担当区分：筆頭著者   記述言語：英語  

DOI： 10.1038/s41440-023-01251-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background Diabetes and hypertension have been associated with adverse left ventricular (LV) remodeling. While they often occur concurrently, their individual effects are understudied. We aimed to assess the independent effects of diabetes and hypertension on LV remodeling in Black adults. Methods and Results The JHS (Jackson Heart Study) participants (n=4143 Black adults) with echocardiographic measures from baseline exam were stratified into 4 groups: neither diabetes nor hypertension (n=1643), only diabetes (n=152), only hypertension (n=1669), or both diabetes and hypertension (n=679). Echocardiographic measures of LV structure and function among these groups were evaluated by multivariable regression adjusting for covariates. Mean age of the participants was 52±1 years, and 63.7% were women. LV mass index was not different in participants with only diabetes compared with participants with neither diabetes nor hypertension (P=0.8). LV mass index was 7.9% (6.0 g/m2) higher in participants with only hypertension and 10.8% (8.1 g/m2) higher in participants with both diabetes and hypertension compared with those with neither (P<0.001). LV wall thickness (relative, posterior, and septal) and brain natriuretic peptide levels in participants with only diabetes were not significantly higher than participants with neither (P>0.05). However, participants with both diabetes and hypertension demonstrated higher LV wall thickness and brain natriuretic peptide levels than participants with neither (P<0.05). Conclusions In this cross-sectional analysis, diabetes was not associated with altered LV structure or function in Black adults unless participants also had hypertension. Our findings suggest hypertension is the main contributor to cardiac structural and functional changes in Black adults with diabetes.

DOI： 10.1161/JAHA.122.026463

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.cpcardiol.2023.101720

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

BackgroundAn arteriovenous fistula (AVF) is the most frequently used dialysis access for haemodialysis. However, it can cause volume loading for the heart and may induce circulatory failure when performed in patients with low cardiac function. This study aimed to characterise patients with low cardiac function when initiating dialysis and determine how cardiac function changes after the dialysis access surgery.MethodsWe conducted a retrospective observational study at two centres incorporating 356 patients with end-stage kidney disease who underwent echocardiography before the dialysis access surgery.ResultsAn AVF and a subcutaneously fixed superficial artery were selected in 70.4% and 23.5% of 81 patients with reduced/mildly reduced (< 50%) left ventricular ejection fraction (LVEF), respectively, and in 94.2% and 1.1% of 275 patients with preserved (>= 50%) LVEF (p < 0.001), respectively. Follow-up echocardiography was performed in 70.4% and 38.2% of patients with reduced/mildly reduced and preserved LVEF, respectively, which showed a significant increase in LVEF (41 +/- 9-44 +/- 12%, p = 0.038) in patients with reduced/mildly reduced LVEF. LVEF remained unchanged in 12 patients with reduced/mildly reduced LVEF who underwent subcutaneously fixed superficial artery (30 +/- 10-32 +/- 15%, p = 0.527). Patients with reduced/mildly reduced LVEF had lower survival rates after surgery than those with preserved LVEF (p = 0.021 for log-rank).ConclusionThe LVEF subcategory was associated with dialysis access selection. After the dialysis access surgery, LVEF was increased in patients with reduced/mildly reduced LVEF. These results may help select dialysis access for patients initiating dialysis.

DOI： 10.1007/s10157-023-02323-3

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その他リンク： https://link.springer.com/article/10.1007/s10157-023-02323-3/fulltext.html

担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: In observational studies, a lower serum vitamin D3 concentration has been associated with an increased risk of cardiovascular disease. However, the associations between serum vitamin D3 levels and left ventricular (LV) structure and heart failure with preserved ejection fraction (HFpEF) have not been well-characterized among Black Americans. The prevalence of vitamin D3 deficiency is higher among Black Americans than in other race/ethnicity groups. We hypothesized that serum vitamin D3 levels are associated with LV concentric remodeling and incident HFpEF in Black Americans. METHODS AND RESULTS: Among 5306 Black Americans in the Jackson Heart Study cohort, we investigated the relationships between serum vitamin D3 levels and LV structure and function, evaluated with echocardiography, and incident HF hospitalization, categorized as either HF with reduced EF (HFrEF; an EF of <50%) or HFpEF (an EF of ≥50%). After adjustment for possible confounding factors, lower vitamin D3 levels were associated with greater relative wall thickness (β for 1 standard deviation [SD] increase -0.003, 95% confidence interval -0.005 to -0.000). Over a median follow-up period of 11 years (range 10.2-11.0 years), 340 participants developed incident HF (7.88 cases per 1000 person-years), including 146 (43%) HFrEF and 194 (57%) HFpEF cases. After adjustment, higher serum vitamin D3 levels were associated with decreased hazard for HF overall (hazard ratio for 1 SD increase 0.88, 95% confidence interval 0.78-0.99) driven by a significant association with HFpEF (hazard ratio for 1 SD increase 0.84, 95% confidence interval 0.71-0.99). CONCLUSIONS: In this community-based Black American cohort, lower serum vitamin D3 levels were associated with LV concentric remodeling and an increased hazard for HF, mainly HFpEF. Further investigation is required to examine whether supplementation with vitamin D3 can prevent LV concentric remodeling and incident HFpEF in Black Americans.

