Search

Abstract Myocardial perfusion imaging (MPI) is a clinical tool which can assess the heart's perfusion status, thereby revealing impairments in patients' cardiac function. Within the MPI modality, the acquired three-dimensional signals are typically represented as a sequence of two-dimensional grayscale tomographic images. Here, we proposed an end-to-end survival training approach for processing gray-scale MPI tomograms to generate a risk score which reflects subsequent time to cardiovascular incidents, including cardiovascular death, non-fatal myocardial infarction, and non-fatal ischemic stroke (collectively known as Major Adverse Cardiovascular Events; MACE) as well as Congestive Heart Failure (CHF). We recruited a total of 1928 patients who had undergone MPI followed by coronary interventions. Among them, 80% (n = 1540) were randomly reserved for the training and 5- fold cross-validation stage, while 20% (n = 388) were set aside for the testing stage. The end-to-end survival training can converge well in generating effective AI models via the fivefold cross-validation approach with 1540 patients. When a candidate model is evaluated using independent images, the model can stratify patients into below-median-risk (n = 194) and above-median-risk (n = 194) groups, the corresponding survival curves of the two groups have significant difference (P

Abstract Background Renal function decline is a frequently encountered complication in patients with chronic coronary syndrome. Aside from traditional cardiovascular risk factors, the inflammatory burden emerged as the novel phenotype that compromised renal prognosis in such population. Methods A cohort with chronic coronary syndrome was enrolled to investigate the association between inflammatory status and renal dysfunction. Levels of inflammatory markers, including high-sensitivity C-reactive protein (hs-CRP), tumour necrosis factor-α (TNF-α), adiponectin, matrix metalloproteinase-9, interleukin-6, lipoprotein-associated phospholipase A2, were assessed. Renal event was defined as > 25% decline in estimated glomerular filtration rate (eGFR). Inflammatory scores were calculated based on the aggregate of hs-CRP, TNF-α, and adiponectin levels. Results Among the 850 enrolled subjects, 145 patients sustained a renal event during an averaged 3.5 years follow-up. Multivariate analysis with Cox regression suggested elevations in hs-CRP, TNF-α, and adiponectin levels were independent risk factors for the occurrence of a renal event. Whereas, Kaplan-Meier curve illustrated significant correlation between high TNF-α (P = 0.005), adiponectin (P

Background: Myocardial bridging (MB) is a congenital coronary anomaly and an important cause of chest pain. The long-term effects of MB on cardiovascular events remain elusive. Methods: We used the National Health Insurance Research Database of Taiwan to conduct an analysis. All patients who had undergone coronary angiography were considered for inclusion. The primary endpoint was a composite of nonfatal myocardial infarction, nonfatal ischemic stroke, and cardiovascular death. Results: We identified 10,749 patients from 2008 to 2018 and matched them with an equal number of controls by propensity-score matching. The mean follow-up period was 5.78 years. In patients without coronary artery disease, MB increased the risk of the composite endpoint (hazard ratio [HR]: 1.57, 95% confidence interval [CI]: 1.44–1.72, p < 0.001), which was driven by increased risks of nonfatal myocardial infarction and cardiovascular death. In patients with significant coronary artery disease, MB did not increase the risk of major adverse cardiovascular events. MB was identical to insignificant coronary artery disease from the viewpoint of clinical outcomes. Conclusions: The presence of MB significantly increases cardiovascular risks in patients with normal coronary vessels. Atherosclerotic coronary artery disease mitigates the effect of MB on cardiovascular outcomes. MB can be considered an insignificant coronary artery disease equivalent.

Background: Osteopontin (OPN) is a noncollagenous matricellular protein which is mainly present in bone matrix. A high OPN level has been associated with heart failure and acute coronary syndrome, however data on patients with chronic coronary syndrome (CCS) are lacking. The present study aimed to evaluate the association between OPN and the prognosis of Taiwanese patients with CCS. Methods: We enrolled participants from the Biosignature Registry, a nationwide prospective cohort study conducted at nine different medical centers throughout Taiwan. The inclusion criteria were participants who had received successful percutaneous coronary intervention at least once previously, and stable under medical therapy for at least 1 month before enrollment. They were followed for at least 72 months. Logistic regression and Cox proportional hazard model were used to investigate the association between OPN and clinical outcomes. The outcomes of this study were the first occurrence of hard cardiovascular events and composite cardiovascular outcomes including cardiovascular mortality, revascularization, hospitalization for acute myocardial infarction (AMI) or heart failure. Results: A total of 666 patients with both hs-CRP and osteopontin measurements were enrolled and followed for 72 months. OPN was correlated positively with AMI-related hospitalization, where the highest tertile (Tertile 3) of baseline OPN had the highest risk of AMI-related hospitalization, which remained significant after multivariate adjustments (HR 3.20, p = 0.017). In contrast, combining OPN and hs-CRP did not improve the prediction of CV outcomes. Conclusion: OPN may be a potentially valuable biomarker in predicting CV outcomes. During 6 years of follow-up period, an OPN level >4810 pg/ml was associated with a significantly higher incidence of AMI-related hospitalization in CCS patients who received successful PCI before the enrollment.

Abstract Blood pressure variability (BPV) is independently associated with higher cardiovascular risks. However, whether BPV is associated with poor outcomes for coronary artery disease (CAD) patients after percutaneous coronary intervention (PCI) remained undetermined. We aimed to investigate the relationship between BPV and the outcomes of CAD patients undergoing PCI. Two thousand seven hundred and sixty‐two CAD patients (1938 males, mean age 69.6 ± 12.9) who received PCI at Taipei Veterans General Hospital from 2006 to 2015 with multiple blood pressure measurements before and after the index PCI were enrolled. We calculated the standard deviation of systolic blood pressure, diastolic blood pressure, and pulse pressure as parameters of BPV. The primary endpoint was the composite of major adverse cardiovascular events [MACE comprising of cardiovascular death, nonfatal myocardial infarction (MI), and non‐fatal stroke] and heart failure hospitalization (HHF). The key secondary endpoint was MACE. Both pre‐PCI and post‐PCI BPV were associated with CV events even after adjusting for co‐morbidities and mean blood pressure. In Cox analysis, for every 1 mmHg increase in systolic BPV, the hazard ratio for the MACE + HHF, MACE, HHF, and cardiovascular death was 1.04 (95%CI: 1.03–1.05), 1.04 (95%CI: 1.02–1.05), 1.05 (95%CI: 1.04–1.06), and 1.06 (95%CI: 1.03–1.09), respectively. The association between BPV and cardiovascular risk is independent of blood pressure control status. The prognostic value of BPV was superior to mean blood pressure in both pre‐PCI and post‐PCI period. BPV is independently associated with cardiovascular events after PCI and has a better prognostic value than mean blood pressure suggesting the importance of maintaining stable blood pressure for CAD patients.

