Apixaban to Prevent Recurrence After Cryptogenic Stroke in Patients With Atrial Cardiopathy: The ARCADIA Randomized Clinical Trial.

Importance: Atrial cardiopathy is associated with stroke in the absence of clinically apparent atrial fibrillation. It is unknown whether anticoagulation, which has proven benefit in atrial fibrillation, prevents stroke in patients with atrial cardiopathy and no atrial fibrillation. Objective: To compare anticoagulation vs antiplatelet therapy for secondary stroke prevention in patients with cryptogenic stroke and evidence of atrial cardiopathy. Design, Setting, and Participants: Multicenter, double-blind, phase 3 randomized clinical trial of 1015 participants with cryptogenic stroke and evidence of atrial cardiopathy, defined as P-wave terminal force greater than 5000 µV × ms in electrocardiogram lead V1, serum N-terminal pro-B-type natriuretic peptide level greater than 250 pg/mL, or left atrial diameter index of 3 cm/m2 or greater on echocardiogram. Participants had no evidence of atrial fibrillation at the time of randomization. Enrollment and follow-up occurred from February 1, 2018, through February 28, 2023, at 185 sites in the National Institutes of Health StrokeNet and the Canadian Stroke Consortium. Interventions: Apixaban, 5 mg or 2.5 mg, twice daily (n = 507) vs aspirin, 81 mg, once daily (n = 508). Main Outcomes and Measures: The primary efficacy outcome in a time-to-event analysis was recurrent stroke. All participants, including those diagnosed with atrial fibrillation after randomization, were analyzed according to the groups to which they were randomized. The primary safety outcomes were symptomatic intracranial hemorrhage and other major hemorrhage. Results: With 1015 of the target 1100 participants enrolled and mean follow-up of 1.8 years, the trial was stopped for futility after a planned interim analysis. The mean (SD) age of participants was 68.0 (11.0) years, 54.3% were female, and 87.5% completed the full duration of follow-up. Recurrent stroke occurred in 40 patients in the apixaban group (annualized rate, 4.4%) and 40 patients in the aspirin group (annualized rate, 4.4%) (hazard ratio, 1.00 [95% CI, 0.64-1.55]). Symptomatic intracranial hemorrhage occurred in 0 patients taking apixaban and 7 patients taking aspirin (annualized rate, 1.1%). Other major hemorrhages occurred in 5 patients taking apixaban (annualized rate, 0.7%) and 5 patients taking aspirin (annualized rate, 0.8%) (hazard ratio, 1.02 [95% CI, 0.29-3.52]). Conclusions and Relevance: In patients with cryptogenic stroke and evidence of atrial cardiopathy without atrial fibrillation, apixaban did not significantly reduce recurrent stroke risk compared with aspirin. Trial Registration: ClinicalTrials.gov Identifier: NCT03192215.

Aortic Arch Plaques and the Long-Term Risk of Stroke and Cardiovascular Events in the Statin Era.

BACKGROUND: Aortic arch plaques are associated with an increased risk of ischemic stroke in patients with cryptogenic stroke or prior embolic events. However, this relationship is unclear in the community. We investigated (1) the long-term risk of stroke and cardiovascular events associated with arch plaques and (2) whether statin therapy prescribed for any indication modified the association. METHODS: A total of 934 stroke-free participants (72±9 years; 37% men) from the CABL study (Cardiovascular Abnormalities and Brain Lesion) were evaluated. Arch plaques were assessed by suprasternal transthoracic echocardiography; plaques ≥4 mm in thickness were classified as large plaques. The primary outcome was ischemic stroke; the secondary outcome was combined cardiovascular events (ischemic stroke, myocardial infarction, and cardiovascular death). The plaque-related risk of outcomes was also analyzed according to the presence of statin treatment. No plaque was used as a reference. RESULTS: Aortic arch plaques were present in 645 participants (69.1%), with large plaques in 114 (12.2%). During a mean follow-up of 11.3±3.6 years, 236 (25.3%) cardiovascular events occurred (76 ischemic strokes, 27 myocardial infarctions, and 133 cardiovascular deaths). Large arch plaques were independently associated with combined events (adjusted hazard ratio, 2.19 [95% CI, 1.40-3.43]) but not stroke alone (adjusted hazard ratio, 1.09 [95% CI, 0.50-2.38]). The association between large plaques and cardiovascular events was significant in participants receiving statins (adjusted hazard ratio, 2.57 [95% CI, 1.52-4.37]) but not in others; however, participants on statin treatment also had a worse risk profile (higher body mass index, greater frequencies of hypertension, diabetes, and coronary artery disease). CONCLUSIONS: Aortic arch plaques may be a marker of cardiovascular risk rather than a direct embolic stroke source in older adults without prior stroke. The efficacy of broader cardiovascular risk factors control, beyond cholesterol levels alone, for primary prevention of cardiovascular events in individuals with aortic arch plaques may require further investigation.

