Associations of Three-Dimensional Anthropometric Body Surface Scanning Measurements and Coronary Artery Disease.

Background and Objectives: The relationship between three-dimensional (3D) scanning-derived body surface measurements and biomarkers in patients with coronary artery disease (CAD) were assessed. Methods and Methods: The recruitment of 98 patients with CAD confirmed by cardiac catheterization and 98 non-CAD patients were performed between March 2016 and December 2017. A health questionnaire on basic information, life style variables, and past medical and family history was completed. 3D body surface measurements and biomarkers were obtained. Differences between the two groups were assessed and multivariable analysis performed. Results: It was found that chest width (odds ratio [OR] 0.761, 95% confidence interval [CI] = 0.586-0.987, p = 0.0399), right arm length (OR 0.743, 95% CI = 0.632-0.875, p = 0.0004), waist circumference (OR 1.119, 95% CI = 1.035-1.21, p = 0.0048), leptin (OR 1.443, 95% CI = 1.184-1.76, p = 0.0003), adiponectin (OR 0.978, 95% CI = 0.963-0.994, p = 0.006), and interleukin 6 (OR 1.181, 95% CI = 1.021-1.366, p = 0.0254) were significantly associated with CAD. The combination of biomarker scores and body measurement scores had the greatest area under the curve and best association with CAD (area under the curve of 0.8049 and 95% CI = 0.7440-0.8657). Conclusions: Our study suggests that 3D derived body surface measurements in combination with leptin, adiponectin, and interleukin 6 levels may direct us to those at risk of CAD, allowing a non-invasive approach to identifying high-risk patients.

Artificial Intelligence-Assisted Identification of Genetic Factors Predisposing High-Risk Individuals to Asymptomatic Heart Failure.

Heart failure (HF) is a global pandemic public health burden affecting one in five of the general population in their lifetime. For high-risk individuals, early detection and prediction of HF progression reduces hospitalizations, reduces mortality, improves the individual's quality of life, and reduces associated medical costs. In using an artificial intelligence (AI)-assisted genome-wide association study of a single nucleotide polymorphism (SNP) database from 117 asymptomatic high-risk individuals, we identified a SNP signature composed of 13 SNPs. These were annotated and mapped into six protein-coding genes (GAD2, APP, RASGEF1C, MACROD2, DMD, and DOCK1), a pseudogene (PGAM1P5), and various non-coding RNA genes (LINC01968, LINC00687, LOC105372209, LOC101928047, LOC105372208, and LOC105371356). The SNP signature was found to have a good performance when predicting HF progression, namely with an accuracy rate of 0.857 and an area under the curve of 0.912. Intriguingly, analysis of the protein connectivity map revealed that DMD, RASGEF1C, MACROD2, DOCK1, and PGAM1P5 appear to form a protein interaction network in the heart. This suggests that, together, they may contribute to the pathogenesis of HF. Our findings demonstrate that a combination of AI-assisted identifications of SNP signatures and clinical parameters are able to effectively identify asymptomatic high-risk subjects that are predisposed to HF.

Effects of National Hospital Accreditation in Acute Coronary Syndrome on In-Hospital Mortality and Clinical Outcomes.

BACKGROUND: Acute coronary syndrome (ACS) is a life-threatening medical condition that accounts for an annual expenditure of more than $300 billion in the United States. Hospital accreditation has been shown to improve patient and hospital outcomes for various conditions. OBJECTIVES: This study aimed to determine the benefits of hospital accreditation in patients with ACS. METHODS: This nationwide population-based cohort study used Taiwan's National Health Insurance Research Database from 1997 to 2011 (n = 249,354). Multivariable logistic regression was used to analyze the risk of in-hospital events among those treated in accredited and non-accredited hospitals, and to compare outcomes in hospitals before and after accreditation. The effect of accreditation on these events was also stratified by accreditation grade. RESULTS: A total of 823 hospitals were included, of which 2.4% were medical centers, 13.7% were regional hospitals, and 83.8% were district hospitals. The in-hospital mortality [odds ratio (OR), 0.82; 95% confidence interval (CI), 0.79-0.85; p < 0.001] and recurrent acute myocardial infarction (AMI) admission (OR, 0.81; 95% CI, 0.71-0.93; p = 0.003) rates were significantly lower in the after-accreditation group than in the before-accreditation group. There was a substantial and marked decrease in the in-hospital mortality rate after accreditation in 2008. CONCLUSIONS: This cohort study demonstrated that ACS accreditation was associated with better in-hospital mortality and recurrent AMI admission rates in ACS patients.

