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Introduction: New guidelines for the management of heart failure (HF) have now incorporated cardiac biomarkers in the definition of those in pre-clinical HF (Stage B). We sought to compare the prevalence and prognosis according to the new vs. old ACC/AHA/HFSA HF Stage classification using data from the ARIC study visit 5 (2011-2013). Methods: The “old” classification included Stage 0 (no HF risk factors), Stage A (at risk for HF; without structural heart disease or symptoms), Stage B (structural heart disease; without HF signs and symptoms), Stage C1 (current or previous HF symptoms without HF hospitalization); Stage C2 (current or previous HF symptoms with HF hospitalization); Stage D (marked HF symptoms interfering with daily life). The “new” HF Stage classification included elevated NT-proBNP and cardiac troponin as evidence of Stage B. We examined all-cause mortality over five years, using tKaplan Meier method and multivariable Cox models. Results: Among 5,004 participants (mean age 75.3 (SD 5.1) years, 57% women, 22% Black), 28% had diabetes, 74% had hypertension, and 15% had coronary artery disease. With the new HF Stage classification, the prevalence of Stage 0/A decreased from 58% (n=2,887) to 27% (n=1,334), and Stage B increased from 29% (n=1,468) to 60% (n=3,021). The prevalence of Stage C2 and C1 were 7.3% and 5.7%, respectively, regardless of the new or old classification (no individuals had Stage D), with corresponding 5-year cumulative mortality of 33% and 21%. The new classification using cardiac biomarkers newly identified individuals as Stage B with mortality risk similar to those who were originally in Stage B (5-y cumulative mortality 10% and 12%, respectively). This “reclassification” left individuals with lower mortality risk as Stage 0/A (5-year cumulative mortality 5% vs. 8% in the new vs. old classification). When we adjusted for potential confounders, individuals newly classified as Stage B had an elevated mortality compared to those with Stage 0/A (HR 1.32 [0.98-1.77]) but not as high as those in original Stage B (1.83 [1.36-2.45]). Conclusions: The new HF classification newly identified a large number of older adults as Stage B, and they indeed had elevated mortality than those who stayed in Stage 0/A. However, after accounting for potential confounders, individuals newly classified as Stage B had slightly lower mortality than those originally in Stage B. Our findings will guide clinicians as to how to interpret new HF classification in terms of prognosis.

Acute coronary syndrome (ACS) may lead to adverse remodelling and impaired cardiac function. Limited data exists on the effect of culprit coronary artery lesion site and impact on longitudinal cardiac remodelling. The present study included a total of 299 patients suffering from ACS treated with percutaneous coronary intervention (PCI). All patients had two echocardiographic examinations. The first echocardiography was median 2(IQR: 1;3) days following PCI, while the follow-up echocardiography (FUE) was median 257(IQR: 96;942) days following the first. Patients were grouped based on coronary artery PCI location; left anterior descending artery (LAD), right coronary artery (RCA) or circumflex artery (Cx). Patients with multiple lesions were excluded. Mean age was 63 ± 11 years and 77% were male. At FUE, mean left ventricular ejection fraction was 42 ± 9% and global longitudinal strain (GLS) was - 13 ± 4%. PCI treatment was allocated as 168 LAD lesions, 95 RCA lesions, and 36 Cx lesions. Linear regression analysis showed that patients with a LAD lesion displayed worsening in E/A (mean ∆ = 0.05, β = - 0.196, p = 0.001) and a larger increase in LVEDV (mean ∆ = 33.18 mL, β = 0.135, p = 0.012). Meanwhile patients with Cx lesion were significantly associated with a larger decrease in E/e' (mean ∆ = 2.6, β = - 0.120, p = 0.028). Patients with Cx lesion were observed to have elevated E/e' at baseline, which normalized at FUE. The present study suggests that culprit coronary artery lesion has a differential impact on myocardial remodelling. This information may potentially aid in understanding the pathophysiological differences in cardiac structure and function amongst patients with ACS.

