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The aim of this study was to investigate alterations in the intrarenal blood pressure (BP) regulation system after renal denervation (RDN) guided by renal nerve stimulation (RNS). Twenty-one dogs were randomized to receive RDN at strong (SRA group, n = 7) or weak (WRA group, n = 7) BP-elevation response sites identified by RNS or underwent RNS only (RNS-control, RSC, n = 7). After 4 weeks of follow-up, renal sympathetic components, the main components of renin-angiotensin system (RAS) and the major transporters involved in sodium and water reabsorption were assessed by immunohistochemical analysis. Compared with RSC treatment, RDN therapy significantly reduced renal norepinephrine and tyrosine hydroxylase levels, decreased the renin content and inhibited the onsite generation of angiotensinogen. Moreover, the expression of exciting axis components, including angiotensin-converting enzyme (ACE), angiotensin II and angiotensin II type-1 receptor, was downregulated, while protective axis components for the cardiovascular system, including ACE2 and Mas receptors, were upregulated in both WRA and SRA groups. Moreover, RDN reduced the abundance of aquaporin-1 and aquaporin-2 in kidneys. Although RDN had a minimal effect on overall NKCC2 expression, its activation (p-NKCC2) and directional enrichment in the apical membrane (mNKCC2) were dramatically blunted. All these changes were more obvious in the SRA group than WRA group. Selective RDN guided by RNS effectively reduced systemic BP by affecting the renal neurohormone system, as well as the sodium and water transporter system, and these effects at sites with a strong BP response were more superior.

Background and Objective: To perform an integrated Cross-Biostatical analysis of four randomized controlled trials (RCTs) to assess the efficacy and safety of oral administration of D&G capsule (D&G) for the maintenance of cardiovascular health. Methods: Data from the populations of four completed RCTs were pooled for this integrated Cross-Biostatical analysis. Mean changes from baseline in IMT and lipid profile were the main lines of attention; treatment differences were compared between D&G and Placebo groups. Primary outcome was Carotid artery intima-media thickness (IMT). Secondary outcome was the lipid profile. Analyses included primary and secondary outcome measures repeated at individual time points. Results: The pooled RCT data involved 453 subjects (245 DG 208 Placebo); demographic characteristics were similar between treatment groups. Taking all 4 groups together, the mean improvements in IMT from baseline to week 24 were 0.9163 to 0.8939 in D&G group, and 0.8997 to 0.8964 in Placebo group. A statistically significant improvement after treatment was observed (P

To evaluate the impact of PM2.5 air pollution on atherogenic processes in modernizing Southern versus Northern China, we studied 1323 asymptomatic Chinese in Southern and Northern China in 1996–2007. PM2.5 exposure and metabolic syndrome (MS) were noted. Brachial flow-mediated dilation (endothelial function FMD) and carotid intima-media thickness (IMT) were measured by ultrasound. Although age and gender were similar, PM2.5 was higher in Northern China than in Southern China. The Northern Chinese were characterized by lower lipids, folate and vitamin B12, but higher age, blood pressures, MS and homocysteine (HC) (p = 0.0015). Brachial FMD was significantly lower and carotid IMT was significantly greater (0.68 ± 0.13) in Northern Chinese, compared with FMD and IMT (0.57 ± 0.13, p < 0.0001) in Southern Chinese. On multivariate regression, for the overall cohort, carotid IMT was significantly related to PM2.5, independent of location and traditional risk factors (Model R2 = 0.352, F = 27.1, p < 0.0001), while FMD was inversely related to gender, age, and northern location, but not to PM2.5. In Southern Chinese, brachial FMD was inversely correlated to PM2.5, independent of age, whereas carotid IMT was significantly related to PM2.5, independent of age and gender. In Northern Chinese, brachial FMD was inversely related to gender only, but not to PM2.5, while carotid IMT was related to traditional risk factors. Despite a higher PM2.5 pollution in Northern China, PM2.5 pollution was more significantly associated with atherogenic surrogates in Southern compared to Northern Chinese. This has potential implications for atherosclerosis prevention.

Background: Air Pollution (AP) and metabolic syndrome (MS) are important global health hazards of the 21st century, in mainland China in particular, and AP has been associated with increased prevalence of cardiovascular diseases, and stroke. Methods: To evaluate the impact of metabolic syndrome on AP-related atherogenesis, 1557 Han Chinese adults (mean age 47.2±11.8 years, male 47%) in Hong Kong, Macau, Pun Yu, Yu County (Shanxi coalmine) and 3-Gorges (Yangtze River) were studied. Cardiovascular risk profiles and metabolic syndrome (IDF criteria) were evaluated. PM2.5 (satellite sensor modeling), and atherosclerotic surrogates, brachial reactivity (FMD) and carotid Intima-media thickness (IMT) (ultrasound), were measured. Results: The yearly PM2.5 concentration ranged from 34.0μg/m³ in Hong Kong to 93.8μg/m³ in 3-Gorges Territories. MS was diagnosed in 340 subjects (21.8%). Smoking status, gender and PM2.5 were similar in the MS cohort versus those without MS. Blood pressures (SBP and DBP), waist circumference, triglycerides and glucose were higher, but high-density lipidcholesterol was lower in the MS cohort, compared to the other subjects. Brachial FMD was significantly lower and carotid IMT significantly higher (0.70±0.13 mm, 95% CI 0.68-0.71 mm vs. 0.63mm±0.14mm, 95% CI 0.62-0.64 mm) in the MS cohort than those without (P

Renal nerve stimulation (RNS) can result in substantial blood pressure (BP) elevation, and the change was significantly blunted when repeated stimulation after ablation. However, whether RNS could provide a meaningful renal nerve mapping for identification of optimal ablation targets in renal denervation (RDN) is not fully clear. Here, we compared the antihypertensive effects of selective RDN guided by two different BP responses to RNS and explored the nerve innervations at these sites in Kunming dogs. Our data indicated that ablation at strong-response sites showed a more systolic BP-lowering effect than at weak-response sites ( P =0.002), as well as lower levels of tyrosine hydroxylase and norepinephrine in kidney and a greater reduction in plasma norepinephrine ( P =0.004 for tyrosine hydroxylase, P =0.002 for both renal and plasma norepinephrine). Strong-response sites showed a greater total area and mean number of renal nerves than weak-response sites ( P =0.012 for total area and P R =0.649; P =0.012 and R =0.643; P =0.013). Changes of plasma norepinephrine and renal norepinephrine levels at 4 weeks were also correlated with systolic BP changes at 4 weeks ( R =0.837, P R =0.927, P

