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AimsHeart 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 resultsTwo-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.ConclusionLV 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.

Elevated blood pressure (BP) level is one of the most consistently identified risk factors for silent brain disease. BP values obtained at the proximal segment of the aorta (central BP) are more directly involved than brachial BP in the pathogenesis of cardiovascular disease. However, the association between central BP and silent cerebrovascular disease has not been clearly established. Participants in the CABL (Cardiovascular Abnormalities and Brain Lesions) study (n=993; mean age, 71.7±9.3 years; 37.9% men) underwent 2-dimensional echocardiography, arterial wave reflection analysis for determination of central BPs, and brain magnetic resonance imaging. Central BPs were calculated from the radial pulse waveform. Subclinical silent cerebrovascular disease was defined as silent brain infarction and white matter hyperintensity volume. Both brachial (P=0.014) and central pulse pressure (P=0.026) were independently associated with silent brain infarctions after adjustment for clinical variables, but not adjusting for each other. None of the brachial BP values was associated with upper quartile of white matter hyperintensity volume in multivariable analysis. Both central systolic BP (P

AimsAlthough ambulatory blood pressure (BP) is a better predictor of cardiovascular outcomes than office BP, its association with subclinical cerebrovascular disease is not clarified. We investigated the associations of office and ambulatory BP values with subclinical cerebrovascular disease in a population based, predominantly elderly cohort without prior stroke.Methods and resultsEight hundred and twenty-eight participants underwent 24-h ambulatory BP monitoring (ABPM), 2D echocardiography and brain magnetic resonance imaging in the Cardiac Abnormalities and Brain Lesion (CABL) study. Daytime, night-time, and 24-h BPs, nocturnal dipping pattern, morning surge (MS), and 24-h variability were assessed. Subclinical cerebrovascular disease was defined as silent brain infarcts (SBIs) and white matter hyperintensity volume (WMHV). The association of BP measures with the presence of SBI and upper quartile of log-WMHV (log-WMHV4) was analysed. SBIs were detected in 111 patients (13.4%). Mean log-WMHV was -0.99 ± 0.94. In multivariable analysis, only night-time systolic BP (SBP) was significantly associated with SBI [odds ratio (OR) 1.15 per 10 mmHg, P = 0.042], independent of cardiovascular risk factors, and pertinent echocardiographic parameters. Although daytime, night-time, 24-h BPs, and non-dipping pattern were all significantly associated with log-WMHV4 (all P

In diagnostic studies, a continuous biomarker is often dichotomized for the diagnosis of binary disease status. Various criteria have been studied for the cut point selection of the continuous biomarker in receiver operating characteristic (ROC) analysis, in particular, the Youden index, the closest-to-(0,1) index, and the concordance probability index. Recently, Wang, Tian, and Zhao (2017) established a Wilks theorem for a smoothed empirical likelihood ratio statistic of Youden index. However, it is not directly useful for statistical inference compared to the cut point. In addition, the optimal cut point may vary with different criteria. In this article, we study smoothed empirical likelihood for optimal cut point selection with Youden index, closest-to-(0,1) criterion, and concordance probability. We develop confidence estimation for the optimal cut points based on the smoothed empirical likelihood ratio statistics. We examine the empirical performance by extensive simulation studies. We also illustrate the method with a real dataset. [ABSTRACT FROM AUTHOR]

Background and purposeAlthough increased heart rate (HR) is a predictor of cardiovascular events and mortality, its possible association with subclinical cerebrovascular disease, which is prevalent in the elderly, has not been evaluated. This study aimed to investigate the association of daytime, nighttime, 24-hour HR, and HR variability with subclinical cerebrovascular disease in an elderly cohort without history of stroke.MethodsThe study cohort consisted of 680 participants (mean age, 73±7 years; 42% men) in sinus rhythm who underwent 24-hour ambulatory blood pressure and HR monitoring, 2-dimensional echocardiography, and brain magnetic resonance imaging as part of the CABL study (Cardiac Abnormalities and Brain Lesion). Subclinical cerebrovascular disease was defined as silent brain infarcts and white matter hyperintensity volume (WMHV). The relationship of HR measures with the presence of silent brain infarct and upper quartile of log WMHV (log WMHV4) was analyzed.ResultsPresence of silent brain infarct was detected in 93 participants (13.7%); mean log WMHV was -0.92±0.93 (median, -1.05; min, -5.88; max, 1.74). Multivariate analysis showed that only nighttime HR (adjusted odds ratio, 1.29 per 10 bpm; 95% confidence interval, 1.03-1.61; P=0.026) was significantly associated with log WMHV4, independent of traditional cardiovascular risk factors, ambulatory systolic blood pressure, and echocardiographic parameters. No similar association was observed for daytime HR and HR variability. There was no significant association between all HR measures and silent brain infarct.ConclusionsIn a predominantly elderly cohort, elevated nighttime HR was associated with WMHV, suggesting an independent role of HR in subclinical cerebrovascular disease.