Background: Limited data exist on American College of Cardiology/American Heart Association valvular heart disease (VHD) stage prevalence, progression, and association with incident cardiovascular diseases in late life. Methods: Participants in the ARIC study (Atherosclerosis Risk in Communities), a prospective community-based cohort study, underwent protocol echocardiography at ARIC visits 5 (2011–2013) and 7 (2018–2019), and their aortic stenosis, aortic regurgitation, mitral stenosis, and mitral regurgitation stage were defined according to American College of Cardiology/American Heart Association guidelines. The overall VHD stage prevalence at visit 5 was measured. The associations between VHD stages and incident adjudicated death, heart failure, coronary heart disease, stroke, and atrial fibrillation were assessed with Cox proportional hazard models adjusted for age, sex, race, hypertension, diabetes, prior myocardial infarction, heart failure, body mass index, study center, systolic blood pressure, estimated glomerular filtration rate, and low-density lipoprotein at visit 5. Longitudinal changes in VHD stage prevalence over ≈6 years were estimated with inverse probability of attrition weights to account for participant attrition. Results: Among 6118 ARIC participants, the mean±SD age was 76±5 years, 42% were male, and 22% reported Black race. Stage A VHD was present in 39%, stage B in 17%, and stage C/D in 1.1%;, 0.7% had previously undergone valve replacement or repair. A graded association was observed between stage A, B, and C/D VHD and risk of all-cause mortality, incident heart failure, incident atrial fibrillation, and incident coronary heart disease, but not incident stroke. Similar findings were observed for stages of each valvular lesion individually. During the 6.6 years (interquartile range, 6.1–7.0 years) between visits 5 and 7 (mean age, 81±4 years), the prevalence of freedom from VHD stage decreased from 43% to 24%, whereas the prevalence of stage C/D VHD increased from 1% to 7%. Conclusions: Subclinical VHD is common in older adults, with 39% at risk (stage A) and 17% with progressive VHD (stage B), and is independently associated with risk of incident cardiovascular events. VHD stages progress over 6 years in late life, with a several-fold increase in prevalence of severe VHD (stage C/D), highlighting the public health importance of interventions to mitigate VHD progression.

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 to 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=1,974) and at all field centers at study visit 5 (2011–2013; n=4,651) 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(trend)=0.004 and

AimsTo determine the prevalence and incidence of AF among HF subtypes in a biracial community-based cohort.MethodsWe studied 6,496 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 ResultsAmong 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=5,761), 610 of them developed AF. Prevalent HF was associated with increased risk of AF [hazard ratio (95%CI) 2.3 (1.6-3.3) for HFpEF, 4.6 (2.4-8.6) for HFmEF, 3.8 (1.8-8.2) for HFrEF, 2.3 (0.9-5.6) for unclassified HR].ConclusionAF 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.

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 = 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. Funding Agencies|National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human ServicesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, HHSN268201700004I]; Swedish Heart Association, Sweden; Swedish Society of Medicine, Sweden; Region Ostergotland, Sweden; NIH/NHLBIUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [R01HL135008, R01HL143224, R01HL150342, R01HL148218, K24HL152008]

