we assessed if LA functional parameters provide additional prognostic information over LAVImin. During a median follow-up of 2.5 years, 107 patients (31%) experienced a primary composite end point. LAVImin was associated with increased risk of a primary composite outcome (hazard ratio [HR], 1.35; 95% CI, 1.12-1.61) and HF hospitalization alone (HR, 1.42; 95% CI, 1.17-1.71) after adjusting for clinical confounders and ejection fraction. In contrast, indexed maximal LA volume was not related to the primary composite outcome, but related to HF alone (HR, 1.25; 95% CI, 1.02-1.54). In comparison with indexed maximal LA volume, LAVImin was significantly more prognostic for primary composite outcome ( for comparison=0.032). Both LA emptying fraction and LA strain were prognostic of primary outcome independent of LAVImin (all <0.05). Conclusions In patients with HF with preserved ejection fraction, LAVImin was more predictive of cardiovascular outcome than indexed maximal LA volume, suggesting this measure may be more physiologically relevant and might better identify patients at high risk for cardiovascular events. LA functional parameters provide prognostic information independent of LAVImin. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00094302.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.120.019545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8475710PMC
August 2021

Mid- to Late-Life Inflammation and Risk of Cardiac Dysfunction, HFpEF and HFrEF in Late Life.

J Card Fail 2021 12 25;27(12):1382-1392. Epub 2021 Jul 25.

Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. Electronic address:

Background: Epidemiologic data supporting the association of accumulated inflammation from mid- to late life with late-life risk of cardiac dysfunction and heart failure (HF) is limited.

Methods And Results: Among 4011 participants in the Atherosclerosis Risk in Communities study who were free of prevalent cardiovascular disease at study Visit 5, accumulated inflammation was defined as time-averaged high-sensitivity c-reactive protein (hsCRP) over 3 visits spanning 1990 to 2013. Associations with left ventricular (LV) function at Visit 5 and with incident adjudicated HF post Visit 5 were assessed using linear and Cox regression, adjusting for demographics and comorbidities. Higher accumulated hsCRP was associated with greater LV mass index, lower e', higher E/e', and higher adjusting for demographics (all P ≤0.01), but only with higher pulmonary artery systolic pressure after adjustment for comorbidities (P = 0.024). At 5.3 ± 1.2 year follow-up, higher accumulated hsCRP was associated with greater risk of incident HF (HR 1.31 [95% CI 1.18-1.47], P < 0.001), HFrEF (1.26 [1.05-1.52], P = 0.01), and HFpEF (1.30 [1.11-1.53], P = 0.001) in demographic-adjusted models, but not after adjustment for comorbidities (all P > 0.10). Only Visit 5 hsCRP remained associated with incident HF (1.12 [1.02-1.24], P = 0.02) after full adjustment.

Conclusions: Greater accumulated inflammation is associated with worse LV function and heightened HF risk in late-life. These relationships are attenuated after adjusting for HF risk factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cardfail.2021.07.006DOI Listing
December 2021

Association of heart failure subtypes and atrial fibrillation: Data from the Atherosclerosis Risk in Communities (ARIC) study.

Int J Cardiol 2021 Sep 8;339:47-53. Epub 2021 Jul 8.

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA. Electronic address:

Aims: To determine the prevalence and incidence of AF among HF subtypes in a biracial community-based cohort.

Methods: We studied 6496 participants in the Atherosclerosis Risk in Community study (mean age, 75.8 ± 5.3, 59% women, 23% black) who attended the 2011-2013 visit. HF was identified from physician adjudicated diagnosis, hospital discharges, and self-report. HF subtypes were based on echocardiography. A left ventricular ejection fraction <40% represents HF with reduced ejection fraction (HFrEF), 40%-49% for HF with midrange ejection fraction (HFmEF), and ≥ 50% for HF with preserved ejection fraction (HFpEF). AF was ascertained through 2017 from study electrocardiograms, hospital discharges, and death certificates. Confounder-adjusted logistic regression and Cox models were used to estimate associations of HF subtype with prevalent and incident AF.

Results: Among eligible participants, 393 had HF (HFpEF = 232, HFmEF = 41, HFrEF = 35 and unclassified HF = 85) and 735 had AF. Compared to those without HF, all HF subtypes were more likely to have prevalent AF [odds ratio (95% confidence interval (CI)) 7.4 (5.6-9.9) for HFpEF, 8.1 (4.3-15.3) for HFmEF, 10.0 (5.0-20.2) for HFrEF, 8.8 (5.6-14.0) for unclassified HF]. Among participants without AF at baseline (n = 5761), 610 of them developed AF. Prevalent HF was associated with increased risk of AF [hazard ratio (95%CI) 2.3 (1.6-3.2) for HFpEF, 5.0 (2.7-9.3) for HFmEF, 3.5 (1.7-7.6) for HFrEF, 1.9 (0.9-3.7) for unclassified HF].

Conclusion: AF and HF frequently co-occur, with small differences by HF subtype, underscoring the importance of understanding the interplay of these two epidemics and evaluating shared preventive and therapeutic strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijcard.2021.07.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419094PMC
September 2021

Supplemental Association of Clonal Hematopoiesis With Incident Heart Failure.

J Am Coll Cardiol 2021 07;78(1):42-52

Department of Epidemiology, Brown University, Providence, Rhode Island, USA; Care New England, Center for Primary Care and Prevention, Pawtucket, Rhode Island, USA; Department of Family Medicine, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA. Electronic address:

Background: Age-related clonal hematopoiesis of indeterminate potential (CHIP), defined as clonally expanded leukemogenic sequence variations (particularly in DNMT3A, TET2, ASXL1, and JAK2) in asymptomatic individuals, is associated with cardiovascular events, including recurrent heart failure (HF).

