Gil Ja Shin

Enhanced cardioprotective effects by coexpression of two isoforms of hepatocyte growth factor from naked plasmid DNA in a rat ischemic heart disease model

The therapeutic potential of pCK‐HGF‐X7, a naked DNA designed to express two isoforms of hepatocyte growth factor (HGF723 and HGF728), was studied in the rat ischemic heart disease model.

Catheter-based adenovirus-mediated local intravascular gene delivery of a soluble TGF-β type II receptor using an Infiltrator in porcine coronary arteries: efficacy and complications

Enhanced extracellular matrix (ECM) accumulation is an important finding in human restenotic arterial neointima after angioplasty. Transforming growth factor β1(TGF-β1) is known to regulate the synthesis and turnover of a variety of ECM components, and may play an important role in restenosis. Recombinant adenoviral vector expressing an ectodomain of the TGF-β type II receptor fused to the human immunoglobulin Fc portion (AdTβ-ExR) inhibits the action of TGF-β probably either by adsorbing TGF-β or by acting as a dominant negative receptor. We carried out a catheter-based local adenovirus mediated gene delivery using an Infiltrator in porcine coronary arteries to know the pattern of gene expression, efficacy and procedural complications. Twenty four coronary arteries in 13 pigs were used for intravascular gene delivery by intramural injection with either AdTβ-ExR or adenovirus expressing b-galactosidase (AdCALacZ). Direct immunofluorescent staining and reverse transcription polymerase chain reaction (RTPCR) were used for detection of type II TGF-β receptor and its mRNA respectively. X-Gal histochemistry was performed to identify b-galactosidase. Both soluble TGF-β receptor and b-galactosidase were expressed locally in the media and adventita at injected arterial segments without any significant dissemination to remote area. Intravascular gene transfection performed with various titer of each adenoviral vector showed that AdTβ-ExR of 5x10(8) pfu and AdCALacZ of 2.5 x 10(8) pfu were the minimum titer for the expression of each transgene. Infiltration of CD3 positive T cells was detected by immunohistochemical staining in the area of each transgene expression, and tends to decrease over time after gene delivery. Pathological study of 24 treated arteries showed complications such as disruption of external elastic lamina with hemorrhage (n = 4), minimal disruption of internal elastic lamina and endothelial layer, and medial thickening. In conclusion, catheter-based local intravascular gene delivery of adenoviral vector is feasible and effective in a selected artery, but must be undertaken with caution due to possible lethal complications. Local delivery of soluble TGF-β type II receptor in this way may provide an effective intravascular gene therapy to inhibit TGF-β signal pathway without any significant systemic side effect.

Postoperative B-type natriuretic Peptide levels associated with prolonged hospitalization in hypertensive patients after non-cardiac surgery.

Background and Objectives B-type natriuretic peptide (BNP) is an important marker for the diagnosis of heart failure and is useful towards predicting morbidity and mortality after non-cardiac surgery. Nevertheless, information on the relationship between postoperative BNP levels and perioperative prognosis after non-cardiac surgery is scarce. The purpose of the study was to assess whether postoperative BNP levels could be used as a predictor of prolonged hospitalization in elderly hypertensive patients after non-cardiac surgery. Subjects and Methods Ninety-seven (97) patients, aged 55 years or older (mean age: 73.12±10.05 years, M : F=24 : 73) were enrolled in a prospective study from May 2005 through August 2010. All patients underwent total knee or hip replacement. Postoperative BNP and other diagnostic data were recorded within 24 hours of surgery. Patients that required a prolonged hospital stay due to operative causes, such as wound infection and re-operation, were excluded. Results The length of hospital stay was significantly correlated with postoperative BNP levels (p=0.031). Receiver operating characteristic curves demonstrated postoperative BNP levels as predictors of hospital stay ≥30 days with areas under the curve of 0.774 (95% confidence interval: 0.679-0.87, p<0.0001). A BNP cut-off value above 217.5 pg/mL had a sensitivity of 80.6% and a specificity of 66.7% for predicting postoperative hospital stays of 30 days or more. Conclusion Postoperative BNP levels may predict the length of hospital stays after non-cardiac surgery in hypertensive patients. Elevated BNP levels were associated with prolonged hospitalization after elective orthopedic surgery.

Normal Echocardiographic Measurements in a Korean Population Study: Part I. Cardiac Chamber and Great Artery Evaluation

Background Measurement of the cardiac chamber is essential, and current guidelines recommend measuring and reporting values for both sides of the cardiac chamber during echocardiographic evaluation. Normal echocardiographic reference values have been suggested previously, but detailed information about right-sided chambers and values according to gender was not included. Methods This is a prospective multicenter (23 centers) study evaluating normal Korean adult subjects using comprehensive echocardiography. We included normal adult subjects (age; 20-79 years old) who had no significant cardiac disorders or illnesses, such as hypertension or diabetes, which could affect cardiac structure and function. We measured the cardiac chamber including both right and left ventricles as well as atria according to current echocardiography guidelines and compared values according to gender and age groups. Results A total of 1003 subjects were evaluated and the mean age was 48 ± 16 years. Left ventricular (LV) dimensions increased, but LV volume decreased in older subjects. Right ventricular (RV) area decreased in women and older subjects, and the RV long-axis dimension showed a similar trend. Left atrial (LA) volume increased in men but there were no differences in LA volume index between men and women. The dimension of great arteries increased in men and older subjects. Conclusion Since there were considerable differences between men and women and in the different age groups, and the trends differed significantly between different echo variables, normal echocardiographic cutoff values should be differentially applied based on age and gender.

