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The objective of this study was to evaluate the renin-angiotensin system genetic effects and pharmacogenetic interactions for angiotensin-converting enzyme (ACE) inhibitors in hypertensive coronary artery disease (CAD) patients.Subjects with hypertension and angiographic CAD were recruited from 1995 to 2003. Baseline characteristics and genetic polymorphisms [ACE gene insertion/deletion (I/D) polymorphism, six polymorphisms of the angiotensinogen (AGT) gene, and A1166C polymorphisms of the angiotensin II type I receptor gene (AGT1R)] were collected. Patients were assigned to 2 groups (ACE inhibitor or No-ACE inhibitor) and followed-for up to 12 years. Kaplan-Meier curves and Cox regression models were used to demonstrate the survival and major cardiovascular events (MACE) event-free survival trends. Pharmacogenetic effects were determined by several Cox regression models.Of the 518 patients in our study, 290 were treated with ACE inhibitors and 228 were not. Prescription of ACE inhibitors was associated with a lower rate of MACE at 4000 days. In addition, ACE I/D gene D was associated with a higher rate of MACE in a multivariate regression analysis [hazard ration (HR): 1.64, 95% confidence interval (CI): 1.27-1.98, p0.001]. This effect could be attenuated by the pharmacogenetic interaction of ACE inhibitors and the ACE gene (ACE in hibitors*ACE D gene, HR: 0.68, 95% CI: 0.52-0.84, p = 0.014).The use of ACE inhibitors was associated with a significant decrease in MACE in hypertensive patients diagnosed with CAD. Genetic variants were also associated with event-free survival, but their effects were modified by the use of ACE inhibitors.Angiotensin-converting enzyme inhibitors; Coronary artery disease; Hypertension; Pharmacogenetic.

Microalbuminuria may be an early sign of intra-renal vascular dysfunction and a marker of vascular risk in the general population as well as in high-risk individuals. However, the association between albuminuria and PAD has been demonstrated only in few small studies. The aim of current study is to evaluate the relative impact of albuminuria and glomerular filtration rate on the risk of peripheral artery disease (PAD) in a nationally representative sample population. Data (ankle brachial index [ABI], urine albumin, fasting glucose, and glomerular filtration rate [GFR] estimated using the Modification of Diet in Renal Disease [MDRD] Study equation) were collected on 7068 adults from the National Health and Nutrition Examination Survey (NHANES 1999-2004). PAD was defined as ABI0.9 or1.4. There was a trend towards an association between the presence of abnormal renal function (GFR60mL/min/1.73m(2)) and PAD in the non-diabetic patients (OR of 1.43, 95% CI: 0.98-2.09; P=0.07) where as the presence of abnormal renal function was strongly associated PAD in the diabetic patients (OR of 2.3, 95% CI: 1.34-3.95; P=0.046). On the contrary, albuminuria was independently associated with PAD in the non-diabetic (OR, 1.87; 95% CI, 1.38-2.52; P=0.0003) but not in the diabetic patients (OR: 1.08, 95% CI: 0.68-1.73, P=0.7411). We concluded that albuminuria, independent of renal function, is strongly associated with PAD in non-diabetic subjects. As diabetes develops and HbA1c level increases, the predictive value of albuminuria gradually diminishes after adjustment for renal function.