Association between non-alcoholic fatty liver disease and subclinical left ventricular dysfunction in the general population.

Aims: Emerging evidence suggests an association between non-alcoholic fatty liver disease (NAFLD) and heart failure (HF). We investigated the relationship between NAFLD and left ventricular (LV) functional remodelling in a general population sample without overt cardiac and liver disease. Methods and results: We included 481 individuals without significant alcohol consumption who voluntarily underwent an extensive cardiovascular health check. The fatty liver index (FLI) was calculated for each participant, and NAFLD was defined as FLI ≥ 60. All participants underwent 2D transthoracic echocardiography; LV global longitudinal strain (LVGLS) was assessed with speckle-tracking analysis. Univariable and multivariable linear regression models were constructed to investigate the possible association between NAFLD and LVGLS. Seventy-one (14.8%) participants were diagnosed with NAFLD. Individuals with NAFLD exhibited larger LV size and LV mass index than those without NAFLD, although left atrial size and E/e' ratio did not differ between groups. Left ventricular global longitudinal strain was significantly reduced in participants with vs. without NAFLD (17.1% ± 2.4% vs. 19.5% ± 3.1%, respectively; P < 0.001). The NAFLD group had a significantly higher frequency of abnormal LVGLS (<16%) than the non-NAFLD group (31.0% vs. 10.7%, respectively; P < 0.001). Multivariable linear regression analysis demonstrated that higher FLI score was significantly associated with impaired LVGLS independent of age, sex, conventional cardiovascular risk factors, and echocardiographic parameters (standardized ß -0.11, P = 0.031). Conclusion: In the general population without overt cardiac and liver disease, the presence of NAFLD was significantly associated with subclinical LV dysfunction, which may partly explain the elevated risk of HF in individuals with NAFLD.

Left Atrial Strain and Incident Atrial Fibrillation in Older Adults.

Atrial fibrillation (AF) is frequent in older adults and associated with left atrial (LA) dysfunction. LA strain (LAε) and LA strain rate (LASR) may detect subclinical LA disease. We investigated whether reduced LAε and LASR predict new-onset AF in older adults without history of AF or stroke. LAε and LASR were assessed by speckle-tracking echocardiography in 824 participants from the community-based Cardiovascular Abnormalities and Brain Lesions study. Positive longitudinal LAε and LASR during ventricular systole, LASR during early ventricular diastole, and LASR during LA contraction were measured. Cause-specific hazards regression model evaluated the association of LAε and LASR with incident AF, adjusting for pertinent covariates. The mean age was 71.1 ± 9.2 years (313 men, 511 women). During a mean follow-up of 10.9 years, new-onset AF occurred in 105 participants (12.7%). Lower LAε and LASR at baseline were observed in patients with new-onset AF (all p <0.01). In multivariable analysis, positive longitudinal LAε (adjusted hazard ratio [HR] per SD decrease 2.05, confidence interval [CI] 1.24 to 3.36) and LASR during LA contraction (HR per SD increase 2.24, CI 1.37 to 3.65) remained associated with new-onset AF, independently of LA volumes and left ventricular function. Along with positive longitudinal LAε, reduced LASR during ventricular systole predicted AF in participants with LA volume below the median value (HR 2.54, CI 1.10 to 6.09), whereas reduced LASR during LA contraction predicted AF in participants with larger LA (HR 2.35, CI 1.31 to 4.23). In conclusion, reduced positive longitudinal LAε and LASR predict new-onset AF in older adults regardless of LA size and may improve AF risk stratification.

The 2022 FASEB Virtual Catalyst Conference on the Cardiac Interatrial Septum and Stroke Risk, December 7, 2022.

