Clinical manifestations and genetic characteristics in the Taiwan thoracic aortic aneurysm and dissection cohort - a prospective cohort study.

BACKGROUND: Thoracic aortic aneurysm and dissection (TAAD) is a devastating but treatable disease if detected early. The clinical manifestations and genetic characteristics underlying TAAD patients in Taiwan, however, remain unclear. METHODS: We consecutively recruited patients referred for TAAD screening and/or management at a tertiary medical center in Taiwan. All patients received a comprehensive survey of the clinical manifestations and a genetic testing with a 29-gene next-generation sequencing (NGS) panel. RESULTS: Patients (n = 107) were referred for different reasons, and could be grouped into 4 categories: known aortic aneurysm or dissection (AoAD) (n = 57), Marfanoid features (n = 36), having family members of suspected AoAD (n = 11), and ectopic lens (n = 3). AoAD were confirmed in 73 (68.2%) of the entire cohort. Among all the clinical manifestations, skin striae distensae was the only physical sign that showed significant association with AoAD (p = 0.007 after adjusted). Disease-causing genes/variants were identified in 46 patients (43.0%); FBN1 was the most prevalent disease-causing gene, followed by TGFBR1, TGFBR2 and FBN2. A positive genetic testing was not only an independent predictor of AoAD (hazard ratio (HR) 3.468, 95% confidence interval (CI) [1.541-7.807], p = 0.003), but also had a higher chance of dissection among the patients with known dilated aorta (HR 4.552, 95% CI [1.578-13.135], p = 0.005). CONCLUSION: The presence of skin striae distensae may serve as a clinical cue for physicians to search for AoAD in subjects who are at risk. The NGS panel test not only helps confirm the diagnosis, but also stratify the risk of dissection among patients with dilated aorta.

Modification effect of sex and obesity on the correlation of LEP polymorphisms with leptin levels in Taiwanese obese women.

BACKGROUND: Obesity has become the main health issue in developed countries as it impacts life expectancy and increases mortality of cerebrovascular or cardiovascular diseases. The leptin is one of the adipokines which presents in the serum in proportion to the amount of adipose tissue and is translated from LEP gene. It involves in energy homeostasis, lipid and glucose metabolisms, modulation of immune systems, and thermogenesis. Many previous studies have revealed controversial results between LEP polymorphisms and leptin levels in different ages and ethnicities. Herein, we investigated the impacts of LEP polymorphism against leptin levels in Taiwanese subjects. METHODS: In 599 Taiwanese subjects, excluding clinically overt systemic disease, age below 18 years old, and C-reactive protein (CRP) level of above 10 mg/L, few of LEP polymorphisms were genotyped with TaqMan SNP genotyping assays, were further analyzed for association with leptin level in univariate and multivariate linear regression analyses with Bonferroni correction for multiple tests in stratified groups. The univariate and stepwise multivariate linear regression analyses were performed to determine the coefficient of determinant of LEP polymorphisms over leptin level. RESULTS: Significant associations were found between LEP polymorphisms and leptin levels in obese women. Circulating leptin level was positively correlated with inflammatory, insulin resistance markers, and visceral obesity markers in all subjects. Furthermore, stratified and interaction analyses revealed that LEP polymorphisms, rs7799039 and rs2167270, were significantly associated with leptin levels in obese women-8%-10% of which could be explained by LEP polymorphisms. CONCLUSION: The LEP polymorphisms are independently associated with leptin levels in Taiwanese obese women. Further, the genetic determinants for leptin levels may be different between obese and nonobese, and in different sex individuals. The obesity status and female sex may exert modification effect on transcription of LEP, particularly in obese women.

Doses of renin-angiotensin system inhibitors but not beta-blockers predict outcome after ST-elevation myocardial infarction.

