Sung-Won Jang

Prognosis of heart failure patients with reduced and preserved ejection fraction and coexistent chronic obstructive pulmonary disease

The long‐term prognosis of patients with heart failure with preserved left ventricular ejection fraction (HFPEF) and coexistent chronic obstructive pulmonary disease (COPD) has not been previously investigated. The primary aim of this study was to determine whether the long‐term prognosis of HFPEF patients with COPD differs from that of heart failure patients with reduced left ventricular ejection fraction (HFREF) and COPD. The secondary aim was to identify independent predictors of event‐free survival in patients with HF and COPD.

Decaffeinated green tea extract improves hypertension and insulin resistance in a rat model of metabolic syndrome

BACKGROUND Oxidative stress and endothelial dysfunction are closely associated with hypertension and insulin resistance (IR) in metabolic syndrome (MetS). It is still controversial whether green tea extract (GTE) may have blood pressure (BP) lowering effect. Decaffeinated GTE might be presumed to have strong antioxidative effect and BP-lowering effect as compared with catechins. Thus we investigated whether decaffeinated-GTE could attenuate hypertension and IR by improving endothelial dysfunction and reducing oxidative stress in a rat model of MetS. METHODS AND RESULTS 20 Otsuka Long-Evans Tokushima Fatty (OLETF) rats at 13 weeks old, MetS rats, were randomized into a saline treated group (OLETF; n = 10) and a group treated with decaffeinated-GTE (25 mg/kg/day) (GTE-OLETF; n = 10). Intraperitoneal glucose tolerance tests and BP measurements were performed at 13 and 25 weeks. Decaffeinated-GTE significantly reduced BP (OLETF vs. GTE-OLETF; 130 ± 7 vs. 121 ± 3 mmHg, p = 0.01), fasting/postprandial 2 h glucose (141 ± 18/159 ± 13 vs. 115 ± 7/132 ± 16 mg/dL, p = 0.009/0.002) and insulin levels (4.8 ± 2.3 vs. 2.4 ± 1.3 ng/mL, p < 0.001). Decaffeinated-GTE significantly reduced vascular reactive oxygen species (ROS) formation and NADPH oxidase activity, and improved endothelium dependent relaxation in the thoracic aorta of OLETF rats. Decaffeinated-GTE also suppressed the expression of p47 and p22phox (NADPH oxidase subunits) in the immunohistochemical staining, and stimulated phosphorylation of endothelial nitric oxide synthase (eNOS) and Akt in the immunoblotting of aortas. CONCLUSIONS Decaffeinated-GTE reduced the formation of ROS and NADPH oxidase activity and stimulated phosphorylation of eNOS and Akt in the aorta of a rat model of MetS, which resulted in improved endothelial dysfunction and IR, and eventually lowered BP.

Metabolically obese status with normal weight is associated with both the prevalence and severity of angiographic coronary artery disease

OBJECTIVE We evaluated prevalence and severity of angiographic coronary artery disease (CAD) according to groups by metabolically obese (MO) and/or weight status. MATERIAL/METHODS Normal weight was defined as body mass index (BMI, kg/m²)<25 and obesity was defined as BMI≥25. The MO was determined using the National Cholesterol Education Program-Adult Treatment Panel III classification with Korean-specific cutoffs for abdominal obesity. Therefore, a total of 856 subjects were categorized as follows: (1) metabolically healthy and normal weight (MHNW); (2) metabolically obese but normal weight (MONW); (3) metabolically healthy but obese (MHO); and (4) metabolically abnormally obese (MAO). The presence of obstructive lesion≥50% of coronary artery was considered as an angiographic CAD and the Gensini scoring system was used for the severity. RESULTS MONW or MO showed a higher prevalence of CAD than MHNW or non-MO after adjustment for age and sex, respectively (MONW, odds ratio [OR]=1.69, 95% confidence interval [CI]: 1.13-2.51 and MO, OR=1.44, 95% CI: 1.09-1.91). In subjects without diabetes mellitus (DM), MONW or MO showed a marginally higher prevalence of CAD (MONW, OR=1.58, 95% CI: 0.96-2.61 and MO, OR=1.41, 95% CI: 0.96-2.08). MONW was independently associated with a higher severity of angiographic CAD than MHNW after age, sex, glomerular filtration rate, smoking status, high sensitive C-reactive protein, and use of anti-platelet and anti-angina drugs (β=0.118, P=0.005). And MO was associated with a higher severity of angiographic CAD than non-MO after adjustment for age and sex (β=0.077, P=0.024). The above associations were also consistent in subjects without DM (MONW, β=0.147, P=0.003 and MO, β=0.129, P=0.005). CONCLUSIONS MONW or MO is associated with both the prevalence and severity of angiographic CAD after adjustment for age and sex and MONW is independently associated with the severity of angiographic CAD irrespective of DM. Therefore, subjects with MO but normal weight (MONW) should be carefully examined for angiographic CAD.