BACKGROUND Previous studies showed that radiofrequency energy delivery of the renal artery could induce an immediate and substantial blood pressure (BP)-elevation response, which might be indicative of the increase in central sympathetic nervous activity. OBJECTIVE The current study was to investigate whether the presence of BP-elevation response to radiofrequency energy delivery can serve as a surrogate to predict BP reduction following renal artery sympathetic denervation (RDN). METHOD Data were collected on 67 patients undergoing RDN for drug-resistant hypertension. The BP-elevation response to radiofrequency application was defined as elevation of SBP by at least 10 mmHg during radiofrequency energy delivery. The extent of BP reduction at 1, 3, 6, 12 months after RDN were analyzed. Multivariable linear regression analysis of baseline and procedural characteristics was performed to identify the determinants of BP reduction after RDN. RESULTS Ten patients (14.9%) were classified as nonresponders to radiofrequency delivery and showed significantly lower BP reduction compared with responders. The SBP reductions of radiofrequency delivery responders vs. nonresponders were 31.2 ± 8.6 vs. 11.4 ± 8.6 mmHg, 36.3 ± 10.0 vs. 14.6 ± 10.6 mmHg, 39.9 ± 9.9 vs. 15.2 ± 8.8 mmHg, and 40.0 ± 8.7/13.5 ± 5.8 mmHg (P

Background Air pollution has been associated with an increase in cardiovascular diseases incidence. To evaluate whether air pollution can accelerate atherogenic processes, we assessed the effects of air pollution on important surrogate markers of atherosclerosis [brachial flow-mediated dilation (FMD) and carotid intima-media thickness (IMT)]. Methods A total of 1656 Han Chinese (mean age 46.0 + 11.2 years; male 47%) in Hong Kong, Macau, Pun Yu, Yu County and the 3-Gorges Territories (Yangtze River) were studied between 1996 and 2007 [Chinese Atherosclerosis in the Aged and Young Project (the CATHAY Study)]. Cardiovascular risk profiles were evaluated. Particulate matter with an aerodynamic diameter Results Health parameters [age, gender, body mass index, waist : hip ratio (WHR) and glucose)] were similar in lowest and highest PM2.5 exposure tertiles, systolic and diastolic blood pressures and triglycerides were higher (P Conclusions Air pollution is strongly associated with markers of early atherosclerosis, suggesting a potential target for preventive intervention.

Renal nerve stimulation (RNS) can result in substantial blood pressure (BP) elevation, and the change was significantly blunted when repeated stimulation after ablation. However, whether RNS could provide a meaningful renal nerve mapping for identification of optimal ablation targets in renal denervation (RDN) is not fully clear. Here, we compared the antihypertensive effects of selective RDN guided by two different BP responses to RNS and explored the nerve innervations at these sites in Kunming dogs. Our data indicated that ablation at strong-response sites showed a more systolic BP-lowering effect than at weak-response sites (P=0.002), as well as lower levels of tyrosine hydroxylase and norepinephrine in kidney and a greater reduction in plasma norepinephrine (P=0.004 for tyrosine hydroxylase, P=0.002 for both renal and plasma norepinephrine). Strong-response sites showed a greater total area and mean number of renal nerves than weak-response sites (P=0.012 for total area and P0.001 for mean number). Systolic BP-elevation response to RNS before RDN and blunted systolic BP-elevation to RNS after RDN were correlated with systolic BP changes at 4 weeks follow-up (R=0.649; P=0.012 and R=0.643; P=0.013). Changes of plasma norepinephrine and renal norepinephrine levels at 4 weeks were also correlated with systolic BP changes at 4 weeks (R=0.837, P0.001 and R=0.927, P0.001). These data suggest that selective RDN at sites with strong BP-elevation response to RNS could lead to a more efficient RDN. RNS is an effective method to identify the nerve-enriched area during RDN procedure and improve the efficacy of RDN.

The Supplemental Materials of pre-peer review manuscript submitted to American Journal of Physiology-Heart and Circulatory Physiology.

Renal denervation (RDN) is a well-known innovative therapy for hypertension. However, the effects of global RDN on blood pressure (BP) lowering are quite variable. Insufficient and futile denervation is considered a major factor contributing to the variable results. Mapping renal nerves by renal nerve stimulation (RNS) is the most promising technique to improve the efficacy of RDN. We summarize the clinical and experimental data available regarding RNS-guided RDN and explain the roles of renal efferent nerves, afferent nerves and vagal nerves in BP changes. We further identify five different BP response patterns to RNS and provide an explanation of the underlying neuroanatomical basis.

Background: The emergency department (ED) has a pivotal influence on the management of acute heart failure (AHF), but data concerning current ED management are scarce. This Beijing AHF Registry Study investigated the characteristics, ED management, and short- and long-term clinical outcomes of AHF. Methods: This prospective, multicenter, observational study consecutively enrolled 3335 AHF patients who visited 14 EDs in Beijing from January 1, 2011, to September 23, 2012. Baseline data on characteristics and management were collected in the EDs. Follow-up data on death and readmissions were collected until November 31, 2013, with a response rate of 92.80%. The data were reported as median (interquartile range) for the continuous variables, or as number (percentage) for the categorical variables. Results: The median age of the enrolled patients was 71 (58–79) years, and 46.84% were women. In patients with AHF, coronary heart disease (43.27%) was the most common etiology, and myocardium ischemia (30.22%) was the main precipitant. Most of the patients in the ED received intravenous treatments, including diuretics (79.28%) and vasodilators (74.90%). Fewer patients in the ED received neurohormonal antagonists, and 25.94%, 31.12%, and 33.73% of patients received angiotensin converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, and spironolactone, respectively. The proportions of patients who were admitted, discharged, left against medical advice, and died were 55.53%, 33.58%, 7.08%, and 3.81%, respectively. All-cause mortalities at 30 days and 1 year were 15.30% and 32.27%, respectively. Conclusions: Substantial details on characteristics and ED management of AHF were investigated. The clinical outcomes of AHF patients were dismal. Thus, further investigations of ED-based therapeutic approaches for AHF are needed.

It is controversial whether angiotensin II receptor blockers provide better protection than calcium antagonists against atrial fibrillation (AF) recurrence in hypertensive patients. This study was designed to compare the effect of nifedipine- and telmisartan-based antihypertensive treatments for preventing AF recurrence in hypertensive patients with paroxysmal AF. A total of 149 hypertensive patients with paroxysmal AF were randomized to nifedipine- or telmisartan-based antihypertensive treatment groups. The target blood pressure (BP) was P =0.742), and Kaplan–Meier analysis showed no significant difference in the freedom from AF recurrence (log-rank test; P =0.48). However, the rate of developing persistent AF in telmisartan group was lower than that in nifedipine group (5.4% versus 16.0%; P =0.035). Patients in telmisartan group had lower values of left atrial diameter, left atrial volume index, and left ventricular mass index at the end of follow-up. The effects of telmisartan in preventing AF recurrences in hypertensive patients with paroxysmal AF after intensive lowering BP is similar to that of nifedipine, but telmisartan has more potent effects on preventing progression to persistent AF.