BACKGROUND:\ud Angiotensin-converting enzyme inhibitors attenuate left ventricular (LV) enlargement after acute myocardial infarction (AMI). Preclinical data suggest similar benefits with combined angiotensin receptor neprilysin inhibition, but human data are conflicting. The PARADISE-MI Echo Study (Prospective ARNI Versus ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After Myocardial Infarction) tested the effect of sacubitril/valsartan compared with ramipril on LV function and adverse remodeling after high risk-AMI.\ud \ud METHODS:\ud In a prespecified substudy, 544 PARADISE-MI participants were enrolled in the Echo Study to undergo protocol echocardiography at randomization and after 8 months. Patients were randomized within 0.5 to 7 days of presentation with their index AMI to receive a target dose of sacubitril/valsartan 200 mg or ramipril 5 mg twice daily. Echocardiographic measures were performed at a core laboratory by investigators blinded to treatment assignment. The effect of treatment on change in echo measures was assessed with ANCOVA with adjustment for baseline value and enrollment region. The primary end points were change in LV ejection fraction (LVEF) and left atrial volume (LAV), and prespecified secondary end points included changes in LV end-diastolic and end-systolic volumes.\ud \ud RESULTS:\ud Mean age was 64±12 years; 26% were women; mean LVEF was 42±12%; and LAV was 49±17 mL. Of 544 enrolled patients, 457 (84%) had a follow-up echo at 8 months (228 taking sacubitril/valsartan, 229 taking ramipril). There was no significant difference in change in LVEF (P=0.79) or LAV (P =0.62) by treatment group. Patients randomized to sacubitril/valsartan demonstrated less increase in LV end-diastolic volume (P=0.025) and greater decline in LV mass index (P=0.037), increase in tissue Doppler e’lat (P=0.005), decrease in E/e’lat (P=0.045), and decrease in tricuspid regurgitation peak velocity (P=0.024) than patients randomized to ramipril. These differences remained significant after adjustment for differences in baseline characteristics. Baseline LVEF, LV end-diastolic volume, LV end-systolic volume, LV mass index, LAV, and Doppler-based diastolic indices were associated with risk of cardiovascular death or incident heart failure.\ud \ud CONCLUSIONS:\ud Treatment with sacubitril/valsartan compared with ramipril after AMI did not result in changes in LVEF or LAV at 8 months. Patients randomized to sacubitril/valsartan had less LV enlargement and greater improvement in filling pressure. Measures of LV size, systolic function, and diastolic properties were predictive of cardiovascular death and incident heart failure after AMI in this contemporary, well-treated cohort.

AIMS: Despite adequate treatment, recent studies have hypothesized that malaria may affect long-term cardiovascular function. We aimed to investigate the long-term risk of cardiovascular events and death in individuals with a history of imported malaria in Denmark.METHODS: Using nationwide Danish registries, we followed individuals with a history of malaria for the risk of incident heart failure (HF), myocardial infarction (MI), cardiovascular death and all-cause death (1 January 1994 to 1 January 2017). The population was age- and sex-matched with individuals without a history of malaria from the Danish population (ratio 1:9). We excluded patients with known HF and ischaemic heart disease at inclusion.RESULTS: We identified 3912 cases with a history of malaria (mean age 33 ± 17 years, 57% male, 41% Plasmodium falciparum infections). The median follow-up was 9.8 years (interquartile range 3.9-16.4 years). Event rates per 1000 person-years for individuals with a history vs. no history of malaria were HF: 1.84 vs. 1.32; MI: 1.28 vs. 1.30; cardiovascular death: 1.40 vs. 1.77; and all-cause death: 5.04 vs. 5.28. In Cox proportional hazards models adjusted for cardiovascular risk factors, concomitant pharmacotherapy, region of origin, household income and educational level, malaria was associated with HF (HR: 1.59 [1.21-2.09], P = 0.001), but not MI (HR: 1.00 [0.72-1.39], P = 1.00), cardiovascular death (HR: 1.00 [0.74-1.35], P = 0.98) or all-cause death (HR 1.11 [0.94-1.30], P = 0.21). Specifically, P. falciparum infection was associated with increased risk of HF (HR: 1.64 [1.14-2.36], P = 0.008).CONCLUSION: Individuals with a history of imported malaria, specifically P. falciparum, may have an increased risk of incident HF.

Global Longitudinal Strain (GLS) is a well-established predictor of heart failure (HF) following acute coronary syndrome (ACS). We aim to investigate the prognostic value of GLS obtained at a follow-up consultation, as well as the change in GLS for long-term risk of incident HF. A total of 235 ACS patients had an echocardiogram performed immediately after percutaneous coronary intervention (PCI) and a follow-up echocardiogram (FUE) median 215 (IQR: 71; 878) days after the first echocardiogram. Endpoint was incident HF. Follow-up time after FUE was median 4.8 (IQR: 3.7; 5.6) years. Patients diagnosed with HF before FUE were excluded. Mean age was 63 ± 11 years and 77% were male. Baseline GLS was on average 12.7 ± 3.9%, FUE GLS was on average 13.5 ± 3.9% and mean improvement in GLS was 0.73 ± 3.68% between the 2 echocardiograms. A total of 57 (24%) patients suffered incident HF following the FUE. FUE GLS provided significantly higher prognostic information for risk of incident HF than ∆GLS when assessed by the C-statistics (C-statistics: 0.71 vs. 0.61, P = 0.021). Furthermore, after multivariable adjustments only FUE GLS [HR = 1.15, 95% CI (1.02; 1.29), P = 0.018, per 1% decrease] remained an independent predictor of incident HF. In patients with ACS, who do not develop HF before FUE, FUE GLS was an independent predictor of long-term risk of incident HF while ∆GLS was not.