Association between Polymorphisms of Antioxidant Gene (MnSOD, CAT, and GPx1) and Risk of Coronary Artery Disease.

OBJECTIVE: Reactive oxygen species (ROS) been cited as one of the major causes of atherosclerosis and coronary artery disease which are possible agents inducing DNA damage. Manganese superoxide dismutase (MnSOD), catalase (CAT), and glutathione peroxidase-1 (GPx1) have evolved to address primary defense against free radical mediated damage in mitochondria. The aim of this study was to delineate the association of MnSOD, CAT, and GPx1 polymorphisms and risk of CAD in Taiwan. METHODS: We conducted a case-control study with 657 participants recruited at a medical center. All subjects were evaluated by noninvasive stress test and then quantitative coronary angiography to confirm the diagnosis of CAD. 447 CAD cases were defined as >50% stenosis of coronary artery and 210 controls were stenosed below 50%. Polymorphisms of MnSOD (Val16Ala), CAT (C-262T), and GPx1 (Pro198Leu) genes were determined by polymerase chain reaction methods. Multivariate logistic regression model was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The MnSOD Val/Ala+Ala/Ala genotype was significantly associated with an increased risk of CAD compared to the Val/Val genotype (OR = 1.86, 95% CI = 1.15-3.01). This polymorphism was also associated with the severity of CAD of single and two vessel diseases. The corresponding ORs were 2.31 (95% CI = 1.32-4.03) and 1.92 (95% CI = 1.02-3.61), respectively. Among cigarette smokers, the harmful genetic effect of MnSOD Ala allele on CAD risk was much higher (OR = 2.23, 95% CI = 1.02-4.88). However, the interaction between MnSOD genotype and cigarette smoking on CAD risk was not significant. No significant association between CAT and GPx1 polymorphisms and CAD risk was observed. CONCLUSION: Our results suggest that MnSOD polymorphism is an independent risk factor for susceptibility to CAD in the Chinese population.

Effects of a multidisciplinary disease management programme with or without exercise training for heart failure patients: Secondary analysis of a randomized controlled trial.

BACKGROUND: Heart failure is a complex syndrome that causes substantial functional impairment and poor outcomes. Although multidisciplinary disease management programmes are effective, the role of additional outpatient-based exercise training and the effects of multidisciplinary disease management programmes for patients with contraindications to exercise training are unclear. OBJECTIVES: To compare the effects of the multidisciplinary disease management programme with and without exercise training on heart failure-related rehospitalization, disease knowledge, and functional capacity. DESIGN: Secondary analysis of a randomized controlled trial. PARTICIPANTS AND SETTING: Data for 212 patients hospitalized for heart failure at a local teaching hospital in Taiwan were analysed. METHODS: Patients' data were assigned to three groups: control (n = 71), multidisciplinary disease management programme without exercise training (n = 70) or multidisciplinary disease management programme with exercise training (n = 71). The multidisciplinary disease management programme included comprehensive assessments, individualized education, optimizing medications, pre-scheduled clinic visits, and encouraging regular physical activity at home. Outpatient-based exercise training was performed only in the multidisciplinary disease management programme with exercise training group. The control and the multidisciplinary disease management programme without exercise training groups were further divided into subgroups with and without contraindications to exercise training. Patients were followed up monthly for heart failure-related rehospitalizations for 1 year. Cox proportional hazard models and Kaplan-Meier analyses were used to identify the significant predictors of heart failure-related rehospitalizations. A generalized estimation equation model was used to analyse the secondary outcomes, including disease knowledge and 6-min walking distance at baseline and 6 and 12 months after discharge. RESULTS: At 12 months after discharge, the multidisciplinary disease management programme with and without exercise training groups had significantly lower heart failure-related rehospitalization rates and better disease knowledge compared with the control group (p < 0.01). Only the multidisciplinary disease management programme with exercise training group had a significant improvement in 6-min walking distance (p < 0.05). For patients with contraindications to exercise, the multidisciplinary disease management programme significantly reduced heart failure-related rehospitalization rates at 12 months after discharge (p < 0.05). For those without contraindications, the event-lowering effect was only noted for the multidisciplinary disease management programme with exercise training group (p < 0.05). CONCLUSIONS: Outpatient-based exercise training is recommended to be incorporated into multidisciplinary disease management programmes for patients without exercise contraindications to improve disease outcomes and functional capacity. For patients with contraindications to exercise, a multidisciplinary disease management programme is recommended to improve patient outcomes.

