The intrarenal blood pressure modulation system is differentially altered after renal denervation guided by different intensities of blood pressure responses.

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.

Selective renal denervation guided by renal nerve stimulation: mapping renal nerves for unmet clinical needs.

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.

Selective Renal Denervation Guided by Renal Nerve Stimulation in Canine.

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<0.001 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, P<0.001 and R=0.927, P<0.001). 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.

Blood pressure elevation response to radiofrequency energy delivery: one novel predictive marker to long-term success of renal denervation.

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 ±â€Š8.6 vs. 11.4 ±â€Š8.6 mmHg, 36.3 ±â€Š10.0 vs. 14.6 ±â€Š10.6 mmHg, 39.9 ±â€Š9.9 vs. 15.2 ±â€Š8.8 mmHg, and 40.0 ±â€Š8.7/13.5 ±â€Š5.8 mmHg (P < 0.001 for all) at 1, 3, 6, and 12 months, respectively. On multiple linear regression analysis, higher baseline office SBP, the presence of BP-elevation response to radiofrequency energy delivery, and especially larger number of BP-elevation response points, were independent predictors of SBP reduction at 6-month and 12-month follow-up. CONCLUSION: Baseline SBP and BP-elevation response during radiofrequency ablation, as well as larger positive response points to radiofrequency energy delivery could be an effective intraprocedural predictive markers to long-term procedural success of RDN.

Characteristics, Management, and Outcomes of Acute Heart Failure in the Emergency Department: A Multicenter Registry Study with 1-year Follow-up in a Chinese Cohort in Beijing.

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.

Renal Artery Vasodilation May Be An Indicator of Successful Sympathetic Nerve Damage During Renal Denervation Procedure.

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.

The effect of two different renal denervation strategies on blood pressure in resistant hypertension: Comparison of full-length versus proximal renal artery ablation.

BACKGROUND: 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. OBJECTIVE: 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). METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Atrial overexpression of angiotensin-converting enzyme 2 improves the canine rapid atrial pacing-induced structural and electrical remodeling. Fan, ACE2 improves atrial substrate remodeling.

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-ß1. 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.

Selective proximal renal denervation guided by autonomic responses evoked via high-frequency stimulation in a preclinical canine model.

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.

Radiofrequency ablation versus antiarrhythmic medication for treatment of ventricular premature beats from the right ventricular outflow tract: prospective randomized study.

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<0.001, log-rank test). In a Poisson generalized estimating equations (GEE) regression model, RFCA was associated with a greater decrease in the burden of VPBs (incidence rate ratio 0.105; 95% confidence intervals [0.104-0.105]; P<0.001) compared with AADs. In a liner GEE model, the left ventricular eject fraction had a tendency to increase after the treatment in both groups (coefficient, 0.584; 95% confidence intervals [0.467-0.702]; P<0.001). In a Cox proportional model, the QS morphology in lead I was the only predictor of VPB recurrence free for catheter ablation (hazards ratio, 0.154; 95% confidence intervals [0.044-0.543]; 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.

HDL-C, triglycerides and carotid IMT: a meta-analysis of 21,000 patients with automated edge detection IMT measurement.

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, the same software for IMT measurement by automatic edge detection on CCA in a plaque-free region, following the Mannheim consensus, and certification of all sonographers. Using the best view of the CCA, the sonographer had to confirm that the quality index was ≥ 0.5 on a measurement performed on 10-mm length. We used individual data meta-analysis to estimate the cross-sectional associations of lipids with CCA-IMT. RESULTS: Overall, 21,587 patients with complete information on lipids and CCA-IMT were available. Age- and sex-adjusted CCA-IMT differed by -7.8 µm (95% CI -9.1 to -6.5 µm, P < 0.001) per 1 SD higher HDL-C level. After further adjustment for other atherosclerosis risk factors, the relationship was attenuated, but remained significant (regression coefficient, -3.7 µm; P < 0.001). This was found regardless of LDL-C levels (P for heterogeneity = 0.70). After adjustment for age and sex, triglycerides were positively associated with CCA-IMT, 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.

Ten years' research on a cardiovascular tonic: a comprehensive approach-from quality control and mechanisms of action to clinical trial.