There is emerging evidence that the cardiac interatrial septum has an important role as a thromboembolic source for ischemic strokes. There is little consensus on treatment of patients with different cardiac interatrial morphologies or pathologies who have had stroke. In this paper, we summarize the important background, diagnostic, and treatment considerations for this patient population as presented during the Federation of American Societies for Experimental Biology (FASEB) Virtual Catalytic Conference on the Cardiac Interatrial Septum and Stroke Risk, held on December 7, 2022. During this conference, many aspects of the cardiac interatrial septum were discussed. Among these were the embryogenesis of the interatrial septum and development of anatomic variants such as patent foramen ovale and left atrial septal pouch. Also addressed were various mechanisms of injury such as shunting physiologies and the consequences that can result from anatomic variants, as well as imaging considerations in echocardiography, computed tomography, and magnetic resonance imaging. Treatment options including anticoagulation and closure were addressed, as well as an in-depth discussion on whether the left atrial septal pouch is a stroke risk factor. These issues were discussed and debated by multiple experts from neurology, cardiology, and radiology.

Subclinical Left Ventricular Dysfunction and Ventricular Arrhythmias in Older Adults With Normal Ejection Fraction.

Background Premature ventricular contractions (PVCs) and nonsustained ventricular tachycardia (NSVT) are known to be associated with reduced left ventricular (LV) ejection fraction and adverse outcomes in patients with structural heart disease. The relationship between subclinical LV dysfunction and ventricular arrhythmias in the general population is not established. Methods and Results Participants in the SAFARIS (Subclinical Atrial Fibrillation and Risk of Ischemic Stroke) study with normal left ventricular ejection fraction (n=503; mean age 77 years, 63% women) underwent 14-day electrocardiographic monitoring and 2-dimensional echocardiography. Frequent PVCs were defined as PVCs >500 per 24 hours and NSVT as ≥4 consecutive ventricular ectopic beats. Reduced LV global longitudinal strain (GLS) was used as an indicator of subclinical LV dysfunction. Seventy-six participants (15.1%) had PVCs >500/d, 117 (23.3%) had NSVT episodes. LV GLS was significantly reduced in both frequent PVCs and NSVT groups (P<0.01). In multivariable analyses, lower LV GLS was associated with frequent PVCs (adjusted odds ratio [aOR], 1.19 [95% CI, 1.09-1.30 per unit reduction]; P<0.001) and NSVT (aOR, 1.09 [95% CI, 1.01-1.17]; P=0.036) independently of established risk factors and other echocardiographic parameters. Abnormal LV GLS (>-15.8%) carried a 2-fold increase in risk of ventricular arrhythmias (aOR, 2.18, P=0.029 for PVCs; aOR, 2.09, P=0.026 for NSVT). Conclusions PVCs and NSVT episodes were frequent in this community-based elderly cohort with normal left ventricular ejection fraction and were independently associated with lower LV GLS. The association between LV dysfunction and ventricular arrhythmias is present at an early, subclinical stage, an observation that carries possible preventative implications.

Long term aortic arch plaque progression in older adults.

Background and aims: The presence of aortic arch plaques (AAP) is significantly associated with increased cardiovascular morbidity and mortality. Few studies have examined the incidence of AAP progression and factors which may contribute to it using transthoracic echocardiography (TTE). The objective of this study was to utilize sequential imaging of the aortic arch using TTE to examine the rate of AAP progression and its risk factors in a cohort of older adults. Methods: Participants enrolled in both the Cardiovascular Abnormalities and Brain Lesion study (years 2005-2010) and the Subclinical Atrial Fibrillation and Risk of Ischemic Stroke study (2014-2019) who underwent TTE with assessment of aortic arch plaques at both time points represent the study cohort. Results: 300 participants were included in the study. Mean age was 67.8 ± 7.5 years at baseline, and 76.7 ± 6.8 years at follow-up; 197 (65.7%) were women. At baseline, 87 (29%) had no significant AAP, 182 (60.7%) had evidence of small AAP (2.0-3.9 mm) and 31 (10.3%) had evidence of large (≥4 mm) AAP. At the time of follow-up assessment, 157 (52.3%) of participants exhibited progression of AAP with 70 (23.3%) having mild progression and 87 (29%) having severe progression. There were no significant demographic or clinical predictors of AAP progression except baseline plaque thickness itself which was significantly lower in the group with AAP progression. Conclusions: Our study demonstrates a high prevalence of AAP on TTE exam in a population-based cohort of older adults with a high incidence of AAP progression. TTE is a useful test for baseline and follow up imaging of AAP, even in subjects with no or little AAP at baseline.

Factors associated with the progression of aortic valve calcification in older adults.