Abstract The control rate of hypertension remains concerning, indicating the requirement for better management strategies. The calcium channel blockers brand‐name amlodipine and nifedipine with extended‐release formulations demonstrate similar clinical efficacy. However, the efficacy of generic nifedipine remains obscure. We compared the efficacy of generic nifedipine and brand‐name amlodipine in terms of cardiovascular (CV) outcomes. Patients prescribed generic nifedipine (SRFC CYH) or brand‐name amlodipine besylate (Norvasc, Pfizer) between August 1, 2017, and July 31, 2018, were enrolled; patients with CV events within 3 months were excluded. CV outcomes included CV death, nonfatal myocardial infarction (MI), nonfatal ischemic stroke, hospitalization for heart failure, and composite endpoints of 3P‐ and 4P‐major adverse cardiac events (MACE). A total of 1625 patients treated with nifedipine (SRFC CYH) and 16 587 patients treated with Norvasc were included. After propensity score matching, there were 995 and 4975 patients in the nifedipine CYH and Norvasc groups, respectively. At a mean follow‐up period of 30.3 ± 6.4 months, nifedipine CYH was comparable to Norvasc in terms of CV death (P = .107), nonfatal MI (P = .121), nonfatal ischemic stroke (P = .453), hospitalization for heart failure (P = .330), 3P‐MACE (P = .584), and 4P‐MACE (P = .274). Cox regression analysis revealed that nifedipine CYH and Norvasc had similar efficacy in terms of 3P‐MACE (hazard ratio, 0.970; 95% confidence interval, 0.601–1.565, P = .900) and 4P‐MACE (hazard ratio, 0.880; 95% confidence interval, 0.628–1.233, P = .459). In conclusion, Nifedipine SRFC CYH and Norvasc have comparable clinical efficacy for hypertension management.

Abstract Phosphate has been linked to higher cardiovascular (CV) risk. However, whether phosphate is associated with poor outcomes for patients with coronary artery disease (CAD) after percutaneous coronary interventions (PCIs) remained undetermined. 2,894 CAD patients (2,220 male, aged 71.6 ± 12.2), who received PCI at TVGH from 2006 to 2015, with phosphate measurement, were enrolled. The primary outcome was the composite of major adverse CV events [MACE, comprising of CV death, nonfatal MI, and nonfatal stroke] and heart failure hospitalization (HHF). The key secondary outcome was MACE. There was a J-curve association between phosphate and CV events after adjusted for comorbidities and renal function. Phosphate around 3.2 ± 0.1 mg/dL was associated with the lowest CV risk. In Cox analysis, each 1 mg/dL increases in phosphate was associated with a higher risk of MACE + HHF (HR: 1.12, 95% CI: 1.05–1.21): CV death (HR: 1.37, 95% CI: 1.22–1.55) and HHF (HR: 1.12, 95% CI: 1.02–1.23). Subgroup analyses showed more prominent association between phosphate and MACE + HHF in male, age > 65, bare-metal stents (BMSs), LVEF 70 mg/dL, and emergent PCI. Phosphate has a significant association with the risk of CV events in CAD patients undergoing PCI that was independent of comorbidities and renal function.

Abstract A 69‐year‐old male underwent concomitant left ventricular assist device (LVAD) implantation and aortic valve repair procedure for moderate aortic insufficiency (AI). Due to recurrence of symptomatic heart failure and post‐repair AI deterioration from trivial to moderate‐to‐severe insufficiency 2 months later, transcatheter aortic valve implantation (TAVI) was arranged. During TAVI, intraoperative extracorporeal membrane oxygenation was used to maintain stable haemodynamics and to ensure a safe environment for prosthesis deployment. Postoperative 5 month follow‐up revealed no AI and no paravalvular leakage.

Abstract Hypertension is a frequent manifestation of chronic kidney disease but the ideal blood pressure (BP) target in patients with coronary artery disease (CAD) with end‐stage renal disease (ESRD) (eGFR

ObjectiveSLC12A3 (solute carrier family 12 member 3) gene variants are associated with diabetic nephropathy; however, their association with hypertensive nephropathy remains unknown. We aimed to investigate the association between SLC12A3 gene polymorphisms and renal function in patients with hypertension.MethodsParticipants from three non-diabetic hypertensive cohorts, including young-onset hypertension (cohort 1, n = 882), treatment-naïve hypertension (cohort 2, n = 90), and follow-up cohort (cohort 3, n = 166), underwent genotyping for single nucleotide polymorphisms in SLC12A3. Renal events were defined as a >25 and >50% decline in estimated glomerular filtration rate (eGFR).ResultsIn cohort 1, SLC12A3 rs16963397 C/C or C/G (P = 0.005), rs13334864 C/C or C/T (P = 0.020), and rs7187932 A/A or A/G polymorphisms (P = 0.014) had higher eGFRs compared to their counterparts, with similar findings observed in cohort 2. In cohort 3, over a mean follow-up of 5.8 ± 1.7 years, participants with either SLC12A3 rs16963397 C/C or rs13334864 C/C polymorphisms had more >25 and >50% eGFR decline than their counterparts (log-rank test, P = 0.058 and P = 0.038, respectively). Cox regression analysis revealed that SLC12A3 rs16963397 C/C and rs13334864 C/C polymorphisms were significantly associated with an increased risk of >25% [hazard ratio (HR), 3.294; 95% confidence interval (CI), 1.158–9.368; P = 0.025] and >50% decline in eGFR (HR, 18.630; 95% CI, 1.529–227.005, P = 0.022) than their counterparts.ConclusionSLC12A3 polymorphisms are associated with renal function in Chinese patients with hypertension.

Background: Fatty-acid binding protein-4 (FABP4) has been associated with the metabolic syndrome, diabetes mellitus, atherosclerosis, incident heart failure, and the prognosis of coronary heart disease (CHD). However, recent studies have not reported a significant correlation between FABP4 and cardiovascular (CV) mortality in high-risk patients or those with documented CHD. The present study aimed to evaluate the association between FABP4 and the prognosis in a cohort of patients with CHD who received coronary interventions. Methods: Serum FABP4 levels were measured in 973 patients after a successful intervention for CHD, who were then prospectively followed for 30 months. Result: During this period, 223 patients experienced composite CV outcomes (22.92%), defined as cardiovascular/cerebrovascular death, nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization for refractory or unstable angina, hospitalization for heart failure, and peripheral artery occlusive disease. Kaplan–Meier curves showed a significant association between FABP4 levels at baseline (categorized in tertiles) and composite CV outcomes during follow-up (log-rank test, p