DOI： 10.1016/j.cardfail.2022.07.049

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Tumor necrosis factor (TNF)-α is a potent mediator of inflammation and is involved in the pathophysiology of chronic kidney disease (CKD). However, the effects of TNF-α inhibition on the progression of kidney fibrosis have not been fully elucidated. We examined the effects of TNF-α inhibition by etanercept (ETN) on kidney inflammation and fibrosis in mice with aristolochic acid (AA) nephropathy as a model of kidney fibrosis. C57BL/6 J mice were administered AA for 4 weeks, followed by a 4-week remodeling period. The mice exhibited kidney fibrosis, functional decline, and albuminuria concomitant with increases in renal mRNA expression of inflammation- and fibrosis-related genes. The 8-week ETN treatment partially but significantly attenuated kidney fibrosis and ameliorated albuminuria without affecting kidney function. These findings were accompanied by significant suppression of interleukin (IL)-1β, IL-6, and collagen types I and III mRNA expression. Moreover, ETN tended to reduce the AA-induced increase in interstitial TUNEL-positive cells with a significant reduction in Bax mRNA expression. Renal phosphorylated p38 MAPK was significantly upregulated by AA but was normalized by ETN. These findings indicate a substantial role for the TNF-α pathway in the pathogenesis of kidney fibrosis and suggest that TNF-α inhibition could become an adjunct therapeutic strategy for CKD with fibrosis.

DOI： 10.1038/s41598-021-02864-1

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.mayocp.2021.07.018

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Elevated angiotensin-converting enzyme 2 (ACE2) expression in organs that are potential targets of severe acute respiratory syndrome coronavirus 2 may increase the risk of coronavirus disease 2019 (COVID-19) infection. Previous reports show that ACE2 alter its tissue-specific expression patterns under various pathological conditions, including renal diseases. Here, we examined changes in pulmonary ACE2 expression in two mouse chronic kidney disease (CKD) models: adenine-induced (adenine mice) and aristolochic acid-induced (AA mice). We also investigated changes in pulmonary ACE2 expression due to renin-angiotensin system (RAS) blocker (olmesartan) treatment in these mice. Adenine mice showed significant renal functional decline and elevated blood pressure, compared with controls. AA mice also showed significant renal functional decline, compared with vehicles; blood pressure did not differ between groups. Renal ACE2 expression was significantly reduced in adenine mice and AA mice; pulmonary expression was unaffected. Olmesartan attenuated urinary albumin excretion in adenine mice, but did not affect renal or pulmonary ACE2 expression levels. The results suggest that the risk of COVID-19 infection may not be elevated in patients with CKD because of their stable pulmonary ACE2 expression. Moreover, RAS blockers can be used safely in treatment of COVID-19 patients with CKD.

DOI： 10.1038/s41598-021-96294-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Ovid Technologies (Wolters Kluwer Health)  

<sec xml:lang="en">
<title>Background</title>
<p xml:lang="en">Although Black adults are more likely to die from coronary heart disease (CHD) compared with White adults, few studies have examined the relationship between cigarette smoking and CHD risk among Black adults. We evaluated the relationship between cigarette smoking, incident CHD, and coronary artery calcification in the JHS (Jackson Heart Study).


</sec>
<sec xml:lang="en">
<title>Methods and Results</title>
<p xml:lang="en">We classified JHS participants without a history of CHD (n=4432) by self‐reported baseline smoking status into current, former (smoked at least 400 cigarettes/life) or never smokers at baseline (2000–2004). We further classified current smokers by smoking intensity (number of cigarettes smoked per day [1–19 or ≥20]) and followed for incident CHD (through 2016). Hazard ratios (HR) for incident CHD for each smoking group compared with never smokers were estimated with adjusted Cox proportional hazard regression models. At baseline, there were 548 (12.4%) current, 782 (17.6%) former, and 3102 (70%) never smokers. During follow‐up (median, 13.8 years), 254 participants developed CHD. After risk factor adjustment, CHD risk was significantly higher in current smokers compared with never smokers (HR, 2.11; 95% CI, 1.39–3.18); the difference between former smokers and never smokers (HR, 1.37; 95% CI, 1.0–1.90) did not achieve statistical significance. Among current smokers, we did not observe a dose‐response effect for CHD risk. Additionally, in multivariable logistic regression models with a subset of our analytic cohort, current smokers had greater odds of coronary artery calcification score &gt;0 compared with never smokers (odds ratio, 2.63; 95% CI, 1.88–3.68).


</sec>
<sec xml:lang="en">
<title>Conclusions</title>
<p xml:lang="en">In a large prospective cohort of Black adults, current smoking was associated with a &gt;2‐fold increased risk of CHD over a median follow‐up of greater than a decade.