BACKGROUND: Aortic valve calcification (AVC) is a common valvular abnormality that predisposes to stenosis; AVC progression and factors associated with it remain unclear. We investigated the association of clinical factors and serum biomarkers with AVC progression in a population-based cohort of older adults. METHODS: Participants enrolled in both the Cardiovascular Abnormalities and Brain Lesion study (CABL; years 2005-2010) and the Subclinical Atrial Fibrillation And Risk of Ischemic Stroke study (SAFARIS;2014-2019) represent the study cohort. AVC was defined as bright dense echoes >1 mm in size on ≥1 cusps; each cusp was graded on a scale of 0 (normal) to 3 (severe calcification) at baseline and follow up. Serum biomarkers were measured at the time of follow-up assessment. RESULTS: 373 participants (mean 68.1 ± 7.6 years of age, 146 M/ 227F) were included. 139 (37%) had AVC progression;93 (25%) had mild progression (1 grade), and 46 (12%) had moderate-severe progression (≥2 grades). The only significant clinical predictor of any progression was the use of anti-hypertensive medication which was associated with older age, higher BMI and more frequent hypertension, diabetes and hyperlipidemia. In multivariable analysis including biomarkers, transforming growth factor beta 1 (TGF-ß1) was significantly associated with both all and moderate-severe AVC progression. CONCLUSIONS: A significant number of elderly subjects with AVC show progression of their valve disease; individual vascular risk factors are not associated with AVC progression, although a combined effect may exist. Higher levels of TGF-ß1 are observed in individuals with AVC progression.

Association of Left Atrial Strain With Ischemic Stroke Risk in Older Adults.

Importance: The risk of ischemic stroke is higher among patients with left atrial (LA) enlargement. Left atrial strain (LAε) and LA strain rate (LASR) may indicate LA dysfunction when LA volumes are still normal. The association of LAε with incident ischemic stroke in the general population is not well established. Objective: To investigate whether LAε and LASR are associated with new-onset ischemic stroke among older adults. Design: The Cardiovascular Abnormalities and Brain Lesions study was conducted from September 29, 2005, to July 6, 2010, to investigate cardiovascular factors associated with subclinical cerebrovascular disease. A total of 806 participants in the Northern Manhattan Study who were aged 55 years or older without history of prior stroke or atrial fibrillation (AF) were included, and annual follow-up telephone interviews were completed May 22, 2022. Statistical analysis was performed from June through November 2022. Exposures: Left atrial strain and LASR were assessed by speckle-tracking echocardiography. Global peak positive longitudinal LAε and positive longitudinal LASR during ventricular systole, global peak negative longitudinal LASR during early ventricular diastole, and global peak negative longitudinal LASR during LA contraction were measured. Brain magnetic resonance imaging was used to detect silent brain infarcts and white matter hyperintensities at baseline. Main Outcomes and Measures: Risk analysis with cause-specific Cox proportional hazards regression modeling was used to assess the association of positive longitudinal LAε and positive longitudinal LASR with incident ischemic stroke, adjusting for other stroke risk factors, including incident AF. Results: The study included 806 participants (501 women [62.2%]) with a mean (SD) age of 71.0 (9.2) years; 119 participants (14.8%) were Black, 567 (70.3%) were Hispanic, and 105 (13.0%) were White. During a mean (SD) follow-up of 10.9 (3.7) years, new-onset ischemic stroke occurred in 53 participants (6.6%); incident AF was observed in 103 participants (12.8%). Compared with individuals who did not develop ischemic stroke, participants with ischemic stroke had lower positive longitudinal LAε and negative longitudinal LASR at baseline. In multivariable analysis, the lowest (ie, closest to zero) vs all other quintiles of positive longitudinal LAε (adjusted hazard ratio [HR], 3.12; 95% CI, 1.56-6.24) and negative longitudinal LASR during LA contraction (HR, 2.89; 95% CI, 1.44-5.80) were associated with incident ischemic stroke, independent of left ventricular global longitudinal strain and incident AF. Among participants with a normal LA size, the lowest vs all other quintiles of positive longitudinal LAε (HR, 4.64; 95% CI, 1.55-13.89) and negative longitudinal LASR during LA contraction (HR, 11.02; 95% CI 3.51-34.62) remained independently associated with incident ischemic stroke. Conclusions and Relevance: This cohort study suggests that reduced positive longitudinal LAε and negative longitudinal LASR are independently associated with ischemic stroke in older adults. Assessment of LAε and LASR by speckle-tracking echocardiography may improve stroke risk stratification in elderly individuals.

Epicardial fat accumulation and left heart remodelling in patients with chronic coronary syndrome.