Objectives: In patients with ST-elevation myocardial infarction (STEMI), it is not clear whether low-dose renin-angiotensin system inhibitors and beta-blockers can result in the same benefits achievable with higher target doses. This observational study aims to investigate whether higher doses of angiotensin converting enzyme inhibitors (ACEI)/angiotensin II receptor blockers (ARB) and beta-blockers can improve outcomes in patients with STEMI. Methods: We recorded daily doses of ACEI, ARB, and beta-blockers in 331 patients with STEMI. Echocardiographic studies were performed at baseline and were repeated 6 months later. Clinical events, including all-cause death and heart failure, were followed for 2 years. Results: Patients receiving high-dose ACEI/ARB had less increase in left ventricular end-diastolic volume index (LVEDVI) at 6 months. In multivariable linear regression model, ACEI/ARB dose or beta-blocker dose was not an independent predictor of increase in LVEDVI at 6 months. Kaplan-Meier survival curves showed that doses of ACEI/ARB (p = 0.003) and beta-blockers (p = 0.027) were significant predictors of death and heart failure. In multivariable Cox regression analysis, independent predictors of all-cause death and heart failure were diabetes mellitus (p = 0.001), left ventricular ejection fraction (p = 0.026), and ACEI/ARB dose (p = 0.025). Beta-blockers dose was not a predictor of clinical events in multivariable analysis (p = 0.413). Conclusion: High-dose ACEI/ARB, but not beta-blocker, was associated with lower rate of all-cause death and heart failure in patients with STEMI.

Clinical Outcomes of Repetition of Drug-Coated Balloon for Femoropopliteal Restenosis After Drug-Coated Balloon Treatment.

BACKGROUND: To compare the clinical outcomes of patients undergoing repeated drug-coated balloon (DCB) treatment for femoropopliteal (FP) DCB restenosis with those of patients without repetition-DCB.Methods and Results:From March 2013 to September 2014, 102 patients (118 affected legs) underwent DCB for symptomatic FP disease; 47 patients had restenosis, and 37 underwent reintervention over a 45-month follow-up. We compared the outcomes of repetition-DCB for DCB restenosis with those of patients without repetition. The baseline patient and lesion characteristics were similar between groups. The mean lesion length was 200.8±113.1 and 195.2±134.6 mm, P=0.894, respectively. In addition, the procedural and follow-up outcomes were not different. The rates of freedom from binary restenosis (70% vs. 14%, P=0.001) and clinically driven target lesion revascularization (CD-TLR) (78% vs. 38%, P=0.026) at 1 year were statistically different between groups. Cox regression analysis showed that repetition of DCB was the only predictor for freedom from binary restenosis (hazard ratio [HR]: 6.15, 95% confidence interval (CI) 1.60 to 23.6, P=0.008) and CD-TLR (HR: 5.37, 95% CI 1.32-22.0, P=0.019). CONCLUSIONS: For FP DCB restenosis, repetition of DCB can potentially improve vessel patency and significantly reduce the need for reintervention compared with conventional treatment. However, these observations require further confirmation in larger scale studies.

Associations between TRPV4 genotypes and body mass index in Taiwanese subjects.

Body weight regulation is influenced neuronally via the hypothalamus, which strongly expresses TRPV4. TRPV4 deficiency in mice confers resistance against diet-induced obesity. We investigated the association between TRPV4 gene variants and body mass index (BMI) in Taiwanese subjects. A sample population of 617 Taiwanese subjects was enrolled, and ten TRPV4 gene polymorphisms were selected and genotyped. After adjusting for clinical covariates, significant associations were observed between three studied polymorphisms and BMI using a dominant model (P = 4.83 × 10(-4), P = 1.17 × 10(-4), and P = 3.37 × 10(-4) for rs3742037, rs10735104, and rs3742035, respectively). Obesity as defined according to both the Asian and National Institutes of Health (NIH) criteria was significantly associated with rs10735104 (P = 0.003 and P = 0.037, respectively) in a dominant model. Genotypes at the TRPV4 locus independently affect BMI and obesity status in Taiwanese subjects. This association may broaden our understanding of the role of neuronal influence on body weight regulation. The regulation of TRPV4 channels in skeletal muscle and adipose tissue could also be a new therapeutic target for preventing the development of obesity.