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 (GLSEndo) 11.4%vs 14.5% (p

ImportanceHistologic lesions in the kidney may reflect or contribute to systemic processes that may lead to adverse cardiovascular events.ObjectiveTo assess the association between kidney histopathologic lesion severity and the risk of incident major adverse cardiovascular events (MACE).Design, Setting, and ParticipantsThis prospective observational cohort study included participants without a history of myocardial infarction, stroke, or heart failure from the Boston Kidney Biopsy Cohort recruited from 2 academic medical centers in Boston, Massachusetts. Data were collected from September 2006 and November 2018, and data were analyzed from March to November 2021.ExposuresSemiquantitative severity scores for kidney histopathologic lesions adjudicated by 2 kidney pathologists, a modified kidney pathology chronicity score, and primary clinicopathologic diagnostic categories.Main Outcomes and MeasuresThe main outcome was the composite of death or incident MACE, which included myocardial infarction, stroke, and heart failure hospitalization. All cardiovascular events were independently adjudicated by 2 investigators. Cox proportional hazards models estimated associations of histopathologic lesions and scores with cardiovascular events adjusted for demographic characteristics, clinical risk factors, estimated glomerular filtration rate (eGFR), and proteinuria.ResultsOf 597 included participants, 308 (51.6%) were women, and the mean (SD) age was 51 (17) years. The mean (SD) eGFR was 59 (37) mL/min per 1.73 m2, and the median (IQR) urine protein to creatinine ratio was 1.54 (0.39-3.95). The most common primary clinicopathologic diagnoses were lupus nephritis, IgA nephropathy, and diabetic nephropathy. Over a median (IQR) of 5.5 (3.3-8.7) years of follow-up, the composite of death or incident MACE occurred in 126 participants (37 per 1000 person-years). Compared with the reference group of individuals with proliferative glomerulonephritis, the risk of death or incident MACE was highest in individuals with nonproliferative glomerulopathy (hazard ratio [HR], 2.61; 95% CI, 1.30-5.22; P = .002), diabetic nephropathy (HR, 3.56; 95% CI, 1.62-7.83; P = .002), and kidney vascular diseases (HR, 2.86; 95% CI, 1.51-5.41; P = .001) in fully adjusted models. The presence of mesangial expansion (HR, 2.98; 95% CI, 1.08-8.30; P = .04) and arteriolar sclerosis (HR, 1.68; 95% CI, 1.03-2.72; P = .04) were associated with an increased risk of death or MACE. Compared with minimal chronicity, greater chronicity was significantly associated with an increased risk of death or MACE (severe: HR, 2.50; 95% CI, 1.06-5.87; P = .04; moderate: HR, 1.66; 95% CI, 0.74-3.75; P = .22; mild: HR, 2.22; 95% CI, 1.01-4.89; P = .047) in fully adjusted models.Conclusions and RelevanceIn this study, specific kidney histopathological findings were associated with increased risks of CVD events. These results provide potential insight into mechanisms of the heart-kidney relationship beyond those provided by eGFR and proteinuria.