Higher Plasma Thrombospondin-1 Levels in Patients With Coronary Artery Disease and Diabetes Mellitus

Background and Objectives Thrombospondin-1 (TSP-1) is associated with atherosclerosis in animals with diabetes mellitus (DM). But, no study has investigated the role of TSP-1 in human atherosclerosis. This study investigated the relationship among plasma TSP-1 concentration, DM, and coronary artery disease (CAD). Subjects and Methods The study involved 374 consecutive subjects with suspected CAD, who had undergone coronary angiography to evaluate effort angina. Patients were divided into four groups as follows: DM(-) and CAD(-), DM(-) and CAD(+), DM(+) and CAD(-), and DM (+) and CAD(+). Results We found that plasma TSP-1 levels were higher in patients with DM(+) and CAD(+) (n=103) than those in other patients (n=271) (p<0.01). A multivariate analysis showed that male gender {odds ratio (OR), 2.728; 95% confidence interval (CI), 1.035-7.187}, high density lipoprotein-cholesterol (OR, 0.925; 95% CI, 0.874-0.980), glycated hemoglobin (OR, 1.373; 95% CI, 1.037-1.817), and plasma TSP-1 (OR, 1.004; 95% CI, 1.000-1.008) levels were independently associated with the presence of CAD in patients with DM. Conclusion Plasma TSP-1 levels were higher in patients with DM(+) and CAD(+) than those in other patients, and plasma TSP-1 levels were independently associated with the presence of CAD in patients with DM. These findings show a possible link between human plasma TSP-1 concentration and CAD in patients with DM.

Impact of diabetes duration on the extent and severity of coronary atheroma burden and long-term clinical outcome in asymptomatic type 2 diabetic patients: evaluation by Coronary CT angiography

AIMS We investigated the association between diabetes duration and the extent and severity of coronary artery disease (CAD) as well as long-term clinical outcomes using coronary computed tomography angiography (CCTA) in asymptomatic type 2 diabetic patients. METHODS AND RESULTS We analysed 933 asymptomatic type 2 diabetic patients without known CAD who underwent CCTA. Patients were divided into three groups according to the duration of diabetes: <5 years, 5-10 years, and ≥10 years. Stenosis by CCTA was scored as none (0%), non-obstructive (1-49%), or obstructive (≥50%) for each coronary artery segment. For these patients, we compared the prevalence, extent, and severity of CAD, including coronary artery calcium score (CACS), atheroma burden obstructive score (ABOS), segment involvement score (SIS), and segment stenosis score (SSS). Major adverse cardiac and cerebrovascular events (MACCE), including all-cause mortality, non-fatal myocardial infarction, and stroke, within a follow-up period were also compared.Patients with longer duration of diabetes possessed higher rates of obstructive CAD (P < 0.001). Patients with longer duration of diabetes also manifested greater degree of CACS, ABOS, SIS, and SSS (P < 0.001 for all) with associated higher rate of MACCE (P = 0.025). Presence of obstructive CAD as assessed by CCTA was an independent predictor of MACCE after adjusting for confounding risk factors (hazard ratio: 1.979, confidence interval: 1.178-3.327, P = 0.010). CONCLUSION In asymptomatic diabetic patients, longer diabetes duration is associated with a higher prevalence, extent, and severity of CAD as well as risk of MACCE. Moreover, greater CAD burden increases the risk of MACCE independent of co-existing CAD risk factors.

Comparison of the efficacy between hydrochlorothiazide and chlorthalidone on central aortic pressure when added on to candesartan in treatment-naïve patients of hypertension.

Thiazide-type diuretics are the most commonly used blood pressure (BP)-lowering drug for patients with uncomplicated hypertension. However, it has remained unclear whether hydrochlorothiazide (HCTZ) or chlorthalidone (CTD) shows better improvement in central aortic pressure. We conducted an open-label, randomized, prospective cross-over study with an 8-week active treatment (HCTZ of 25 mg with candesartan of 8 mg or CTD of 12.5 mg with candesartan of 8 mg) with a 4-week washout period (only candesartan during this period). Twenty-eight treatment-naïve patients of hypertension were enrolled (mean age: 50±9 years, male: 44.4%). Central aortic pressure, pulse wave velocity (PWV), augmentation index (AIx) and other BP-derived parameters were measured. After 8 weeks of active treatment, there was no significant difference in changes of central aortic pressure between HCTZ and CTD treatments (Δ=−14±8 vs. −16±7 mm Hg, P=0.645). However, CTD treatment showed a significant reduction in PWV compared with baseline (1321±194 vs. 1439±190 cm s−1, P=0.007) and HCTZ treatment (Δ=−118±82 vs. Δ=5±72 cm s−1, P=0.033), whereas HCTZ treatment showed a marginal, but not a significant reduction in AIx compared with baseline. In conclusion, CTD of 12.5 mg is as potent as HCTZ of 25 mg, when combined with candesartan of 8 mg, in lowering central aortic pressure. In addition, CTD treatment resulted in a significant reduction of PWV.