Aims: Patients with chronic coronary syndrome (CCS) suffer from subsequent cardiovascular events, even after complete revascularization; thus, elucidation of the underlying pathophysiological mechanisms is required. Epicardial adipose tissue (EAT) is increasingly recognized as a metabolically active organ with a key role in the pathogenesis of metabolic-related cardiac diseases. The present study investigated the association between EAT burden and left heart remodelling in patients with CCS. Methods and results: We studied 267 CCS patients (210 men; 71 ± 9 years) with complete revascularization and normal left ventricular (LV) ejection fraction who underwent follow-up echocardiography. All patients underwent the measurement of EAT thickness and speckle-tracking analysis to evaluate LV global longitudinal strain (LVGLS) and left atrial (LA) phasic strain. The mean EAT thickness was 5.0 ± 1.8 mm. Age, sex, body mass index, and diabetes mellitus were independently associated with EAT thickness (all P < 0.05). Multivariable linear regression analysis demonstrated that EAT thickness was significantly associated with LV mass index, early diastolic mitral annular velocity, and LA conduit strain independent of age, sex, and cardiovascular risk factors (all P < 0.05). On the other hand, there was no relationship between EAT thickness and LV systolic parameters including LV ejection fraction and LVGLS. Conclusion: CCS patients with increased EAT thickness had unfavourable left heart remodelling. The assessment of EAT thickness by echocardiography may have clinical utility as a simple surrogate to aid in risk stratification for impaired left heart function in CCS patients.

Prevalence, Determinants, and Prognostic Value of Left Atrial Dysfunction in Patients With Chronic Coronary Syndrome and Normal Left Ventricular Ejection Fraction.

Patients with chronic coronary syndrome (CCS), even when they have complete revascularization and normal left ventricular (LV) systolic function, experience subsequent cardiovascular disease (CVD), highlighting the importance of surrogate markers to prevent adverse consequences. Speckle-tracking echocardiography-derived left atrial (LA) reservoir strain has emerged as a sensitive marker for CVD in various clinical settings. The present study investigated the prevalence, determinants, and prognostic value of LA dysfunction in CCS. We included 278 consecutive patients with CCS with completed percutaneous coronary intervention and preserved LV ejection fraction who underwent follow-up echocardiography. Speckle-tracking analysis was performed to assess LA reservoir strain, and LA dysfunction was defined as LA reservoir strain ≤24%. The primary outcome comprised new-onset atrial fibrillation, heart failure hospitalization, acute coronary syndrome, stroke, or all-cause death. At baseline, 28 patients (10.1%) had LA dysfunction. Multivariable analysis identified age, hypertension, LV ejection fraction, and multivessel disease as independent determinants of LA reservoir strain (all p <0.05). During a median follow-up of 4.8 years, the primary outcome occurred in 60 patients (21.6%). LA dysfunction carried a significant risk for primary outcome independent of traditional risk factors, LV parameters, and LA size (adjusted hazard ratio 3.10, p = 0.003); the risk increase remained significant even after excluding atrial fibrillation from the primary outcome (adjusted hazard ratio 2.27, p = 0.043). In conclusion, approximately 10% of patients with CCS with normal LV ejection fraction had LA dysfunction associated with adverse cardiovascular outcomes. Further studies are needed to explore whether therapeutic interventions affecting LA remodeling may help prevent CVD events.

Subclinical left ventricular systolic dysfunction and incident stroke in the elderly: long-term findings from Cardiovascular Abnormalities and Brain Lesions.

AIMS: Heart disease is associated with an increased risk for ischaemic stroke. However, the predictive value of reduced left ventricular ejection fraction (LVEF) for stroke is controversial and only observed in patients with severe reduction. LV global longitudinal strain (LV GLS) can detect subclinical LV systolic impairment when LVEF is normal. We investigated the prognostic role of LV GLS for incident stroke in a predominantly elderly cohort. METHODS AND RESULTS: Two-dimensional echocardiography with speckle tracking was performed in the Cardiac Abnormalities and Brain Lesions (CABL) study. Among 708 stroke-free participants (mean age 71.4 ± 9.4 years, 60.9% women), abnormal LV GLS (>-14.7%: 95% percentile of the subgroup without risk factors) was detected in 133 (18.8%). During a mean follow-up of 10.8 ± 3.9 years, 47 participants (6.6%) experienced an ischaemic stroke (26 cardioembolic or cryptogenic, 21 other subtypes). The cumulative incidence of ischaemic stroke was significantly higher in participants with abnormal LV GLS than with normal LV GLS (P < 0.001). In multivariate stepwise logistic regression analysis, abnormal LV GLS was associated with ischaemic stroke independently of cardiovascular risk factors including LVEF, LV mass, left atrial volume, subclinical cerebrovascular disease at baseline, and incident atrial fibrillation [hazard ratio (HR): 2.69, 95% confidence interval (CI): 1.47-4.92; P = 0.001]. Abnormal LV GLS independently predicted cardioembolic or cryptogenic stroke (adjusted HR: 3.57, 95% CI: 1.51-8.43; P = 0.004) but not other subtypes. CONCLUSION: LV GLS was a strong independent predictor of ischaemic stroke in a predominantly elderly stroke-free cohort. Our findings provide insights into the brain-heart interaction and may help improve stroke primary prevention strategies.

