Bai-Chin Lee

Endothelial Progenitor Cells in Primary Aldosteronism: A Biomarker of Severity for Aldosterone Vasculopathy and Prognosis

CONTEXT Primary aldosteronism (PA) is associated with a higher incidence of cardiovascular events, probably through mineralocorticoid receptor (MR)-dependent endothelial cell dysfunction, in comparison with essential hypertension (EH). OBJECTIVE Our objective was to investigate the number and function of endothelial progenitor cells (EPC) in PA and the relationship with arterial stiffness and disease progression. DESIGN AND SETTING We conducted a prospective study of the change of EPC number and outcome of PA patients after treatment at a tertiary medical center. PRIMARY OUTCOMES Changes in arterial stiffness and EPC number after treatment and the curability of hypertension were assessed. PATIENTS A total of 113 PA patients (87 patients diagnosed with aldosterone-producing adenoma, 26 with idiopathic hyperaldosteronism) and 55 patients with EH participated. RESULTS PA patients had higher arterial stiffness than EH patients (P = 0.006), with a lower numbers of circulating EPC and endothelial colony-forming units (P < 0.05). The differences were ameliorated at 6 months after unilateral adrenalectomy or treatment with spironolactone. Expression of MR was identified in the EPC. The number of circulating EPC was inversely correlated with the plasma aldosterone concentration (P = 0.021), arterial stiffness (P = 0.029) and serum high-sensitivity C-reactive protein (P = 0.03). High-dose aldosterone (10(-5) and 10(-6) m) attenuated EPC proliferation and angiogenesis in vitro. Among the 45 patients who underwent unilateral adrenalectomy, 32 (71%) were cured of hypertension. The preoperative number of EPC [log(EPC number percent) >-3.6] predicted the curability of hypertension after adrenalectomy (P = 0.003). CONCLUSIONS The relative deficiency of EPC in PA patients may contribute to aldosterone vasculopathy, which can be reversed by adrenalectomy and spironolactone. High aldosterone levels attenuated EPC proliferation and angiogenesis. Circulating EPC number may be a valuable biomarker to identify PA patients with a high incidence of arterial stiffness and to predict postoperative residual hypertension of aldosterone-producing adenoma.

A Prediction Model for the Risk of Incident Chronic Kidney Disease

BACKGROUND Chronic kidney disease is a health burden for the general population. We designed a cohort study to construct prediction models for chronic kidney disease in the Chinese population. METHODS A total of 5168 participants were followed up during a median of 2.2 (interquartile range, 1.5-2.9) years, and 190 individuals (3.7%) developed chronic kidney disease, defined by a glomerular filtration rate of less than 60 mL/min/1.73 m(2). RESULTS We developed a point system to estimate chronic kidney disease risk at 4 years using the following variables: age (8 points), body mass index (2 points), diastolic blood pressure (2 points), and history of type 2 diabetes (1 point) and stroke (4 points) for the clinical model, with the addition of uric acid (2 points), postprandial glucose (1 point), hemoglobin A1c (1 point), and proteinuria 100 mg/dL or greater (6 points) for the biochemical model. Similar discrimination measures were found between the clinical model (area under the receiver operating characteristic curve, 0.768; 95% confidence interval (CI), 0.738-0.798) and the biochemical model (area under the receiver operating characteristic curve, 0.765; 95% CI, 0.734-0.796). The area under the receiver operating characteristic curve of the clinical model was 0.667 (95% CI, 0.631-0.703) for the external validation data from community-based cohort participants. The optimal cutoff value for the clinical model was set as 7, with a sensitivity of 0.76 and a specificity of 0.66. CONCLUSION We constructed a clinical point-based model to predict the 4-year incidence of chronic kidney disease. This prediction tool may help to target Chinese subjects at risk of developing chronic kidney disease.

Postprandial Glucose Improves the Risk Prediction of Cardiovascular Death Beyond the Metabolic Syndrome in the Nondiabetic Population

