Sun Ningling

Efficacy and tolerability of long-acting nifedipine GITS/OROS monotherapy or combination therapy in hypertensive patients: results of a 12-week international, prospective, multicentre, observational study.

AbstractBackground: Achieving the maximum reduction in cardiovascular morbidity and mortality is the primary goal of blood pressure (BP) control. Current guidelines recommend several antihypertensive classes as first-line therapy for this purpose but the decision on which agent/s to use will likely be based upon the treating physician’s clinical experience. Observational studies provide a useful way of ascertaining the efficacy and tolerability of an anti-hypertensive in a real-life clinical setting. Objective: The aim of this observational study was to determine the efficacy, tolerability and physician/patient satisfaction with long-acting nifedipine (gastrointestinal therapeutic system [GITS]/osmotic-controlled release oral delivery system [OROS]) in a large multinational cohort of hypertensive patients. Methods: This observational study was conducted in adults (aged ≥18 years) with previously untreated or treated hypertension. The decision to prescribe nifedipine 30 or 60 mg once daily was made by the treating physician. Patients then attended up to three clinic visits any time over a 12-week period when medication could be up- or down-titrated or switched. The mean reduction in systolic BP (SBP)/diastolic BP (DBP) from first visit and whether target BP (<140/<90 mmHg or <130/<80 mmHg [for patients with diabetes mellitus]) had been achieved were recorded at the final visit and stratified according to hypertension grade and presence of cardiovascular risk factors. Subjective assessment of efficacy was reported by physicians and patients. All adverse events and their possible relationship to study drug were recorded. All assessments were performed on patients who received at least one dose of nifedipine GITS/OROS. Results: A total of 14 344 patients received nifedipine GITS/OROS treatment (58.7% male; 77.7% non-diabetic; mean age 57.5 years); 14266 had at least one follow-up visit over a mean 10.2-week period, and 8000 patients had three visits over a mean 12-week period. Initially, 12 826 (89.4%) patients received nifedipine 30 mg, and 6912 patients (48.2%) overall received concomitant antihypertensive agents. The overall mean reduction in SBP/DBP was −27.7/−14.1 mmHg; BP reduction was linked to hypertension grade, age, the presence of five or more cardiovascular risk factors, and prior treatment. Target BP was achieved in 2485/7432 patients (33.4%) receiving nifedipine GITS/OROS monotherapy and in 1751/6912 (25.3%) receiving combination therapy (i.e. GITS/OROS plus any other antihypertensive agent). Non-diabetic patients with moderate (n = 3413) and high (n= 1138) risk reached their target BP goal in 62.5% and 54.2% of cases, respectively; the corresponding values in diabetic patients (moderate-added risk n = 8; high-added risk n=684) were 75.0% and 54.8%, respectively. A total of 229 patients (1.6%) reported experiencing 286 adverse events. Physician/patient satisfaction with treatment was high. Conclusion: Long-acting nifedipine GITS/OROS, alone or in combination with other antihypertensive agents, provides effective and well tolerated treatment of hypertension in a broad spectrum of patients routinely seen in day-to-day clinical practice.

Efficacy and safety of nifedipine GITS in asians with hypertension : Results of a post-marketing surveillance study in China

AbstractObjective: This post-marketing surveillance study assessed the efficacy, safety and tolerability of treatment with nifedipine GITS (gastrointestinal therapeutic system) in hypertensive patients with different risk profiles under normal daily practice conditions in China. Methods: A total of 7395 patients were included in 564 outpatient clinics. Patients received 30mg or 60mg of nifedipine GITS, which could be up- and down-titrated if necessary. Efficacy, safety and tolerability data were collected at up to three follow-up visits. Patient documentation was completed using standardised and barcoded case report forms. Descriptive and explorative analyses of the data were performed. Results: At endpoint, 93% of patients were receiving 30mg of nifedipine GITS and 7% were taking 60mg of nifedipine GITS. The mean observation period was 9 ± 7 weeks. At endpoint, the mean BP reduction was 27.7/14.8mm Hg; 43% of patients had a systolic BP <140mm Hg, and 58% had a diastolic BP <90mm Hg. BP control as recommended by international guidelines was achieved in 43.5% of all patients. A total of 3163 patients (42.8%) received additional antihypertensive medication, of which ACE inhibitors were most commonly used (40.7%), followed by β-adrenoceptor antagonists (25.8%).Twenty-nine patients (0.4%) experienced a total of 39 adverse events. Subjective physicians’ assessments of efficacy, tolerability and patient acceptance of nifedipine GITS treatment returned ratings of ‘very good’ and ‘good’ in 91–95% of each category. Conclusions: Nifedipine GITS proved to be effective and well tolerated for the treatment of hypertension in 7395 Chinese patients under normal daily practice conditions. The results confirm the findings and experience of previously performed clinical studies.