Objectives: This study sought to evaluate whether CHIP is associated with incident HF.

Methods: CHIP status was obtained from whole exome or genome sequencing of blood DNA in participants without prevalent HF or hematological malignancy from 5 cohorts. Cox proportional hazards models were performed within each cohort, adjusting for demographic and clinical risk factors, followed by fixed-effect meta-analyses. Large CHIP clones (defined as variant allele frequency >10%), HF with or without baseline coronary heart disease, and left ventricular ejection fraction were evaluated in secondary analyses.

Results: Of 56,597 individuals (59% women, mean age 58 years at baseline), 3,406 (6%) had CHIP, and 4,694 developed HF (8.3%) over up to 20 years of follow-up. CHIP was prospectively associated with a 25% increased risk of HF in meta-analysis (hazard ratio: 1.25; 95% confidence interval: 1.13-1.38) with consistent associations across cohorts. ASXL1, TET2, and JAK2 sequence variations were each associated with an increased risk of HF, whereas DNMT3A sequence variations were not associated with HF. Secondary analyses suggested large CHIP was associated with a greater risk of HF (hazard ratio: 1.29; 95% confidence interval: 1.15-1.44), and the associations for CHIP on HF with and without prior coronary heart disease were homogenous. ASXL1 sequence variations were associated with reduced left ventricular ejection fraction.

Conclusions: CHIP, particularly sequence variations in ASXL1, TET2, and JAK2, represents a new risk factor for HF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jacc.2021.04.085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313294PMC
July 2021

Left atrial structure and function of the amyloidogenic V122I transthyretin variant in elderly African Americans.

Eur J Heart Fail 2021 08 9;23(8):1290-1295. Epub 2021 Jun 9.

Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA.

Aims: African-American carriers of the transthyretin (TTR) valine-to-isoleucine substitution (V122I) are at increased risk of heart failure, yet many have relatively subtle abnormalities of left ventricular (LV) function. We sought to explore the influence of this mutation on left atrial (LA) structure and function in this population.

Methods And Results: We assessed 1225 genotyped African-Americans (age range, 67-89 years) participating in the Atherosclerosis Risk in Communities study who underwent echocardiography and were in sinus rhythm at study Visit 5 (2011 to 2013). Six LA parameters [LA maximum/minimum volume index, ejection fraction, and LA reservoir, conduit, and contractile longitudinal strains (LS)] were compared between V122I TTR variant carriers (n = 46) and non-carriers (n = 1179). LA minimum volume index was significantly greater and LA contractile LS was worse in carriers than non-carriers (19.5 ± 10.6 mL/m vs. 16.3 ± 8.4 mL/m ; 15.0 ± 5.8% vs. 16.8 ± 5.7%, respectively, both P < 0.05). Carriers had a significantly higher number of LA abnormalities than non-carriers (1.8 ± 2.2 vs. 1.1 ± 1.6, P = 0.009). The number of subjects with at least four LA abnormalities was significantly increased among carriers compared with non-carriers (27% vs. 12%; odds ratio 2.43; 95% confidence interval 1.06-5.58 after adjusting for age, sex, body mass index, and LV wall thickness and global LS).

Conclusions: Left atrial enlargement and dysfunction were common in V122I TTR carriers with sinus rhythm than non-carriers, suggesting that abnormalities of LA function may represent early markers of subclinical disease in these individuals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ejhf.2200DOI Listing
August 2021

Combining diastolic dysfunction and natriuretic peptides to risk stratify patients with heart failure with reduced ejection fraction.

Int J Cardiol 2021 07 19;335:59-65. Epub 2021 Apr 19.

Cardiovascular Division, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.

Background: Diastolic dysfunction (DD) might help to risk stratify patients with heart failure (HF) with reduced ejection fraction (HFrEF). Nonetheless, HF guidelines/risk scores don't consider DD. We aimed to show the independent prognostic value of DD for nonfatal HF/death in patients with HFrEF on top of natriuretic peptides (NP).

Methods: We analyzed 1155 baseline echocardiograms of the MADIT-CRT study (LVEF≤30%, QRS ≥ 130 ms, NYHA class I/II), classifying DD according to 2016 ASE/EACVI classification.

Results: Patients were 64 ± 11 years-old, 24% females, LVEF was 24 ± 5%, 58% had abnormal BNP (≥100 pg/ml). While 45% had impaired relaxation, 33% had pseudonormal filling, 12% restrictive pattern, 6% indeterminate diastolic function, 4% were not classifiable due to missing data. During a follow-up of 2.1 ± 1.0 years, there were 233 HF/death. Compared to patients without pseudonormal/restrictive filling and with normal NP (23%), patients with pseudonormal/restrictive filling, alone (15%) or combined to elevated NP (30%), were at higher risk of events (respectively p = 0.025 and p < 0.001), as opposed to those with abnormal NP alone (22%; p = 0.55). Adding DD to conventional markers of risk and NP improved prediction (C-statistic 0.733 versus 0.708, p = 0.024). DD was the first parameter to be considered to risk stratify MADIT-CRT population, according to Classification-And-Regression-Tree analysis.

Conclusions: Among HFrEF patients with mild symptoms, pseudonormal/restrictive filling, either alone or combined with elevated NP, was associated with high risk of events, as opposed to isolated elevation of NP. DD provided incremental risk prediction for death/HF beyond commonly used markers. These data might suggest to integrate DD into HF guidelines/risk scores.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijcard.2021.04.028DOI Listing
July 2021

Association of Left Ventricular Systolic Function With Incident Heart Failure in Late Life.

JAMA Cardiol 2021 05;6(5):509-520

Department of Medicine, Cardiovascular Medicine Division, Brigham and Women's Hospital, Boston, Massachusetts.