Aspirin associated with risk reduction of secondary primary cancer for patients with head and neck cancer: A population-based analysis.

As reported by the Taiwan Cancer Registry in 2013 squamous cell carcinoma of head and neck cancer (HNSCC) was the sixth most frequently diagnosed cancer and the 5th most common cause of cancer related death and its incidence and mortality rate is still rising. The co-occurrence of HNSCC and secondary primary cancer (SPC) and the chemopreventive effect of aspirin on certain malignancies had been reported. Therefore we conducted this national study to investigate the use of aspirin associated with risk reduction of secondary primary cancer for patients with head and neck cancer in Taiwan. We searched the Registry for Catastrophic Illness in the National Health Insurance Research Database (NHIRD) for 18,234 patients (3,576 aspirin users and 14,667 non-aspirin users) diagnosed with HNSCC during 2000-2005. The SPC incidence density during follow-up in 2000-2011 was compared between the groups. For HNSCC patients, aspirin use after diagnosis was significantly associated with SPC risk reduction by 25% (adjusted HR, 0.75; 95% CI, 0.63-0.89; p = 0.001) after multivariate analysis. In the subgroup analysis, we found that esophageal cancer and stomach cancer incidence were significantly reduced after aspirin use (adjusted HR, 0.60; 95% CI, 0.41-0.90; p = 0.01 for esophageal cancer; adjusted HR, 0.27; 95% CI, 0.08-0.87; p = 0.03 for stomach cancer). Aspirin use for 1-3 years was associated with SPC risk reduction by 35% (adjusted HR, 0.65; 95% CI, 0.49-0.87; p = 0.003). SPC risk reduction extended continuously for more than 3 years of follow up (adjusted HR, 0.72; 95% CI, 0.53-0.98; p = 0.030). Our data shows aspirin use was associated with reduced SPC incidence for HNSCC patients, attributed mainly to reduced risk of esophageal and stomach cancer.

Metabolic profile provides prognostic value better than galectin-3 in patients with heart failure.

BACKGROUND: Metabolic profiles have been shown to provide prognostic information in patients with heart failure (HF). Galectin-3 (Gal-3), indicating cardiac fibrosis, is a documented biomarker of prognosis in HF. It is unknown whether metabolic profiles provide prognostic value better than Gal-3. METHODS AND RESULTS: This study analyzed 212 hospitalized HF patients, measuring metabolic score (composed by butyrylcarnitine, dimethylarginine/arginine ratio, spermidine, and total essential amino acids) and Gal-3. Endpoints were composite events (death/HF-related re-hospitalization). The median of metabolic scores and Gal-3 levels were 3.1 (1.3-5.2) and 17.8ng/mL (4.7-100ng/mL), respectively. Patients with higher metabolic scores had worse functional classes, higher atrial fibrillation incidences, levels of Gal-3 and B-type natriuretic peptide (BNP), but lower albumin levels and glomerular filtration rate. Correlations of metabolic score to Gal-3 and BNP were significant, but weak (r=0.34 and 0.41, respectively, both p<0.001). During a follow-up period of 4.2±1.4 years, there were 91 (42.9%) composite events. In univariate analysis, significant predictors of composite events were age, functional class, atrial fibrillation, levels of hemoglobin, log (Gal-3), log (BNP) and metabolic score. In multivariable analysis, adjusted for above variables, metabolic score remained a strong predictor of combined endpoints (hazard ratio=2.596, 95% confidence interval=1.649-4.087, p<0.001). C-statistics for the prediction of composite events significantly increased when metabolic score was incorporated into the model with established risk factors, BNP and Gal-3 [0.76 (0.70-0.83) vs. 0.66 (0.58-0.74), p=0.032]. CONCLUSIONS: Metabolic profile provides prognostic value for HF patients better than Gal-3.

Factors Associated With Inadequate Effectiveness of a Multidisciplinary Disease Management Program in Heart Failure Patients Stratified by Galectin 3 Level.