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DOI： 10.1161/jaha.120.017320

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.mayocp.2020.09.042

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.1038/s41440-020-00567-0

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その他リンク： http://www.nature.com/articles/s41440-020-00567-0

担当区分：筆頭著者,　責任著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.amjcard.2020.08.025

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background Blacks are disproportionately affected by stroke compared with whites; however, less is known about the relationship between stroke and cigarette smoking in blacks. Therefore, we evaluated the relationship between cigarette smoking and all incident stroke in the JHS (Jackson Heart Study). Methods and Results JHS participants without a history of stroke (n=4410) were classified by self-reported baseline smoking status into current, past (smoked at least 400 cigarettes/life), or never smokers at baseline (2000-2004). Current smokers were further classified by smoking intensity (number of cigarettes smoked per day [1-19 and ≥20]) and followed up for incident stroke (through 2015). Hazard ratios (HRs) for incident stroke for current and past smoking compared with never smoking were estimated with adjusted Cox proportional hazard regression models. After adjusting for cardiovascular risk factors, the risk for stroke in current smokers was significantly higher compared with never smokers (HR, 2.48; 95% CI, 1.60-3.83) but there was no significant difference between past smokers and never smokers (HR, 1.10; 95% CI, 0.74-1.64). There was a dose-dependent increased risk of stroke with smoking intensity (HR, 2.28 [95% CI, 1.38-3.86] and HR, 2.78 [95% CI, 1.47-5.28] for current smokers smoking 1-19 and ≥20 cigarettes/day, respectively). Conclusions In a large cohort of blacks, current cigarette smoking was associated with a dose-dependent higher risk of all stroke. In addition, past smokers did not have a significantly increased risk of all stroke compared with never smokers, which suggests that smoking cessation may have potential benefits in reducing the incidence of stroke in blacks.

DOI： 10.1161/JAHA.119.014990

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Hypertensive diseases in pregnancy have been associated with altered cardiac structure and function, yet these associations have not been systematically investigated in larger populations including African Americans. We evaluated the relationships between hypertensive diseases in pregnancy with cardiac structure and function later in life in the Genetic Epidemiology Network of Arteriopathy (GENOA) study. METHODS: We investigated 1013 African American women sibships with echocardiographic measurements from the GENOA study (Phase II, 2000-05; Jackson, MS). Women were classified as self-reported nulliparous (n = 61), a history of normotensive pregnancies (n = 780), a history of a hypertensive pregnancies (n = 152), or a history of preeclampsia (n = 20). We compared adjusted associations among these 4 groups with echocardiographic measurements of cardiac structure and function using generalized estimating equations, accounting for familial clustering. RESULTS: Among 1013 women with echocardiographic data (mean age 62 ± 9.5 years), women with a history of hypertensive pregnancy had lower left ventricular ejection fraction (LVEF) (P = 0.043) compared to nulliparous women and higher left atrial systolic dimension (LASD) compared to women with a history of normotensive pregnancies (P = 0.010), After adjusting for cardiovascular risk factors. There were no statistically significant differences in other echocardiographic parameters among these groups. CONCLUSIONS: A history of hypertension in pregnancy is associated with lower LVEF later in life, compared to nulliparous women and higher LASD compared to women with a history of normotensive pregnancies. However, given the multiple comparisons considered, this finding should be interpreted cautiously and requires further study.

DOI： 10.1016/j.preghy.2020.05.010

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Chronic kidney disease (CKD) progresses to end-stage renal failure via renal tubulointerstitial fibrosis. Malnutrition, inflammation, and arteriosclerosis interact to exacerbate the poor prognosis of CKD, and their effective management is thus essential. The traditional Japanese medicine Rikkunshito (RKT) exerts appetite-stimulating effects via ghrelin, which attenuates inflammation and fibrosis. We evaluated the therapeutic effect of RKT in unilateral ureter obstruction (UUO)-induced renal fibrosis/inflammation and body weight loss in mice. UUO and sham-operated mice were fed a standard diet or diet containing 3.0% RKT. Renal fibrosis was investigated by histopathology and macrophage infiltration was determined by immunohistochemistry. Expression levels of genes associated with fibrosis, inflammation, ghrelin, and mitochondrial function were determined by quantitative reverse transcription-polymerase chain reaction and western blot analyses. RKT treatment partially prevented UUO-induced weight loss but failed to attenuate renal fibrosis and inflammation. Renal expression of sirtuin 1, a ghrelin-downstream signalling molecule, and gene expression of peroxisome proliferator-activated receptor-γ coactivator 1α and Bcl-2/adenovirus E1B interacting protein 3 were unaffected by RKT. These results indicate that RKT inhibits weight loss but does not improve renal fibrosis or inflammation in a rapidly progressive renal fibrosis mouse model. RKT may have a protective effect on weight loss associated with CKD.

DOI： 10.1038/s41598-020-58214-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/s41598-019-52566-y

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.jchf.2019.06.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1536/ihj.18-394.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1161/JAHA.118.010674.

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/s41440-018-0062-0.