Importance: Limited data exist regarding the association of subtle subclinical systolic dysfunction and incident heart failure (HF) in late life.

Objective: To assess the independent associations of subclinical impairments in systolic performance with incident HF in late life.

Design, Setting, And Participants: This study was a time-to-event analysis of participants without heart failure in the Atherosclerosis Risk in Communities (ARIC) study, a prospective, community-based cohort study, who underwent protocol echocardiography at the fifth study visit (January 1, 2011, to December 31, 2013). Findings were validated independently in participants in the Copenhagen City Heart Study (CCHS). Data analysis was performed from June 1, 2018, to February 28, 2020.

Exposures: Left ventricular ejection fraction (LVEF), longitudinal strain (LS), and circumferential strain (CS) measured by 2-dimensional and strain echocardiography.

Main Outcomes And Measures: Main outcomes were incident adjudicated HF and HF with preserved and reduced LVEF at a median follow-up of 5.5 years (interquartile range, 5.0-5.8 years). Cox proportional hazards regression models adjusted for demographics, hypertension, diabetes, obesity, smoking, coronary disease, estimated glomerular filtration rate, LV mass index, e', E/e', and left atrial volume index. Lower 10th percentile limits were determined in 374 participants free of cardiovascular disease or risk factors.

Results: Among 4960 ARIC participants (mean [SD] age, 75 [5] years; 2933 [59.0%] female; 965 [19%] Black), LVEF was less than 50% in only 76 (1.5%). In the 3552 participants with complete assessment of LVEF, LS, and CS, 983 (27.7%) had 1 or more of the following findings: LVEF less than 60%, LS less than 16.0%, or CS less than 23.7%. Modeled continuously or dichotomized, worse LVEF, LS, and CS were each independently associated with incident HF. The adjusted hazard ratio (HR) per SD decrease in LVEF was 1.41 (95% CI, 1.29-1.55); the HR for LVEF less than 60% was 2.59 (95% CI, 1.99-3.37). Similar findings were observed for continuous LS (HR, 1.37; 95% CI, 1.22-1.53) and dichotomized LS (HR, 1.93; 95% CI, 1.46-2.55) and for continuous CS (HR, 1.39; 95% CI, 1.22-1.57) and dichotomized CS (HR, 2.30; 95% CI, 1.64-3.22). Although the magnitude of risk for incident HF or death associated with impaired LVEF was greater using guideline (HR, 2.99; 95% CI, 2.19-4.09) compared with ARIC-based limits (HR, 1.88; 95% CI, 1.58-2.25), the number of participants classified as impaired was less (104 [2.1%] based on guideline thresholds compared with 692 [13.9%] based on LVEF <60%). The population-attributable risk associated with LVEF less than 60% was 11% compared with 5% using guideline-based limits, a finding replicated in 908 participants in the CCHS.

Conclusions And Relevance: These findings suggest that relatively subtle impairments of systolic function (detected based on LVEF or strain) are independently associated with incident HF and HF with reduced LVEF in late life. Current recommended assessments of LV function may substantially underestimate the prevalence of prognostically important impairments in systolic function in this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamacardio.2021.0131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970394PMC
May 2021

Layer-specific global longitudinal strain obtained by speckle tracking echocardiography for predicting heart failure and cardiovascular death following STEMI treated with primary PCI.

Int J Cardiovasc Imaging 2021 Jul 10;37(7):2207-2215. Epub 2021 Mar 10.

Cardiovascular Non-Invasive Imaging Research Laboratory, Department of Cardiology, Herlev & Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28Post 835, 2900, Copenhagengen, Denmark.

The aim of this study was to evaluate layer-specific global longitudinal strain (GLS), obtained by speckle tracking, in predicting outcomes following ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). Echocardiography, including layer-specific GLS, was performed at median two days after the STEMI in a prospective study of STEMI patients treated with pPCI between September 2006 and December 2008. The outcome was the composite of heart failure hospitalization and/or cardiovascular death (HF/CVD). A total of 349 patients were included. Mean age was 62.2 ± 11.5 years, 76% were male, and mean ejection fraction (LVEF) was 46 ± 9. Seventy-seven (22%) patients developed HF/CVD during median follow-up 5.4 years. Patients with HF/CVD had lower absolute values for all GLS-layers: endocardial (GLS) 11.4%vs 14.5% (p < 0.001), midmyocardial (GLS) 9.8% vs 12.5% (p < 0.001) and epicardial (GLS) 8.5% vs 10.9% (p < 0.001). In unadjusted analysis, all layers were significant predictors of HF/CVD; hazard ratio (HR) per 1% decrease for GLS: HR 1.18 (95%CI 1.11-1.25), GLS: HR 1.22 (95%CI 1.14-1.30) and GLS: HR 1.26 (95%CI 1.16-1.36), p < 0.0001 for all. The risk of HF/CVD increased incrementally with increasing tertiles for all layers, being more than three times higher in 3rd tertile compared to 1st tertile. In multivariable models, including baseline clinical and echocardiographic parameters, only GLS and GLS remained independent predictors of HF/CVD. Global longitudinal strain obtained from all myocardial layers were significant predictors of incident HF and CVD following STEMI, however, only GLS and GLS remained independent predictors after multivariable adjustment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10554-021-02202-6DOI Listing
July 2021

Hemodynamic Effects of Sacubitril-Valsartan Versus Enalapril in Patients With Heart Failure in the EVALUATE-HF Study: Effect Modification by Left Ventricular Ejection Fraction and Sex.

Circ Heart Fail 2021 03 5;14(3):e007891. Epub 2021 Mar 5.

Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (S.D.S., A.M.S., B.L.C., A.S.D.).