The objective of this study was to evaluate the effects of angiotensin-converting enzyme (ACE) inhibitors and pharmacogenetic interaction on the survival of the patients with diastolic heart failure (DHF). A total of 285 subjects with DHF confirmed by echocardiography were recruited in the period between 1995 and 2003. Baseline characteristics (age, sex, prior history, medication, and echocardiographic findings) and genetic polymorphisms (ACE gene insertion/deletion (I/D) polymorphism; T174M, M235T, G-6A, A-20C, G-152A, and G-217A polymorphisms of the angiotensinogen (AGT) gene; and A1166C polymorphisms of the angiotensin II type I receptor (AT1R)) were collected and matched (by propensity score) in those who received and those who did not receive ACE inhibitors. The patients were followed up to 10 years. Kaplan-Meier curves and Cox regression models were used to demonstrate the survival trend. The 85 patients who received ACE inhibitors and the other 85 patients who did not were found to have comparable baseline characteristics and polymorphism distribution. Prescription of ACE inhibitors was associated with a significant decrease in overall mortality (hazard ratio (HR), 0.45; 95% confidence interval (CI), 0.24-0.83; P=0.01), and a lower rate of cardiovascular events at 4000 days (HR, 0.53; 95% CI, 0.32-0.90; P=0.02). In addition, ACE I/D gene D allele was associated with higher overall mortality as compared with the I allele (HR, 2.04; P=0.003). This effect was diminished in those who received ACE inhibitors. The use of ACE inhibitor was associated with a significant decrease in long-term mortality and cardiovascular events in the patients with DHF. Genetic variants in the renin-angiotensin system genes were also associated, but their effects could be modified by the use of ACE inhibitors.

Introduction. The sarcoplasmic reticulum Ca2+ ATPase (SERCA) is essential for the regulation of the intracellular calcium level in cardiomyocytes. Previous studies have found that angiotensin II (Ang II) decreased SERCA2 gene expression in ventricular myocytes. Alteration of SERCA activity is important in the mechanism of atrial fibrillation. The present study was undertaken to examine Ang II effects on atrial myocytes. Materials and methods. An ~1.75-kb promoter region of SERCA2 gene was cloned with the pGL3 luciferase vector. The direct effects of Ang II on SERCA2 gene expression in HL-1 atrial myocytes were examined by promoter activity assay, followed by Western blot analysis for protein levels and quantitative real-time reverse transcription polymerase chain reaction for mRNA amounts. Results. Ang II did not increase the promoter activity of the 1,754-bp promoter-receptor construct of the SERCA2 gene. The levels of SERCA2 protein and mRNA were also unchanged at different time points after Ang II treatment. Conclusions. Although Ang II had prominent effects on SERCA2 in ventricular myocytes, it did not alter SERCA2 gene expression and protein levels in atrial myocytes. We provide a model for further investigation of the regulation of SERCA2 gene expression in atrial myocytes.

OBJECTIVE: Patients with symptoms of heart failure and preserved left ventricular (LV) systolic function are commonly encountered in clinical practice especially in peritoneal dialysis (PD) patients. We hypothesized that adiposity might influence LV diastolic function through systemic inflammation in this specific group. METHODS: We designed a cross-sectional study in 173 prevalent PD patients. LV diastolic dysfunction was diagnosed by echocardiography. PD patient without LV diastolic dysfunction served as the control group. Serum inflammatory biomarkers were examined including tissue necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). The location and amount of adipose tissue were assessed by computerized tomography (CT) at the level of the fourth lumbar vertebra. RESULTS: Subjects with LV diastolic dysfunction had higher levels of the pro-inflammation cytokines and more visceral and peritoneal fat (all P

Severe inflammation leads to cardiac diastolic dysfunction, an independent prognostic marker for the mortality of critically ill patients. We investigated the possible molecular mechanism from inflammatory cytokines (tumor necrosis factor α [TNF-α] and interleukin 6 [IL-6]) causing left ventricular (LV) diastolic dysfunction in critically burned patients. We consecutively enrolled 56 critically burned patients who were admitted to the intensive care unit and performed transthoracic echocardiography to evaluate LV diastolic function. Sarcoplasmic reticulum Ca²⁺-ATPase 2 (SERCA2) gene expression in HL-1 cardiomyocytes was used as a molecular phenotype of diastolic heart failure. Soluble plasma levels of TNF-α and IL-6 were measured in all subjects. The effect of serum from the burned patients on SERCA2 gene expression of HL-1 cardiomyocytes was investigated. The total body surface area of burned patients was proportional to serum level of IL-6 and TNF-α (P < 0.001 for each). Significant correlations were found for TNF-α and decelerating time, E/A, and E/Em (r² = 0.59, 0.45, and 0.52; P