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担当区分：筆頭著者,　責任著者  

DOI： 10.1016/j.jjcc.2017.11.004

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担当区分：筆頭著者  

DOI： 10.1161/CIRCULATIONAHA.117.031912

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

AimOsteoprotegerin (OPG) is associated with a poor prognosis in patients with heart failure with preserved ejection fraction (HFpEF). OPG has also been associated with fibrosis and collagen cross-linking, which increase arterial and left ventricle (LV) myocardial stiffness. Little is known about the relation of OPG and LV structure and function in African-Americans who are disproportionately affected by HFpEF.Methods and resultsOur analysis included 1172 participants with preserved LV ejection fraction (&gt;50%) from the African-American cohort in the Genetic Epidemiology Network of Arteriopathy Study (mean age 63 years, 72% female). We used diastolic wall strain indicator measured by echocardiography to assess LV myocardial stiffness. Diastolic wall strain was calculated as (LV posterior thickness at end-systole-LV posterior thickness at end-diastole)/LV posterior thickness at end-systole. Associations between OPG levels and indices of arterial and LV structure and function were evaluated by using generalized linear mixed models and adjusted for possible confounders. OPG levels were correlated with age, female sex, presence of hypertension and diabetes, and lower estimated glomerular filtration rate (P&lt;0.05 for all). Multivariable analysis revealed that higher OPG levels were associated with greater LV mass index, increased LV myocardial stiffness, and higher N-terminal prohormone brain natriuretic peptide levels (P&lt;0.05 for all).ConclusionIn African-Americans, higher OPG levels were associated with characteristics common in patients with HFpEF and were significantly associated with known precursors to HFpEF. These findings indicate a potential role for OPG in the pathophysiology of HFpEF in African-Americans.

DOI： 10.2459/JCM.0000000000000549

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Public Library of Science (PLoS)  

DOI： 10.1371/journal.pone.0184914

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

Background: Left ventricular false tendons (LVFTs) are chord-like structures that traverse the LV cavity and are generally considered to be benign. However, they have been associated with arrhythmias, LV hypertrophy and LV dilation in some small studies. We hypothesize that LVFTs are associated with LV structural and functional changes assessed by echocardiography.
Methods: We retrospectively evaluated echocardiographic and clinical parameters of 126 patients identified as having LVFTs within the past 2 years and compared them to 85 age-matched controls without LVFTs.
Results: There were no significant differences in age (52 +/- 18 versus 54 +/- 18 years, P = 0.37), sex (55% versus 59% men, P = 0.49), race (36% versus 23% white, P = 0.07), systolic blood pressure (131 +/- 22 versus 132 +/- 23 mmHg, P = 0.76) or body mass index (BMI, 31 +/- 8 versus 29 +/- 10 kg/m(2), P = 0.07) between controls and patients with LVFTs, respectively. Patients with LVFTs had more prevalent heart failure (43% versus 21%, P = 0.001). Patients with LVFTs had more LV dilation, were 2.5 times more likely to have moderate-to-severe mitral regurgitation, had more severe diastolic dysfunction and reduced LV systolic function (18% lower) compared with controls (all P &lt; 0.05). After adjustment for covariates, basal and middle LVFT locations were associated with reduced LV systolic function (P &lt; 0.01), and middle LVFTs were associated with LV dilation (P &lt; 0.01).
Conclusions: Our findings suggest that LVFTs may not be benign variants, and basal and middle LVFTs may have more deleterious effects. Further prospective studies should be performed to determine their pathophysiological significance and whether they play a causal role in LV dysfunction.

DOI： 10.1016/j.amjms.2017.05.015

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS  

Background: Clinical risk factors associated with heart failure (HF) symptoms in aortic stenosis (AS) patients with preserved ejection fraction (EF) have not been fully identified. We hypothesized that left ventricular (LV) diastolic stiffness is associated with HF symptoms in patients with AS.
Methods and Results: We retrospectively evaluated 275 patients with at least moderate AS (aortic valve area &lt;1.5 cm(2)) and preserved EF (&gt;50%). LV diastolic stiffness was evaluated with the use of echocardiographic parameters, diastolic wall strain (DWS, a measure of LV wall stiffness), and K-LV (a marker of LV chamber stiffness). There were 69 patients with HF. Patients with HF were older, were more likely to be African American, had a higher body mass index, and had more hypertension and coronary artery disease (P &lt; .05 for all). Aortic valve area index and mean pressure gradient across the aortic valve were not different between patients with and without HF. Despite similar echocardiographic parameters of AS severity, patients with HF had stiffer LV (DWS 0.21 +/- 0.06 vs 0.25 +/- 0.06 [P &lt; .01], K-LV 0.17 +/- 0.11 vs 0.13 +/- 0.08 [P &lt; .01]). Logistic regression analyses revealed that after adjusting for age, race, body mass index, history of hypertension, and coronary artery disease, LV diastolic stiffness parameters remained significantly associated with HF symptoms.
Conclusions: LV diastolic stiffness is independently associated with HF in AS patients with preserved EF.

DOI： 10.1016/j.cardfail.2017.05.002

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

Background-Enlargement of the proximal aorta is associated with aortic wall tissue remodeling, including fragmentation of the elastin fibers, increased synthesis of collagen, and calcification, all of which are associated with aortic wall stiffening. We hypothesized that the proximal aortic diameter (AoD) is associated with cardiovascular events in a community-based cohort of blacks.
Methods and Results-We investigated the associations between AoD and cardiovascular events among 3018 black participants (mean age, 55.9 years; 69% women) without past history of cardiovascular disease in the Jackson Heart Study. AoD was measured using echocardiography at the level of the sinuses of Valsalva at end diastole. Cardiovascular event was defined as incident myocardial infarction, fatal coronary artery disease, stroke, or heart failure hospitalization. Cox proportional hazards regression models were used to evaluate the association between baseline AoD and cardiovascular events. Over a median follow-up of 8.3 years, there were 258 cardiovascular events (incident rate, 10.5 per 1000 person-years). After adjustment for traditional risk factors, increased AoD was significantly associated with cardiovascular events (hazard ratio per 1-cm increase, 1.72; 95% CI, 1.10-2.69; P&lt;0.05). Participants in the top AoD quintile had a higher incidence of cardiovascular events compared to those not in the top quintile (hazard ratio, 1.47; 95% CI, 1.11-1.94; P&lt;0.005) after adjustment for risk factors.
Conclusions-Greater AoD was associated with an increased risk of cardiovascular events in a community-based cohort of blacks. AoD may be useful as a predictor of incident cardiovascular events and further investigation is warranted.