Abstract Increased sympathetic nervous system (SNS) activity leads to increased risk of cardiovascular morbidity and mortality. This study investigated whether there were sex differences in SNS activity among Chinese patients with hypertension. Ethnic Chinese non‐diabetic hypertensive patients aged 20–50 years were enrolled in Taiwan. A total of 970 hypertensive patients (41.0 ± 7.2 years) completed the study, 664 men and 306 women. They received comprehensive evaluations including office blood pressure (BP) measurement, 24‐h ambulatory BP monitoring, and 24‐h urine sampling assayed for catecholamine excretion. Compared to women, men were younger, had higher body mass index (BMI), office systolic BP (SBP), office diastolic BP (DBP), 24‐h ambulatory BP, and 24‐h urine catecholamine excretion. In men, 24‐h urine total catecholamine levels were correlated with 24‐h SBP (r = 0.103, p = .008) and 24‐h DBP (r = 0.083, p = .033). In women, however, there was no correlation between 24‐h urine total catecholamine levels and 24‐h ambulatory BP. Multivariate linear regression indicated that being male (β = 1.65, 95% confidence interval [CI] 0.01–3.29, p = .048) and 24‐h urine total catecholamine (β = 5.03, 95% CI 0.62–9.44, p = .025) were both independently associated with 24‐h SBP; being male was independently associated with 24‐h DBP (β = 3.55, 95% CI 2.26–4.85, p

Abstract Background Evidence on association between body composition and outcomes of transcatheter aortic valve implantation (TAVI) is limited for Asian patients. This study investigated the prognostic role of body composition parameters in Taiwanese patients undergoing TAVI. Materials and methods Data of consecutive patients undergoing TAVI for severe aortic stenosis between May 1, 2010 and August 31, 2019 were prospectively collected in this observational study. The association between body composition parameters (body mass index [BMI], body surface area [BSA], lean body mass [LBM], and LBM index) and cumulative mortality was analyzed using Cox proportional hazard regression model. Results A total of 221 patients (mean age 81.4 years), including 125 (56.6%) males, were included with median follow-up duration of 23.8 months. In males, multivariate analysis revealed that higher BMI (P = 0.035), BMI ≥ 20 kg/m2 (P = 0.026), and higher LBM index (P = 0.023) significantly predicted lower overall all-cause cumulative mortality. In females, none of the body composition parameters was significantly associated with all-cause cumulative mortality. Paradoxical association between BMI and estimated all-cause cumulative mortality was only significant among male patients. Conclusion In Taiwanese TAVI patients, the prognostic effects of BMI and LBM index on cumulative mortality were only observed in males, not in females. Sex differences must be considered when stratifying risk among patients undergoing TAVI.

Objective: This study aimed to develop machine learning-based prediction models to predict masked hypertension and masked uncontrolled hypertension using the clinical characteristics of patients at a single outpatient visit.Methods: Data were derived from two cohorts in Taiwan. The first cohort included 970 hypertensive patients recruited from six medical centers between 2004 and 2005, which were split into a training set (n = 679), a validation set (n = 146), and a test set (n = 145) for model development and internal validation. The second cohort included 416 hypertensive patients recruited from a single medical center between 2012 and 2020, which was used for external validation. We used 33 clinical characteristics as candidate variables to develop models based on logistic regression (LR), random forest (RF), eXtreme Gradient Boosting (XGboost), and artificial neural network (ANN).Results: The four models featured high sensitivity and high negative predictive value (NPV) in internal validation (sensitivity = 0.914–1.000; NPV = 0.853–1.000) and external validation (sensitivity = 0.950–1.000; NPV = 0.875–1.000). The RF, XGboost, and ANN models showed much higher area under the receiver operating characteristic curve (AUC) (0.799–0.851 in internal validation, 0.672–0.837 in external validation) than the LR model. Among the models, the RF model, composed of 6 predictor variables, had the best overall performance in both internal and external validation (AUC = 0.851 and 0.837; sensitivity = 1.000 and 1.000; specificity = 0.609 and 0.580; NPV = 1.000 and 1.000; accuracy = 0.766 and 0.721, respectively).Conclusion: An effective machine learning-based predictive model that requires data from a single clinic visit may help to identify masked hypertension and masked uncontrolled hypertension.

Background/purpose: Although the lung function test has played an important role in respiratory care for a long time, valid spirometry reference values in the Chinese population in Taiwan remain to be elucidated. Methods: 2963 healthy Taiwanese subjects aged 21 to 88 years (1765 males, 59.6%) from February 2015 to February 2017 were enrolled. The subjects attempted to meet the 2005 American Thoracic Society (ATS) and the European Respiratory Society (ERS) guidelines when performing forced expiratory spirograms. We would like to establish the spirometry predictive equations for forced expiratory volume (FEV1), forced vital capacity (FVC), FEV1/FVC, and lower limit of normal (LLN) in Taiwan and compare with other Asian populations. Results: We established the spirometry predictive equations using a linear model for the entire population, using age and height as independent variables, which best predicted all spirometry parameters for sea level and highland subjects. We found that the values of FEV1 and FVC for the Taiwanese subjects in our study were systematically lower than those reported in South Korea, Japan, and China, but higher than the values in Yang's 1993 and Pan's 1997 Taiwan study. Conclusion: This study addressed the up-to-date spirometry reference equations and values for a healthy adult Chinese population in Taiwan. Keywords: FEF25–75%, FEV1/FVC, Forced spirometry, Lung function, Taiwan

Background/purpose: Dysphagia was associated with increased prevalence of aspiration pneumonia (AP) in studies that were criticized for either their small sample size or lack of prospective design. Using a considerably larger nationwide, population-based database and a long-term prospective cohort design, our study aimed to explore the relationship between dysphagia and the subsequent development of AP. Materials and methods: From 2000 to 2009, we gathered a study cohort consisting of 6979 newly diagnosed cases of dysphagia from Taiwan's National Health Insurance Research Database. For the control group, another 20,937 individuals without dysphagia were matched for age, sex, and comorbidity. The two cohorts were followed-up to observe the occurrence of AP and correlated mortality. Results: During an average of 3.88 ± 2.73 years of follow-up, we observed 315 cases of new AP [non-dysphagia (193, 0.92%) vs. dysphagia (122, 1.75%), p