OBJECTIVE With increasing evidence about the cardiovascular risk associated with postprandial nonfasting glucose and lipid dysmetabolism, it remains uncertain whether the postprandial glucose concentration increases the ability of metabolic syndrome to predict cardiovascular events. RESEARCH DESIGN AND METHODS This was an observational study of 15,145 individuals aged 35–75 years without diabetes or cardiovascular diseases. Postprandial glucose was obtained 2 h after a lunch meal. Metabolic syndrome was diagnosed using the criteria of the U.S. National Cholesterol Education Program Adult Treatment Panel III. Cardiovascular and all-cause deaths were primary outcomes. RESULTS During a median follow-up of 6.7 years, 410 individuals died, including 82 deaths from cardiovascular causes. In a Cox model adjusting for metabolic syndrome status as well as age, sex, smoking, systolic blood pressure, LDL, and HDL cholesterol levels, elevated 2-h postprandial glucose increased the risk of cardiovascular and all-cause death (per millimole per liter increase, hazard ratio 1.26 [95% CI 1.11–1.42] and 1.10 [1.04–1.16], respectively), with significant trends across the postprandial glucose quintiles. Including 2-h postprandial glucose into a metabolic syndrome–included multivariate risk prediction model conferred a discernible improvement of the model in discriminating between those who died of cardiovascular causes and who did not (integrated discrimination improvement 0.4, P = 0.005; net reclassification improvement 13.4%, P = 0.03); however, the improvement was only marginal for all-cause death. CONCLUSIONS Given the risk prediction based on metabolic syndrome and established cardiovascular risk factors, 2-h postprandial glucose improves the predictive ability to identity nondiabetic individuals at increased risk of cardiovascular death.

Cell therapy generates a favourable chemokine gradient for stem cell recruitment into the infarcted heart in rabbits

Stem cell recruitment into the heart is determined by a concentration gradient of stromal‐derived factor 1 (SDF‐1) from bone marrow to peripheral blood and from blood to injured myocardium. However, this gradient is decreased in chronic myocardial infarction (MI). This study evaluated the effect of cell therapy using bone marrow stromal cells (BMSCs) on an SDF‐1 gradient in post‐infarction rabbits.

Effect of Cardiac Rehabilitation on Myocardial Perfusion Reserve in Postinfarction Patients

Cardiac rehabilitation is believed to increase myocardial perfusion reserve (MPR), but this has not been adequately studied because of poor delineation of infarcted myocardium in previous studies. The purpose of this study was to determine the effect of cardiac rehabilitation on MPR in the remote and infarcted myocardium with contrast-enhanced magnetic resonance imaging; 39 postinfarction patients were recruited for this study and randomly assigned to a training group (n = 20) or a nontraining group (n = 19). Those in the training group participated in a 3-month rehabilitation training program at an exercise intensity of 55% to 70% of peak oxygen uptake (VO2); those in the nontraining group continued their usual lifestyle. Nineteen age-, weight-, and height-matched subjects without cardiovascular risk factors were selected as healthy controls. After myocardial infarction, a reduction in perfusion reserve was seen not only in the infarcted myocardium, but also in the remote myocardium. In the training group, exercise capacity increased by 15% (p <0.01), to the same level as in healthy controls. The post-training MPR increased in both remote (30%, p <0.01) and infarcted myocardium (25%, p <0.05) and reached the same level as in healthy controls. The change in exercise capacity correlated with the change in MPR in the remote myocardium (r = 0.55, p <0.001 for peak VO2). In the nontraining group, exercise capacity and MPR were unchanged. In conclusion, cardiac rehabilitation improves perfusion reserve in both infarcted and remote myocardium, with a parallel increase in exercise capacity.

Exercise training improves cardiac function in infarcted rabbits: involvement of autophagic function and fatty acid utilization.

To explore whether exercise can improve cardiac function in a post‐myocardial infarction (MI) rabbit model and to determine contributing factors in the left ventricle (LV).

Effect of cardiac rehabilitation on angiogenic cytokines in postinfarction patients

Objective: To determine whether cardiac rehabilitation influences plasma levels of angiogenic cytokines and their correlation with myocardial blood flow (MBF). Design: Randomised controlled study. Setting: Tertiary cardiac centre. Patients: 39 postinfarction patients randomised to either a 3-month training group (n = 20) or a non-training group (n = 19), and 19 normal controls. Interventions: Cardiac rehabilitation. Main outcome measures: MBF by cardiac magnetic resonance imaging, and plasma levels of stem cell factor (SCF), stromal-derived factor-1 (SDF-1), and vascular endothelial growth factor (VEGF) measured at enrolment and at 3 months after randomisation. Results: At baseline, when compared with the healthy subjects, postinfarction patients had a lower MBF in the infarcted myocardium during dipyridamole-induced stress (1.65 (0.58) vs 2.77 (0.78) ml/min/g, p<0.001) but higher plasma levels of VEGF (3.65 (0.75) vs 2.77 (0.59) pg/ml, p<0.001 expressed as the natural logarithm) and SDF-1 (2113 (345) vs 1869 (309) pg/ml, p = 0.009). Only SDF-1 was inversely associated with stress MBF in both remote (r = −0.39, p = 0.03) and infarcted myocardium (r = −0.62, p<0.001). After 3 months, the training group’s stress MBF had increased by 33% in the remote (p<0.001) and 28% in infarcted myocardium (p = 0.02), while VEGF decreased by 9% (p = 0.01), and SDF-1 decreased by 11% (p = 0.02). The change in SDF-1 was inversely correlated with the change in stress MBF in both remote (r = −0.40, p = 0.01) and infarcted myocardium (r = −0.50, p = 0.001). In the non-training group, MBF and cytokines were unchanged. Conclusion: Cardiac rehabilitation improves stress MBF in postinfarction patients, with an inverse decrease in circulating angiogenic cytokines.