DOI： 10.1161/JAHA.116.005005

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OXFORD UNIV PRESS  

BACKGROUND
Physical activity (PA) has been associated with decreased left ventricular (LV) hypertrophy in previous studies. However, little is known about the relationship between PA and LV structure and factors which influence this relationship among African Americans.
METHODS
We evaluated 1,300 African Americans with preserved LV ejection fraction (EF &gt; 50%) from the Genetic Epidemiology Network of Arteriopathy (GENOA) Study (mean age 62.4 years, 73% women). PA index was calculated as 3 * heavy activity hours + 2 * moderate activity hours + slight activity hours/day. The relationship between PA index and LV structure was evaluated using generalized estimating equation. The association between PA index and LV mass index by age group, sex, body mass index (BMI), history of hypertension, diabetes or coronary heart disease, estimated glomerular filtration rate, and current smoking status were plotted.
RESULTS
After adjustment for these factors, higher PA index was independently associated with lower LV mass index (P &lt; 0.05). There were significant interactions between PA index and obesity (BMI = 30) and history of hypertension on LV mass index (P for interaction &lt; 0.05, for both). Higher PA index was associated with lower LV mass index more in obese or hypertensive participants compared with nonobese or nonhypertensive participants.
CONCLUSIONS
Higher PA index was associated with reduced LV hypertrophy in obese and hypertensive African Americans. Prospective studies aimed at assessing whether increasing PA prevents LV hypertrophy and potentially reduces the risk of heart failure in these at risk groups are warranted.

DOI： 10.1093/ajh/hpx044

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS  

Background: Early-diastolic left ventricular (LV) longitudinal expansion is delayed with diastolic dysfunction. We hypothesized that, in patients with heart failure (HF), regardless of LV ejection fraction (EF), there is diastolic temporal nonuniformity with a delay of longitudinal relative to circumferential expansion.
Methods and Results: Echocardiography was performed in 143 HF patients-50 with preserved EF (HFpEF) and 93 with reduced EF (HFrEF)-as well as 31 normal control subjects. The delay of early-diastolic mitral annular velocity from the mitral Doppler E (TE-e ') was measured as a parameter of the longitudinal expansion delay. The delay of the longitudinal early-diastolic global strain rate (SRE) relative to circumferential SRE (Delay(C-L)) was calculated as a parameter of temporal nonuniformity. Intra-LV pressure difference (IVPD) was estimated with the use of color M-mode Doppler data as a parameter of LV diastolic suction. Although normal control subjects had symmetric LV expansion in early diastole, TE-e ' and Delay(C-L) were significantly prolonged in HF regardless of EF (P &lt;.01 vs control for all). Multivariate analysis revealed that Delay(C-L) was the independent determinant of IVPD among the parameters of LV geometry and contraction (beta = -0.21; P &lt; .05).
Conclusion: An abnormal temporal nonuniformity of early-diastolic expansion is present in HF regardless of EF, which was associated with reduced LV suction.

DOI： 10.1016/j.cardfail.2016.04.007

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Background-Time to peak velocity (TPV) is an echocardiographic variable that can be easily measured and reflects a late peaking murmur, a classic physical finding suggesting severe aortic stenosis (AS). The aim of this study was to investigate the usefulness of TPV to evaluate AS severity.
Methods and Results-This study included 700 AS patients, whose aortic valve area (AVA) was &lt;1.5 cm(2), and 200 control patients. The TPV was defined as the time from aortic valve opening to when the flow velocity across the aortic valve reaches its peak. AS severity was classified as follows: High gradient severe AS, mean pressure gradient &gt;= 40 mm Hg and AVA index (AVAI) &lt;0.6 cm(2)/m(2); Low gradient severe AS, mean pressure gradient &lt;40 mm Hg, AVAI &lt;0.6 cm(2)/m(2), and dimensionless index &lt;0.25; moderate AS, mean pressure gradient &lt;40 mm Hg, AVAI &gt;= 0.6 cm(2)/m(2). The area under the receiver operating characteristic curve of TPV to predict high gradient severe AS was 0.94 (95% CI: 0.92-0.97, P&lt;0.001). TPV was significantly delayed in low gradient severe AS compared with moderate AS both in patients with preserved (102 +/- 13 ms versus 83 +/- 13 ms, P&lt;0.001) and with reduced ejection fraction (110 +/- 18 ms versus 88 +/- 13 ms, P&lt;0.001). Delayed TPV was associated with increased all-cause mortality or need for aortic valve replacement after adjustment for confounders (hazard ratio for first quartile, reference is fourth quartile: 7.31, 95% CI 4.26-12.53, P&lt;0.001).
Conclusions-TPV is useful to evaluate AS severity and predict poor prognosis of AS patients.