Background: Some personality types are associated with cardiovascular (CV) diseases and may be related to clinical outcomes in coronary artery disease (CAD). This study investigates the association between type D personality and clinical outcomes in stable CAD patients in an Asian cohort. Methods: Stable CAD patients were enrolled and prospectively followed up for at least 1 year in Taiwan. The inclusion criteria were at least one successful percutaneous coronary intervention (PCI) and stable medical treatment for at least 1 month before enrollment. Vulnerability to psychological distress was measured by the Type D Personality Scale (DS14) after enrollment. The end point was the occurrence of total CV events. Cox regression models of CV events were used to investigate the role of type D personality in clinical outcomes. Results: The study included 777 patients, among which 122 (15.77%) had type D personality. Forty-two CV events were identified: 3 cardiac deaths, 5 nonfatal myocardial infarctions, 1 stroke, 4 congestive heart failures (CHF), 6 peripheral arterial occlusive disorder cases, and 23 readmissions for angina/revascularization treatment. Patients with type D personality had significantly higher incidence of future CV events (9.84% vs. 4.58%, p = 0.018%) and admission for angina/revascularization (5.74% vs. 2.44%, p = 0.049). Patients with subsequent CV events were more likely to have type D personality (28.57% vs. 14.97%, p=0.018). After proportional Cox regression analysis, type D personality remained an independent predictor of future CV events (HR: 3.21, 95% CI: 1.06–9.69). In subgroup analyses, type D personality was especially associated with higher risk of total CV events among females, the elderly, hypertension patients, diabetes patients, and non-smokers. Conclusion: Type D personality was an independent predictor of CV outcomes in an Asian cohort of stable CAD patients. This personality type may be identified in risk stratification for secondary prevention after PCI. Keywords: Type D personality, Coronary artery disease

Non-viral gene delivery holds promises for treating inherited diseases. However, the limited cloning capacity of plasmids may hinder the co-delivery of distinct genes to the transfected cells. Previously, the conjugation of maleimide-functionalized polyurethane grafted with small molecular weight polyethylenimine (PU-PEI600-Mal) using 1,6-hexanedithiol (HDT) could promote the co-delivery and extensive co-expression of two different plasmids in target cells. Herein, we designed HDT-conjugated PU-PEI600-Mal for the simultaneous delivery of CRISPR/Cas9 components to achieve efficient gene correction in the induced pluripotent stem cell (iPSC)-derived model of Fabry cardiomyopathy (FC) harboring GLA IVS4 + 919 G > A mutation. This FC in vitro model recapitulated several clinical FC features, including cardiomyocyte hypertrophy and lysosomal globotriaosylceramide (Gb3) deposition. As evidenced by the expression of two reporter genes, GFP and mCherry, the addition of HDT conjugated two distinct PU-PEI600-Mal/DNA complexes and promoted the co-delivery of sgRNA/Cas9 and homology-directed repair DNA template into target cells to achieve an effective gene correction of IVS4 + 919 G > A mutation. PU-PEI600-Mal/DNA with or without HDT-mediated conjugation consistently showed neither the cytotoxicity nor an adverse effect on cardiac induction of transfected FC-iPSCs. After the gene correction and cardiac induction, disease features, including cardiomyocyte hypertrophy, the mis-regulated gene expressions, and Gb3 deposition, were remarkably rescued in the FC-iPSC-differentiated cardiomyocytes. Collectively, HDT-conjugated PU-PEI600-Mal-mediated dual DNA transfection system can be an ideal approach to improve the concurrent transfection of non-viral-based gene editing system in inherited diseases with specific mutations.

BackgroundFibroblast growth factor (FGF)-23 levels rise as kidney function declines. Whether elevated FGF-23 levels are associated with an increased risk for contrast-associated acute kidney injury (CA-AKI) and major adverse cardiovascular events (MACE) in patients undergoing coronary angiography remain uncertain.MethodsIn total, 492 patients receiving coronary angiography were enrolled. Their serum FGF-23 levels were measured before administration of contrast media. The occurrence of CA-AKI was defined as a rise in serum creatinine of 0.5 mg/dL or a 25% increase from the baseline value within 48 h after the procedure. All patients were followed up for at least 1 year or until the occurrence of MACE including death, nonfatal myocardial infarction (MI), and ischemic stroke.ResultsOverall, CA-AKI occurred in 41 (8.3%) patients. During a median follow-up of 2.6 years, there were 24 deaths, 3 nonfatal MIs, and 7 ischemic strokes. Compared with those in the lowest FGF-23 tertile, individuals in the highest FGF-23 tertile had a significantly higher incidence of CA-AKI (P < 0.001) and lower incidence of MACE-free survival (P = 0.001). In multivariate regression analysis, higher FGF-23 level was found to be independently associated with a graded risk for CA-AKI (OR per doubling, 1.90; 95% CI 1.48-2.44) and MACE (HR per doubling, 1.25; 95% CI 1.02-1.52).ConclusionsElevated FGF-23 levels were associated with an increased risk for CA-AKI and future MACE among patients undergoing coronary angiography. FGF-23 may play a role in early diagnosis of CA-AKI and predicting clinical outcomes after coronary angiography.

Abstract Background Soluble receptor for advanced glycation end-products (sRAGE) and advanced glycation end-products (AGE) have been associated with risks of cardiovascular disease. Because sRAGE is regarded as a scavenger to AGE, we hypothesized that the ratio of AGE to sRAGE (AGE/sRAGE) is associated with albuminuria in hypertensive patients. Methods In this cross-sectional study, a total of 104 patients with essential hypertension were recruited. Hypertension was defined as a systolic blood pressure ≥ 140 mmHg, a diastolic blood pressure ≥ 90 mmHg, or use of antihypertensive treatment. Albuminuria was defined as albumin excretion rate ≧ 20 μg/min. Multivariate logistic regression analyses were performed to evaluate the association between AGE/sRAGE and albuminuria. Results Among the 104 patients, 30 (28.8%) patients had albuminuria and 74 (71.2%) patients did not. Patients with albuminuria had higher AGE (2.15 vs. 1.71 μg/mL), lower sRAGE (424.5 vs. 492.5 pg/ml) and higher AGE/sRAGE (3.79 vs. 3.29 μg/pg) than those without albuminuria. Multivariate logistic regression model revealed that AGE/sRAGE (OR = 1.131, 95% CI = 1.001–1.278, P = 0.048) was independently associated with albuminuria. There was no significant relationship between AGE and sRAGE alone with albuminuria. Conclusion This study suggests that the ratio of AGE to sRAGE may be a surrogate biomarker for microvascular injury. Further prospective studies of the prognostic value of the ratio in relation to microvasular injury are needed.

BackgroundFew studies have reported on the clustering pattern of CVD risk factors, including sedentary behavior, systemic inflammation, and cadiometabolic components in the general population.ObjectiveWe aimed to explore the clustering pattern of CVD risk factors using exploratory factor analysis to investigate the underlying relationships between various CVD risk factors.MethodsA total of 5606 subjects (3157 male, 51.5±11.7 y/o) were enrolled, and 14 cardiovascular risk factors were analyzed in an exploratory group (n = 3926) and a validation group (n = 1676), including sedentary behaviors.ResultsFive factor clusters were identified to explain 69.4% of the total variance, including adiposity (BMI, TG, HDL, UA, and HsCRP; 21.3%), lipids (total cholesterol and LDL-cholesterol; 14.0%), blood pressure (SBP and DBP; 13.3%), glucose (HbA1C, fasting glucose; 12.9%), and sedentary behavior (MET and sitting time; 8.0%). The inflammation biomarker HsCRP was clustered with only adiposity factors and not with other cardiometabolic risk factors, and the clustering pattern was verified in the validation group.ConclusionThis study confirmed the clustering structure of cardiometabolic risk factors in the general population, including sedentary behavior. HsCRP was clustered with adiposity factors, while physical inactivity and sedentary behavior were clustered with each other.