OBJECTIVE: This study investigated whether multidisciplinary disease management programs (MDPs) exert the same effects in heart failure (HF) patients across risk levels stratified by galectin-3 (Gal-3) level and what factors are associated with inadequate effectiveness of MDP. METHODS: We used a longitudinal follow-up design based on a previous randomized trial. A total of 355 stabilized hospitalized HF patients were enrolled. The effects of MDP on death and HF-related rehospitalization were analyzed according to Gal-3 levels. RESULTS: During the 4-year follow-up, Gal-3 levels predicted mortality and composite events ( p < .001). Multivariable analysis demonstrated the event-lowering effect of MDP (hazard ratio [HR] = 0.49, p = .001 for death and HR = 0.50, p < .001 for composite events). However, the effect of MDP was inadequate for those with high Gal-3 levels (≥17.9 ng/ml), whose 4-year composite event rate was 43% in the MDP arm. Further analysis showed that, in patients with Gal-3 ≥ 17.9 ng/ml, the independent factors associated with a high composite event rate were no MDP, older age, worse New York Heart Association functional class, no angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker use, higher predischarge natriuretic peptide levels, and wider QRS complexes. CONCLUSIONS: The effectiveness of MDP for HF patients at high risk was inadequate. Our findings identified the characteristics of these MDP nonresponders. Better integration of advanced care plans based on strategies guided by Gal-3 level is needed to improve care quality.

Estimating systemic fibrosis by combining galectin-3 and ST2 provides powerful risk stratification value for patients after acute decompensated heart failure.

BACKGROUND: Two fibrosis biomarkers, galectin-3 (Gal-3) and suppression of tumorigenicity 2 (ST2), provide prognostic value additive to natriuretic peptides and traditional risk factors in patients with heart failure (HF). However, it is to be investigated whether their combined measurement before discharge provides incremental risk stratification for patients after acute HF. METHODS: A total of 344 patients with acute HF were analyzed with Gal-3, and ST2 measured. Patients were prospectively followed for 3.7 ± 1.3 years for deaths, and composite events (death/HF-related re-hospitalizations). RESULTS: The levels of Gal-3 and ST2 were only slightly related (r = 0.20, p < 0.001). The medians of Gal-3 and ST2 were 18 ng/mL and 32.4 ng/mL, respectively. These biomarkers compensated each other and characterized patients with different risk factors. According to the cutoff at median values, patients were separated into four subgroups based on high and low Gal-3 (HG and LG, respectively) and ST2 levels (HS and LS, respectively). Kaplan-Meier survival curves showed that HGHS powerfully identified patients at risk of mortality (Log rank = 21.27, p < 0.001). In multivariable analysis, combined log(Gal-3) and log(ST2) was an in-dependent predictor. For composite events, Kaplan-Meier survival curves showed a lower event- -free survival rate in the HGHS subgroup compared to others (Log rank = 34.62, p < 0.001; HGHS vs. HGLS, Log rank = 4.00, p = 0.045). In multivariable analysis, combined log(Gal-3) and log(ST2) was also an independent predictor. CONCLUSIONS: Combination of biomarkers involving heterogeneous fibrosis pathways may identify patients with high systemic fibrosis, providing powerful risk stratification value.

GSTM1, GSTT1, GSTP1, and GSTA1 genetic variants are not associated with coronary artery disease in Taiwan.

BACKGROUND AND OBJECTIVE: The genetic variants of xenobiotic-metabolizing enzymes, such as those encoded by glutathione-S-transferase (GST) genes, may be associated with the risk of coronary artery disease (CAD). To investigate the genetic factors for CAD, we examined the GSTM1, GSTT1, GSTP1, and GSTA1 genotypes in a CAD cohort in Taiwan. METHODS: Our study included 458 CAD participants and 209 control participants who received coronary angiography to assess CAD. The severity of CAD was defined as the number of coronary vessels with 50% or greater stenosis. Sequence variation of the GSTM1 and GSTT1 genes was determined using a polymerase chain reaction (PCR). The GSTP1 (Ile105Val), and GSTA1 (-69C>T) genetic variants were identified using a combination of PCR and restriction fragment length polymorphism analysis. Logistic regression analysis was used to calculate the odds ratios (ORs) and 95% confidence intervals. RESULTS: Among the GST genetic variants examined, the GSTT1 null genotype was more prevalent in CAD participants with 3 stenosed vessels than in control participants (OR=1.64, P=.02). This association was no longer observed after adjusting for age, sex, smoking, alcohol use, diabetes mellitus, and serum levels of total cholesterol and high-density lipoprotein cholesterol (OR=1.28, P=.40). Both univariate and multivariate logistic regression analyses found no significant associations between CAD and the other genetic variants, either separately or in combination. In addition, no effects of interactions between the genotypes and environmental factors, such as cigarette smoking, were significantly associated with the risk of CAD. CONCLUSION: The GST genetic variants examined were not associated with susceptibility to CAD in our Taiwanese cohort. This null association requires further confirmation with larger samples.