Heart rate variability in patients with different manifestations of gastroesophageal reflux disease

BACKGROUND Autonomic nervous dysfunction has frequently been observed in patients with gastroesophageal reflux diseases (GERD) and impacts the pathogenesis of GERD. However, the characteristics that distinguish between GERD patients with different manifestations remain unknown. AIM To investigate the autonomic nervous function in subgroups of GERD patients. PATIENTS Of the 164 participants in this study, 57 were healthy controls, 34 had non-erosive reflux disease (NERD), 40 had symptomatic esophagitis (SE), and 33 asymptomatic esophagitis (AE). METHODS Resting autonomic activity was assessed by measuring the 5-min heart rate variability (HRV) and HRV indices including time-domain parameters (standard deviation of normal-to-normal intervals [SDNN] and root mean square of successive differences [RMSSD]) and frequency-domain parameters (low-frequency power [LF; 0.04-0.15 Hz], high-frequency power [HF; 0.15-0.4 Hz], and LF/HF power ratio). Mental stress was assessed by use of a self-reported questionnaire (Brief Symptom Rating Scale [BSRS]). RESULTS HF power was (ANOVA, p=0.041) but time-domain parameters, LF power, LF/HF power ratio, and BSRS parameters were not significantly different between the four groups. A higher HF power was found in examinees with NERD than in those with SE and AE (LSD methods: both p=0.02). When split into two groups (erosive vs. non-erosive), nearly all measures of autonomic tonus were significantly lower in the erosive than non-erosive group. Age and the presence of endoscopic esophagitis influenced the RMSSD and HF power results in the regression analysis. Mental stress or gender did not correlate with any HRV index. CONCLUSION In comparison with NERD subjects, autonomic tonus in patients with endoscopically confirmed esophagitis (even without symptom) is lower. This finding may suggest that the structural state of esophagus but not symptomatology dictates autonomic function status.

Plasma fatty acids and the risk of metabolic syndrome in ethnic Chinese adults in Taiwan

BackgroundEvidence of predictive power of various fatty acids on the risk of metabolic syndrome was scanty. We evaluated the role of various fatty acids, including saturated fat, monounsaturated fat, transfat, n-6 fatty acid, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), for the risk of the metabolic syndrome in Taiwan.ResultsA nested case-control study based on 1000 cases of metabolic syndrome and 1:1 matched control subjects. For saturated fat, monounsaturated fat and transfat, the higher the concentration the higher the risk for metabolic syndrome: participants in the highest quintile had a 2.22-fold (95% confidence interval [CI], 1.66 to 2.97) higher risk of metabolic syndrome. In addition, the participants in higher EPA quintiles were less likely to have the risk of metabolic syndrome (adjusted risk, 0.46 [0.34 to 0.61] for the fifth quintile). Participants in the highest risk group (low EPA and high transfat) had a 2.36-fold higher risk of metabolic syndrome (95% CI, 1.38 to 4.03), compared with those in the lowest risk group (high EPA and low transfat). For prediction power, the area under ROC curves increased from 0.926 in the baseline model to 0.928 after adding fatty acids. The net reclassification improvement for metabolic syndrome risk was substantial for saturated fat (2.1%, P = 0.05).ConclusionsPlasma fatty acid components improved the prediction of the metabolic syndrome risk in Taiwan.

High serum level of matrix metalloproteinase-1 and its rapid surge after intervention in patients with significant carotid atherosclerosis.

High tissue matrix metalloproteinase (MMP) activity has been reported to be associated with atherosclerosis and plaque rupture. The aim of this study was to elucidate the diagnostic value of serum MMP-1 in carotid stenosis and its dynamic change after stenting. We measured high-sensitivity C-reactive protein (hs-CRP) and MMP-1 in 37 patients with carotid stenosis (>or= 50%) and 84 controls. In 30 patients who underwent stenting, MMP-1 and hs-CRP were assessed immediately after stenting. We found that patients with carotid stenosis exhibited significantly higher MMP-1 compared with controls, but there was no difference in hs-CRP. Moreover, MMP-1 was elevated immediately after stenting. In multivariate analyses, MMP-1 was negatively correlated with statin and angiotensin converting enzyme inhibitor/angiotensin-II receptor blocker use in controls. In conclusion, higher levels and rapid surge after stenting in patients with carotid stenosis indicate that MMP-1 is an important composition of plaques, and suggest its potential role in the assessment of plaque burden and stability of carotid stenosis.