The in vivo effect of transforming growth factor-beta 1 (TGF-beta 1) was studied in a model system in which arterial intimal thickening was induced by injury of rabbit arteries with a balloon catheter (BCI). Intimal area and its ratio to medial area in carotid arteries after BCI were significantly higher in rabbits treated with 10 micrograms/kg TGF-beta 1 and 10 mg/kg aspirin i.v. QD (TGF-beta 1 group) than in those treated with 10 mg/kg aspirin i.v. QD only (control group). Intimal cell numbers in the TGF-beta 1 and control groups were not significantly different from each other, but matrix volume in the intimal layer was significantly higher in the TGF-beta 1 group. By immunohistochemical and Northern blot analyses, the fibronectin content in carotid intimal and medial layers was greater in the TGF-beta 1 group compared with that in the control group. Thus, in intimal thickenings induced by BCI. TGF-beta 1 mainly enhanced the formation of matrix containing fibronectin. Moreover, the mRNAs of TGF-beta 1 and type II receptors were detected in carotid arteries 7 and 14 days after, but not before, BCI. Thus, TGF-beta 1 influences the process of intimal thickening induced by BCI through a receptor-mediated mechanism in vivo. The significance of this fact is discussed in relation to the development of atherosclerosis.

BackgroundAlthough epicardial adipose tissue (EAT) is associated with coronary artery disease (CAD), it is unclear whether EAT volume (EAV) can be used to diagnose high-risk coronary plaque burden associated with coronary events. This study aimed to investigate (1) the prognostic impact of low-attenuation non-calcified coronary plaque (LAP) burden on patient level analysis, and (2) the association of EAV with LAP volume in patients without known CAD undergoing coronary computed tomography angiography (CCTA).Materials and MethodsThis retrospective study consisted of 376 patients (male, 57%; mean age, 65.2 ± 13 years) without known CAD undergoing CCTA. Percent LAP volume (%LAP, <30 HU) was calculated as the LAP volume divided by the vessel volume. EAT was defined as adipose tissue with a CT attenuation value ranging from −250 to −30 HU within the pericardial sac. The primary endpoint was a composite event of death, non-fatal myocardial infarction, and unstable angina and worsening symptoms requiring unplanned coronary revascularization >3 months after CCTA. The determinants of %LAP (Q4) were analyzed using a multivariable logistic regression model.ResultsDuring the follow-up period (mean, 2.2 ± 0.9 years), the primary endpoint was observed in 17 patients (4.5%). The independent predictors of the primary endpoint were %LAP (Q4) (hazard ratio [HR], 3.05; 95% confidence interval [CI], 1.09–8.54; p = 0.033] in the Cox proportional hazard model adjusted by CAD-RADS category. Cox proportional hazard ratio analysis demonstrated that %LAP (Q4) was a predictor of the primary endpoint, independnet of CAD severity, Suita score, EAV, or CACS. The independent determinants of %LAP (Q4) were CACS ≥218.3 (p < 0.0001) and EAV ≥125.3 ml (p < 0.0001). The addition of EAV to CACS significantly improved the area under the curve (AUC) to identify %LAP (Q4) than CACS alone (AUC, EAV + CACS vs. CACS alone: 0.728 vs. 0.637; p = 0.013).ConclusionsCCTA-based assessment of EAV, CACS, and LAP could help improve personalized cardiac risk management by administering patient-suited therapy.