To investigate the correlation between the CHADS2 score and risk of contrast-induced nephropathy (CIN), we conducted a retrospective study in patients who underwent elective percutaneous coronary intervention (PCI) and compared its accuracy with previous scoring systems. Methods: A total of 539 patients who underwent elective PCI were enrolled. Based on their underlying diseases, such as hypertension, diabetes, and kidney disease, CHADS2 score, R2CHADS2 score, and Mehran's risk score were calculated for each patient. Incidence of CIN was defined as a rise in serum creatinine >0.5 mg/dL or >25% increase in baseline within 48 hours after PCI. All study participants were followed up until October 2014, or until the occurrence of major adverse cardiovascular events (MACEs). Results: Overall, 55 cases (10.2%) of CIN and 90 cases (16.7%) of MACEs were identified after participants were followed up for 1.57 ± 1.46 years. The study cohort was divided into three groups according to CHADS2 scores: score 0, score 1–2, and score 3–6. In multivariate analysis, an increase of 1 point in the CHADS2 score was independently associated with a 37% increase in the risk of CIN (odds ratio, 1.37; 95% confidence interval, 1.00–1.87; p = 0.048) and a 49% increase in MACEs (hazard ratio, 1.49; 95% confidence interval, 1.18–1.88, p = 0.001). In pairwise comparison, the discriminatory performance of CHADS2 score was not inferior to either R2CHADS2 score (p = 0.226) or Mehran's risk score (p = 0.075). Conclusion: CHADS2 score could be a simple and useful predictor for CIN in patients undergoing elective PCI.

Endothelial progenitor cells (EPCs) may contribute to ischemia-induced angiogenesis in atherosclerotic diseases. The protein kinase C (PKC) family is involved in the regulation of angiogenesis, however the role of PKCα in EPCs during angiogenesis is unclear. The aim of this study was to evaluate the role of PKCα in EPCs during angiogenesis. Phorbol-12-myristate-13-acetate (PMA), a PKCα activator, significantly increased the activity and expression of matrix metalloproteinases (MMP) -2 and -9 in human (late outgrowth) EPCs in vitro. The MMPs promoted the migratory function and vascular formation of EPCs, which then contributed to neovascularization in a mouse hindlimb-ischemia model. Reactive oxygen species derived from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enhanced the expression of MMPs to increase the bioactivity of EPCs during angiogenesis. The mitogen-activated protein kinase (MAPK) signal pathway was associated with the activation of NADPH oxidase. PMA extensively activated the extracellular signal-regulated kinase (Erk) signal pathway to increase the expression of MMP-9. PMA also activated the p38, Erk, and c-Jun N-terminal kinase signal pathways to increase the expression of MMP-2. PMA-stimulated EPCs enhanced neovascularization in a mouse model of hindlimb ischemia via nuclear factor-κB translocation to up-regulation of the expression of MMP-2 and MMP-9. PMA could activate PKCα and promote the angiogenesis capacity of human EPCs via NADPH oxidase-mediated, redox-related, MMP-2 and MMP-9 pathways. The PKCα-activated, NADPH oxidase-mediated, redox-related MMP pathways could contribute to the function of human EPCs for ischemia-induced neovascularization, which may provide novel insights into the potential modification of EPCs for therapeutic angiogenesis.

Several studies have already reported that serum potassium (SK) correlated inversely with adverse events among patients with preexisting cardiovascular disease and impaired renal function; less is known about the prognostic value of SK at the normal range in community-based elderly individuals. This study aimed to examine whether low normal SK value was associated with cardiovascular and all-cause mortalities in elderly people. Methods: A prospective study was conducted using two independent elderly Taiwanese community cohorts that included 2065 individuals with relatively normal SK values (2.8–5.6 mmol/L). The participants were grouped as follows: low (2.8–3.4 mmol/L), low-normal SK (3.5–3.8 mmol/L), normal (3.9–4.4 mmol/L), and high-normal SK (4.5–5.6 mmol/L). Proportional hazards model was applied to compare the association between SK concentration groups and mortality. Results: The relationship between baseline SK and all-cause and cardiovascular mortality was U-shaped, with the lowest mortality rates observed in patients with SK levels of 3.9–4.4 mmol/L. The low-normal SK group had significantly higher risks of all-cause (hazard ratio, 1.3; 95% confidence interval, 1.0–1.6) and cardiovascular mortality (hazard ratio, 1.6; 95% confidence interval, 1.1–2.3) than the normal SK group. The high-normal SK group had higher but nonsignificant risk compared to the normal group. Conclusion: Our findings suggest that low-normal SK may be used as a marker of poor survival for elderly outpatient cares.

The hypothesis that treatment with phytosterols in patients with nonalcoholic fatty liver disease (NAFLD) may increase circulating endothelial progenitor cells (EPCs) levels was tested in the study. Forty patients with an abdominal ultrasonographic diagnosis of NAFLD were randomly assigned to phytosterols powder treatment at 1.8 g/day for 4 weeks (n = 20) or a control group, with crossover to the alternate therapy for another 4 weeks after a 2-week wash-out period. Flow cytometry with quantification of EPC markers in peripheral blood samples was used to assess circulating EPC levels. Phytosterols treatment significantly decreased levels of low-density lipoproteins, fasting glucose, and hemoglobin-A1C. Treatment with phytosterols in patients with NAFLD markedly suppressed high sensitivity C-reactive protein concentrations, and enhanced superoxide dismutase, as compared to baseline. We also showed that administration of phytosterols significantly increased the insulin-like growth factor-1 concentrations (change from baseline of 22.47%, P

Lower health literacy (HL) is associated with several cardiovascular disease (CVD) risk factors such as diabetes, hypertension, and metabolic syndrome (MS). The aim of our study was to investigate the association between HL and the Framingham 10-year risk score of CVD.From 2015-2016, 1010 subjects aged 23 to 88 years receiving health check-up in Taipei Veterans General Hospital had complete clinical evaluations and laboratory examinations. Fatty liver was diagnosed by ultrasonography. The short form questionnaire adapted from the Mandarin Health Literacy Scale was used to assess HL. The Framingham risk score was calculated by patient characteristics.Subjects with higher BMIs were associated with lower HL scores. The proportion of subjects with MS was higher in the lower health literacy score group (≤ 9) at 28.8%; further analysis found that lower HL was significantly associated with MS in women but not in men. The Spearman's rho demonstrated that the HL score was significantly associated with the BMI-based (rho = -0.11; P < 0.001) or lipid-based (rho = -0.09; P < 0.004) Framingham risk score.Higher HL scores were associated with less CVD risk such as lower BMIs, less MS in women, and less fatty liver disease. Furthermore, HL had an inverse association with the Framingham risk score as expected. Therefore, HL in patients with CVD risk should be improved and considered as an important issue in terms of CVD reduction.