Aortic valve sclerosis and subclinical LV dysfunction in the general population with normal LV geometry.

AIMS: Aortic valve sclerosis (AVS) without hemodynamically significant obstruction is related to cardiovascular morbidity and mortality independent of left ventricular (LV) hypertrophy, although the underlying mechanisms remain unknown. This study investigated the prevalence of AVS and its association with subclinical LV systolic and diastolic dysfunction in individuals with normal LV geometry free of cardiovascular disease. METHODS: We examined 962 participants with normal LV geometry and free from significant AV stenosis who underwent standard and speckle-tracking echocardiography. AVS was categorized into 4 groups as follows: no AVS, AV thickening, calcification on one leaflet and calcification on ≥2 leaflets. RESULTS: Among the 962 participants, 767 (79.7%) individuals were classified as no AVS, 74 (7.7%) as AV thickening, 87 (9.0%) as calcification on one leaflet, and 34 (3.5%) as calcification on ≥2 leaflets. The prevalence of subclinical LV diastolic dysfunction (E/e' ratio ≥13) and systolic dysfunction (LV global longitudinal strain (GLS) > -17.0% for men and > -18.0% for women) were greater in AVS groups than those in no AVS group. Subclinical LV diastolic impairment was evident from AV thickening and systolic dysfunction was observed at AV calcification. Multivariable logistic regression analysis demonstrated that AV thickening as well as calcification were independently associated with subclinical LV diastolic impairment (all p < 0.05), while only AV calcification on ≥2 leaflets conferred significant increased risk of impaired LVGLS. CONCLUSIONS: AVS was observed in approximately 20% individuals without cardiac disease and was associated with subclinical LV diastolic and systolic function even in the absence of LV morphological change.

We investigated the prevalence of aortic valve sclerosis (AVS) and its association with subclinical left ventricular (LV) systolic and diastolic dysfunction in 962individuals with normal LV geometry free of cardiac disease. In this study population, AVS characterized by thickening or calcification was present in 20% of individuals. Subclinical LV diastolic dysfunction appeared from AV thickening and systolic dysfunction by LV global longitudinal strain was observed at calcification on ≥2 leaflets; these associations were independent of age, sex and cardiovascular risk factors.

Association of arterial properties with left ventricular morphology and function in the community.

OBJECTIVES: Arterial structural and functional remodeling is recognized as a key determinant of incident heart failure, although the contribution of arterial properties on left ventricular (LV) remodeling is not fully studied. Aortic dilatation is an early manifestation of arterial remodeling and estimated pulse wave velocity (ePWV) is emerging as a simple measure of arterial stiffness. This study aimed to characterize the association of aortic size and ePWV with LV morphology and function. METHODS: The study cohort consisted of 539 participants without overt cardiac disease who underwent extensive cardiovascular examination. Aortic root diameter was measured by two-dimensional echocardiography and ePWV was calculated from a regression equation using age and mean blood pressure. LV global longitudinal strain (LVGLS) was obtained by speckle-tracking echocardiography. RESULTS: Aortic root diameter and ePWV were correlated with LV mass index and LVGLS, while only ePWV was related to E / e' ratio. In multivariable analysis, aortic root diameter and ePWV were significantly related to LV mass index and LVGLS (all P  < 0.05), and the association of aortic root size and ePWV with LVGLS was independent of LV mass index and E / e' ratio. Individuals with both aortic root enlargement and increased ePWV had significantly larger LV mass index and reduced LVGLS compared with those either or those with normal aortic size and ePWV (both P  < 0.05). CONCLUSION: Aortic root size and ePWV were independently associated with unfavorable LV remodeling in individuals free of cardiac disease, which might provide useful information into the pathogenesis-linking arterial remodeling and heart failure.