Objective Myosin binding protein C (MYBPC3) plays a role in ventricular relaxation. The aim of the study was to investigate the association between cardiac myosin binding protein C (MYBPC3) gene polymorphisms and diastolic heart failure (DHF) in a human case-control study. Methods A total of 352 participants of 1752 consecutive patients from the National Taiwan University Hospital and its affiliated hospital were enrolled. 176 patients diagnosed with DHF confirmed by echocardiography were recruited. Controls were matched 1-to-1 by age, sex, hypertension, diabetes, renal function and medication use. We genotyped 12 single nucleotide polymorphisms (SNPs) according to HapMap Han Chinese Beijing databank across a 40 kb genetic region containing the MYBPC3 gene and the neighboring DNA sequences to capture 100% of haplotype variance in all SNPs with minor allele frequencies ≧5%. We also analyzed associations of these tagging SNPs and haplotypes with DHF and linkage disequilibrium (LD) structure of the MYBPC3 gene. Results In a single locus analysis, SNP rs2290149 was associated with DHF (allele-specific p = 0.004; permuted p = 0.031). The SNP with a minor allele frequency of 9.4%, had an odds ratio 2.14 (95% CI 1.25–3.66; p = 0.004) for the additive model and 2.06 for the autosomal dominant model (GG+GA : AA, 95% CI 1.17–3.63; p = 0.013), corresponding to a population attributable risk fraction of 12.02%. The haplotypes in a LD block of rs2290149 (C-C-G-C) was also significantly associated with DHF (odds ratio 2.10 (1.53–2.89); permuted p = 0.029). Conclusions We identified a SNP (rs2290149) among the tagging SNP set that was significantly associated with early DHF in a Chinese population.

Whereas uterine leiomyoma is a common woman disease, intravenous leiomyomatosis with intracaval and intracardiac complications is a rare condition. The initial presentation is dependent upon the severity of the intracardiac involvement, although complete surgery is the best treatment. The case of a 39-year-old woman is described here, with an initial presentation of dyspnea and right heart failure. Leiomyomatosis originating from the uterus and extending to the inferior vena cava and right atrium was diagnosed from various preoperative studies. The patient was resuscitated because of respiratory failure and severe right heart failure. However, she was operated successfully through a two-stage approach and remained well postoperatively. This case illustrates an intriguing presentation of intravenous leiomyomatosis and a curative surgical intervention even in critical condition.

Summary Background Cardiac function is an important predictor for life expectancy in elderly subjects. Tai Chi Chuan (TCC) is a generalized tolerable exercise for the aged population. The current study evaluated the effects of TCC on the vascular compliance and resistance as well as cardiac function of a general healthy elderly population. Materials and methods A total of 122 consecutive subjects were enrolled from the general population. Yang style TCC was practiced three times a week for 1hour each session for a duration of 5 months. Subjects were categorized as "adherents" ( n =33) if they participated in >48 (80%) sessions, or as "non-adherents" ( n =34). Biochemistry data, including fasting glucose, serum cholesterol, triglycerides, uric acid, were recorded before and after the 5-month intervention. Hemodynamic variables, including vascular compliance, resistance, cardiac output, stroke volume, and left ventricular ejection fraction, were obtained before and after the program using a Dynapulse 200M monitor. Results Serum triglyceride levels declined after TCC practice (the changes in triglycerides were −3.12 mg/dL and 18.8 mg/dL for the adherent and non-adherent groups, respectively; p =0.03). Significant differences between the adherent and non-adherent groups existed in left ventricular contractility, cardiac output, cardiac index, stroke volume, and brachial artery compliance ( p p =0.01; p p p =0.02, respectively). Conclusion A 5-month TCC intervention can have a favorable impact on some biochemical indices of cardiovascular risk. This intervention can also have favorable effects upon hemodynamic parameters. These findings indicate that TCC intervention may offer enhanced cardioprotective effects in the aged population.