Edema index-guided disease management improves 6-month outcomes of patients with acute heart failure.

The efficacy of heart failure (HF) management programs is compromised by the challenge of early identification of patients at imminent risk. Segmental multifrequency bioelectrical impedance analysis can generate an "edema index" (EI) as a surrogate for the body fluid status. In this study, we tested whether integration of EI-guided management improved the 6-month outcomes of HF patients under multidisciplinary care. In total, 159 patients with acute HF were randomized into control, case management (CM), and EI-guided CM (EI) groups (n = 53 in each group). In the EI group, a management algorithm was designed based on the measured EI. The analyzed endpoints included HF-related and all cause-related events during the 6-month follow-up period. In the 6 months, there were 11 (6.9%) deaths, 19 (11.9%) HF-related rehospitalizations, and 45 (28.3%) all-cause-related rehospitalizations. Compared to the control (26.4%) and CM groups (15.1%), the EI group had a lower rate of HF-related death and rehospitalization (3.8%, P = 0.004). Multivariate analysis revealed that EI-guided management was an independent predictor of a lower HF-related event rate (hazard ratio = 0.15, 95%CI = 0.03~0.66, P = 0.012). Patients with a higher pre-discharge EI were older, had lower blood albumin and hemoglobin levels, and had a higher functional class and incidences of diabetes mellitus and chronic kidney disease. An increase in the pre-discharge EI by 0.001 increased the HF-related event rate by 6% (P = 0.002). Use of EI-guided management lowered this risk (P = 0.03). In conclusion, an EI-based HF management program demonstrated an event-lowering effect superior to traditional nurse-led multidisciplinary care in 6 months after an acute HF episode.

Increased leukocyte Rho-associated coiled-coil containing protein kinase activity predicts the presence and severity of coronary vasospastic angina.

OBJECTIVE: Although inhibition of Rho-associated coiled-coil containing protein kinase (ROCK) has been shown to prevent coronary vasospastic angina (CVA), direct evidence linking ROCK activity and CVA is lacking. Accordingly, we investigated whether ROCK activity is an independent marker for CVA and is altered after treatment with antispastic medications. METHODS AND RESULTS: We prospectively studied 31 Taiwanese patients who were diagnosed with CVA and 33 control subjects. Subject demographics were recorded, and blood samples were obtained at baseline in all participants and in CVA patients after 3 months of antispastic treatment. Compared with control subjects, leukocyte ROCK activity was greater in CVA patients (136% versus 91%, P<0.001). A cutoff value for leukocyte ROCK activity of 104% predicted the presence of CVA with specificity and sensitivity rates of 88% and 84%, respectively. ROCK activity increased with the severity of CVA (P for trend<0.001). Following 3-month treatment of antispastic agents, leukocyte ROCK activity, high-sensitivity C-reactive protein, and interleukin-6 levels were reduced by 43%, 42% and 27%, respectively (P<0.05 for all). CONCLUSIONS: Increased levels of leukocyte ROCK activity independently predicted the presence of CVA and correlated with CVA severity. Treatment with antispastic agents substantially reduced the level of leukocyte ROCK activity.

Levels of blood periostin decrease after acute myocardial infarction and are negatively associated with ventricular function after 3 months.