Autonomic nervous system plays a crucial role in maintaining and regulating vessel tension. Renal denervation (RDN) may induce renal artery vasodilation by damaging renal sympathetic fibers. We conducted this animal study to evaluate whether renal artery vasodilation could be a direct indicator of successful RDN. Twenty-eight Chinese Kunming dogs were randomly assigned into three groups and underwent RDN utilizing temperature-controlled catheter (group A, n = 11) or saline-irrigated catheter (group B, n = 11) or sham procedure (group C, n = 6). Renal angiography, blood pressure (BP) and renal artery vasodilation measurements were performed at baseline, 30-minute, 1-month, and 3-month after interventions. Plasma norepinephrine concentrations were tested at baseline and 3-month after intervention. Results showed that, in addition to significant BP reduction, RDN induced significant renal artery vasodilation. Correlation analyses showed that the induced renal artery vasodilation positively correlated with SBP reduction and plasma norepinephrine reduction over 3 months after ablation. Post hoc analyses showed that saline-irrigated catheter was superior to TC catheter in renal artery vasodilation, especially for the acute dilatation of renal artery at 30-minute after RDN. In conclusion, renal artery vasodilation, induced by RDN, may be a possible indicator of successful renal nerve damage and a predictor of blood pressure response to RDN.

Renal denervation (RDN) is used to manage blood pressure (BP) in patients with resistant hypertension (rHT), but effectiveness is still a concern, and key arterial portion for successful RDN is not clear.The aim of this study was to investigate the efficacy and safety of proximal versus full-length renal artery ablation in patients with resistant hypertension (rHT).Forty-seven patients with rHT were randomly assigned to receive full-length ablation (n = 23) or proximal ablation (n = 24) of the renal arteries. All lesions were treated with radiofrequency energy via a saline-irrigated catheter. Office BP was measured during 12 months of follow-up and ambulatory BP at baseline and 6 months (n = 15 in each group).Compared with full-length ablation, proximal ablation reduced the number of ablation points in both the right (6.1 ± 0.7 vs. 3.3 ± 0.6, P 0.001) and the left renal arteries (6.2 ± 0.7 vs. 3.3 ± 0.8, P 0.001), with significantly shorter RF delivery time (P 0.001), but higher RF power (P = 0.011). Baseline office BPs was 179.4 ± 13.7/102.8 ± 9.4 mm Hg in the full-length group and 181.9 ± 12.8/103.5 ± 8.9 mm Hg in the proximal group (P 0.5). Similar office BPs was reduced by -39.4 ± 11.5/-20.9 ± 7.1 mm Hg at 6 months and -38.2 ± 10.3/-21.5 ± 5.8 mm Hg at 12 months in the full-length group (P 0.001), -42.0 ± 11.6/-21.4 ± 7.9 mm Hg at 6 months and -40.9 ± 10.3/-22.1 ± 5.6 mm Hg at 12 months in the proximal group (P 0.001), and progressive BP reductions were observed over the 6 months (P 0.001) in both groups. The drop in ambulatory 24-hr SBP and DBP were significantly less than the drop in office BP (P 0.001). No renovascular or other adverse complications were observed.The results indicate that proximal RDN has a similar efficacy and safety profile compared with full-length RDN, and propose the proximal artery as the key portion for RDN. © 2016 Wiley Periodicals, Inc.

Patients with chronic kidney disease (CKD) have a high risk for cardiovascular disease. Ultrasound measurements of the intima media thickness (IMT) in the carotid arteries is a strong predictor for cardiovascular events in the general population and dialysis patients. However, it is unclear whether carotid IMT is useful for the prediction of cardiovascular events in predialysis patients with CKD. The prediction power of carotid ultrasonography for cardiovascular event, rate of renal function decline, and all-cause mortality was tested in a cohort of 203 Chinese patients with stages 3 to 4 CKD. The average IMT was 0.808 +/- 0.196 mm; 121 (59.6%) patients had atherosclerotic plaques visualized. IMT correlated with patient age (r = 0.373, P < 0.001), serum LDL level (r = 0.164, P = 0.021), Charlson's comorbidity score (r = 0.260, P < 0.001), and serum C-reactive protein (r = 0.279, P < 0.001). Carotid IMT was significantly higher in patients with diabetes than in those without diabetes (0.930 +/- 0.254 versus 0.794 +/- 0.184; P = 0.002). At 48 mo, the cardiovascular event-free survival was 94.4, 89.8, 77.7, and 65.9% for IMT quartiles I, II, III, and IV, respectively (log rank test, P = 0.006). By multivariate analysis with the Cox proportional hazard model, each higher quartile of IMT conferred 41.6% (95% confidence interval 6.4 to 88.4%; P = 0.017) excess hazard for developing cardiovascular event. The actuarial survival at 48 mo was 96.3, 98.0, 95.7, and 85.7% for IMT quartiles I, II, III and IV, respectively (log rank test, P = 0.127), and the difference was not statistically significant after Cox proportional hazard model to adjust for confounders. Carotid IMT did not correlate with the rate of renal function decline in these patients. Carotid IMT is a strong predictor of cardiovascular disease in Chinese predialysis patients and may be usefully applied for risk stratification in this group of patients.

Background— Electric stimulation has been proved to be available to monitor the efficacy of renal denervation (RDN). This study was to evaluate the effectiveness of high-frequency stimulation (HFS)–guided proximal RDN. Methods and Results— A total of 13 Chinese Kunming dogs were included and allocated to proximal RDN group (n=8) and control group (n=5). HFS (20 Hz, 8 V, pulse width 2 ms) was performed from proximal to distal renal artery in all dogs. Radiofrequency ablations were delivered in proximal RDN group and only at the proximal positive sites where systolic blood pressure (BP) increased ≥10 mm Hg during HFS. Postablation HFS was performed over the previously stimulated sites. BP, heart rate, and plasma norepinephrine were analyzed. In 8 denervated dogs, preablation HFS caused significant BP increases of 6.0±5.0/3.4±5.5, 16.9±11.7/11.1±8.5, and 17.1±8.4/8.5±5.3 mm Hg during the first, second, and third 20 s of HFS at the proximal positive sites. After ablation, these sites showed a negative response to postablation HFS with increases of BP by 1.3±3.0/1.0±2.5, 0.8±3.9/1.5±3.4, and 1.5±4.5/0.7±3.8 mm Hg. Of note, no radiofrequency applications were delivered at the positive sites of middle renal artery, repeated HFS increased BP only by 3.3±5.3/2.8±4.2, 5.3±6.6/3.8±4.7, and 2.9±4.6/1.3±3.2 mm Hg, failed to reproduce the previous BP increases of 6.2±5.6/5.3±4.4, 15.0±9.3/10.2±6.2, and 14.9±7.7/8.4±4.7 mm Hg. At 3 months, BP and plasma norepinephrine substantially decreased in proximal RDN group. Whereas controls showed minimal BP decreases and had similar plasma norepinephrine concentrations as baseline. Conclusions— Renal afferent nerves can be mapped safely, and HFS-guided targeted proximal RDN can achieve apparent BP reduction and sympathetic inhibition.