Fabry disease (FD) is an X-linked inherited lysosomal storage disease caused by α-galactosidase A (GLA) deficiency. Progressive intracellular accumulation of globotriaosylceramide (Gb3) is considered to be pathogenically responsible for the phenotype variability of FD that causes cardiovascular dysfunction; however, molecular mechanisms underlying the impairment of FD-associated cardiovascular tissues remain unclear. In this study, we reprogrammed human induced pluripotent stem cells (hiPSCs) from peripheral blood cells of patients with FD (FD-iPSCs); subsequently differentiated them into vascular endothelial-like cells (FD-ECs) expressing CD31, VE-cadherin, and vWF; and investigated their ability to form vascular tube-like structures. FD-ECs recapitulated the FD pathophysiological phenotype exhibiting intracellular Gb3 accumulation under a transmission electron microscope. Moreover, compared with healthy control iPSC-derived endothelial cells (NC-ECs), reactive oxygen species (ROS) production considerably increased in FD-ECs. Microarray analysis was performed to explore the possible mechanism underlying Gb3 accumulation-induced ROS production in FD-ECs. Our results revealed that superoxide dismutase 2 (SOD2), a mitochondrial antioxidant, was significantly downregulated in FD-ECs. Compared with NC-ECs, AMPK activity was significantly enhanced in FD-ECs. Furthermore, to investigate the role of Gb3 in these effects, human umbilical vein endothelial cells (HUVECs) were treated with Gb3. After Gb3 treatment, we observed that SOD2 expression was suppressed and AMPK activity was enhanced in a dose-dependent manner. Collectively, our results indicate that excess accumulation of Gb3 suppressed SOD2 expression, increased ROS production, enhanced AMPK activation, and finally caused vascular endothelial dysfunction. Our findings suggest that dysregulated mitochondrial ROS may be a potential target for treating FD.

Fabry disease (FD) is a rare inherited disorder characterized by a wide range of systemic symptoms; it is particularly associated with cardiovascular and renal problems. Enzyme replacement therapy and pharmacological chaperone migalastat are the only approved and effective treatment strategies for FD patients. It is well documented that alpha-galactosidase A (GLA) enzyme activity deficiency causes globotriaosylceramide (Gb3) accumulation, which plays a crucial role in the etiology of FD. However, the detailed mechanisms remain unclear, and the lack of a reliable and powerful disease model is an obstacle. In this study, we created such a model by using CRISPR/Cas9-mediated editing of GLA gene to knockout its expression in human embryonic stem cells (hESCs). The cardiomyocytes differentiated from these hESCs (GLA-null CMs) were characterized by the accumulation of Gb3 and significant increases of cell surface area, the landmarks of FD-associated cardiomyopathy. Furthermore, we used mass spectrometry to compare the proteomes of GLA-null CMs and parental wild type CMs and found that the Rab GTPases involved in exocytotic vesicle release were significantly downregulated. This caused impairment of autophagic flux and protein turnover, resulting in an increase of reactive oxygen species and apoptosis. To summarize, we established a FD model which can be used as a promising tool to study human hypertrophic cardiomyopathy in a physiologically and pathologically relevant manner and to develop new therapies by targeting Rab GTPases signaling-related exosomal vesicles transportation.

ObjectiveWe prospectively investigate the relation between baseline circulating endothelial progenitor cells and the subsequent development of restenosis after angioplasty of hemodialysis vascular access.BackgroundEffect of angioplasty for hemodialysis vascular access is greatly attenuated by early and frequent restenosis. Circulating endothelial progenitor cells (EPCs) play a key role in vascular repair but are deficient in hemodialysis patients.MethodAfter excluding 14 patients due to arterial stenosis, central vein stenosis, and failed angioplasty, 130 patients undergoing angioplasty for dysfunctional vascular access were prospectively enrolled. Flow cytometry with quantification of EPC markers (defined as CD34+, CD34+KDR+, CD34+KDR+CD133+) in peripheral blood immediately before angioplasty procedures was used to assess circulating EPC numbers. Patients were followed clinically for up to one year after angioplasty.ResultsDuring the one-year follow-up, 95 patients (73%) received interventions for recurrent access dysfunction. Patients in the lower tertile of CD34+KDR+ cell count had the highest restenosis rates (46%) at three month (early restenosis), compared with patients in the medium and upper tertiles of CD34+KDR+ cell count (27% and 12% respectively, p = 0.002). Patients in the lower tertile of CD34+KDR+ cell count received more re-interventions during one year. Patients with early restenosis had impaired EPC adhesive function and increased senescence and apoptosis. In multivariate analysis, the CD34+KDR+ and CD34+KDR+CD133+ cell counts were independent predictors of target-lesion early restenosis.ConclusionOur results suggest that the deficiency of circulating EPCs is associated with early and frequent restenosis after angioplasty of hemodialysis vascular access.

OBJECTIVES: Reduced number and impaired function of circulating endothelial progenitor cells (EPCs) in patients with chronic kidney disease have been reported. However, there is little data about the association between circulating EPC levels and risk of contrast-induced nephropathy (CIN). The aim of this study was to investigate the relationship between circulating EPCs and CIN in patients after angiography. METHODS AND RESULTS: A total of 77 consecutive patients undergoing elective percutaneous coronary intervention (PCI) and percutaneous transluminal angioplasty (PTA) were enrolled. Flow cytometry with quantification of EPC markers (defined as CD34+, CD34+KDR+, and CD34+KDR+CD133+) in peripheral blood samples was used to assess EPC number before the procedure. CIN was defined as an absolute increase ≧0.5 mg/dl or a relative increase ≧25% in the serum creatinine level at 48 hours after the procedure. Eighteen (24%) of the study subjects developed CIN. Circulating EPC levels were significantly lower in patients who developed CIN than in those without CIN (CD34+KDR+, 4.11±2.59 vs. 9.25±6.30 cells/105 events, P

OBJECTIVES: Possible association between diabetes mellitus (DM) and Alzheimer's disease (AD) has been controversial. This study used a nationwide population-based dataset to investigate the relationship between DM and subsequent AD incidence. METHODS: Data were collected from Taiwan's National Health Insurance Research Database, which released a cohort dataset of 1,000,000 randomly sampled people and confirmed it to be representative of the Taiwanese population. We identified 71,433 patients newly diagnosed with diabetes (age 58.74 ± 14.02 years) since January 1997. Using propensity score, we matched them with 71,311 non-diabetic subjects by time of enrollment, age, gender, hypertension, hyperlipidemia, and previous stroke history. All the patients were followed up to December 31, 2007. The endpoint of the study was occurrence of AD. RESULTS: Over a maximum 11 years of follow-up, diabetic patients experienced a higher incidence of AD than non-diabetic subjects (0.48% vs. 0.37%, p