DOI： 10.1161/JAHA.116.003907

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1097/FJC.0000000000000397

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MOSBY-ELSEVIER  

Background: The left ventricle fills in early diastole because of a progressive intraventricular pressure difference (IVPD) that extends from the left atrium to the left ventricular (LV). The aim of this study was to test the hypothesis that in patients with symptomatic heart failure (HF) regardless of LV ejection fraction (EF), an increase in left atrial (LA) pressure maintains early diastolic filling because of a preserved IVPD from the left atrium to the mid left ventricle, while the IVPD from the mid left ventricle to the apex is diminished because of reduced LV suction.
Methods: One hundred fifty-one patients with HF (50 with HF with preserved EF [HFpEF; EF &gt;= 50%] and 101 with HF with reduced EF [HFrEF; EF &lt; 50%]) and 28 normal controls were prospectively enrolled. The IVPDs from the left atrium to the LV apex (total IVPD), the left atrium to the mid left ventricle (basilar IVPD), and the mid left ventricle to the apex (apical IVPD) were determined using color M-mode Doppler echocardiographic data to integrate the Euler equation. The propagation of early diastolic filling was also assessed by color M-mode Doppler.
Results: The mean LV EF was 0.63 +/- 0.07 in patients with HFpEF, 0.32 +/- 0.09 in those with HFrEF, and 0.64 +/- 0.06 in controls. Peak early diastolic transmitral flow velocities (E) were similar among the groups, and basilar IVPDs were maintained in the HFpEF and HFrEF groups (HFpEF, 1.59 +/- 0.62 mm Hg; HFrEF, 1.49 +/- 0.75 mm Hg; controls, 1.80 +/- 0.61 mm Hg; P = NS, analysis of variance). However, apical IVPDs were decreased in both HF groups (HFpEF, 1.18 +/- 0.56 mm Hg [P &lt; .01 vs controls]; HFrEF, 0.87 +/- 0.48 mm Hg [P &lt; .01 vs controls]; controls, 1.65 +/- 0.62 mm Hg), resulting in decreased total IVPDs in patients with HF (HFpEF, 2.55 +/- 0.80 mm Hg [P &lt; .01 vs controls]; HFrEF, 2.16 +/- 0.80 mm Hg [P &lt; .01 vs controls]; controls, 3.17 +/- 0.91 mm Hg). E/e' ratios were increased in patients with HF, consistent with elevated LA pressure. In patients with HF, E was correlated with basilar IVPD but not with apical IVPD, whereas propagation of the filling was correlated with the apical IVPD but not with the basilar IVPD.
Conclusions: In patients with HFpEF and those with HFrEF, apical IVPDs were reduced while basilar IVPDs were maintained by elevated LA pressure, resulting in preserved E.

DOI： 10.1016/j.echo.2015.01.002

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Background: A small proximal aortic diameter (AoD) is thought to be associated with a higher characteristic impedance of the proximal aorta. However, there has been no evidence of a relationship between directly evaluated AoD and directly measured central aortic pressure or the outcome of patients with cardiovascular diseases. Methods and Results: (a) In 135 patients without heart failure (HF), who underwent coronary catheterization, we retrospectively examined the relationship between the AoD and the central aortic pressure or aortic elastance. The AoD adjusted with covariates was inversely correlated with the central pulse pressure (cPP; coefficient = -0.75; P = 0.04; model R-2 = 0.575) and the effective arterial elastance index (coefficient = -0.12; P = 0.001; model R-2 = 0.366). (b) In 197 patients who were hospitalized due to HF, we examined the relationship between the AoD (evaluated using echocardiography) and the outcome using a Cox proportional hazard model. Fifty-three patients died from various causes during the follow-up period (2.2 +/- 1.1 years). Multivariable analysis revealed that the AoD remained an independent risk factor for all-cause death (hazard ratio for 1 s.d. increase of the AoD: 0.68, 95% confidence interval: 0.50-0.92, P = 0.013) and cardiovascular death (hazard ratio for 1 s.d. increase of the AoD: 0.63, 95% confidence interval: 0.43-0.93, P = 0.019). Conclusions: A small AoD was associated with a higher cPP and aortic stiffening in the patients without HF, as well as with a poor outcome for HF patients. Although it is easy to evaluate the AoD, it may offer important information regarding the pulsatile load and may be useful for risk stratification of HF patients.