ImportanceMost studies, especially in primary prevention patients, have evaluated N-terminal B-type natriuretic peptide (NT-proBNP) at one time point. Evaluation of change in NT-proBNP may improve risk stratification for incident cardiovascular events.ObjectiveTo assess the association between change in NT-proBNP and risk for incident heart failure (HF) and death.Design, Setting, and ParticipantsParticipants were recruited from 4 US communities enrolled in the Atherosclerosis Risk in Community (ARIC) study. Individuals who attended ARIC visits 2 and 4 (approximately 6 years apart) with measurements of NT-proBNP and without prevalent HF were included. Assays of NT-proBNP were conducted between 2011 and 2013, and analysis took place between July 2021 and October 2022.ExposuresThe primary exposure variable was NT-proBNP change between visits 2 and 4, modeled as change categories (Main Outcomes and MeasuresThe primary outcome measures were incident HF hospitalization and all-cause death. The association between changes in cardiovascular risk factors with change in NT-proBNP was further assessed.ResultsA total of 9776 individuals (mean [SD] age, 57.1 [5.7] years at visit 2; 5523 [56.5%] women) were included in the study. Compared with participants with NT-proBNP level less than 125 pg/mL at both visits, participants with NT-proBNP level of 125 pg/mL or higher at both visits had an increase in incident HF (adjusted hazard ratio [HR], 2.40 [95% CI, 2.00-2.88]) and mortality risk (HR, 1.68 [95% CI, 1.47-1.91). Participants with NT-proBNP levels of 125 pg/mL or higher at visit 2 and less than 125 pg/mL at visit 4 had similar risk for HF and death (HR, 1.01 [95% CI, 0.71-1.43]; HR, 0.79 [95% CI, 0.61-1.01]) compared with the group with NT-proBNP levels of less than 125 pg/mL at both visits. The percent change in NT-proBNP was positively associated with HF and death (HR, 1.06 [95% CI, 1.02-1.10]; HR, 1.05 [95% CI, 1.03-1.08] per 1-SD increase, respectively). Change in systolic blood pressure, low-density lipoprotein cholesterol, triglyceride level, body mass index, and estimated glomerular filtration rate were significantly associated with change in NT-proBNP.Conclusions and RelevanceIn this study, 6-year change in NT-proBNP reflected dynamic change in risk for HF events and death among community-dwelling adults without prevalent clinical HF. These results support the utility of serial NT-proBNP measurements to improve risk stratification of patients with pre-HF.

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 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.

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 (

Background: Aldosterone production and mineralocorticoid receptor activation are implicated in myocardial fibrosis and cardiovascular events. Methods: Cardiac structure and function were assessed in 4547 participants without prevalent heart failure (HF) in the ARIC study (Atherosclerosis Risk in Communities), with echocardiography, aldosterone, and plasma renin activity measurement (2011–2013). Subjects were characterized by plasma renin activity as suppressed (≤0.5 ng/mL per hour) or unsuppressed (>0.5 ng/mL per hour). Cross-sectional relationships with cardiac structure and function, and longitudinal relationships with outcomes (HF hospitalization; HF and all-cause death; HF, death, myocardial infarction, and stroke; and incident atrial fibrillation) were assessed. Models were adjusted for demographic and anthropometric characteristics and additively, for blood pressure and antihypertensives. Results: Evidence of primary aldosteronism physiology was prevalent (11.6% with positive screen) and associated with echocardiographic parameters. Renin suppression was associated with greater left ventricular mass, left ventricular volumes, and left atrial volume index, and a lower E/A ratio (adjusted P Conclusions: Renin suppression and aldosterone excess, consistent with primary aldosteronism pathophysiology, were associated with cardiac structural and functional alterations and may represent an early target for mitigation of fibrosis with mineralocorticoid receptor antagonists.

Little is known about the long-term outcomes of mild valvular lesions.To examine the associations of 3 major types of valvular lesions (aortic stenosis, trace or mild aortic regurgitation, and trace or mild mitral regurgitation) with risk of cardiovascular mortality, coronary heart disease (CHD), stroke, heart failure, and atrial fibrillation.This cohort study analyzed data from the ongoing Atherosclerosis Risk in Communities study and focused on Black participants in the Jackson, Mississippi, site who underwent echocardiography at visit 3 from 1993 to 1995. Data analysis was conducted between April 2021 and February 2022.Three valvular lesions were analyzed: aortic sclerosis, aortic regurgitation (trace or mild), and mitral regurgitation (trace or mild).The outcomes were cardiovascular mortality, coronary heart disease, heart failure, stroke, and atrial fibrillation. Multivariable Cox proportional hazards regression models were used to examine the independent associations between the 3 valvular lesions and these outcomes.A total of 2106 Black participants were included, with a mean (SD) age of 59.1 (5.6) years and 1354 women (64.3%). The baseline prevalence was 7.7% for aortic sclerosis, 15.1% for aortic regurgitation (6.1% with trace, and 9.0% with mild), and 43.0% for mitral regurgitation (29.4% with trace, and 13.6% with mild). During a median (interquartile interval) follow-up of 22.5 (15.6-23.5) years, 890 participants developed at least 1 cardiovascular outcome. Each valvular lesion was significantly associated with at least 1 cardiovascular outcome: aortic sclerosis was associated with cardiovascular mortality (adjusted hazard ratio [HR], 1.54; 95% CI, 1.06-2.22), mild mitral regurgitation was associated with atrial fibrillation (HR, 1.47; 95% CI, 1.09-1.99), and trace or mild aortic regurgitation was associated with all outcomes (HRs ranging from 1.45 [95% CI, 1.17-1.81] to 1.75 [95% CI, 1.29-2.37]) except stroke. The total number of valvular lesions had graded associations with all cardiovascular outcomes except stroke: the HR of cardiovascular mortality was 1.77 (95% CI, 1.18-2.65) for those with 2 to 3 lesions and was 1.44 (95% CI, 1.05-1.96) for those with 1 lesion vs no lesions.Results of this study indicate an association between valvular lesions, even at mild stage, and a long-term risk of cardiovascular events, suggesting the importance of recognizing and monitoring these valvular conditions.