Age-Specific Relation of Cardiovascular Health Metrics With Incident Cardiovascular Disease.

We examined the age-related differences in cardiovascular health (CVH) metrics for incident cardiovascular disease (CVD). Analyses were conducted using data from the JMDC Claims Database from 2005 to 2020 (n = 2,728,427; mean age 44.9 ± 11.0 years; 56.2% men). Participants were categorized on the basis of age: 20 to 49 years (n = 1,800,161), 50 to 59 years (n = 644,703), and 60 to 75 years (n = 283,563). Ideal CVH metrics included nonsmoking, body mass index <25 kg/m2, physical activity at goal, not skipping breakfast, blood pressure <120/80 mm Hg, fasting plasma glucose <100 mg/dL, and total cholesterol <200 mg/dL. Over a mean follow-up of 1,194 ± 917 days, 5,988 myocardial infarction (MI), 53,409 angina pectoris, 26,530 stroke, and 52,712 heart failure (HF) events were recorded. Number of the nonideal CVH metrics was associated with incident MI, angina pectoris, stroke, and HF in all age categories. However, the association of the number of nonideal CVH metrics with incident CVD was modified by age categories and was more pronounced in participants aged 20 to 49 years. Similarly, the relative risk reduction at 1 year for each CVD event under the virtual condition that an individual with 2 nonideal CVH metrics has decreased them to zero, decreased with age. For example, relative risk reduction for MI was 0.51 in participants aged 20 to 49 years, 0.48 in those aged 50 to 59 years, and 0.40 in those aged 60 to 75 years. In conclusion, CVH metrics were more strongly associated with incident CVD including HF among younger individuals suggesting the importance of optimizing modifiable risk factors and lifestyles in young participants for the primary CVD prevention.

Blood pressure categorization and subclinical left ventricular dysfunction in antihypertensive medication-naive subjects.

AIMS: The impact of blood pressure (BP) levels on subclinical left ventricular (LV) dysfunction and possible sex-specific difference remains unclarified. This study investigated the relationship between BP categories given in the new 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guideline and subclinical LV dysfunction in subjects free of cardiac disease. METHODS AND RESULTS: We examined antihypertensive medication-naive 858 individuals who underwent extensive cardiovascular health check-up. LV global longitudinal (LVGLS) and circumferential strain (LVGCS) were assessed by two-dimensional speckle-tracking echocardiography. Participants were categorized into four groups: normal BP, elevated BP, isolated diastolic hypertension (IDH), and systolic hypertension (SH). Among the 858 participants, 422 individuals had normal BP, 113 had elevated BP, 160 had IDH, and 163 had SH. Prevalence of abnormal LVGLS (>-18.6%) was greatest in SH (19.0%), followed by IDH (17.5%), elevated BP (14.2%), and normal BP (7.1%, P < 0.001); no significant differences were observed for LVGCS (P = 0.671). In the multivariable analyses, IDH and SH were associated with impaired LVGLS [adjusted odds ratio (OR) 2.69 and 2.66, P < 0.001], and borderline significance was observed for elevated BP (adjusted OR 1.90, P = 0.060); there was no significant association between any of the BP groups and LVGCS. In sex-stratified analysis, IDH and SH carried the significant risk of abnormal LVGLS in both sexes, while elevated BP was associated with LVGLS only in women. CONCLUSIONS: Isolated diastolic hypertension and SH redefined by ACC/AHA guideline carried significant risk for LVGLS, but not LVGCS. Elevated BP was associated with LVGLS only in women. Our findings provide information on cardiac correlates of the newly established BP categories.

Systemic Arterial Correlates of Cervical Carotid Artery Tortuosity : The Northern Manhattan Study.