Membranous interventricular septal aneurysm resulted in complete atrioventricular block

A 43-year-old woman presented with dyspnoea and chest discomfort. She was a current smoker and had been on antihypertensive medications for 2 years. Resting ECG showed complete atrioventricular block with right bundle branch block pattern. Transthoracic echocardiography showed a membranous interventricular septal aneurysm without …

Imatinib Mesylate Attenuates Myocardial Remodeling Through Inhibition of Platelet-Derived Growth Factor and Transforming Growth Factor Activation in a Rat Model of Hypertension

Imatinib mesylate is a specific tyrosine kinase inhibitor that may block the platelet-derived growth factor and transforming growth factor pathways. These pathways are known to provoke fibroblast activation. We evaluated whether imatinib, by inhibiting these pathways, prevents diastolic dysfunction and attenuates myocardial remodeling using spontaneously hypertensive rats (SHRs). Eight-week-old male SHRs were randomly assigned to either imatinib treatment group (30 mg/kg per day; n=10; SHR-I) or hypertensive control group (distilled water, n=10; SHR-C). Wistar–Kyoto rats were used as normal controls (n=10). At 16 weeks, all rats underwent hemodynamic studies and Doppler echocardiography and then were euthanized. Their hearts were extracted for histopathologic, immunoblotting, and quantitative reverse transcriptase polymerase chain reaction analyses. Although imatinib did not affect blood pressure, it markedly reduced perivascular and interstitial fibrosis in the hearts of SHR. Echocardiogram showed that imatinib significantly reduced the left ventricular wall thickness (septal/posterior wall; SHR-C versus SHR-I, 18±1/19±2 versus 15±1/15±1 mm; P<0.001) and increased the E/A ratio (SHR-C versus SHR-I, 1.59±0.11 versus 1.84±0.16; P=0.001). Also, imatinib significantly reduced the mRNA expression of collagen type I, III, and platelet-derived growth factor receptor-&bgr; phosphorylation in the hearts of SHR. In addition, imatinib reduced collagen production by inhibiting the phosphorylation of c-abl and platelet-derived growth factor receptor-&bgr; in rat cardiac fibroblasts. In conclusion, these results suggest that imatinib could attenuate myocardial remodeling and improve left ventricular diastolic dysfunction in a hypertensive rat model by affecting platelet-derived growth factor and transforming growth factor-&bgr;1 pathway without the blood pressure–lowering effect.

Systolic synchrony is impaired in nonleft ventricular hypertrophy of never-treated hypertensive patients.

Objective The objective of the current study was to confirm the degrees of dyssynchrony in patients with nonleft ventricular hypertrophy (LVH) and never-treated hypertension compared with normal controls or patients with LVH and never-treated hypertension. Methods and results We enrolled 200 consecutive never-treated hypertensive patients and 104 age-matched and sex-matched normal controls. The following parameters were evaluated by echocardiography comprising conventional Doppler, tissue Doppler imaging, and strain imaging: global dyssynchrony; systolic dyssynchrony (longitudinal); diastolic dyssynchrony; and contractile diastolic dyssynchrony. Systolic dyssynchrony in the LVH group with hypertension was more aggravated than in normal controls (P < 0.001). In addition, global, diastolic, and contractile diastolic dyssynchrony in the LVH group with hypertension were more aggravated than in the non-LVH group with hypertension (all P < 0.001), but systolic dyssynchrony was not different between the two groups. All of the above associations remained significant after adjustment for confounding factors. Conclusion Systolic synchrony was impaired in patients with non-LVH and never-treated hypertension to a similar degree in the LVH group with never-treated hypertension.

A Patient With Dysphagia due to an Aortic Aneurysm

Dysphagia aortica is difficulty in swallowing caused by extrinsic compression of the esophagus due to an ectatic, tortuous, or aneurysmatic atherosclerotic thoracic aorta. This condition is very uncommon, and it is usually associated with old age, women with short stature, hypertension, and kyphosis. We report herein a case involving a patient with dysphagia who had an aortic aneurysm.