Background: Treatment with sacubitril-valsartan reduces mortality and heart failure (HF) events in HF with reduced ejection fraction and may reduce HF hospitalization in women with HF with preserved ejection fraction.

Methods: EVALUATE-HF randomized 464 participants (109 women) with HF with reduced ejection fraction to sacubitril-valsartan or enalapril for 12 weeks. Documented left ventricular ejection fraction (LVEF) ≤0.40 within the prior 12 months was required, although core laboratory LVEF>0.40 was permitted. Assessments of aortic stiffness (pulse pressure and characteristic impedance, Z) were performed at baseline and at trough and 4 hours postdose at weeks 4 and 12.

Results: In models of change from baseline adjusted for baseline value, treatment with sacubitril-valsartan produced greater overall reductions in mean arterial pressure (treatment group difference, -3.0±0.8 mm Hg, <0.001) and pulse pressure (-3.0±0.8 mm Hg, <0.001). Postdose reductions in Z were greater in the sacubitril-valsartan group (-16±6 dyne×second/cm, =0.012). Post hoc analyses found evidence of effect modification by LVEF (interaction =0.036). With LVEF<0.40, postdose reductions in Z were greater in the sacubitril-valsartan group (trough, -3±8 dyne×second/cm versus post-dose, -17±8 dyne×second/cm; interaction =0.024) with no sex difference (treatment×sex interaction, =0.3). With LVEF≥0.40, treatment with sacubitril-valsartan was associated with greater overall reductions in Z in women (women, -80±21 dyne×second/cm versus men, -20±13 dyne×second/cm; interaction =0.019).

Conclusions: In prespecified analyses that include pre- and postdose assessments at 4 and 12 weeks, treatment with sacubitril-valsartan was associated with greater postdose reductions in aortic Z. In a post hoc analysis, sacubitril-valsartan was associated with sustained reductions in Z in women with LVEF≥0.40. Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT02874794.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.007891DOI Listing
March 2021

Soluble Angiotensin-Converting Enzyme 2, Cardiac Biomarkers, Structure, and Function, and Cardiovascular Events (from the Atherosclerosis Risk in Communities Study).

Am J Cardiol 2021 05 2;146:15-21. Epub 2021 Feb 2.

Department of Medicine, Baylor College of Medicine, Houston, Texax; Center for Cardiometabolic Disease Prevention, Baylor College of Medicine, Houston, Texas. Electronic address:

Membrane-bound angiotensin-converting enzyme 2 is important in regulation of the renin-angiotensin-aldosterone system, but the association of cleaved soluble ACE2 (sACE2) with cardiovascular disease (CVD) is unclear. We evaluated the association of sACE2 with cardiac biomarkers, structure, and function and cardiovascular events in the Atherosclerosis Risk in Communities Study. sACE2 was measured in a subset of 497 participants (mean age 78±5.4 years, 53% men, 27% black); Cox regression analyses assessed prospective associations of sACE2 with time to first CVD event at median 6.1-year follow-up. sACE2 was higher in men, blacks, and participants with prevalent CVD, diabetes, or hypertension. Higher sACE2 levels were associated with significantly higher biomarkers of cardiac injury (high-sensitivity cardiac troponin I and T, N-terminal pro-B-type natriuretic peptide), greater left ventricular mass index, and impaired diastolic function in linear regression analyses, and with increased risk for heart failure hospitalization (adjusted hazard ratio per natural log unit increase [HR] 1.32, 95% confidence interval [CI] 1.10 to 1.58), CVD events (HR 1.34, 95% CI 1.13 to 1.60), and all-cause death (HR 1.26, 95% CI 1.01 to 1.57). In an elderly biracial cohort, sACE2 was positively associated with biomarkers reflecting myocardial injury and neurohormonal activation, left ventricular mass index, impaired diastolic function, CVD, events and all-cause death.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjcard.2021.01.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038970PMC
May 2021

Association of NT-ProBNP, Blood Pressure, and Cardiovascular Events: The ARIC Study.

J Am Coll Cardiol 2021 02;77(5):559-571

Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA; Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA; Center for Cardiometabolic Disease Prevention, Baylor College of Medicine, Houston, Texas, USA; Section of Cardiology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA. Electronic address:

Background: Although intensive blood pressure reduction has cardiovascular benefits, the absolute benefit is greater in those at higher cardiovascular disease (CVD) risk.

Objectives: This study examined whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) helps identify subjects at higher risk for CVD events across systolic blood pressure (SBP), diastolic blood pressure (DBP), or pulse pressure (PP) categories.

Methods: Participants from the ARIC (Atherosclerosis Risk In Communities) study visit 4 (1996 to 98) were grouped according to SBP, DBP, or PP categories and further stratified by NT-proBNP categories. Cox regression models were used to estimate hazard ratios for incident CVD (coronary heart disease, ischemic stroke, or heart failure hospitalization) and mortality across combined NT-proBNP and/or BP categories, adjusting for CVD risk factors.

Results: There were 9,309 participants (age: 62.6 ± 5.6 years; 58.3% women) with 2,416 CVD events over a median follow-up of 16.7 years. Within each SBP, DBP, or PP category, a higher category of NT-proBNP (100 to <300 or 300 pg/ml, compared with NT-proBNP <100 pg/ml) was associated with a graded increased risk for CVD events and mortality. Participants with SBP 130 to 139 mm Hg but NT-proBNP ≥300 pg/ml had a hazards ratio of 3.4 for CVD (95% confidence interval: 2.44 to 4.77) compared with a NT-proBNP of <100 pg/ml and SBP of 140 to 149 mm Hg.