The PARC-AALA (Paroi arterielle et Risque Cardiovasculaire in Asia Africa/ Middle East and Latin America) study was designed to evaluate the correlation between intima-media thickness of the common carotid artery (CCAIMT), carotid plaque and absolute cardiovascular risk in a multi-ethnic population. An international, cross-sectional, study including 79 centres from 21 countries in Asia, Africa, the Middle East and Latin America. Two thousand three hundred and twenty-eight subjects, meeting all inclusion criteria, were stratified by risk factors groups (no modifiable factor or at least both uncontrolled hypertension and hypercholesterolemia). CCAIMT, presence of plaque and cardiovascular risk factors were assessed for each individual. Some intergeographical characteristics in demographics, and risk factors were found accompanying early atherosclerosis marker differences. In Asia where the subjects were at lower risk, the mean CCAIMT was 4% lower than in Africa/Middle East and Latin America. On multiple linear regression analysis CCAIMT and carotid plaque were independently associated with increased Framingham cardiovascular score (FCS) without heterogeneity across geographic regions. CCAIMT and carotid plaque explained roughly 20% of the FCS in both genders. The PARC-AALA study confirms the correlation between CCAIMT and FCS in three different populations. Intima-media thickness (IMT) and plaque evaluation may represent a complementary predictive tool for detection of cardiovascular disease in individuals.

The purpose of this trial was to compare the long-term efficacy of low-dose amiodarone with losartan and perindopril (both combined with low-dose amiodarone) for the prevention of atrial fibrillation (AF) recurrence in patients with lone paroxysmal AF.One-hundred and seventy-seven patients with lone paroxysmal AF were randomly assigned to three treatment groups: group 1 received low-dose amiodarone alone, group 2 received low-dose amiodarone plus losartan, and group 3 received low-dose amiodarone plus perindopril. Left atrial diameter was measured with transthoracic echocardiogram at baseline and 6, 12, 18, and 24 months after randomization. The primary endpoint was the incidence of AF documented by 12-lead ECG or Holter after 14 days and within 24 months after randomization. The primary endpoint was reached in 24 patients (41%) in group 1, 11 (19%) in group 2, and 14 (24%) in group 3 (P = 0.02). The Kaplan-Meier survival analysis demonstrated a significant reduction in AF recurrence in group 2 (P = 0.006, log-rank test) as well as in group 3 (P = 0.04, log-rank test) when compared with group 1. No difference in the AF recurrence-free survival was found between group 2 and group 3. After 24 months follow-up, the left atrial diameter in group 2 and group 3 was significantly smaller than that in group 1 (36 +/- 2.3 and 35 +/- 2.4 vs. 38 +/- 2.4 mm, P0.001 for both comparisons).The results of this study suggest that the combination of perindopril or losartan with low-dose amiodarone is more effective than low-dose amiodarone alone for the prevention of AF recurrence in patients with lone paroxysmal AF. Adding losartan or perindopril to amiodarone can inhibit left atrial enlargement in this group of patients.

Podocyte slit diaphragm plays an important role in the control of glomerular permeability. We hypothesize that studying the gene expression profile of podocyte in urinary sediment may provide diagnostic and prognostic information on acquired proteinuric diseases.We studied 28 patients who required kidney biopsy for acquired proteinuric diseases (diabetic glomerulosclerosis, 9 cases; IgA nephropathy, 10 cases; minimal change disease, 5 cases; membranous nephropathy, 5 cases). We also studied 10 cases of diabetic microalbuminuria and 9 healthy controls. The mRNA expressions of nephrin (NephRNA), podocin (PodRNA) and synaptopodin (SynRNA) in urinary sediment were measured by real time quantitative PCR. After recruitment, all patients were followed for at least 12 months.There were significant differences in the NephRNA and PodRNA in the urinary sediment between diagnosis groups (p0.005). On the other hand, SynRNA was only marginally significant between diagnosis groups (p0.05). Although statistically significant, the degree of proteinuria had only modest correlations with the urinary expression of nephrin. After a median follow up for 23 months, there was a significant correlation between the rate of decline in renal function and NephRNA (r=0.559, p=0.001) and PodRNA (r=0.530, p=0.002), but not SynRNA (r=0.054, p=NS). The correlation remained statistically significant after multivariate analysis to adjust for the degree of proteinuria and initial renal function.Urinary mRNA expression of podocyte markers, such as nephrin and podocin, are significantly different between proteinuric disease categories. Further, NephRNA and PodRNA correlated with the rate of decline in renal function. Our results suggest that urinary podocyte gene expression may be a useful non-invasive tool which provides additional information for the management of proteinuric diseases.

Danshen (Salvia miltiorrhiza) and Gegen (Radix puerariae) are two herbs used in traditional Chinese medicine, most commonly for their putative cardioprotective and anti-atherosclerotic effects. In this study, we investigated the effect of a preparation of these herbs on two key processes in the early stages of atherosclerosis; macrophage lipid loading and monocyte adhesion to endothelial cells. Human monocyte derived macrophages (HMDMs) were treated with 0.1-1.0 mg/ml of the herbal mixture in aqueous buffers and loaded with acetylated LDL (AcLDL) (50 microg/ml) for 72 h, and analyzed for cholesterol (C) and cholesteryl esters (CE), via HPLC. Human endothelial cell monolayers were also treated with 0.1-1.0 mg/ml of the herbal mixture and monocyte adhesion measured. Cell adhesion molecules E-selectin, ICAM-1 and VCAM-1 were assessed via ELISA. Compared to control conditions, the herbal mixture induced a significant dose-related decrease in the total cholesterol (free and esterified) in the HMDMs (p

OBJECTIVE: We sought to study arterial endothelial function and carotid intima-media thickness (IMT), both early markers of atherosclerosis, in overweight compared to normal children. DESIGN: Case–control comparison. SUBJECTS: A total of 36 asymptomatic overweight children (body mass index (BMI)>23; mean 25±3) aged 9–12 y and 36 age- and gender-matched nonobese healthy children (BMI

The purpose of this study was to investigate whether atrial overexpression of angiotensin-converting enzyme 2 (ACE2) by homogeneous transmural atrial gene transfer can reverse atrial remodeling and its mechanisms in a canine atrial-pacing model. Twenty-eight mongrel dogs were randomly divided into four groups: Sham-operated, AF-control, gene therapy with adenovirus-enhanced green fluorescent protein (Ad-EGFP) and gene therapy with Ad-ACE2 (Ad-ACE2) (n = 7 per subgroup). AF was induced in all dogs except the Sham-operated group by rapid atrial pacing at 450 beats/min for 2 weeks. Ad-EGFP and Ad-ACE2 group then received epicardial gene painting. Three weeks after gene transfer, all animals except the Sham group underwent rapid atrial pacing for another 3 weeks and then invasive electrophysiological, histological and molecular studies. The Ad-ACE2 group showed an increased ACE2 and Angiotensin-(1–7) expression, and decreased Angiotensin II expression in comparison with Ad-EGFP and AF-control group. ACE2 overexpression attenuated rapid atrial pacing-induced increase in activated extracellular signal-regulated kinases and mitogen-activated protein kinases (MAPKs) levels, and decrease in MAPK phosphatase 1(MKP-1) level, resulting in attenuation of atrial fibrosis collagen protein markers and transforming growth factor-β1. Additionally, ACE2 overexpression also modulated the tachypacing-induced up-regulation of connexin 40, down-regulation of connexin 43 and Kv4.2, and significantly decreased the inducibility and duration of AF. ACE2 overexpression could shift the renin–angiotensin system balance towards the protective axis, attenuate cardiac fibrosis remodeling associated with up-regulation of MKP-1 and reduction of MAPKs activities, modulate tachypacing-induced ion channels and connexin remodeling, and subsequently reduce the inducibility and duration of AF. Electronic supplementary material The online version of this article (doi:10.1007/s00395-015-0499-0) contains supplementary material, which is available to authorized users.