Aims N-terminal pro-B-type natriuretic peptide (NT-proBNP), cardiac troponin T (cTnT) and soluble ST2 (sST2) provide complementary prognostic information in heart failure with reduced ejection fraction (HFrEF). We aimed to assess the association between changes in these markers with changes in cardiac structure, function and health status. Methods and results Patients in the EVALUATE-HF trial (n = 464) were randomized to sacubitril/valsartan or enalapril for 12 weeks, followed by 12-week open-label sacubitril/valsartan. Cardiac biomarkers, echocardiography, and Kansas City Cardiomyopathy Questionnaires (KCCQ) were completed at baseline, and after 12 and 24 weeks. A total of 410 patients (88%) had serial biomarker measurements available (mean age 67 ± 9 years, 75% male and 75% white). After 24 weeks of treatment, NT-proBNP, sST2 and cTnT decreased by median (Q1, Q3) −31% (−55%, +6%), −6% (−19%, +8%) and − 3% (−13%, +8%), respectively (all p 0.05) Conclusion In HFrEF, serial changes in NT-proBNP correlate with changes in several key measures of cardiac structure and health status. cTnT changes correlate with changes in left ventricular mass and sST2 with changes in health status. These data highlight possible complementary pathophysiologic implications of changes in NT-proBNP, cTnT and sST2. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT02874794.

AIMS/HYPOTHESIS: Elevated circulating growth differentiation factor-15 (GDF-15), a marker of cellular stress, is associated with both heart failure (HF) and diabetes. However, it is unclear to what extent GDF-15 is associated with HF among individuals with and without diabetes. METHODS: We evaluated 10,570 participants free of HF at Visit 3 (1993–1995) of the Atherosclerosis Risk in Communities study. We used Cox regression to evaluate the joint associations of GDF-15 and diabetes with incident HF. Models were adjusted for traditional cardiovascular risk factors. RESULTS: Among a total of 10,570 individuals (mean age of 60.5 years, 58% women, 27% black adults), elevated GDF-15 (≥75th percentile) was more common in people with diabetes compared with those without diabetes (32.8% vs 23.6%, p