BACKGROUND: Pulse pressure (PP) is a risk factor for cardiovascular disease. It has been reported that ambulatory blood pressure (BP) and nighttime BP parameters are heritable traits. However, the genetic association of pulse pressure and its clinical impact remain undetermined. METHOD AND RESULTS: We conducted a genome-wide association study of PP using ambulatory BP monitoring in young-onset hypertensive patients and found a significant association between nighttime PP and SNP rs897876 (p = 0.009) at chromosome 2p14, which contains the predicted gene FLJ16124. Young-onset hypertension patients carrying TT genotypes at rs897876 had higher nighttime PP than those with CT and CC genotypes (TT, 41.6 ± 7.3 mm Hg; CT, 39.1 ± 6.0 mm Hg; CC, 38.9 ± 6.3 mm Hg; p

BACKGROUND: Recent research indicates hypertensive patients with microalbuminuria have decreased endothelial progenitor cells (EPCs) and increased levels of endothelial apoptotic microparticles (EMP). However, whether these changes are related to a subsequent decline in glomerular filtration rate (GFR) remains unclear. METHODS AND RESULTS: We enrolled totally 100 hypertensive out-patients with eGFR ≥ 30 mL/min/1.73 m(2). The mean annual rate of GFR decline (△GFR/y) was -1.49 ± 3.26 mL/min/1.73 m(2) per year during the follow-up period (34 ± 6 months). Flow cytometry was used to assess circulating EPC (CD34(+)/KDR(+)) and EMP levels (CD31(+)/annexin V(+)) in peripheral blood. The △GFR/y was correlated with the EMP to EPC ratio (r= -0.465, p

OBJECTIVES: The epidemiology of idiopathic central serous chorioretinopathy (CSCR) is not well understood in an Asian population. The present study aimed to investigate the incidence and risk factors for corticosteroid-unrelated CSCR using Taiwan's National Health Insurance Research Database. METHODS AND RESULTS: From 2001 to 2006, a total of 786 patients (500 [63.6%] males) who were newly diagnosed with CSCR, aged from 20 to 64 years and had no history of corticosteroid prescription were identified as incident cases of idiopathic CSCR. 3606 age-, gender-, and enrollment time-matched subjects were randomly selected as the control group. The mean annual incidence was 0.21‰ (0.27‰ for males, and 0.15‰ for females; P

OBJECTIVES: New-onset atrial fibrillation (AF) commonly occurs in patients with acute myocardial infarction (AMI). Data regarding the value of the CHADS2 score in patients hospitalized for AMI is limited. This study aimed to determine whether the CHADS2 score is associated with new-onset AF and if it can help identify the patients who will benefit most from statin use for the prevention of arrhythmia after AMI. METHODS: A total of 724 consecutive AMI patients were enrolled in this study. The patients were divided into 3 groups according to their CHADS2 scores: group 1, score 0; group 2, score 1-2; and group 3, score 3-6. The study endpoint was an episode of new-onset AF that lasted more than 30 seconds during hospitalization at the coronary care unit. RESULTS: Seventy-eight (10.8%) patients developed new-onset AF, and 273 (37.7%) were on a statin upon admission. The incidence of new-onset AF increased significantly from 5.8% in group 1 to 11.3% in group 2 and 14.3% in group 3 (χ(2) for linear trend, P = 0.017). Statin use (odds ratio [OR], 0.22; 95% CI, 0.06-0.85) and CHADS2 score (OR, 1.53; 95% CI, 1.02-2.28) were independent predictors of new-onset AF in AMI patients. Patients with CHADS2 score ≤2 had significantly reduced C-reactive protein level and lower risk of developing new-onset AF if they were taking statins (P < 0.05). Multivariate logistic regression analysis demonstrated the benefit of statin use for preventing new-onset AF in patients with CHADS2 scores ≤2 (OR, 0.34; 95% CI, 0.14-0.81). CONCLUSIONS: The CHADS2 score is a convenient scoring system for predicting the incidence of new-onset AF and may help in identifying the patients who will benefit most from statin use for the prevention of arrhythmia after AMI.

Bisphosphonates are a class of pharmacologic compounds that are commonly used to treat postmenopausal osteoporosis and malignant osteolytic processes. Studies have shown that bone marrow-derived endothelial progenitor cells (EPCs) play a significant role in postnatal neovascularization. Whether the nitrogen-containing bisphosphonate zoledronate inhibits ischemia-induced neovascularization by modulating EPC functions remains unclear.Unilateral hindlimb ischemia was surgically induced in wild-type mice after 2 weeks of treatment with vehicle or zoledronate (low-dose: 30 μg/kg; high-dose: 100 μg/kg). Doppler perfusion imaging demonstrated that the ischemic limb/normal side blood perfusion ratio was significantly lower in wild-type mice treated with low-dose zoledronate and in mice treated with high-dose zoledronate than in controls 4 weeks after ischemic surgery (control vs. low-dose vs. high-dose: 87±7% vs. *61±18% vs. **49±17%, *p

OBJECTIVES: Precise mechanisms of atrial fibrillation (AF) are uncertain, but their association with esophageal disorders has been recently proposed. The association between gastroesophageal reflux disease (GERD), the most common gastroesophageal disorder, and AF remains undetermined. We therefore aimed to investigate the association between GERD and later development of AF. METHODS AND RESULTS: Patients with GERD were identified from the 1,000,000-person cohort dataset sampled from the Taiwan National Health Insurance database. The study cohort comprised 29,688 newly diagnosed adult GERD patients; 29,597 randomly selected age-, gender-, comobidity-matched subjects comprised the comparison cohort. Cox proportional hazard regressions were performed as a means of comparing the AF-free survival rate for the two cohorts. During a maximum three years of follow-up, a total of 351 patients experienced AF, including 184 (0.62%) patients in the GERD cohort and 167 (0.56%) in the control group. The log-rank test showed that patients with GERD had significantly higher incidence of AF than those without GERD (p = 0.024). After Cox proportional hazard regression model analysis, GERD was independently associated with the increased risk of AF (hazard ratio, 1.31; 95% confidence interval, 1.06-1.61, p = 0.013). CONCLUSION: GERD was independently associated with an increased risk of future AF in a nationwide population-based cohort.

OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is associated with advanced atherosclerosis and a higher risk of cardiovascular disease. Increasing evidence suggests that injured endothelial monolayer is regenerated by circulating bone marrow derived-endothelial progenitor cells (EPCs), and levels of circulating EPCs reflect vascular repair capacity. However, the relation between NAFLD and EPC remains unclear. Here, we tested the hypothesis that patients with nonalcoholic fatty liver disease (NAFLD) might have decreased endothelial progenitor cell (EPC) levels and attenuated EPC function. METHODS AND RESULTS: A total of 312 consecutive patients undergoing elective coronary angiography because of suspected coronary artery disease were screened and received examinations of abdominal ultrasonography between July 2009 and November 2010. Finally, 34 patients with an ultrasonographic diagnosis of NAFLD, and 68 age- and sex-matched controls without NAFLD were enrolled. Flow cytometry with quantification of EPC markers (defined as CD34(+), CD34(+)KDR(+), and CD34(+)KDR(+)CD133(+)) in peripheral blood samples was used to assess circulating EPC numbers. The adhesive function, and migration, and tube formation capacities of EPCs were also determined in NAFLD patients and controls. Patients with NAFLD had a significantly higher incidence of metabolic syndrome, previous myocardial infarction, hyperuricemia, and higher waist circumference, body mass index, fasting glucose and triglyceride levels. In addition, patients with NAFLD had significantly decreased circulating EPC levels (all P

Hypertension is a complex disorder with high prevalence rates all over the world. We conducted the first genome-wide gene-based association scan for hypertension in a Han Chinese population. By analyzing genome-wide single-nucleotide-polymorphism data of 400 matched pairs of young-onset hypertensive patients and normotensive controls genotyped with the Illumina HumanHap550-Duo BeadChip, 100 susceptibility genes for hypertension were identified and also validated with permutation tests. Seventeen of the 100 genes exhibited differential allelic and expression distributions between patient and control groups. These genes provided a good molecular signature for classifying hypertensive patients and normotensive controls. Among the 17 genes, IGF1, SLC4A4, WWOX, and SFMBT1 were not only identified by our gene-based association scan and gene expression analysis but were also replicated by a gene-based association analysis of the Hong Kong Hypertension Study. Moreover, cis-acting expression quantitative trait loci associated with the differentially expressed genes were found and linked to hypertension. IGF1, which encodes insulin-like growth factor 1, is associated with cardiovascular disorders, metabolic syndrome, decreased body weight/size, and changes of insulin levels in mice. SLC4A4, which encodes the electrogenic sodium bicarbonate cotransporter 1, is associated with decreased body weight/size and abnormal ion homeostasis in mice. WWOX, which encodes the WW domain-containing protein, is related to hypoglycemia and hyperphosphatemia. SFMBT1, which encodes the scm-like with four MBT domains protein 1, is a novel hypertension gene. GRB14, TMEM56 and KIAA1797 exhibited highly significant differential allelic and expressed distributions between hypertensive patients and normotensive controls. GRB14 was also found relevant to blood pressure in a previous genetic association study in East Asian populations. TMEM56 and KIAA1797 may be specific to Taiwanese populations, because they were not validated by the two replication studies. Identification of these genes enriches the collection of hypertension susceptibility genes, thereby shedding light on the etiology of hypertension in Han Chinese populations.

OBJECTIVE: Cardiovascular risk increases with the presence of both metabolic syndrome (MetS) and hypertension (HTN). Although the adiponectin (ADIPOQ) gene has been reported to be involved in MetS, its association with HTN remained undetermined. This study aimed to investigate the association of ADIPOQ gene with the phenotypes of HTN and MetS. METHODS: A total of 962 participants from 302 families from the Taiwan young-onset hypertension genetic study were enrolled. Plasma adiponectin were measured, and association analysis was conducted by using GEE regression-based method. Another study, of 1448 unrelated participants, was conducted to replicate the association between ADIPOQ gene and variable phenotypes of MetS with or without HTN. RESULTS: Among 962 subjects from family samples, the lowest plasma adiponectin value was observed in MetS with HTN component (9.3±0.47 µg/ml) compared with hypertensives (13.4±0.74 µg /ml) or MetS without HTN (11.9±0.60 µg/ml, P

Young-onset hypertension has a stronger genetic component than late-onset counterpart; thus, the identification of genes related to its susceptibility is a critical issue for the prevention and management of this disease. We carried out a two-stage association scan to map young-onset hypertension susceptibility genes. The first-stage analysis, a genome-wide association study, analyzed 175 matched case-control pairs; the second-stage analysis, a confirmatory association study, verified the results at the first stage based on a total of 1,008 patients and 1,008 controls. Single-locus association tests, multilocus association tests and pair-wise gene-gene interaction tests were performed to identify young-onset hypertension susceptibility genes. After considering stringent adjustments of multiple testing, gene annotation and single-nucleotide polymorphism (SNP) quality, four SNPs from two SNP triplets with strong association signals (-log(10)(p)>7) and 13 SNPs from 8 interactive SNP pairs with strong interactive signals (-log(10)(p)>8) were carefully re-examined. The confirmatory study verified the association for a SNP quartet 219 kb and 495 kb downstream of LOC344371 (a hypothetical gene) and RASGRP3 on chromosome 2p22.3, respectively. The latter has been implicated in the abnormal vascular responsiveness to endothelin-1 and angiotensin II in diabetic-hypertensive rats. Intrinsic synergy involving IMPG1 on chromosome 6q14.2-q15 was also verified. IMPG1 encodes interphotoreceptor matrix proteoglycan 1 which has cation binding capacity. The genes are novel hypertension targets identified in this first genome-wide hypertension association study of the Han Chinese population.

Background: Women usually have higher risk after receiving percutaneous coronary interventions (PCIs) than men with coronary artery disease (CAD). The aim of this study was to investigate the association of sex differences with future outcomes in CAD patients undergoing PCI, to assess the role of age, and to extend observed endpoints to stroke and congestive heart failure. Methods: Six thousand six hundred forty-seven patients with CAD who received successful PCIs. The associations between clinic outcomes and sex were analyzed. The primary outcome was major cardiovascular events (MACE), including cardiac death, nonfatal myocardial infraction, and nonfatal stroke. The secondary outcome was MACE and hospitalization for heart failure (total CV events). Results: During a mean of 52.7 months of follow-up, 4833 men and 1614 women received PCI. Univariate and multivariate analyses showed that women were independently associated with an increased risk of cardiac death (HR, 1.78; 95% CI, 1.32-2.41), hospitalization for heart failure (HR, 1.53; 95% CI, 1.23-1.89), MACE (HR, 1.34; 95% CI, 1.10-1.63), and total CV events (HR, 1.39; 95% CI, 1.20-1.62). In the subgroup analysis, women aged under 60 years had higher cardiovascular risks than men of the same age category. Conclusion: Women with CAD after successful PCI had poorer cardiovascular outcomes than men. Additionally, younger women (aged <60 years) were especially associated with a higher risk of developing future adverse cardiovascular outcomes. [ABSTRACT FROM AUTHOR]