Background— The purpose of this study was to compare the efficacy of radiofrequency catheter ablation (RFCA) versus antiarrhythmic drugs (AADs) for treatment of patients with frequent ventricular premature beats (VPBs) originating from the right ventricular outflow tract (RVOT). Methods and Results— A total of 330 eligible patients were included in the study and were randomly assigned to RFCA or AADs group. The absolute number and the burden of VPBs on 12-lead Holter monitors were measured at baseline and at 1st, 3rd, 6th, and 12th months after randomization. Left ventricular eject fraction was evaluated by transthoracic echocardiogram at baseline and at 3 and 6 months after randomization. During the 1-year follow-up period, VPB recurrence was significantly lower in patients randomized to RFCA group (32 patients, 19.4%) versus AADs group (146 patients, 88.6%; P P P P =0.004). Conclusions— Catheter ablation is more efficacious than AADs for preventing VPB recurrence in patients with frequent VPBs originating from the RVOT. QS morphology in lead I was associated with better outcome after ablation.

Objective: To compare the dietary intake of Chinese people living in Pan Yu, Hong Kong, San Francisco and Sydney with respect to cardiovascular health, using the Mediterranean diet score, examining the effects of age, gender, urbanization and acculturation on the diet score. Subjects: A total of 500 men and 510 women in Hong Kong were recruited as a territory-wide stratified random sample. Subjects were recruited in response to local advertisements for the other three sites: Pan Yu, 58 men, 95 women; San Francisco, 166 men, 192 women; Sydney, 95 men, 73 women. Method: Food-frequency questionnaire over a 7 week period. A high/healthy score was taken as ≥4 for men and ≥3 for women, representing a dietary pattern beneficial for cardiovascular health. Results: In Hong Kong, more women in the middle age group (35–54) had a high score than other age groups, and overall more women had high scores than men. In comparing the four geographical regions, Pan Yu had the highest number of subjects with high score, and Hong Kong had the lowest. With the exception of the younger population and men in Hong Kong, the percentage of the population with a high score in all sites is greater than among elderly Greeks consuming a more traditional heart-healthy Mediterranean diet. Conclusion: Considerable variations in Chinese dietary patterns exist with respect to age, gender and geographic location. Overall, the Chinese diet is comparable to the Mediterranean diet and may be expected to have similar health benefits that have been documented for the traditional Mediterranean diet. European Journal of Clinical Nutrition (2001) 55, 215–220

The increasing prevalence of traditional atherosclerotic risk factors have been documented in Asia but the real impact on prevalence of coronary heart disease (CHD) remains unclear. Smoking, hypertension, hypercholesterolaemia, diabetes mellitus and obesity are present in only 50% of CHD. In community studies of Chinese in Hong Kong and southern mainland-China, aging, smoking and hypercholesterolaemia were found to have a less impact on endothelial function in the Chinese compared with Caucasians in London and Sydney. As endothelial dysfunction is an early event in atherogenesis, there will be a strong need to search for newer risk factors for CHD in Asia, which may become more important in many Asian countries now in the process of modernization. Recently, heterozygous hyperhomocysteinaemia (with or without folate deficiency) was found to be an independent risk factor for arterial endothelial dysfunction, and hyperhomocysteinaemia in association with smoking was a significant risk factor for premature coronary heart disease in Hong Kong Chinese. Other newer factors which have emerged include folate deficiency, low HDL-cholesterol, insulin resistance, abdominal obesity, Methylene-tetrahydrofolate Reductase and Angiotensin Converting Enzyme gene polymorphism.

Objective: Common carotid artery (CCA) intima-media thickness (IMT), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), but not triglyceride levels, are markers of future cardiovascular events. The relationship between these three factors is, however, unclear. Methods: We included six large observational studies that used the same harmonized, B-mode ultrasound protocol,thesamesoftwareforIMTmeasurementbyautomaticedgedetectiononCCAinaplaque-freeregion, followingthe Mannheim consensus,andcertificationofallsonographers. Using the best viewof the CCA, the sonographerhadto confirmthat thequalityindex was � 0.5 on ameasurement performedon10-mmlength. We used individual data meta-analysis to estimate the cross-sectional associations of lipids with CCA-IMT. Results: Overall,21,587patients withcompleteinformation onlipids andCCA-IMTwere available. Age-and sex-adjusted CCA-IMT differed by � 7.8 mm (95% CI � 9.1 to � 6.5 mm, P < 0.001) per 1 SD higher HDL-C level. Afterfurtheradjustmentforotheratherosclerosisriskfactors,therelationshipwasattenuated,butremained significant (regression coefficient, � 3.7 mm; P < 0.001). This was found regardless of LDL-C levels (P for heterogeneity ¼ 0.70). After adjustment for age and sex, triglycerides were positively associated with CCAIMT, overall and in each LDL-C subgroup, but not after further adjustments for other risk factors. Conclusions: Relationships between HDL-C and triglyceride levels and CCA-IMT were consistent with that previously observed with clinical events by the Emergency Risk Collaboration group, including at low LDL-C levels. This reinforces the need to verify whether raising HDL-C levels decreases both CCA-IMT and future clinical events.