DOI： 10.1038/hr.2013.111

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Chronic heart failure (CHF) with preserved left ventricular (LV) ejection fraction (HFpEF) is observed in half of all patients with CHF and carries the same poor prognosis as CHF with reduced LV ejection fraction (HFrEF). In contrast to HFrEF, there is no established therapy for HFpEF. Chronic inflammation contributes to cardiac fibrosis, a crucial factor in HFpEF; however, inflammatory mechanisms and mediators involved in the development of HFpEF remain unclear. Therefore, we sought to identify novel inflammatory mediators involved in this process. METHODS AND RESULTS: An analysis by multiplex-bead array assay revealed that serum interleukin-16 (IL-16) levels were specifically elevated in patients with HFpEF compared with HFrEF and controls. This was confirmed by enzyme-linked immunosorbent assay in HFpEF patients and controls, and serum IL-16 levels showed a significant association with indices of LV diastolic dysfunction. Serum IL-16 levels were also elevated in a rat model of HFpEF and positively correlated with LV end-diastolic pressure, lung weight and LV myocardial stiffness constant. The cardiac expression of IL-16 was upregulated in the HFpEF rat model. Enhanced cardiac expression of IL-16 in transgenic mice induced cardiac fibrosis and LV myocardial stiffening accompanied by increased macrophage infiltration. Treatment with anti-IL-16 neutralizing antibody ameliorated cardiac fibrosis in the mouse model of angiotensin II-induced hypertension. CONCLUSION: Our data indicate that IL-16 is a mediator of LV myocardial fibrosis and stiffening in HFpEF, and that the blockade of IL-16 could be a possible therapeutic option for HFpEF.

DOI： 10.1371/journal.pone.0068893

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Objectives: Prognosis of heart failure with preserved ejection fraction (HFpEF) remains poor because of unknown pathophysiology and unestablished therapeutic strategy. This study aimed to identify a potential therapeutic intervention for HFpEF through metabolomics-based analysis.
Methods and results: Metabolomics with capillary electrophoresis time-of-flight mass spectrometry was performed using plasma of Dahl salt-sensitive rats fed high-salt diet, a model of hypertensive HFpEF, and showed decreased free-carnitine levels. Reassessment with enzymatic cycling method revealed the decreased plasma and left-ventricular free-carnitine levels in the HFpEF model. Urinary free-carnitine excretion was increased, and the expression of organic cation/carnitine transporter 2, which transports free-carnitine into cells, was down-regulated in the left ventricle (LV) and kidney in the HFpEF model. L-Carnitine was administered to the hypertensive HFpEF model. L-Carnitine treatment restored left-ventricular free-carnitine levels, attenuated left-ventricular fibrosis and stiffening, prevented pulmonary congestion, and improved survival in the HFpEF model independent of the antihypertensive effects, accompanied with increased expression of fatty acid desaturase (FADS) 1/2, rate-limiting enzymes in forming arachidonic acid, and enhanced production of arachidonic acid, a precursor of prostacyclin, and prostacyclin in the LV. In cultured cardiac fibroblasts, L-carnitine attenuated the angiotensin II-induced collagen production with increased FADS1/2 expression and enhanced production of arachidonic acid and prostacyclin. L-Carnitine-induced increase of arachidonic acid was canceled by knock-down of FADS1 or FADS2 in cultured cardiac fibroblasts. Serum free-carnitine levels were decreased in HFpEF patients.
Conclusions: L-carnitine supplementation attenuates cardiac fibrosis by increasing prostacyclin production through arachidonic acid pathway, and may be a promising therapeutic option for HFpEF.

DOI： 10.1097/HJH.0b013e3283569c5a

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OXFORD UNIV PRESS  

Left ventricular (LV) fibrosis and stiffening play crucial roles in the development of heart failure with preserved ejection fraction (HFPEF). Plasma level of digitalis-like factors (DLFs) is increased in patients with hypertension, a principal underlying cardiovascular disease of HFPEF. Digitalis-like factors inhibit ion-pumping function of Na/K-ATPase and activate the Ca-2 entry mode of Na/Ca-2 exchanger (NCX). Digitalis-like factors are known to promote collagen production in fibroblasts. The aim of this study was to explore whether the pharmacological inhibition of the NCX entry mode is effective in the prevention of LV fibrosis and in the development of HFPEF.
(i) Dahl salt-sensitive rats fed 8 NaCl diet from age 6 weeks served as hypertensive HFPEF model. In this model, 24 h urine excretion of DLFs was greater than that in the age-matched control at compensatory hypertrophic and heart failure stages. (ii) Continuous administration of ouabain for 14 weeks developed LV fibrosis without affecting blood pressure in SpragueDawley rats. (iii) Ouabain elevated intracellular Ca-2 concentration through the entry of extracellular Ca-2, increased the phosphorylation level of p42/44 mitogen-activated protein kinases, and enhanced H-3-proline incorporation in cardiac fibroblast; and SEA0400, the inhibitor of the NCX entry mode, suppressed these effects. (iv) In the HFPEF model, administration of SEA0400 at subdepressor dose improved the survival rate in association with the attenuation of LV fibrosis and stiffening.
Digitalis-like factors and the subsequently activated NCX entry mode may play an important role in the development of hypertensive HFPEF, and the blockade of the NCX entry mode may be a new therapeutic strategy for this phenotype of heart failure.