Conclusions: Elevated NT-proBNP is independently associated with CVD and mortality across SBP, DBP, and PP categories and helps identify subjects at the highest risk. Participants with stage 1 hypertension but elevated NT-proBNP had greater cardiovascular risk compared with those with stage 2 SBP but lower NT-proBNP. Future studies are needed to evaluate use of biomarker-based strategies for CVD risk assessment to assist with initiation or intensification of BP treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jacc.2020.11.063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7945981PMC
February 2021

Echocardiographic measures and subsequent decline in kidney function in older adults: the Atherosclerosis Risk in Communities Study.

Eur Heart J Cardiovasc Imaging 2021 Jan 31. Epub 2021 Jan 31.

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 2024 E. Monument St., Suite 2-600, Baltimore, MD 21287, USA.

Aims : Heart failure increases the risk of kidney disease progression. However, whether cardiac function and structure are associated with the risk of incident chronic kidney disease (CKD) is not well characterized in a community setting.

Methods And Results : Among 4188 participants (mean age 75 years and 22% blacks) of the Atherosclerosis Risk in Communities Study without prevalent CKD in 2011-13, we examined the association of echocardiographic measures of left ventricular (LV) mass index, ejection fraction, left atrial volume index (LAVi), right ventricular (RV) fractional area change, and peak RV-right atrium (RA) gradient, with the subsequent risk of incident CKD, as defined by >25% decline to estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, hospitalization with CKD diagnosis, or incident end-stage kidney disease. Multivariable Cox regression models were used to estimate hazard ratios (HRs). The risk of incident CKD was monotonically increased with each of higher LV mass index [adjusted HR 2.61 (1.92-3.55) for highest quartile (Q4) vs. lowest (Q1)], lower ejection fraction [1.54 (1.17-2.04) for Q1 vs. Q4], higher LAVi [2.12 (1.56-2.89) for Q4 vs. Q1], and higher peak RV-RA gradient [2.17 (1.45-3.25) for Q4 vs. Q1] but not with RV function. The associations were consistent between subgroups by sex and race.

Conclusion : Among community-dwelling older individuals, LV mass index, ejection fraction, LAVi, and peak RV-RA gradient were independently associated with the risk of incident CKD. Our results further support that heart disease is associated with the risk of kidney disease progression and suggest the value of echocardiography for assessing cardiac and kidney health in older populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ehjci/jeaa418DOI Listing
January 2021

High-Sensitivity Cardiac Troponin, Natriuretic Peptide, and Long-Term Risk of Acute Kidney Injury: The Atherosclerosis Risk in Communities (ARIC) Study.

Clin Chem 2021 01;67(1):298-307

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Background: Cardiac markers such as high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B natriuretic peptide (NTproBNP) are predictors of developing acute kidney injury (AKI) during hospitalization for surgery or revascularization. However, their associations with the long-term risk of AKI in the general population are uncharacterized.

Methods: We conducted a prospective cohort study in 10 669 participants of the Atherosclerosis Risk in Communities Study (visit 4, 1996-1998, mean age, 63 years, 56% female, 22% black race) to examine the association of plasma concentrations of hs-cTnT and NTproBNP with the incident hospitalization with AKI. We used multivariable Cox regression analysis to estimate hazard ratios (HRs).

Results: During follow-up, 1907 participants had an incident hospitalization with AKI. Participants with higher concentrations of hs-cTnT had a higher risk of hospitalization with AKI in a graded fashion (adjusted HR, 1.88 [95%CI , 1.59-2.21] for ≥14 ng/L, 1.36 [1.18-1.57] for 9-13 ng/L, and 1.16 [1.03-1.30] for 5-8 ng/L compared to <5 ng/L). The graded association was also observed for NTproBNP (HR, 2.27 [1.93-2.68] for ≥272.7 pg/mL, 1.67 [1.45-1.93] for 142.4-272.6 pg/mL, and 1.31 [1.17-1.47] for 64.0-142.3 pg/mL compared to <64.0 pg/mL). The addition of hs-cTnT and NTproBNP to a model with established predictors significantly improved 10-year risk prediction for hospitalization with AKI (Δc-statistic, 0.015 [95%CI, 0.006-0.024]).

Conclusions: In middle-aged to older black and white adults in the community, higher concentrations of hs-cTnT and NTproBNP were robustly associated with an increased risk of hospitalization with AKI. These results suggest the usefulness of hs-cTnT and NT-proBNP to identify people at risk of AKI in the general population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/clinchem/hvaa288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793230PMC
January 2021

Associations Between Atrial Cardiopathy and Cerebral Amyloid: The ARIC-PET Study.

J Am Heart Assoc 2020 12 8;9(24):e018399. Epub 2020 Dec 8.

The Johns Hopkins University School of Medicine Baltimore MD.

Background Atrial fibrillation (AF) is a risk factor for cognitive decline, possibly from silent brain infarction. Left atrial changes in structure or function (atrial cardiopathy) can lead to AF but may impact cognition independently. It is unknown if AF or atrial cardiopathy also acts on Alzheimer disease-specific mechanisms, such as deposition of β-amyloid. Methods and Results A total of 316 dementia-free participants from the ARIC (Atherosclerosis Risk in Communities) study underwent florbetapir positron emission tomography, electrocardiography, and 2-dimensional echocardiography. Atrial cardiopathy was defined as ≥1: (1) left atrial volume index >34 mL/m; (2) P-wave terminal force >5000 µV×ms; and (3) serum NT-proBNP (N-terminal pro-B-type natriuretic peptide) >250 pg/mL. Cross-sectional associations between global cortical β-amyloid (>1.2 standardized uptake value ratio) and adjudicated history of AF and atrial cardiopathy, each, were evaluated using multivariable logistic regression. Participants (mean age, 76 years) were 56% women and 42% Black individuals. Odds of elevated florbetapir standardized uptake value ratio were significantly increased among those with atrial cardiopathy (odds ratio, 1.81; 95% CI, 1.02-3.22) and doubled for those with enlarged left atrial volume index after adjustment for demographics/risk factors (95% CI, 1.04-4.61). There was no association between P-wave terminal force or NT-proBNP and elevated florbetapir standardized uptake value ratio, nor between AF and elevated standardized uptake value ratio. Conclusions Among healthy, nondemented community-dwelling older individuals, we report an association between atrial cardiopathy, left atrial volume index, and elevated brain amyloid, by positron emission tomography, without a similar association in individuals with AF. Potential limitations include reverse causation and survival bias. Ongoing work will help determine if changes in cardiac structure and function precede or occur simultaneously with amyloid deposition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.120.018399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955392PMC
December 2020