Background Left ventricular diastolic dysfunction is common in patients with systolic heart failure andthe restrictive type of filling pattern appears to be associated with increased cardiac mortality. Both atrial and brain (or ventricular) natriuretic peptides are also proven markers of the severity of heart failure. The aim of this study was to determine in a large cohort of patientswith systolic heart failure whether diastolic abnormalities, and in particular the restrictive filling pattern of transmitral flow velocity, correlate with plasma atrial and brain natriuretic peptide levels. Methods Sixty-eight consecutive patients with symptomatic systolic heart failure (ejection fraction

Background High-intensity focused ultrasound (HIFU) can achieve accurate and focused deep tissue ablation through an extracorporeal emission. Cardiac ablation using HIFU applied transthoracically must overcome potential interference from intervening thoracic structures. The aim of this study was to explore the efficacy and safety of septal ablation that was induced using transthoracic HIFU. Methods Twenty-one canines were pretreated to improve acoustic transmission. Single ablations were induced by targeting transthoracic HIFU with acoustic power of 400 W for 3 sec at the middle and basal septum in eight canines. Extended ablations were performed to create larger lesions at the basal septum in eight more canines. The three-dimensional morphology of a basal septum lesion induced by a single ablation was analyzed. The temperature at the ablative targets was measured in the other five canines. Results The cardiomyocytes in the lesions underwent necrosis with a clear boundary. The three-dimensional morphology of the lesions appeared approximately as ellipsoids with a flatter endocardial side. The peak temperature at a power of 400 W for 3 sec was 93.27 ± 2.54°C, and it remained >50°C for nearly 10 sec. No procedure-related complications were observed. Conclusions Ultrasound-guided transthoracic HIFU has the potential to safely create small dot or large mass lesions in the septum without a thoracotomy or a catheter.

Although the mortality rate from coronary artery disease in Hong Kong is only one-fourth of that of northern Europe and the United States, the disease has been and remains the second major cause of death (after all cancers combined). Beginning in 1987, we have conducted a case-control study of acute myocardial infarction in four Hong Kong hospitals. This study, one of the biggest case-control studies conducted in the Chinese population of both men and women, confirms the importance of several risk factors-cigarette smoking, history of hypertension, history of diabetes, body fatness, and lack of physical activity-previously described in data collected in western populations. In addition, more adverse childhood experience was also found to be an important risk factor of acute myocardial infarction. Further research in appropriate intervention measures in education in the prevention and cessation of smoking, the control of blood pressure, diabetes, and overweight, and adequate exercise could significantly help reduce the risk of acute myocardial infarction in the Hong Kong Chinese population.

Objective: To assess the importance of an abnormal lipid profile as a risk factor in relation to non-biochemical risk factors, and to define the risk levels for lipid, lipoprotein and apolipoprotein in a Chinese population. Patients and Methods: Serum lipids, lipoproteins, apolipoproteins and other cardiovascular risk factors were studied in 89 Chinese men 3 months after acute myocarial infarction and 56 controls. Results: Cases had higher mean total cholesterol (TC), LDL- and VLDL-cholesterol, triglycerides and apolipoprotein B (Apo B), and lower mean HDL-cholesterol and apolipoprotein AI (Apo AI). Mean BMI was also higher, as was the prevalence of smokers and subjects with a history of hypertension. In univariate analysis, the odds ratios for TG ≥ 1.6 mmol/l, LDL-cholesterol ≥ 4.1 mmol/l, VLDL-cholesterol ≥ 0.73 mmol/l, Apo B ≥ 104 mg/dl were of the same order of magnitude as being a current smoker, having a BMI ≥ 24.3 kg/m 2 , and a history of a hypertension. High HDL-cholesterol (≥ 1.39 mmol/l) and Apo AI (≥ 139 mg/dl) were protective factors. The odds ratios for successively higher quartile values of cholesterol were not statistically significant. Multiple logistic regression identified smoking habit, history of hypertension, obesity, high Apo B and low Apo AI concentrations as independent risk factors for myocardial infarction. Conclusions: In a Chinese population, low serum Apo AI and high Apo B are risk factors for myocardial infarction of a comparable magnitude to smoking, hypertension and obesity.

Thrombolytic therapy using recombinant-tissue plasminogen activator, urokinase and streptokinase for acute myocardial infarction was instituted in the coronary care unit of the Prince of Wales Hospital in Hong Kong in 1988. To evaluate its impact on hospital mortality of acute myocardial infarction, the database of 465 patients (mean age 65.2 ± 12.6 yr) admitted into the coronary care unit in the period between 1985–1990 was collected prospectively and their clinical course reviewed. Three hundred and thirty-five patients were males and 130 were females. Patients in the prethrombolytic era (1985–1987) and the thrombolytic era (1988–1990) were matched for age, proportion of females and clinical severity. One hundred and two patients (39.5%) received thrombolytic therapy. The overall hospital mortality (18.6%) in the thrombolytic era and that for each sex (18.2% in the males; 19.5% in the females) were significantly lower than those of prethrombolytic era (27.1%, 23.4% and 37.7%, respectively). No death was due to bleeding complication. The benefit of thrombolytic therapies in the Chinese was confirmed. More effort is needed to popularise this concept in the Chinese communities, to shorten the prehospital delay of patients and to extend its utilisation to the elderly patients.

A 51-year-old man with good health previously presented with a 1-month history of shortness of breath on exertion. Transthoracic echocardiography revealed marked biventricular hypertrophy, mild mitral regurgitation, and moderate tricuspid regurgitation, suggestive of hypertrophic cardiomyopathy (Figure 1A and 1B; Movie I and Movie II). In the parasternal short-axis view, thickening of the left atrial wall and para-aortic tissue were evident, which is unusual in typical hypertrophic cardiomyopathy, a disease that primarily affects the ventricular myocardium (Figure 1C and Movie III). Computerized tomographic arteriography revealed no coronary artery disease. His heart failure symptoms worsened, and atrial fibrillation developed. At the same time, maculopapular skin rash developed on the upper trunk and the head and neck region. Hypercalcemia with an adjusted serum calcium level greater than 4 mmol/L was recorded. Other blood chemistry and hematologic examinations were unremarkable. His conditions deteriorated rapidly and, despite maximal supportive measures, he died 1 week after hospitalization. Limited clinical postmortem examination revealed a well-built gentleman with a heart weighing 790 g (Figure 2A). The walls of all 4 chambers of the heart were diffusely thickened by tan-colored infiltrative growth. The left and right ventricular …