BACKGROUND: A recent study showed that periostin (PN) induced reentry of differentiated cardiomyocytes into the cell cycle and improved heart function after acute myocardial infarction (AMI). This study sought to investigate whether PN levels increase after AMI and whether they provide prognostic value. METHODS AND RESULTS: We recruited 123 patients: 45 with AMI, 45 with stable coronary artery disease (CAD), and 33 healthy controls (CON). Blood PN and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels were measured. Echocardiography was repeated 3 months after AMI. In the AMI group, the PN levels 1.3 ± 1.2 days after AMI were significantly lower than those in the CAD and CON groups (175 ± 60, 245 ± 68, and 232 ± 63 ng/mL, respectively, P = 0.001). The NT-pro-BNP levels were significantly higher in the AMI group, compared to the CON and CAD groups (10.07 ± 28.2 [median, 0.70] vs 0.08 ± 0.06 [median, 0.05] and 1.1 ± 4.2 [median, 0.09] ng/mL, respectively; P = 0.02). The PN levels further decreased 8 ± 2 days after AMI (from 175 ± 60 to 143 ± 57 ng/mL; P = 0.003). However, NT-pro-BNP levels did not significantly change. With respect to the echocardiographic parameters 3 months after AMI, the PN levels measured before discharge were negatively associated with the left ventricular ejection fraction (rs = -0.50; P = 0.001), end diastolic (rs = 0.42; P = 0.009) and systolic (rs = 0.46; P = 0.004) diameters. The NT-pro-BNP levels were not significantly correlated with these parameters. CONCLUSION: Acute myocardial infarction is associated with a decrease in blood PN levels, and PN concentrations predict cardiac function 3 months after AMI.

The diagnostic value of computed tomographic coronary angiography in patients with acute myocardial infarction versus stable angina pectoris: a preliminary report.

BACKGROUND: Computed tomographic coronary angiography (CTA) is a non-invasive alternative to conventional coronary angiography (CCA) in detecting chronic coronary artery disease (CAD). However, the value of CTA in estimating acute myocardial infarction (AMI) has not been evaluated. METHODS: CTA and CCA were performed on 10 patients with non-ST-elevated AMI and 17 patients with stable angina pectoris. The plaque components and stenosis severity were assessed by both modalities to clarify the diagnostic values of CTA in AMI and stable angina pectoris. RESULTS: A high total coronary artery calcium (CAC) score was significantly correlated with the presence of CAD and the target lesion CAC score (p < 0.01). The AMI group tended to have a lower target CAC score (p = 0.10) and target plaque burden (p = 0.27), compared to the stable angina pectoris group. To estimate the coronary artery stenotic severity, CTA and CCA had concordant correlations in all segments, except in the proximal left anterior descending (LAD) artery. The calcium score and calcification fraction percentage in the proximal LAD artery were significantly higher than those of other segments (p < 0.01). Compared to CCA, CTA overestimated the severity of stenosis in the proximal LAD arterial segment in the stable angina pectoris group (p = 0.028), but not in the AMI group. CONCLUSIONS: CTA has diagnostic values similar to those of CCA in detecting coronary lesions in patients with AMI or stable angina pectoris. However, a high level of plaque CAC in the stable angina pectoris group may lead to an overestimation of the severity of coronary stenosis, especially in the proximal LAD arterial segment. Although less remarkable, the impact of CAC on the diagnostic value of CTA was still substantial in patients with AMI.

Real-time three-dimensional echocardiography provides advanced haemodynamic information associated with intra-dialytic hypotension in patients with autonomic dysfunction.

BACKGROUND: Real-time three-dimensional echocardiography (RT3DE) has emerged as a more accurate and effective tool for assessing left ventricular (LV) function, compared to traditional two-dimensional (2D) methods. In this study, we used this new tool to revise the controversial relationship between LV function and intra-dialytic hypotension. METHODS: This study enrolled 29 intra-dialytic hypotensive patients (the IDH group) and 34 controls (the CON group) on regular maintenance haemodialysis. The RT3DE- and 2D-derived ejection fraction (EF), stroke volume index (SVI) and ratio of early transmitral inflow velocity to diastolic early tissue velocity were assessed at pre-dialysis and mid-dialysis. The intravascular volume was assessed by the inferior vena cava collapsibility index. RESULTS: Pre-dialysis evaluation showed no difference in RT3DE- and 2D-derived parameters between the two groups. At mid-dialysis, the IDH group had a lower 2D EF (54 +/- 9.1 versus 62 +/- 6.8% in the CON group, P < 0.001), RT3DE EF (53 +/- 6 versus 60 +/- 7% in the CON group, P < 0.001) and SVI (24.3 +/- 8 versus 30.6 +/- 12.2 mL in the CON group, P = 0.02). From pre-dialysis to mid-dialysis, the IDH group had greater decrease in the change in 2D EF (-4.8% +/- 12.6% versus 5% +/- 13.7% in the CON group, P = 0.004), RT3DE EF (-11.8 +/- 10.3 versus -3.4 +/- 11.5% in the CON group, P = 0.003) and SVI (-17.3 +/- 18.5 versus -9.2 +/- 19.8% in the CON group, P = 0.004). The calculated cardiac index change also showed a greater decrease in the IDH group (-17.8 +/- 20.2 versus -5.7 +/- 18.5% in the CON group, P = 0.02). No significant difference in the ratio of early transmitral inflow velocity to diastolic early tissue velocity, heart rate, systemic vascular resistance index or inferior vena cava collapsibility index was found between the two groups at the baseline or mid-dialysis. A lack of an increase in heart rate and the systemic vascular resistance index in the IDH group during the hypotensive episodes implies that these patients have autonomic dysfunction. Multivariate analysis showed that the RT3DE EF change of < -9.5% (odds ratio = 6, P = 0.003) and the presence of diabetes (odds ratio = 4.4, P = 0.013) had significant and independent associations with intra-dialytic hypotension. CONCLUSIONS: By adopting RT3DE to assess LV performance, our data demonstrated that an inadequate compensation in the LV systolic function is the main mechanism mediating the occurrence of intra-dialytic hypotension in patients with autonomic dysfunction.

