The obesity paradox is not observed in chronic heart failure patients with metabolic syndrome

Although being overweight or obese is a risk factor for cardiovascular disease, obese subjects often live longer than their lean peers, and this is known as the obesity paradox. We investigated the impact of obesity on cardiac prognosis in chronic heart failure (CHF) patients, with or without metabolic syndrome. Design and Methods: We divided 374 consecutive CHF patients into two groups according to their mean body mass index (BMI) and prospectively followed them for 2 years. Results: There were 126 cardiac events, including 32 cardiac deaths and 94 re-hospitalizations. Kaplan-Meier analysis revealed a significantly lower cardiac event rate in the higher BMI group (log-rank test P < 0.001) in all patients and those patients without metabolic syndrome. There was no association between BMI and cardiac prognosis in patients with metabolic syndrome. Cox hazard analysis revealed that a higher BMI was associated with favorable cardiac outcomes in all patients and patients without metabolic syndrome, after adjusting for confounding factors. However, this finding did not extend to patients with metabolic syndrome. Conclusions: The advantages of obesity are not found in CHF patients with metabolic syndrome

Association of plasma thioredoxin-1 with renal tubular damage and cardiac prognosis in patients with chronic heart failure

AbstractBackgroundThioredoxin-1 (Trx-1) is an abundant 12.5kDa redox protein expressed in almost all eukaryotic cells that protect against the development of heart failure and kidney dysfunction. Plasma Trx-1 levels are considered as a reliable marker for oxidative stress. However, it remains to be determined whether plasma Trx-1 levels can predict cardiac prognosis in patients with chronic heart failure (CHF).Methods and resultsWe measured plasma Trx-1 levels and urinary β2-microglobulin–creatinine ratio (UBCR), a marker for renal tubular damage, in 156 consecutive patients with CHF and 17 control subjects. The patients were prospectively followed for a median follow-up period of 627 days and 46 cardiac events were observed. The patients with cardiac events had significantly higher plasma Trx-1 levels and UBCR levels than the cardiac event-free patients. Multivariate Cox proportional hazard analysis revealed that an elevated Trx-1 level was independently associated with poor outcome in patients with CHF after adjustment for confounding factors (hazard ratio, 1.74; 95% confidence interval, 1.33–2.29; p<0.0001). UBCR was increased with higher plasma Trx-1 levels. Kaplan–Meier analysis demonstrated that the highest Trx-1 tertile was associated with the highest risk of cardiac events.ConclusionPlasma Trx-1 level was associated with renal tubular damage and cardiac prognosis, suggesting that it could be a useful marker to identify patients at high risk for comorbid heart failure and renal tubular damage

High-mobility group box 1-mediated heat shock protein beta 1 expression attenuates mitochondrial dysfunction and apoptosis

AbstractAimsApoptosis of cardiomyocytes is thought to account for doxorubicin cardiotoxicity as it contributes to loss of myocardial tissue and contractile dysfunction. Given that high-mobility group box 1 (HMGB1) is a nuclear DNA-binding protein capable of inhibiting apoptosis, we aimed to clarify the role of HMGB1 in heat shock protein beta 1 (HSPB1) expression during doxorubicin-induced cardiomyopathy.Methods and resultsMitochondrial damage, cardiomyocyte apoptosis, and cardiac dysfunction after doxorubicin administration were significantly attenuated in mice with cardiac-specific overexpression of HMGB1 (HMGB1-Tg) compared with wild type (WT) -mice. HSPB1 levels after doxorubicin administration were significantly higher in HMGB1-Tg mice than in WT mice. Transfection with HMGB1 increased the expression of HSPB1 at both the protein and mRNA levels, and HMGB1 inhibited mitochondrial dysfunction and apoptosis after exposure of cardiomyocytes to doxorubicin. HSPB1 silencing abrogated the inhibitory effect of HMGB1 on cardiomyocyte apoptosis. Doxorubicin increased the binding of HMGB1 to heat shock factor 2 and enhanced heat shock element promoter activity. Moreover, HMGB1 overexpression greatly enhanced heat shock element promoter activity. Silencing of heat shock factor 2 attenuated HMGB1-dependent HSPB1 expression and abrogated the ability of HMGB1 to suppress cleaved caspase-3 accumulation after doxorubicin stimulation.ConclusionsWe report the first in vivo and in vitro evidence that cardiac HMGB1 increases HSPB1 expression and attenuates cardiomyocyte apoptosis associated with doxorubicin-induced cardiomyopathy. Cardiac HMGB1 increases HSPB1 expression in cardiomyocytes in a heat shock factor 2-dependent manner

Increased epicardial adipose tissue volume predicts insulin resistance and coronary artery disease in non-obese subjects without metabolic syndrome

Background/objectives: Epicardial adipose tissue (EAT) reportedly secretes various adipokines that evoke insulin resistance in patients with obesity or metabolic syndrome. However, it remains unclear whether EAT also plays a role in the development of insulin resistance in lean subjects. The purpose of this study was to investigate the impact of EAT volume on the presence of insulin resistance and coronary artery disease in non-obese subjects without metabolic syndrome. Methods: We prospectively studied 624 consecutive patients who underwent multidetector computed tomography (MDCT) and measured EAT volume between January 2009 and June 2011. Obesity was defined as body mass index ≥25 kg/m2, and metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria. After we excluded 385 patients with obesity or metabolic syndrome, 239 patients were enrolled in the present study. Results: There were 102 (42.7%) subjects with insulin resistance (homeostasis model assessment ratio [HOMA-R] >2.5) and 88 (36.8%) subjects with coronary artery disease. After adjusting for age, gender, and body mass index, increased EAT volume (≥35 ml mean EAT volume) was independently associated with insulin resistance (odds ratio 2.6, 95% confidence interval 1.5–4.8). Furthermore, increased EAT volume was also associated with coronary artery disease (odds ratio 1.9, 95% confidence interval 1.0–3.6) after adjustment of age, gender, body mass index, and the presence of insulin resistance. Conclusion: Increased EAT volume may play a key role in the development of insulin resistance and coronary artery disease, even in non-obese subjects without metabolic syndrome