Background: An improvement in kidney function has been reported after percutaneous valvular replacement therapies, implying pathophysiological contribution of valvular heart disease to chronic kidney disease (CKD). However, this association has not been investigated in community dwelling populations. Hypothesis: Valvular abnormality is associated with prevalent and incident CKD. Methods: We evaluated the association between valvular abnormality and prevalent CKD (primarily defined as estimated glomerular filtration rate [eGFR] 2 ) in 5,216 participants (mean age 75.5 [SD 5.1] years) from the ARIC study (2011-2013) using logistic regression. Then, 3,752 participants without prevalent CKD were analyzed for incident CKD (progression to eGFR 2 with ≥25% decline or hospitalization/deaths with CKD diagnosis) using Cox models. Valvular abnormality included echocardiography-based aortic stenosis (AS), aortic regurgitation (AR), and mitral regurgitation (MR). Results: There were 1.4% (n=74) with any AS, 10.6% (n=555) with any AR, and 43.1% (n=2,249) with any MR. The majority (57-96%) had mild or trace abnormality. After adjustment for potential confounders, any MR and moderate/severe AR showed significant associations with prevalent CKD (adjusted odds ratio 1.17 [95% CI 1.03-1.34] and 2.82 [1.12-7.10]), as did any AS in a sensitivity analysis with prevalent CKD defined including albuminuria ≥30 mg/g (1.83 [1.10-3.05]). Only any AS showed an independent association with incident CKD (adjusted hazard ratio: 2.12 [1.13-4.00]). The 5-year cumulative incidence of CKD was 17.3% in any AS and 7.4% in no AS (Figure). Conclusions: Different types of valvular abnormality were associated with prevalent CKD. Prospectively, only AS was associated with incident CKD. These findings suggest an etiological link between valvular abnormality and CKD and highlight the importance of clinical attention to kidney function in individuals with AS.

Introduction: The AHA/ACC framework of valvular heart disease (VHD) stages emphasizes the progressive nature of VHD. Limited data exist regarding the association of VHD stages with prognostic cardiac biomarkers of myocardial stress (NT-proBNP) and injury (high sensitivity troponin-T [hs-TnT]). Methods: Among 6,078 participants in the community-based Atherosclerosis Risk in Communities (ARIC) who underwent echocardiography at the 5 th study visit (2011-2013) and were free of prior valve replacement, we classified VHD stages based on quantitative and qualitative assessments of mitral and aortic valve stenosis and regurgitation. Multivariable linear regression models were used to relate VHD stages to concentrations of NT-proBNP and hs-TnT at Visit 5. Biomarker values were log-transformed. Models were adjusted for age, sex, race, hypertension, diabetes, heart failure, prior myocardial infarction, body mass index, atrial fibrillation, study center, and systolic blood pressure at Visit 5. Results: The mean age was 76±5, 58% were women, 22% were Black. Stage A VHD was present in 2,362 participants (39%), Stage B in 1011 (17%), and Stage C or D in 65 (1%). In multivariable models, higher VHD stage was associated with a graded increase in NT-proBNP and hs-TnT concentrations (Figure) . Compared to participants free of VHD, even Stage A (‘at risk’) participants demonstrated higher concentrations of both NT-proBNP (p Conclusion: Worse VHD stages, even in the absence of severe stenosis or regurgitation, are associated with higher concentrations of markers of myocardial stress (NT-proBNP) and injury (hs-TnT) independent of traditional cardiovascular risk factors. Figure: Concentrations (median, IQR) of NT-proBNP and hs-TnT by VHD stage. *p

Introduction: Heart Failure (HF) has shared genetic architecture with its risk factors, including atrial fibrillation (AF), body mass index (BMI), coronary heart disease (CHD), systolic blood pressure (SBP), and type 2 diabetes (T2D). The risk prediction performance of polygenic risk scores (PRS) for those HF risk factors and HF itself over an established risk equation warrants investigation. Methods: Within the Atherosclerosis Risk in Communities (ARIC) study, six PRSs were constructed for AF, BMI, CHD, SBP, T2D, and HF by summing the product of pre-computed weights from genome-wide association studies and SNP allele dosages in European and African Americans separately. The association between PRSs and incident HF was assessed using cox proportional hazard models, and the 10-, 20-, and 30-year risk prediction performance of PRS over the ARIC HF risk equation was assessed using C-statistics. Associations between AF PRS and HF subtypes, echocardiographic measures, and 4,877 proteins were examined. Results: Over 30 years follow-up, 1,922 (22%) and 735 (29%) HF cases developed in 8,624 European (mean age=54.2, 52% female) and 2,525 African (mean age=53.3, 61% female) Americans. The PRSs for AF and HF were associated with incident HF in both European and African Americans (P-4 ). Protein analyses revealed that 61 proteins were associated with AF PRS, where NT-proBNP and Coagulation factor X showed the strongest positive and negative associations respectively. Conclusions: The PRS of AF was associated with incident HF, and had significant incremental value over an established HF risk prediction equation. These findings suggest that PRS may be useful in identifying individuals with high risk of HF.