Interaction between cigarette smoking and high-sensitivity C-reactive protein in the development of coronary vasospasm in patients without hemodynamically significant coronary artery disease.

BACKGROUND: Interaction between 2 major risk factors, cigarette smoking and high-sensitivity C-reactive protein (hs-CRP), has not been evaluated in patients with coronary vasospasm (CV) without hemodynamically significant coronary artery disease. METHODS: From 1999 to 2005, patients undergoing diagnostic coronary angiography with or without proven CV and without coronary stenosis >50% were evaluated. A total of 621 subjects (335 and 286 with and without CV, respectively) were enrolled in the study. The levels of hs-CRP, measured immediately before coronary angiography, were examined in a subset of 314 patients. RESULTS: Subjects with CV were likely to be older, men, current smokers, and have high hs-CRP levels. The most significant factors for CV were smoking and hs-CRP. In the nonsmoker group, elevated risk of developing CV was only demonstrated in patients with the highest hs-CRP tertile (>5.01 mg/L, P = 0.012). In the smoker group, however, a positively monotonic trend of association was demonstrated between hs-CRP tertile and CV risk, with multivariate-adjusted odds ratios of 1.11, 3.09 (P = 0.012), and 4.12 by the hs-CRP tertiles, suggesting that smokers developed CV at a lower hs-CRP level than nonsmokers and there was a positive interaction between smoking and hs-CRP. CONCLUSIONS: The smokers developed CV at a lower hs-CRP level compared with the nonsmokers. A positive interaction between smoking and hs-CRP was demonstrated for this disease in our study population.

Late reperfusion of a totally occluded infarct-related artery increases granulocyte-colony stimulation factor and reduces stroma-derived factor-1alpha blood levels in patients with ongoing ischemia after acute myocardial infarction.

After acute myocardial infarction (AMI), reopening of a totally occluded infarct-related artery (IRA) at a subacute stage is still controversial in symptom-free patients. However, in patients with persistent ischemic symptoms and inadequate collaterals to the infarct area, recanalization is thought to provide beneficial effects. In addition to augmenting myocardial perfusion, we hypothesized that the benefit of recanalization involves the manipulation of circulating stem cell-mobilizing cytokines. This study included 30 patients with a totally occluded IRA and ongoing ischemic symptoms (the study group) and 30 patients with a partially occluded IRA (the control group). All patients underwent successful angioplasty and/or stenting. Before and immediately after the coronary intervention, blood granulocyte-colony-stimulating factor (G-CSF), stem-cell factor (SCF), vascular endothelial growth factor (VEGF), and stroma-derived factor-1 (SDF-1alpha) were measured. After recanalization, G-CSF levels significantly increased in the study group compared to the control group (P=0.03). SDF-1alpha levels in the study group decreased relative to the controls (P=0.02). However, no significant changes in VEGF or SCF levels between the two groups were found. In the multivariate analysis, reopening of a totally occluded IRA was independently and significantly associated with changes in G-CSF and SDF-1alpha levels after recanalization. In conclusion, our data suggest that the benefits of late reperfusion of a totally occluded IRA in patients with ongoing myocardial ischemia may involve mechanisms associated with stem cell-mobilizing and plaque-stabilizing cytokines. This study provides the rationale to investigate serial changes in cytokines and the numbers of circulating progenitors after reperfusion in the future.