DOI： 10.1093/eurheartj/ehr106

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：INT HEART JOURNAL ASSOC  

Nemaline myopathy is a representative form of congenital myopathy, and is characterized by nemaline bodies in muscle fibers. Here we report a 47-year-old man with congenital nemaline myopathy complicated with dilated cardiomyopathy-related heart failure, and restrictive respiratory failure. The complication of dilated cardiomyopathy in nemaline myopathy has rarely been reported. In this case, nemaline bodies were detected in the cardiac muscle fibers, demonstrating the presence of underlying disease-related myocardial degeneration. The patient responded to the combination of conventional therapy for heart failure including beta-blocker and noninvasive continuous positive-pressure ventilation for respiratory failure. His general condition has been stable during a 10-month follow up period. (Int Heart J 2011; 52: 401-405)

DOI： 10.1536/ihj.52.401

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OXFORD UNIV PRESS  

Aims The prevalence of heart failure with preserved ejection fraction (HFpEF) has increased in the past two decades, and diabetes mellitus (DM) is frequently associated with HFpEF. Although it has been demonstrated that left ventricular (LV) diastolic and vascular functional abnormalities are generally observed in HFpEF, it remains to be clinically elucidated how an asymptomatic stage progresses to symptomatic HFpEF in DM patients. We aimed to identify risk factors associated with incident HFpEF in DM patients and to evaluate the contribution of LV relaxation and compliance to the development of HFpEF.
Methods and results The study included 544 consecutive Japanese DM patients with ejection fraction &gt;= 50%. Patients with coronary artery disease or serum creatinine &gt;= 2.0 mg/dL were excluded. Multiple logistic regression analysis revealed that obesity, female gender, anaemia, and impaired LV compliance were independently associated with the prevalence of HFpEF, and that age, LV mass index, an index of LV relaxation, estimated glomerular filtration rate, and history of hypertension were not. There was no difference in haemoglobin A1c or brachial-ankle pulse wave velocity between the DM patients with and without HFpEF.
Conclusions This study suggests that exacerbation of LV compliance impairment, rather than of relaxation abnormality or vascular stiffening, plays a crucial role in the induction of HFpEF in DM patients regardless of the severity of DM and renal dysfunction. Anaemia and obesity may also contribute to the transition from asymptomatic stage to symptomatic HFpEF even without further progression of LV diastolic dysfunction.

DOI： 10.1093/eurjhf/hfr019

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER IRELAND LTD  

The beneficial effects of beta-blocker therapy on the clinical outcomes of heart failure with reduced ejection fraction (HFREF) are attributed to the improvement in ejection fraction (EF) and left ventricular (LV) reverse remodeling. Previous studies only reported the beta-blocker therapy-induced improvement of diastolic function accompanied by the increase in EF in HFREF patients. This retrospective study aimed to elucidate whether beta-blocker therapy improves diastolic function even without an increase in EF. Out of the consecutive 11,830 echocardiographic reports, HFREF patients without an increase in EF following long-term beta-blocker therapy comprised the study subjects (n= 19). During the mean follow-up of 17 months, beta-blocker therapy significantly decreased peak mitral E-wave velocity (70 +/- 25-50 +/- 18 cm/s, p&lt; 0.01) and ratio of peak mitral E- to A-wave velocities (E/A ratio) (1.4 +/- 0.8-0.9 +/- 0.4, p&lt; 0.05), prolonged deceleration time of the mitral E-wave velocity (DcT) (167 +/- 54-206 +/- 61 ms, p &lt;0.05), and improved New York Heart Association functional class (2.3 +/- 0.7-1.8 +/- 0.4, p &lt; 0.01) without changes in LV volume. Because DcT and E/A ratio are well known to correlate with LV filling pressures in patients with reduced EF, our results indicate a reduction in LV filling pressures without changes in LV volume, suggesting a reduction in LV stiffness. Thus, long-term beta-blocker therapy is likely to improve diastolic function even without a concomitant increase in EF in HFREF patients, which may be also responsible for the beta-blocker-induced improvement of their symptoms of heart failure. (C) 2010 Japanese College of Cardiology. Published by Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.jjcc.2010.04.001

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

A 65-year-old female was first treated under a diagnosis of rheumatoid arthritis at the age of 62 years. Just after subcutaneous rheumatoid nodules appeared, she suddenly complained of shortness of breath and vomiting. The diagnosis was overt congestive heart failure with complete atrioventricular block and severe mitral regurgitation. She was treated with temporary pacing, and a permanent pacemaker was implanted 1 month later. She suffered recurrence of congestive heart failure and died 8 months later. Autopsy revealed a giant rheumatoid nodule located on the mitral valve and extending to the atrioventricular node. Presumedly this solitary giant nodule had induced complete atrioventricular block and severe mitral regurgitation.

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ELSEVIER SCIENCE INC  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS  

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記述言語：日本語   出版者・発行元：一般社団法人日本機械学会  

This paper discusses the stiffness evaluating method that can be applied to the mouse's left ventricle which size is extremely small. Based on a ring model for evaluating a specimen, we introduce FPH(Force Per Height) as an index of elasticity. By combining tensile data and geometric information, we calculate FPH in experiments. Then, we show experimental results showing the correlation between FPH and the conventional method in rat. We also show the statistical results where normal and diseased rats can be separated. Finally, the experimental results showing the applicability to mouse are shown.

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS  

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記述言語：英語   出版者・発行元：社団法人日本循環器学会  

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記述言語：英語   出版者・発行元：社団法人日本循環器学会  

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記述言語：英語   出版者・発行元：社団法人日本循環器学会  

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記述言語：英語   出版者・発行元：社団法人日本循環器学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：SPRINGER TOKYO  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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