Severe Hypoglycemia, Cardiac Structure and Function, and Risk of Cardiovascular Events Among Older Adults With Diabetes.

Diabetes Care 2021 01 16;44(1):248-254. Epub 2020 Nov 16.

Department of Epidemiology and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

Objective: To assess the association of severe hypoglycemia measured at baseline with cardiovascular disease (CVD) among community-dwelling older individuals with diabetes, a group particularly susceptible to hypoglycemia.

Research Design And Methods: We included older adults with diabetes from the Atherosclerosis Risk in Communities (ARIC) study who attended visit 5 (2011-2013, baseline). Severe hypoglycemia at baseline was defined with use of first position ICD-9 codes from hospitalizations, emergency department visits, and ambulance calls. We examined cross-sectional associations of severe hypoglycemia with echocardiographic indices of cardiac structure-function. We prospectively evaluated the risks of incident or recurrent CVD (coronary heart disease, stroke, or heart failure) and all-cause mortality, from baseline to 31 December 2018, using negative binomial and Cox regression models.

Results: Among 2,193 participants (mean [SD] age 76 [5] years, 57% female, 32% Blacks), 79 had a history of severe hypoglycemia at baseline. Severe hypoglycemia was associated with a lower left ventricular (LV) ejection fraction (adjusted β-coefficient -3.66% [95% CI -5.54, -1.78]), higher LV end diastolic volume (14.80 mL [95% CI 8.77, 20.84]), higher E-to-A ratio (0.11 [95% CI 0.03, 0.18]), and higher septal E/e' (2.48 [95% CI 1.13, 3.82]). In adjusted models, severe hypoglycemia was associated with incident or recurrent CVD (incidence rate ratio 2.19 (95% CI 1.24, 3.88]) and all-cause mortality (hazard ratio 1.71 [95% CI 1.10, 2.67]) among those without prevalent CVD.

Conclusions: Our findings suggest that a history of severe hypoglycemia is associated with alterations in cardiac function and is an important marker of future cardiovascular risk in older adults.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/dc20-0552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783928PMC
January 2021

Pulmonary vascular dysfunction among people aged over 65 years in the community in the Atherosclerosis Risk In Communities (ARIC) Study: A cross-sectional analysis.

PLoS Med 2020 10 15;17(10):e1003361. Epub 2020 Oct 15.

Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.

Background: Heart failure (HF) risk is highest in late life, and impaired pulmonary vascular function is a risk factor for HF development. However, data regarding the contributors to and prognostic importance of pulmonary vascular dysfunction among HF-free elders in the community are limited and largely restricted to pulmonary hypertension. Our objective was to define the prevalence and correlates of abnormal pulmonary pressure, resistance, and compliance and their association with incident HF and HF phenotype (left ventricular [LV] ejection fraction [LVEF] ≥ or < 50%) independent of LV structure and function.

Methods And Findings: We performed cross-sectional and time-to-event analyses in a prospective epidemiologic cohort study, the Atherosclerosis Risk in Communities study. This is an ongoing, observational study that recruited 15,792 persons aged 45-64 years between 1987 and 1989 (visit 1) from four representative communities in the United States: Minneapolis, Minnesota; Jackson, Mississippi; Hagerstown, Maryland; and Forsyth County, North Carolina. The current analysis included 2,810 individuals aged 66-90 years, free of HF, who underwent echocardiography at the fifth study visit (June 8, 2011, to August 28, 2013) and had measurable tricuspid regurgitation by spectral Doppler. Echocardiography-derived pulmonary artery systolic pressure (PASP), pulmonary vascular resistance (PVR), and pulmonary arterial compliance (PAC) were measured. The main outcome was incident HF after visit 5, and key secondary end points were incident HF with preserved LVEF (HFpEF) and incident HF with reduced LVEF (HFrEF). The mean ± SD age was 76 ± 5 years, 66% were female, and 21% were black. Mean values of PASP, PVR, and PAC were 28 ± 5 mm Hg, 1.7 ± 0.4 Wood unit, and 3.4 ± 1.0 mL/mm Hg, respectively, and were abnormal in 18%, 12%, and 14%, respectively, using limits defined from the 10th and 90th percentile limits in 253 low-risk participants free of cardiovascular disease or risk factors. Left heart dysfunction was associated with abnormal PASP and PAC, whereas a restrictive ventilatory deficit was associated with abnormalities of PASP, PVR, and PAC. PASP, PVR, and PAC were each predictive of incident HF or death (hazard ratio per SD 1.3 [95% CI 1.1-1.4], p < 0.001; 1.1 [1.0-1.2], p = 0.04; 1.2 [1.1-1.4], p = 0.001, respectively) independent of LV measures. Elevated pulmonary pressure was predictive of incident HFpEF (HFpEF: 2.4 [1.4-4.0, p = 0.001]) but not HFrEF (1.4 [0.8-2.5, p = 0.31]). Abnormal PAC predicted HFrEF (HFpEF: 2.0 [1.0-4.0, p = 0.05], HFrEF: 2.8 [1.4-5.5, p = 0.003]), whereas abnormal PVR was not predictive of either (HFpEF: 0.9 [0.4-2.0, p = 0.85], HFrEF: 0.7 [0.3-1.4, p = 0.30],). A greater number of abnormal pulmonary vascular measures was associated with greater risk of incident HF. Major limitations include the use of echo Doppler to estimate pulmonary hemodynamic measures, which may lead to misclassification; inclusions bias related to detectable tricuspid regurgitation, which may limit generalizability of our findings; and survivor bias related to the cohort age, which may result in underestimation of the described associations.