Polymorphisms of cytochrome P450 1A1, cigarette smoking and risk of coronary artery disease.

Epidemiological evidence has demonstrated a strong relationship between cigarette smoking and coronary artery disease (CAD). Cytochrome P450 1A1 (CYP1A1) is a key enzyme that metabolizes the cigarette toxin relevant to smoking-induced atherogenesis. This case-control study examined the role of CYP1A1 polymorphisms, CYP1A1 2A (T6235C) and CYP1A1 2C (A4889G), in susceptibility to smoking-related CAD. We recruited 481 patients with 50% or more luminal obstructions in the coronary artery and 228 normal subjects at a medical center in Taiwan. Information on socio-demographic and smoking status was obtained using a self-administered questionnaire. Genotypes of CYP1A1 2A and CYP1A1 2C polymorphisms were determined by polymerase chain reaction or in combination with restriction fragment length polymorphism methods. The results did not show any significant association between CYP1A1 2A polymorphism and CAD risk. However, the CYP1A1 2C G allele was more prevalent in controls (p=0.035) with a dose-response protective effect for CAD. Compared to the A/A genotype, the multivariate logistic regression analysis showed that carrying the CYP1A1 2C G/G genotype was associated with a significantly decreased risk for CAD (OR=0.32, 95% CI=0.15-0.70). The beneficial effect of the CYP1A1 2C G/G genotype was even greater for never smokers than those carrying the A/A genotype (OR=0.23, 95% CI=0.08-0.71). The interaction between genotype and smoking status was not statistically significant. Our findings suggest that the CYP1A1 2C G/G genotype may reduce the risk for CAD in the Taiwanese population and this effect appeared to be more pronounced among never smokers.

Serum interleukin-6 levels, not genotype, correlate with coronary plaque complexity.

An increased serum interleukin-6 (IL-6) level is associated with an increased risk of cardiovascular events in healthy subjects. However, it is unknown whether the level of serum IL-6 or genetic IL-6 polymorphism is correlated with the complexity of coronary plaque in patients with stable coronary artery disease (CAD). Patients with stable CAD (n = 135) were divided into 3 groups: insignificant coronary plaque (n = 77), simple coronary plaque (n = 15), and complex coronary plaque (n = 43). IL-6-174G > C polymorphism and serum levels of IL-6 and C-reactive protein (CRP) were investigated. No significant difference in the distribution of IL-6 genotypes was found among the groups. The presence of complex coronary plaque was associated with higher serum concentrations of IL-6 (P = 0.026) and CRP (P < 0.0001). To predict the presence of complex lesions, IL-6 > 5.8 ng/L and CRP > 2.6 mg/L had sensitivities of 86% and 74%, and specificities of 61% and 62%, respectively. By multivariate analysis, IL-6 > 5.8 ng/L and CRP > 2.6 mg/L were independently related to the presence of complex coronary plaque (P = 0.0002 and 0.004, respectively). IL-6 > 5.8 ng/L and CRP > 2.6 mg/L were associated with a 4.5-fold increase in the odds of having complex coronary plaque (P < 0.005). A simple measurement of the serum IL-6 level in patients with CAD can potentially identify subjects with complex coronary lesions and provide the option of aggressive medical strategies in a clinical setting.

Analysis of left ventricular changes after acute myocardial infarction using transthoracic real-time three-dimensional echocardiography.

BACKGROUND: Little information is available regarding the relationship between three-dimensional (3-D) echocardiographic parameters in acute stage of acute myocardial infarction (AMI) and subsequent left ventricular (LV) remodeling after AMI. METHODS: Consecutive patients with AMI were analyzed for echocardiographic predictors of subsequent LV remodeling after AMI using two-dimensional (2-D) echocardiography and real-time 3-D echocardiography at baseline and month 3 of follow-up. LV adverse and favorable remodeling were defined as a >10% and 42 mL/m(2) of 75%, 71%, 75%, and 71%, respectively. CONCLUSIONS: LVESVI assessed by 3-D echocardiography was the most predictive parameter indicating favorable LV remodeling after AMI. LV shape on contraction changed from elliptical shape to more globular in the adverse remodeling process after AMI.