INTRODUCTION: The association between cervical internal carotid artery (cICA) tortuosity and atherosclerosis is a matter of debate. Additionally, some genetic syndromes characterized by connective tissue remodeling are associated with arterial tortuosity, raising the possibility that cICA tortuosity may not only be atherosclerotic. In this study, we hypothesized that cICA tortuosity is not associated with imaging biomarkers of atherosclerosis. METHODS: The Northern Manhattan Study (NOMAS) was a prospective, multiethnic cohort of stroke-free individuals who underwent brain MRA, carotid ultrasound and transthoracic echocardiogram from 2003-2008. The cICA tortuosity was scored in each carotid as 0 = no tortuosity, 1 = tortuosity <90°, 2 = tortuosity ≥90°. A summary cICA tortuosity score (possible range 0-4) was created by adding up the tortuosity score from each carotid. Participants were assessed for atherosclerotic markers by using B­mode carotid sonography and transthoracic echocardiography. RESULTS: Of 558 participants 178 (31.9%) had any cervical ICA tortuosity (tortuosity score >0). The cICA tortuosity score was higher in women and was associated with diastolic and systolic blood pressures and height (all P < 0.05). In models adjusted for demographics and risk factors, only the association with diastolic blood pressure remained significant (ß = 0.002, P = 0.02). Similarly, cICA tortuosity was associated with larger aortic root diameter (B = 1.03 ± 0.36, P = 0.004) but not with other markers of carotid or aortic atherosclerosis. CONCLUSION: Cervical ICA tortuosity is associated with a higher diastolic blood pressure and larger aortic root diameter but not with other measures of atherosclerosis. Determining the risks of vascular events associated with this non-atherosclerotic phenotype may help for a better risk stratification for individuals with cICA tortuosity.

Atrioventricular and Ventricular Functional Interdependence in Individuals Without Overt Cardiac Disease.

Background Left atrial (LA) and right ventricular (RV) performance play an integral role in the pathophysiology and prognosis of heart failure. We hypothesized that subclinical left ventricular dysfunction adversely affects LA/RV geometry and function even in a preclinical setting. This study aimed to investigate the atrioventricular and ventricular functional interdependence in a community-based cohort without overt cardiovascular disease. Methods and Results Left ventricular global longitudinal strain (LVGLS), RV free-wall longitudinal strain and LA phasic strain were assessed by speckle-tracking echocardiography in 1080 participants (600 men; 62±12 years) between 2014 and 2018. One hundred and forty-three participants (13.2%) had an abnormal LVGLS (>-18.6%). LA reservoir strain, conduit strain, and RV free-wall longitudinal strain were significantly decreased in abnormal LVGLS group compared with normal LVGLS group (all P<0.001). LA and RV dysfunction (LA reservoir strain<31.4% and RVLS>-19.2%) were present in 18.9% and 19.6% of participants with abnormal LVGLS. Decreased LVGLS was associated with worse LA reservoir strain, conduit strain and RV free-wall longitudinal strain (standardized ß=-0.20, -0.19 and 0.11 respectively, all P<0.01) independent of cardiovascular risk factors. LA and/or RV dysfunction concomitant with abnormal LVGLS carried significantly increased risk of elevated B-type natriuretic peptide levels (>28.6 pg/mL for men and >44.4 pg/mL for women) compared with normal LVGLS (odds ratio, 2.01; P=0.030). Conclusions LA/RV dysfunction was present in 20% individuals with abnormal LVGLS and multi-chamber impairment was associated with elevated B-type natriuretic peptide level, which may provide valuable insights for a better understanding of atrioventricular and ventricular interdependence and possibly heart failure preventive strategies.

Independent effect of visceral fat on left atrial phasic function in the general population.

BACKGROUND AND AIMS: Obesity increases the risk for atrial fibrillation (AF), although the impact of abdominal fat distribution on left atrial (LA) morphology and functional remodeling remains unclear. This study aimed to investigate whether increased abdominal adiposity is independently associated with impaired LA function and/or LA enlargement in a sample of the general population and to evaluate the role of adipokines in this association. METHODS AND RESULTS: The study cohort consisted of 527 participants (362 men; 57 ± 10 years) without overt cardiac disease who underwent laboratory testing, abdominal computed tomographic examination and echocardiography. Abdominal adiposity was quantitatively assessed as visceral fat area (VFA) and subcutaneous fat area (SFA) at the level of the umbilicus. Speckle-tracking echocardiography was performed to assess LA phasic function including reservoir, conduit and pump strain. LA reservoir and conduit strain decreased with increasing VFA quartiles (both p < 0.05), whereas no significant differences were observed in LA volume index and pump strain. When stratified by SFA, there were no significant differences in LA size and function across the quartiles. In multivariable analysis, VFA was significantly associated with LA conduit strain independent of cardiovascular risk factors, and pertinent laboratory and echocardiographic parameters (standardized ß = -0.136, p = 0.019). VFA was correlated with serum adiponectin level (r = -0.51, p < 0.001), but there was no association between adiponectin level and three LA phasic strains. CONCLUSION: In a sample of the general population, VFA accumulation was independently associated with worse LA conduit strain, which may be involved in the pathophysiological mechanism of obesity-related AF.