Conclusions: In this study, we observed abnormalities of PASP, PVR, and PAC in 12%-18% of elders in the community. Higher PASP and lower PAC were independently predictive of incident HF. Abnormally high PASP predicted incident HFpEF but not HFrEF. These findings suggest that impairments in pulmonary vascular function may precede clinical HF and that a comprehensive pulmonary hemodynamic evaluation may identify pulmonary vascular phenotypes that differentially predict HF phenotypes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pmed.1003361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561082PMC
October 2020

Predictors of Mortality by Sex and Race in Heart Failure With Preserved Ejection Fraction: ARIC Community Surveillance Study.

J Am Heart Assoc 2020 10 14;9(19):e014669. Epub 2020 Sep 14.

Duke University School of Medicine Durham NC.

Background Heart failure with preserved ejection fraction (HFpEF) accounts for half of heart failure hospitalizations, with limited data on predictors of mortality by sex and race. We evaluated for differences in predictors of all-cause mortality by sex and race among hospitalized patients with HFpEF in the ARIC (Atherosclerosis Risk in Communities) Community Surveillance Study. Methods and Results Adjudicated HFpEF hospitalization events from 2005 to 2013 were analyzed from the ARIC Community Surveillance Study, comprising 4 US communities. Comparisons between clinical characteristics and mortality at 1 year were made by sex and race. Of 4335 adjudicated acute decompensated heart failure cases, 1892 cases (weighted n=8987) were categorized as HFpEF. Men had an increased risk of 1-year mortality compared with women in adjusted analysis (hazard ratio [HR], 1.27; 95% CI, 1.06-1.52 [=0.01]). Black participants had lower mortality compared with White participants in unadjusted and adjusted analyses (HR, 0.79; 95% CI, 0.64-0.97 [=0.02]). Age, heart rate, worsening renal function, and low hemoglobin were associated with increased mortality in all subgroups. Higher body mass index was associated with improved survival in men, with borderline interaction by sex. Higher blood pressure was associated with improved survival among all groups, with significant interaction by race. Conclusions In a diverse HFpEF population, men had worse survival compared with women, and Black participants had improved survival compared with White participants. Age, heart rate, and worsening renal function were associated with increased mortality across all subgroups; high blood pressure was associated with decreased mortality with interaction by race. These insights into sex- and race-based differences in predictors of mortality may help strategize targeted management of HFpEF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.119.014669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792380PMC
October 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjcard.2020.08.025DOI Listing
December 2020

Factors Associated With Cognitive Impairment in Heart Failure With Preserved Ejection Fraction.

J Cardiovasc Nurs 2022 Jan-Feb 01;37(1):17-30

Background: Cognitive impairment is prevalent in heart failure and is associated with higher mortality rates. The mechanism behind cognitive impairment in heart failure with preserved ejection fraction (HFpEF) has not been established.

Objective: The aim of this study was to evaluate associations between abnormal cardiac hemodynamics and cognitive impairment in individuals with HFpEF.

Methods: A secondary analysis of Atherosclerosis Risk in Communities (Atherosclerosis Risk in Communities) study data was performed. Participants free of stroke or dementia who completed in-person assessments at visit 5 were included. Neurocognitive test scores among participants with HFpEF, heart failure with reduced ejection fraction (HFrEF), and no heart failure were compared. Sociodemographics, comorbid illnesses, medications, and echocardiographic measures of cardiac function that demonstrated significant (P < .10) bivariate associations with neurocognitive test scores were included in multivariate models to identify predictors of neurocognitive test scores among those with HFpEF. Multiple imputation by chained equations was used to account for missing values.

Results: Scores on tests of attention, language, executive function, and global cognitive function were worse among individuals with HFpEF than those with no heart failure. Neurocognitive test scores were not significantly different among participants with HFpEF and HFrEF. Worse diastolic function was weakly associated with worse performance in memory, attention, and language. Higher cardiac index was associated with worse performance on 1 test of attention.

Conclusions: Cognitive impairment is prevalent in HFpEF and affects several cognitive domains. The current study supports the importance of cognitive screening in patients with heart failure. An association between abnormal cardiac hemodynamics and cognitive impairment was observed, but other factors are likely involved.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JCN.0000000000000711DOI Listing
July 2020

Levels and Change in Galectin-3 and Association With Cardiovascular Events: The ARIC Study.

J Am Heart Assoc 2020 07 23;9(13):e015405. Epub 2020 Jun 23.

Section of Cardiology Department of Medicine Baylor College of Medicine Houston TX.