Normal 2-Dimensional Strain Values of the Left Ventricle: A Substudy of the Normal Echocardiographic Measurements in Korean Population Study

Background It is important to understand the distribution of 2-dimensional strain values in normal population. We performed a multicenter trial to measure normal echocardiographic values in the Korean population. Methods This was a substudy of the Normal echOcardiogRaphic Measurements in KoreAn popuLation (NORMAL) study. Echocardiographic specialists measured frequently used echocardiographic indices in healthy people according to a standardized method at 23 different university hospitals. The strain values were analyzed from digitally stored images. Results Of a total of 1003 healthy participants in NORMAL study, 2-dimensional strain values were measured in 501 subjects (265 females, mean age 47 ± 15 years old) with echocardiographic images only by GE echocardiographic machines. Interventricular septal thickness, left ventricular (LV) posterior wall thickness, systolic and diastolic LV dimensions, and LV ejection fraction were 7.5 ± 1.0 mm, 7.4 ± 1.0 mm, 29.9 ± 2.8 mm, 48.9 ± 3.6 mm, and 62 ± 4%, respectively. LV longitudinal systolic strain (LS) values of apical 4-chamber (A4C) view, apical 3-chamber (A3C) view, apical 2-chamber (A2C) view, and LV global LS (LVGLS) were −20.1 ± 2.3, −19.9 ± 2.7, −21.2 ± 2.6, and −20.4 ± 2.2%, respectively. LV longitudinal systolic strain rate (LVLSR) values of the A4C view, A3C view, A2C view, and LV global LSR (LVGLSR) were −1.18 ± 0.18, −1.20 ± 0.21, −1.25 ± 0.21, and −1.21 ± 0.21−s, respectively. Females had lower LVGLS (−21.2 ± 2.2% vs. −19.5 ± 1.9%, p < 0.001) and LVGLSR (−1.25 ± 0.18−s vs. −1.17 ± 0.15−s, p < 0.001) values than males. Conclusion We measured LV longitudinal strain and strain rate values in the normal Korean population. Since considerable gender differences were observed, normal echocardiographic cutoff values should be differentially applied based on sex.

Association between central obesity and circadian parameters of blood pressure from the korean ambulatory blood pressure monitoring registry: Kor-ABP registry.

Central obesity has been reported as a risk for atherosclerosis and metabolic syndrome. The influence of central obesity on diurnal blood pressure (BP) has not been established. In this study, we investigated the influence of central obesity on the circadian parameters of BP by 24 hr ambulatory BP monitoring. Total 1,290 subjects were enrolled from the Korean Ambulatory BP registry. Central obesity was defined as having a waist circumference≥90 cm in males and ≥85 cm in females. The central-obese group had higher daytime systolic BP (SBP), nighttime SBP and diastolic BP (DBP) than the non-obese group (all, P<0.001). There were no differences in nocturnal dipping (ND) patterns between the groups. Female participants showed a higher BP mean difference (MD) than male participants with concerns of central obesity (daytime SBP MD 5.28 vs 4.27, nighttime SBP MD 6.48 vs 2.72) and wider pulse pressure (PP). Central obesity within the elderly (≥65 yr) also showed a higher BP MD than within the younger group (daytime SBP MD 8.23 vs 3.87, daytime DBP 4.10 vs 1.59). In conclusion, central obesity has no influence on nocturnal dipping patterns. However, higher SBP and wider PP are associated with central obesity, which is accentuated in women.

A More Appropriate Cardiac Troponin T Level That Can Predict Outcomes in End-Stage Renal Disease Patients with Acute Coronary Syndrome

Purpose Cardiac troponin T (cTnT), a useful marker for diagnosing acute myocardial infarction (AMI) in the general population, is significantly higher than the usual cut-off value in many end-stage renal disease (ESRD) patients without clinically apparent evidence of AMI. The aim of this study was to evaluate the clinical usefulness of cTnT in ESRD patients with acute coronary syndrome (ACS). Materials and Methods Two hundred eighty-four ESRD patients with ACS were enrolled between March 2002 and February 2008. These patients were followed until death or June 2009. Medical records were reviewed retrospectively. The cut-off value of cTnT for AMI was evaluated using a receiver operating characteristic (ROC) curve. We calculated Kaplan-Meier survival curves, and potential outcome predictors were determined by Cox proportional hazard analysis. Results AMIs were diagnosed in 40 patients (14.1%). The area under the curve was 0.98 in the ROC curve (p<0.001; 95% CI, 0.95-1.00). The summation of sensitivity and specificity was highest at the initial cTnT value of 0.35 ng/mL (sensitivity, 0.95; specificity, 0.97). Survival analysis showed a statistically significant difference in all-cause and cardiovascular mortalities for the group with an initial cTnT ≥0.35 ng/mL compared to the other groups. Initial serum cTnT concentration was an independent predictor for mortality. Conclusion Because ESRD patients with an initial cTnT concentration ≥0.35 ng/mL have a poor prognosis, it is suggested that urgent diagnosis and treatment be indicated in dialysis patients with ACS when the initial cTnT levels are ≥0.35 ng/mL.