Deficiency of Senescence Marker Protein 30 Exacerbates Cardiac Injury after Ischemia/Reperfusion

Early myocardial reperfusion is an effective therapy but ischemia/reperfusion (I/R) causes lethal myocardial injury. The aging heart was reported to show greater cardiac damage after I/R injury than that observed in young hearts. Senescence marker protein 30 (SMP30), whose expression decreases with age, plays a role in reducing oxidative stress and apoptosis. However, the impact of SMP30 on myocardial I/R injury remains to be determined. In this study, the left anterior descending coronary artery was occluded for 30 min, followed by reperfusion in wild-type (WT) and SMP30 knockout (KO) mice. After I/R, cardiomyocyte apoptosis and the ratio of infarct area/area at risk were higher, left ventricular fractional shortening was lower, and reactive oxygen species (ROS) generation was enhanced in SMP30 KO mice. Moreover, the previously increased phosphorylation of GSK-3β and Akt was lower in SMP30 KO mice than in WT mice. In cardiomyocytes, silencing of SMP30 expression attenuated Akt and GSK-3β phosphorylation, and increased Bax to Bcl-2 ratio and cardiomyocyte apoptosis induced by hydrogen peroxide. These results suggested that SMP30 deficiency augments myocardial I/R injury through ROS generation and attenuation of Akt activation

Association of Heart-Type Fatty Acid-Binding Protein with Cardiovascular Risk Factors and All-Cause Mortality in the General Population: The Takahata Study

<div><p>Background</p><p>Despite many recent advances in medicine, preventing the development of cardiovascular diseases remains a challenge. Heart-type fatty acid-binding protein (H-FABP) is a marker of ongoing myocardial damage and has been reported to be a useful indicator for future cardiovascular events. However, it remains to be determined whether H-FABP can predict all-cause and cardiovascular deaths in the general population.</p><p>Methods and Results</p><p>This longitudinal cohort study included 3,503 subjects who participated in a community-based health checkup with a 7-year follow-up. Serum H-FABP was measured in registered subjects. The results demonstrated that higher H-FABP levels were associated with increasing numbers of cardiovascular risk factors, including hypertension, diabetes mellitus, obesity, and metabolic syndrome. There were 158 deaths during the follow-up period, including 50 cardiovascular deaths. Deceased subjects had higher H-FABP levels compared to surviving subjects. Multivariate Cox proportional hazard regression analysis revealed that H-FABP is an independent predictor of all-cause and cardiovascular deaths after adjustments for confounding factors. Subjects were divided into four quartiles according to H-FABP level, and Kaplan-Meier analysis demonstrated that the highest H-FABP quartile was associated with the greatest risks for all-cause and cardiovascular deaths. Net reclassification index and integrated discrimination index were significantly increased by addition of H-FABP to cardiovascular risk factors.</p><p>Conclusions</p><p>H-FABP level was increased in association with greater numbers of cardiovascular risk factors and was an independent risk factor for all-cause and cardiovascular deaths. H-FABP could be a useful indicator for the early identification of high-risk subjects in the general population.</p></div

Clinical characteristics among subjects with 1^st to 4^th quartile.

<p>Data are expressed as mean ± standard deviation or number (%).</p><p>CVD, cardiovascular disease; CKD, chronic kidney disease; Mets, metabolic syndrome; LVH, left ventricular hypertrophy; AF, atrial fibrillation; BP, blood pressure; HbA1c, glycosylated hemoglobin A1c, FBG, fasting blood glucose; eGFR, estimated glomerular filtration rate; BNP, brain natriuretic peptide; H-FABP, heart type fatty acid binding protein. *p<0.05 vs. 1^st quartile, ^†p<0.05 vs. 2^nd quartile, ^‡p<0.05 vs. 3^rd quartile by analysis of variance (ANOVA) with Scheffe post hoc test. ^§p<0.05 by chi-square test.</p

Clinical characteristics of subjects with and without all-cause deaths.

<p>Data are expressed as mean ± standard deviation or number (%).</p><p>CVD, cardiovascular disease; CKD, chronic kidney disease; MetS, metabolic syndrome; LVH, left ventricular hypertrophy; AF, atrial fibrillation; BP, blood pressure; HbA1c, glycosylated hemoglobin A1c, FBG, fasting blood glucose; eGFR, estimated glomerular filtration rate; BNP, brain natriuretic peptide; H-FABP, heart type fatty acid binding protein.</p

Statics for model fit and improvement with the addition of H-FABP on the prediction of all-cause mortality.

<p>AUC, area under the curve; 95%CI, 95% confidence interval; NRI, net reclassification index; IDI, integrated discrimination index; HT, hypertension; DM, diabetes mellitus; Mets, metabolic syndrome; BNP, brain natriuretic peptide; H-FABP, heart type fatty acid binding protein.</p

Univariate Cox proportional hazard analysis for all-cause mortality.

<p>CVD, cardiovascular disease; CKD, chronic kidney disease; MetS, metabolic syndrome; LVH, left ventricular hypertrophy; AF, atrial fibrillation; BP, blood pressure; HbA1c, glycosylated hemoglobin A1c; FBG, fasting blood glucose; eGFR, estimated glomerular filtration rate; BNP, brain natriuretic peptide; H-FABP, heart type fatty acid binding protein.</p