that smoking is a risk factor for both coronary heart disease (CHD) and stroke, independent of the effects of BMI, blood pressure, and cholesterol, with the amelioration of the effects after quitting. Of much interest and importance, Asians and Caucasians (in Australia and New Zealand) had similar increased proportional cardiovascular risk (relative risk) from smoking cigarettes, and similar relative risk reduction from quitting. Moreover young people and women had greater relative risk of cardiovascular disease from smoking, but the effect declined with age. This report also appropriately documented relative and attributable risks for CHD and strokes in different groups. While there were no differences in their relative risk, the attributable risk for CHD from smoking reflected the prevalence of smoking in different groups and, hence, was higher in Chinese men (30%) compared with Australian (13%) and New Zealand men (7%) but was lower in Chinese women (3%) compared with the other two groups (11% for Australia and 6% for New Zealand). However, it should be noted that the overall absolute risk of CAD (fatal and non-fatal) in Australia and New Zealand (2.6%) is still higher than that in Asia (0.35%), possibly reflecting the effects of different genes and gene‐environment interactions in the two regions. Time will tell whether these differences in absolute risk will converge and abolish, with the changing trend of smoking and modernization in the two regions. The greater smoke-related impact on cardiovascular health of young women is of much public health concern, given that the tobacco epidemic is still spreading among women (estimated 530 million by 2025) and that, although prevalence rates are low in Asian women, the high rates in men mean that they are exposed to high levels of passive smoking. Tobacco control policies should, therefore, always include messages specifically targeted at women. The strength of this paper is its large sample size. However, it is important to note that the present study is a retrospective overview ‘meta-analysis’ of 40 observational studies spreading over 37 years from 1961 to 1998, using non-uniform study protocols and data entries for smoking status and smoking (inhalation) habits. The types of cigarette smoked, changes in inhalation habits overtime and years of follow-up were not uniformly available. In addition, information on many important confounding factors, including body mass index, blood pressure, and cholesterol levels were missing in some of these cohorts, and the cholesterol assay understandably were carried out in different laboratories, using different methods and standardization, over a long period of 37 years. It may be quite Atherosclerotic disease including stroke and coronary artery disease (CAD) is the most important health issue of modern society. Cigarette smoking has been associated with this disease in Western countries. 1 In comparison, the impact of smoking on cardiovascular health has been less well documented in Asia, and, in particular, its impact in China where the population at risk currently comes up to one-quarter of the global population is unclear. Interest in the impact of smoking in China is inspired by the fact that although 70% of Chinese males smoke (compared with current prevalence in the range 20‐30% for men in most Western populations), the prevalence of CAD in Chinese men is one-quarter of that for Western men. 2 Furthermore, there is evidence that young Chinese adults have less arterial endothelial dysfunction (a novel surrogate atherosclerosis marker predictive of cardiovascular outcome) than white adults with similar direct or indirect exposure to cigarette smoke. 3 A second cross-sectional study, similarly using a surrogate marker of cardiovascular disease [carotid intimamedia thickness (IMT)], found that Chinese adults who had Western lifestyles had thicker IMT than native rural Chinese, and that the detrimental effect of cigarette smoking on IMT was greater in Westernized Chinese living in Hong Kong and Sydney than it was in native rural Chinese. 4 These differences suggest a relative protection of Chinese from the effect of cigarette smoking, possibly due to certain gene differences, which may be modified by Westernization, and subscribe to a gene‐ environment interaction process, or to an interaction between smoking, changes in lifestyles, and other risk factors in the process of Westernization. While evaluation of the underlying lifestyles, dietary habits, and subsequently physiological and biochemical changes related to such Westernization process are awaited with much interest, these early results call for further studies that examine and compare smoking-related effects in acculturated migrant Chinese population with those in village natives in mainland China. 5 To illuminate this important health issue, the paper from the Asian Pacific Cohort Studies Collaboration in this issue of the journal 6 addressed the problem from an epidemiological perspective. With the strength of large numbers of subjects (n = 562 338) and, therefore, more precise estimates, they confirmed

Acute coronary syndrome may involve cell death and the release of nucleic acids into the circulation. We thus investigated whether plasma DNA concentrations are increased and determined its prognostic significance in patients with ACS.Real-time polymerase chain reaction was used to quantitatively measure the beta-globin gene from blood samples taken from patients presenting to an emergency department with chest pain of probable cardiac cause.Samples from 58 patients with chest pain, and from 21 age- and sex-matched healthy control subjects were analysed. Compared with the control group, median plasma DNA concentrations were increased 1.5-fold in patients with minor cardiac injury, were increased further in patients with STEA and STEMI, and were the highest in those patients who died within 2 years (P=0.0005; post-hoc Dunn's, P0.05). Median plasma DNA concentrations were higher in patients who later developed heart failure (1060 vs. 500 kGE/l; P=0.0095); higher in patients who later reinfarcted (1000 vs. 530 kGE/l; P=0.0298); higher in patients who had a cardiac arrest in that admission (1350 vs. 525 kGE/l; P=0.04); and were higher in patients who were readmitted within 6 months of discharge (725 vs. 475 kGE/l; P=0.04).Plasma DNA is a potential marker for post-ACS complications.

Caffeic acid (3,4-dihydroxycinnamic acid), one of the most common phenolic acids, frequently occurs in fruits, grains and dietary supplements for human consumption as simple esters with quinic acid or saccharides, and are also found in traditional Chinese herbs. Caffeic acid derivatives occur as major water-soluble components of Salvia miltiorrhiza, including caffeic acid monomers and a wide variety of oligomers. This review provides up-to-date coverage of this class of phenolic acids in regard to structural classification, natural resources, chemical and biosyntheses, analytical methods and biological activities including antioxidant, anti-ischemia reperfusion, anti-thrombosis, anti-hypertension, anti-fibrosis, antivirus and antitumor properties. Special attention is paid to both structural classification and biological activities. The structural diversity and the pronounced biological activities encountered in the caffeic acid derivatives of S. miltiorrhiza indicate that this class of compounds is worthy of further studies that may lead to new drug discovery.

Aims To examine the pattern of adherence to statin therapy and to determine the association of adherence to statin therapy and the control of serum low-density lipoprotein (LDL)-cholesterol in a cohort of Hong Kong Chinese patients at high risk of coronary heart disease (CHD). Methods This was a prospective observational cohort study conducted at the outpatient clinics of a public teaching hospital in Hong Kong. Patients at high risk of CHD who had been initiated on statin monotherapy for

The roots of Pueraria thomsonii and Pueraria lobata are officially recorded in Chinese Pharmacopoeia under the same name Radix Puerariae. However, the aqueous root extract of Pueraria lobata showed more potent antioxidant activity than that of Pueraria thomsonii. A qualitative HPLC method was developed to compare the chemical profiles of Pueraria thomsonii and Pueraria lobata, which revealed four major common peaks (daidzein 1, daidzin 2, puerarin 3 and 5-hydroxypuerarin 4) and two major different peaks (3-hydroxypuerarin 5 and 3'-methoxypuerarin 6) in their chromatograms. Semi-quantitative analysis showed that the contents of 1-3 in Pueraria lobata are about three, three, and five times higher than those of Pueraria thomsonii, respectively. The higher contents of isoflavonoids in Pueraria lobata were inferred to be responsible for its more potent antioxidant activity as compared with that of Pueraria thomsonii. The HPLC method developed in this study and chemical markers 1-6 can be used for the rapid identification and evaluation of Radix Puerariae herbs and their aqueous supplements, and the results of this investigation support the use of Pueraria lobata and Pueraria thomsonii in the clinic application and as dietary supplement, respectively.