Hypertension is associated with an increased risk of diastolic dysfunction. Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) have failed to show improvement in clinical outcomes for patients with diastolic dysfunction. In this study, we investigated the effect of changing an ACEi or ARB to a combination of losartan and hydrochlorothiazide (HCTZ) on left ventricular (LV) preload and relaxation in patients with hypertension and diastolic dysfunction. We enrolled 371 hypertensive patients with diastolic dysfunction who had not achieved their treatment goals with an ACEi or ARB. We switched the ACEi or ARB to losartan/HCTZ and followed the patients for 24 weeks. The primary end points were changes in septal mitral annular velocity during diastole (e′) and in the ratio of mitral inflow velocity to e′ velocity (E/e′ ratio) from baseline to the end of follow-up. Mean systolic and diastolic blood pressures (BP) decreased by 22 and 11 mm Hg, respectively, after changing from an ACEi or ARB to losartan/HCTZ. The e′ velocity increased, and the E/e′ ratio and brain natriuretic peptide level decreased significantly. High-sensitivity C-reactive protein also decreased significantly (0.50 vs. 0.29 mg dl−1, P<0.0001). There were only slight or no changes in glucose levels, homeostasis model assessment insulin resistance (HOMA-R), uric acid and electrolytes after the drug change. Changing from an ACEi or ARB to losartan/HCTZ is associated with a reduction in BP, improvement in LV relaxation, improvement in heart failure state and attenuation of systemic inflammation with few adverse effects in patients with hypertension and diastolic dysfunction.

Sensitive cardiac troponin I (cTnI) predicts all-cause and cardiovascular mortality in various clinical settings. However, its clinical significance in hemodialysis (HD) patients with preserved left ventricular ejection fraction (LVEF) has not been fully elucidated. This study investigated the association of cTnI with LV morphology and function, and its long-term outcome in HD patients with preserved LVEF. This prospective study consists of 96 HD patients with preserved LVEF (69 ± 8 years and 63% male) who underwent two-dimensional echocardiographic examination and biomarker tests including cTnI, brain natriuretic peptide, and high-sensitive C-reactive protein. The primary endpoint was all-cause death and secondary endpoint was cardiovascular death. Factors independently associated with cTnI were systolic blood pressure (β = - 0.239, p = 0.011), heart rate (β = 0.216, p = 0.021), LV mass index (β = 0.231, p = 0.020), and E to e' ratio (β = 0.237, p = 0.016). During a mean follow-up of 3.6 years, primary and secondary endpoints were observed in 23 (24%) and 18 (19%) patients, respectively. In the multivariate Cox proportional hazard analysis, the upper cTnI tertile has significantly increased risk of all-cause mortality [hazard ratio (HR), 2.69; 95% confidence interval (CI), 1.139-6.386; p = 0.024] and that of cardiovascular death (HR, 4.56; 95% CI 2.021-16.968; p = 0.006) independent of echocardiographic measures and other serum biomarkers. In HD patients with preserved LVEF, serum cTnI levels were significantly associated with diastolic function and risk of mortality independent of echocardiographic variables and other biomarkers.

Background Although ankle‐brachial index (ABI) and brachial‐ankle pulse wave velocity (baPWV) are significant predictors of major adverse cardiovascular event (MACE), their prognostic value in association with biomarkers has not been fully evaluated in patients with end‐stage kidney disease (ESKD). Hypothesis We hypothesized that ABI/baPWV would provide better prognostic value independent of biomarkers in ESKD patients. Methods This study included 104 ESKD patients treated with maintenance hemodialysis who underwent ABI and baPWV examinations and laboratory tests, including brain‐natriuretic peptide, high‐sensitive cardiac troponin T (hs‐cTnT), and high‐sensitive C‐reactive protein (hs‐CRP). MACE was defined as a composite event of all‐cause death, acute coronary syndrome, and stroke. Results During a mean follow‐up of 3.6 ± 1.7 years, a total of 51 MACE were observed. The independent factors associated with MACE were age >75 years (adjusted hazard ratio [HR], 2.15; P < .05), abnormal ABI (adjusted HR, 2.01; P < .05), left ventricular ejection fraction (LVEF) <50% (adjusted HR, 3.33; P < .001), the upper tertile of hs‐cTnT (adjusted HR, 2.77; P < .05), and hs‐CRP (HR, 1.96; P < .05). However, baPWV did not remain as an independent predictor of MACE in the entire cohort and also in patients without abnormal ABI. The combination of predictors improves the predictive value of MACE, providing increased HR with 4.00 for abnormal ABI + hs‐CRP, 4.42 for abnormal ABI + hs‐cTnT, and 7.04 for abnormal ABI + LVEF <50% (all P < .001). Conclusion Abnormal ABI is a robust predictor of MACE independent of biomarkers and their combination provides better risk stratification compared with a single predictor in ESKD patients.