BackgroundAlthough abnormal left ventricular geometric patterns have prognostic value for morbidity and mortality, their possible association with silent cerebrovascular disease has not been extensively evaluated.MethodsWe examined 665 participants in the CABL study who underwent transthoracic echocardiography and brain magnetic resonance imaging. Participants were divided into 4 geometric patterns: normal geometry (n=397), concentric remodeling (n=89), eccentric hypertrophy (n=126), and concentric hypertrophy (n=53). Subclinical cerebrovascular disease was defined as silent brain infarcts (SBIs) and white matter hyperintensity volume (WMHV; expressed as log-transformed percentage of the total cranial volume).ResultsSilent brain infarcts were observed in 94 participants (14%). Mean log-WMHV was -0.97±0.93. Concentric hypertrophy carried the greatest risk for both SBI (adjusted odds ratio [OR] 3.39, P

Background and purposeAortic arch plaque (AAP) is a risk factor for ischemic stroke, but its association with subclinical cerebrovascular disease is not established. We investigated the association between AAP and subclinical cerebrovascular disease in an elderly stroke-free community-based cohort.MethodsThe CABL study (Cardiovascular Abnormalities and Brain Lesions) was designed to investigate cardiovascular predictors of silent cerebrovascular disease in the elderly. AAPs were assessed by suprasternal transthoracic echocardiography in 954 participants. Silent brain infarcts and white matter hyperintensity volume (WMHV) were assessed by brain magnetic resonance imaging. The association of AAP thickness with silent brain infarcts and WMHV was evaluated by logistic regression analysis.ResultsMean age was 71.6±9.3 years; 63% were women. AAP was present in 658 (69%) subjects. Silent brain infarcts were detected in 138 participants (14.5%). In multivariate analysis adjusted for potential confounders, AAP thickness and large AAP (≥4 mm in thickness) were significantly associated with the upper quartile of WMHV (WMHV-Q4; odds ratio =1.17; 95% confidence interval, 1.04-1.32; P=0.009 and odds ratio =1.79; 95% confidence interval, 1.40-3.09; P=0.036, respectively), but not with silent brain infarcts (odds ratio =1.08; 95% confidence interval, 0.94-1.23; P=0.265 and odds ratio =1.46; 95% confidence interval, 0.77-2.77; P=0.251, respectively).ConclusionsAortic arch atherosclerosis was associated with WMHV in a stroke-free community-based elderly cohort. This association was stronger in subjects with large plaques and independent of cardiovascular risk factors. Aortic arch assessment by transthoracic echocardiography may help identify subjects at higher risk of subclinical cerebrovascular disease, who may benefit from aggressive stroke risk factors treatment.

We consider local polynomial estimation for varying coefficient models and derive corresponding equivalent kernels that provide insights into the role of smoothing on the data and fill a gap in the literature. We show that the asymptotic equivalent kernels have an explicit decomposition with three parts: the inverse of the conditional moment matrix of covariates given the smoothing variable, the covariate vector, and the equivalent kernels of univariable local polynomials. We discuss finite-sample reproducing property which leads to zero bias in linear models with interactions between covariates and polynomials of the smoothing variable. By expressing the model in a centered form, equivalent kernels of estimating the intercept function are asymptotically identical to those of univariable local polynomials and estimators of slope functions are local analogues of slope estimators in linear models with weights assigned by equivalent kernels. Two examples are given to illustrate the weighting schemes and reproducing property. [ABSTRACT FROM AUTHOR]

Summary: Increased iron loss may reduce the effectiveness of iron supplementation. The objective of this study was to determine if daily oral iron supplementation increases iron loss, measured using a stable isotope of iron (58Fe). We enrolled and dewormed 24 iron‐depleted Kenyan children, 24–27 months of age, whose body iron was enriched and equilibrated with 58Fe given at least 1 year earlier. Over 3 months of supplementation (6 mg iron/kg body weight [BW]/day), mean (±SD) iron absorption was 1.10 (±0.28) mg/day. During supplementation, 0.55 (±0.36) mg iron/day was lost, equal to half of the amount of absorbed iron. Supplementation did not increase faecal haem/porphyrin or biomarkers of enterocyte damage and gut or systemic inflammation. Using individual patient data, we examined iron dose, absorption and loss among all available long‐term iron isotopic studies of supplementation. Expressed in terms of body weight, daily iron loss was correlated significantly with iron absorption (Pearson's r = 0.66 [95% confidence interval 0.48–0.78]) but not with iron dose (r = 0.16 [95% CI −0.10–0.40]). The results of this study indicate that iron loss is increased with daily oral iron supplementation and may blunt the efficacy of iron supplements in children. This study was registered at ClinicalTrials.gov as NCT04721964. [ABSTRACT FROM AUTHOR]

BackgroundSilent brain infarcts (SBIs) and white matter hyperintensities are subclinical cerebrovascular lesions associated with incident stroke and cognitive decline. Left ventricular ejection fraction (LVEF) is a predictor of stroke in patients with heart failure, but its association with subclinical brain disease in the general population is unknown. Left ventricular global longitudinal strain (GLS) can detect subclinical cardiac dysfunction even when LVEF is normal. We investigated the relationship of LVEF and GLS with subclinical brain disease in a community-based cohort.Methods and resultsLVEF and GLS were assessed by 2-dimensional and speckle-tracking echocardiography in 439 participants free of stroke and cardiac disease from the Cardiovascular Abnormalities and Brain Lesions (CABL) study. SBIs and white matter hyperintensities were assessed by brain MRI. Mean age of the study population was 69±10 years, 61% were women, LVEF was 63.8±6.4%, GLS was -17.1±3.0%. SBIs were detected in 53 participants (12%), white matter hyperintensity volume was 0.63±0.86%. GLS was significantly lower in participants with SBI versus those without (-15.7±3.5% versus -17.3±2.9%, P