AIM: Intima-media thickness (IMT) has been shown to be useful in the evaluation and monitoring of carotid artery atherosclerosis in patients at risk of cardiovascular events. In this study, we aimed to examine the IMT in patients with nasopharyngeal carcinoma (NPC) who received irradiation to the carotid arteries during radiotherapy, and compared them with a control group. MATERIALS AND METHODS: Fifty-one NPC patients (aged between 39 and 69 years) and a group of 51 age-and sex-matched controls were studied by ultrasound. The IMT at the far wall of the common carotid artery was measured three times and the average value taken in each subject. The IMT of both groups were compared. Risk factors for IMT thickness, including hypertension, smoking, hyperglycaemia, hypercholesterolaemia, history of cerebrovascular accidents and cardiovascular disease, were also studied. RESULTS: The mean carotid IMT of patients in the NPC group (2.2+/−1.5 mm) was statistically greater than that in normal controls (0.7+/−0.15 mm) (P < 0.05). There was no statistically significant difference between the IMT in the right and left common carotid arteries within each group of patients. CONCLUSION: The findings suggest that patients with irradiation have increased arterial IMT. As they are asymptomatic the clinical relevance is not clear. So, N. M. C. etal. (2002) Clinical Radiology57, 600–603.

Background. Epidemiological studies have suggested a link between chronic Helicobacter pylori infection and ischemic heart disease but the underlying mechanism remains elusive. We hypothesized that H. pylori-associated chronic gastritis causes impairment of absorption of vitamin cofactors that are essential in the metabolism of homocysteine and results in hyperhomocysteinemia. Materials and Methods. Forty-nine dyspeptic patients were studied. H. pylori infection was defined by rapid urease test and histology. Fasting serum homocysteine level, which was measured by a validated commercial fluorescence polarization immunoassay, was correlated with H. pylori infection statuses and gastric histology. H. pylori-infected patients were followed up for 24 weeks post eradication for changes in serum homocysteine concentration. Results. Univariate analyses showed that serum homocysteine level correlated with increasing age (p

Background Hyperhomocyst(e)inemia is associated with premature peripheral vascular, cerebrovascular, and coronary artery disease. Because homocysteine has been found to be damaging to endothelial cells in animal and cell culture studies, we evaluated the association between hyperhomocysteinemia and arterial endothelial dysfunction (a marker of early atherosclerosis) in asymptomatic adult subjects. Methods and Results Using high-resolution ultrasound, we measured endothelium-dependent flow-mediated dilation (EDD) and endothelium-independent nitroglycerin-induced dilation (GTN) of the brachial artery in 14 prospectively defined hyperhomocysteinemic (mean plasma homocysteine, 34.8±8.5 μmol/L), nonsmoking, healthy subjects aged 53±9 years and 14 control subjects with low plasma homocysteine levels (9.9±3.2 μmol/L). The two groups were well matched for age; sex; body mass index; blood pressure, blood cholesterol, folate, and vitamin B 12 levels; and vessel diameter. EDD was significantly lower in hyperhomocysteinemic subjects (6.5±1.7%) than in subjects with low homocysteine levels (10.8±1.7%) ( P P =.90). Multivariate analysis confirmed homocysteine level as the strongest predictor for impaired EDD, independent of age, sex, body mass index, or blood pressure, folate, vitamin B 12 , and cholesterol levels. Conclusions Hyperhomocysteinemia is an independent risk factor for arterial endothelial dysfunction in healthy middle-aged adults.

Agents which decrease gastric mucosal blood flow (GMBF) are postulated to have beneficial effects in arresting gastrointestinal bleeding in cirrhotic patients with portal hypertension. Our objective was to test the hypothesis that in a dose that significantly lowers wedged hepatic venous pressure (WHVP), a bolus injection of somatostatin will significantly decrease GMBF in patients with portal hypertensive gastropathy (PHG). In this placebo-controlled, double-blind, crossover study, 20 cirrhotic patients with PHG were randomly assigned to receive either somatostatin followed by placebo (Group A) or placebo followed by somatostatin (Group B). Wedged hepatic venous pressure was monitored. GMBF in the antrum and corpus was assessed by reflectance spectrophotometry. Indices of hemoglobin concentration (IHb) and indices of oxygen content (ISO2) were recorded. Nine patients were assigned to Group A, and 11 to Group B. Mild PHG was seen in 16 patients, and severe PHG in 4 patients. Baseline WHVP, IHb, and ISO2 were similar in both treatment groups. Wedged hepatic venous pressure (WHVP) was significantly lowered [median, 17.6%; interquartile range (-27.0,-12.6%); P = 0.0008] after a 250-microg bolus injection of somatostatin. This dose of somatostatin significantly reduced IHb both in the antrum [-10.2% (-23.4, 0.4%)] and in the corpus [-5.8% (-16.6, 5.6%)] compared to placebo (P = 0.02 and 0.04, respectively). Intravenous bolus injection of 250 microg somatostatin significantly reduces WHVP and GMBF in patients with PHG. Whether this ability to decrease the GMBF in PHG makes somatostatin an effective treatment in acute gastrointestinal bleeding in PHG deserves to be studied.

Background Left ventricular (LV) diastolic dysfunction is common in heart failure and is an important predictor of prognosis and mortality. Less attention has been paid to right ventricular (RV) diastolic function. In this study, we compared RV diastolic function in a large cohort of patients with heart failure (HF) with two groups: patients with pulmonary hypertension and normal LV function (the PHT group) and normal subjects. Methods and Results Transtricuspid and pulmonary artery flow were assessed by two-dimensional Doppler echocardiography at maximum inspiration and expiration in 185 subjects: 114 symptomatic HF patients (ejection fraction 40 mm Hg), and 40 normal subjects. A subset was matched for age and heart rate. The results showed a high prevalence of RV diastolic abnormalities: HF patients had lower tricuspid E-A ratios, lower peak E-wave velocity, and prolonged RV isovolumic relaxation time (all P P Conclusions RV diastolic function is frequently abnormal in HF patients, and this is not related to elevated pulmonary artery systolic pressure alone, although high pulmonary artery pressure by itself also is associated with impaired RV diastolic function. Assessment of the role of right ventricular diastolic function in determining the symptoms and prognosis of heart failure is warranted.

This randomized, double-blind, placebo-controlled study investigated the effects of nebivolol on blood pressure, plasma renin and vasoactive hormones (aldosterone and atrial natriuretic peptide) and the heart (arrhythmias, left ventricular mass and ejection fraction) in 32 hypertensive Chinese patients aged 25-65 years. Patients received either placebo (3 men, 11 women) or nebivolol 5 mg (5 men, 13 women) once daily for 4 weeks. In the nebivolol group, a significant decrease in blood pressures (P less than 0.001) and heart rate (P less than 0.01) was seen. Nebivolol therapy also suppressed plasma renin and aldosterone concentration (P less than 0.02) but increased plasma atrial natriuretic peptide levels (P less than 0.03). No significant changes in routine blood biochemistry were demonstrated in either group. There was a tendency for left ventricular mass to decline, and left ventricular ejection fraction to rise during nebivolol therapy, but these changes did not reach statistical significance. There was no significant change in ectopic activity. None of the 32 subjects had adverse experiences requiring cessation of therapy. In conclusion, nebivolol in a dose of 5 mg daily is effective and well tolerated in patients with essential hypertension. It suppresses plasma renin and aldosterone and stimulates plasma atrial natriuretic peptide.