Sex Difference in the Association Between Brachial Pulse Pressure and Coronary Artery Disease: The Korean Women's Chest Pain Registry (KoROSE)

This study was performed to investigate the association between brachial pulse pressure (PP) and the presence/extent of obstructive coronary artery disease (CAD) in men and women. Study data were obtained from a nation‐wide registry composed of 632 patients (173 men and 459 women, 58.1±10.5 years) with suspected CAD who underwent invasive coronary angiography. PP was higher in patients with obstructive CAD (≥50% stenosis) than those without CAD in both sexes (P=.032 in men; P<.001 in women). However, PP increased proportionally with the increasing number of obstructed coronary arteries in women (P<.001) but not in men (P=.070). Multiple logistic‐regression analyses demonstrated that higher PP (≥50.5 mm Hg) was an independent factor for determining obstructive CAD even after controlling for potential confounders in women (odds ratio, 2.83; 95% confidence interval, 1.40–5.73; P=.004). These results were consistent in 173 selected women matched with 173 men based on age and CAD severity. In conclusion, the association between brachial PP and obstructive CAD was more pronounced in women than in men. Brachial PP can be a simple and useful indicator of CAD especially in women.

Predictive value of CHADS2 score for cardiovascular events in patients with acute coronary syndrome and documented coronary artery disease.

Background/Aims: The CHADS2 score, used to predict the risk of ischemic stroke in atrial fibrillation (AF) patients, has been reported recently to predict ischemic stroke in patients with coronary heart disease, regardless of the presence of AF. However, little data are available regarding the relationship between the CHADS2 score and cardiovascular outcomes. Methods: This was a retrospective study on 104 patients admitted for acute coronary syndrome (ACS) who underwent coronary angiography, carotid ultrasound, and transthoracic echocardiography. Results: The mean age of the subjects was 60.1 ± 12.6 years. The CHADS2 score was as follows: 0 in 46 patients (44.2%), 1 in 31 (29.8%), 2 in 18 (17.3%), and ≥ 3 in 9 patients (8.7%). The left atrial volume index (LAVi) showed a positive correlation with the CHADS2 score (20.8 ± 5.9 for 0; 23.2 ± 6.7 for 1; 26.6 ± 10.8 for 2; and 30.3 ± 8.3 mL/m2 for ≥3; p = 0.001). The average carotid total plaque area was significantly increased with CHADS2 scores ≥ 2 (4.97 ± 7.17 mm2 vs. 15.52 ± 14.61 mm2; p = 0.002). Eight patients experienced cardiovascular or cerebrovascular (CCV) events during a mean evaluation period of 662 days. A CHADS2 score ≥ 3 was related to an increase in the risk of CCV events (hazard ratio, 14.31; 95% confidence interval, 3.53 to 58.06). Furthermore, LAVi and the severity of coronary artery obstructive disease were also associated with an increased risk of CCV events. Conclusions: The CHADS2 score may be a useful prognostic tool for predicting CCV events in ACS patients with documented coronary artery disease.

Higher Blood Pressure Variability in White Coat Hypertension; from the Korean Ambulatory Blood Pressure Monitoring Registry

Background and Objectives Blood pressure variability (BPV) was recently shown to be a risk factor of stroke. White coat hypertension (WCH) used to be regarded as innocuous, but one long-term follow-up study reported that WCH increased stroke rate compared to normotension (NT). In this study, we aimed to evaluate the relationship between WCH and BPV. Subjects and Methods We analyzed 1398 subjects from the Korean Ambulatory Blood Pressure Registry, who were divided into NT (n=364), masked hypertension (n=122), white coat hypertension (n=254), and sustained hypertension (n=658) groups. Results Baseline characteristics were similar among groups. The average real variability (ARV), a highly sensitive BPV parameter, was highest in the WCH group, followed by the sustained hypertension, masked hypertension, and NT groups. The results persisted after being adjusted for covariates. The WCH vs. sustained hypertension results (adjusted mean±standard error) were as follows: 24-h systolic ARV, 22.9±0.8 vs. 19.4±0.6; 24-h diastolic ARV, 16.8±0.6 vs. 14.3±0.5; daytime systolic ARV, 21.8±0.8 vs. 16.8±0.6; and daytime diastolic ARV, 16.2±0.6 vs. 13.4±0.5 (p<0.001 for all comparisons). Conclusion From the registry data, we found that subjects with WCH or masked hypertension had higher BPV than NT. However, long-term follow-up data assessing the clinical influences of WCH on stroke are needed.