Objective. Mortality arising from cardiovascular pathologies remains one of the highest. Maintenance of cardiovascular health therefore remains a universal concern. Interventional therapies and medications have made impressive advances, but preventive measures would be of the same importance. Method. Ten years' search for a simple herbal formula has resulted in a two-herb combination, consisting of Salviae Miltiorrhizae Radix et Rhizoma and Puerariae Lobatae Radix. The formula has been studied extensively on cardiovascular biological platforms and then put on three clinical trials. Results. In the laboratory, the formula was found to have the biological effects of anti-inflammation, anti-oxidation, anti-foam cell formation on vascular endothelium, and vasodilation. Clinical trials using ultrasonic carotid intima thickness as a surrogate marker showed very significant benefits. No significant adverse effects were encountered. Conclusion. It is therefore recommended that the herbal formula could be used as an adjuvant therapy in cardiac patients under treatment or as a preventive agent among the susceptible.

Septal ablation induced by transthoracic high-intensity focused ultrasound in canines.

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.

Effect of nifedipine versus telmisartan on prevention of atrial fibrillation recurrence in hypertensive patients.

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 <130/80 mm Hg. Clinic BP, ECG, Holter monitoring, and echocardiography were followed up for 2 years. The primary end point was the incidence of overall and persistent AF recurrence. During follow-up, there was no statistical difference in the rate of patients lowering to target BP between both groups, whereas nifedipine group had slightly better BP control but similar heart rate control at 24 months. The incidence of AF recurrence was similar in both groups (nifedipine versus telmisartan: 58.7% versus 55.4%; 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.

Renin-angiotensin system-related gene polymorphisms are associated with risk of atrial fibrillation.

BACKGROUND: Renin-angiotensin system (RAS) plays an important role in atrial fibrillation (AF). Recently, many publications have studied the associations between RAS-related gene polymorphisms and AF risk, with inconsistent results. To further evaluate these associations, we carried out a meta-analysis of all the published studies. METHODS: Electronic searches were used to identify published studies evaluating RAS-related gene polymorphisms and AF risk before April 2009. We extracted data sets and performed meta-analysis with standardized methods. RESULTS: A meta-analysis of 12 publications on association between angiotensin-converting enzyme (ACE insertion/deletion) and AF risk was performed. The pooled relative risk (RR) of allele D versus I was 1.19 (95% CI, 1.07-1.32, P < .01), pooled RR of DD and DI versus II was 1.31(95% CI, 1.09-1.58, P < .01) and 1.06 (95% CI, 0.97-1.16, P = .22) respectively. In subgroup analysis, a stronger association was found in hypertensive population, Western ethnic, lone AF, and patients aged > or = 65 years, with pooled RR of DD versus II was 1.74 (95% CI, 1.39-2.18, P < .01), 1.27 (95% CI, 1.01-1.59, P = .04), 1.53 (95% CI, 1.31-1.78, P < .01) and 1.38 (95% CI, 1.10-1.73, P < .01), respectively. CONCLUSION: The results suggested an association between ACE insertion/deletion and AF risk. More large-scale studies are warranted to document the conclusive evidence of the effects of the RAS genes on AF risk.

Carotid intima media thickness predicts cardiovascular diseases in Chinese predialysis patients with chronic kidney disease.

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.

Carotid artery intima media thickness, plaque and Framingham cardiovascular score in Asia, Africa/Middle East and Latin America: the PARC-AALA study.

OBJECTIVE: The PARC-AALA (Paroi artérielle 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Prospective randomized study comparing amiodarone vs. amiodarone plus losartan vs. amiodarone plus perindopril for the prevention of atrial fibrillation recurrence in patients with lone paroxysmal atrial fibrillation.

AIMS: 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. METHODS AND RESULTS: 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, P < 0.001 for both comparisons). CONCLUSION: 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.

Chinese herbs Danshen and Gegen modulate key early atherogenic events in vitro.

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<0.001 by ANOVA). By contrast, the herbs also induced an increase in ICAM-1 expression (p<0.001) and monocyte adhesion at higher concentrations (p<0.05). In conclusion, treatment of cells with this preparation of Danshen and Gegen, a commonly used Chinese health supplement, results in a dose-related suppression of AcLDL uptake by human macrophages, and an increase in the level of ICAM-1 expression and adhesion of monocytes to endothelial cells. These herbs therefore show the ability to modulate key early events in atherosclerosis.