Background Circulating galectin-3 levels provide prognostic information in patients with established heart failure (HF), but the associations between galectin-3 levels and other incident cardiovascular events in asymptomatic individuals at midlife and when remeasured ≈15 years later are largely uncharacterized. Methods and Results Using multivariable Cox proportional hazards models, we identified associations between plasma galectin-3 levels (hazard ratio [HR] per 1 SD increase in natural log galectin-3) and incident coronary heart disease, ischemic stroke, HF hospitalization, and total mortality in ARIC (Atherosclerosis Risk in Communities) participants free of cardiovascular disease at ARIC visit 4 (1996-1998; n=9247) and at ARIC visit 5 (2011-2013; n=4829). Higher galectin-3 level at visit 4 (median age 62) was independently associated with incident coronary heart disease (adjusted HR, 1.30; 95% CI, 1.06-1.60), ischemic stroke (HR, 1.42; 95% CI, 1.01-2.00), HF (HR, 1.44; 95% CI, 1.17-1.76), and mortality (HR, 1.56; 95% CI, 1.35-1.80). At visit 5 (median age, 74), higher galectin-3 level was associated with incident HF (HR, 1.93; 95% CI, 1.15-3.24) and total mortality (HR, 1.70; 95% CI, 1.15-2.52), but not coronary heart disease or stoke. Individuals with the greatest increase in galectin-3 levels from visit 4 to visit 5 were also at increased risk of incident HF and total mortality. Conclusions In a large, biracial community-based cohort, galectin-3 measured at midlife and older age was associated with increased risk of cardiovascular events. An increase in galectin-3 levels over this period was also associated with increased risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.119.015405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670497PMC
July 2020

Mid- to Late-Life Time-Averaged Cumulative Blood Pressure and Late-Life Cardiac Structure, Function, and Heart Failure.

Hypertension 2020 09 15;76(3):808-818. Epub 2020 Jun 15.

Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (K.T., B.C., J.E.J., H.S., S.S., A.M.S.).

Limited data exist regarding systolic blood pressure (SBP) through mid- to late-life and late-life cardiac function and heart failure (HF) risk. Among 4578 HF-free participants in the ARIC study (Atherosclerosis Risk in Communities) attending the fifth visit (2011-2013; age 75±5 years), time-averaged cumulative SBP was calculated as the sum of averaged SBPs from adjacent consecutive visits (visits 1-5) indexed to total observation time (24±1 years). Calculations were performed using measured SBPs and also incorporating antihypertensive medication specific effect constants (underlying SBP). Outcomes included comprehensive echocardiography at visit 5 and post-visit 5 incident HF, HF with preserved ejection fraction, and reduced ejection fraction. Higher cumulative SBP was associated with greater left ventricular mass and worse diastolic measures (all <0.001), associations that were stronger with underlying compared with cumulative SBP (all <0.05). At 5.6±1.2 years follow-up post-visit 5, higher cumulative measured and underlying SBP were associated with incident HF (hazard ratio per 10 mm Hg for measured: 1.12 [1.01-1.24]; underlying: 1.19 [95% CI, 1.10-1.30]) and HF with preserved ejection fraction (measured: 1.15 [1.00-1.33]; underlying: 1.28 [1.14-1.45]), but not HF with reduced ejection fraction (measured: 1.11 [0.94-1.32]; underlying: 1.11 [0.96-1.24]). Associations with HF and HF with preserved ejection fraction were more robust with cumulative underlying compared with measured SBP (all <0.05). Time-averaged cumulative SBP in mid to late life is associated with worse cardiac function and risk of incident HF, especially HF with preserved ejection fraction, in late life. These associations were stronger considering underlying as opposed to measured SBP, highlighting the importance of prevention and effective treatment of hypertension to prevent late-life cardiac dysfunction and HF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.14833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262121PMC
September 2020

Application of Diagnostic Algorithms for Heart Failure With Preserved Ejection Fraction to the Community.

JACC Heart Fail 2020 08 10;8(8):640-653. Epub 2020 Jun 10.

Division of Cardiology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. Electronic address:

Objectives: This study sought to describe characteristics and risk of adverse outcomes associated with the HFPEF and HFA-PEFF scores among participants in the community with unexplained dyspnea.

Background: Diagnosing heart failure with preserved ejection fraction (HFpEF) can be challenging. The HFPEF and HFA-PEFF scores have recently been developed to estimate the likelihood that HFpEF is present among patients with unexplained dyspnea.

Methods: The study included 4,892 ARIC (Atherosclerosis Risk In Communities) study participants 67 to 90 years of age at visit 5 (2011 to 2013) without other common cardiopulmonary causes of dyspnea. Participants were categorized as asymptomatic (76.6%), having known HFpEF (10.3%), and having tertiles of each score among those with ≥moderate, self-reported dyspnea (13.1%). The primary outcome was heart failure (HF) hospitalization or death.

Results: Mean age was 75 ± 5 years, 58% were women, and 22% were black. After a mean follow-up of 5.3 ± 1.2 years, rates of HF hospitalization or death per 1,000 person-years for asymptomatic and known HFpEF were 20.7 (95% confidence interval [CI]: 18.9 to 22.7) and 71.6 (95% CI: 61.6 to 83.3), respectively. Among 641 participants with unexplained dyspnea, rates were 27.7 (95% CI: 18.2 to 42.1), 44.9 (95% CI: 34.9 to 57.7), and 47.3 (95% CI: 36.5 to 61.3) (tertiles of HFPEF score) and 31.8 (95% CI: 20.3 to 49.9), 32.4 (95% CI: 23.4 to 44.9), and 54.3 (95% CI: 43.8 to 67.3) (tertiles of HFA-PEFF score). Participants with unexplained dyspnea and scores above the diagnostic threshold suggested for each algorithm, HFPEF score ≥6 and HFA-PEFF score ≥5, had equivalent risk of HF hospitalization or death compared with known HFpEF. Among those with unexplained dyspnea, 28% had "discordant" findings (only high risk by 1 algorithm), while 4% were high risk by both.

Conclusions: Participants with unexplained dyspnea and higher HFPEF or HFA-PEFF scores face substantial risks of HF hospitalization or death. A significant fraction of patients are classified discordantly by using both algorithms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jchf.2020.03.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8030634PMC
August 2020
-->