485 PLASMA RENIN ACTIVITY LEVELS AND THE ASSOCIATION WITH BLOOD PRESSURE AND URINARY SALT EXCRETION IN PATIENTS WITH ESSENTIAL HYPERTENSION

Objectives: To investigate the distribution of plasma renin activity (PRA) and explore the association with blood pressure and urinary salt excretion in patients with essential hypertension. Methods: 489 patients with essential hypertension were recruited, patients were classified as follows: low renin, <0.20ng/ml/h (20% of the sample); medium renin, 0.20 to 2.06 ng/ml/h(60%); or high renin, >2.06ng/ml/h (20%). Recumbent plasma renin, 24 h ambulatory blood pressure monitoring (ABPM), 24 h urinary salt excretion were measured and analysed. Results: 1) Compared with the other groups, the low renin patients were more likely to be female, and slightly older (P < 0.01). 2) Low renin patients had higher non-dippers (P < 0.01). 3) 24 h blood pressure (contains mean SBP, mean DBP and MAP), 24 h urinary salt excretion were all negative correlated with the plasma renin activity (all P < 0.01). Figure. No caption available. Conclusion: Women patients and older patients were more likely to have lower PRA level. The circadian rhythm of blood pressure changes more significantly in low renin patients. In addition, low renin patients had higher blood pressure and 24 h urinary salt excretion.

1107 RELATIONSHIP BETWEEN 24-HOUR URINARY SODIUM POTASSIUM EXCRETION AND BLOOD PRESSURE AND ARTERIAL STIFFNESS IN HYPERTENSION PATIENTS

Objective: To investigate the relationship between 24-hour urinary sodium potassium excretion and blood pressure and arterial stiffness in hypertension patients. Methods: 224hypertension patients who didn’t take any antihypertensive medicine were randomly recruited. 24-hour urinary sodium (Na), potassium (K) and sodium potassium ratio (Na/K) were measured and calculated through 24-hour urine specimens. According to the results of 24-hour urinary sodium, patients were divided into three groups, group A (urinary sodium ⩽ 100mmol/24 h), group B (urinary sodium >100 and ⩽200mmol/24 h), and group C (urinary sodium >200mmol/24 h). All the subjects underwent 24 hours ambulatory blood pressure monitoring and brachial-ankle pulse wave velocity (baPWV) examination. Results: The urine Na excretion of group A, B, and C was(84.9 ± 12.7)mmol/24 h, (147.0 ± 26.7)mmol/24 h, and(256.1 ± 42.6) mmol/24 h respectively, corresponding to daily salt intake 4.8 g, 8.46 g, 15.14 g. Group C who had the highest salt intake was significantly higher than group A in 24 hours, day, and night blood pressure. Multiple linear regression revealed urinary Na was independently associated with 24 hours, day, and night blood pressure. The baPWV of group A,B,C was (1621.6 ± 288.3)cm/s,(1645.7 ± 301.0)cm/s, and (1741.9 ± 307.0)cm/s respectively, with group C higher than group A and B (P = 0.032,P = 0.046). Multiple linear regression indicated urinary Na and Na/K were independently associated with baPWV (P<0.05), while urinary K was not (Table1). Table 1 Multiple linear regression for association between urinary electrolytes and baPWV Table. No title available. Conclusion: Not only urinary sodium and sodium potassium ratio are associated with blood pressure, but also are independently associated baPWV. Moreover, this relationship between urinary electrolytes and arterial stiffness is independent of blood pressure.

CALCIUM ANTAGONIST COMBINED WITH STATIN THERAPY ON PLASMA INFLAMMATORY MEDIATORS IN PATIENTS WITH HYPERTENSION AND CAROTID ATHEROSCLEROSIS

Objectives To investigate the effect of calcium antagonists (CCB) and statins on carotid plaques and plasma inflammatory mediators, so as to learn the possible mechanism of their anti-atherogenic effect. Methods This is a cross-sectional study. Laboratory tests and carotid ultrasound examination were performed in patients with essential hypertension. All patients were divided into three groups, who were treated with CCB or statins monotherapy or CCB and statins combination therapy respectively. Laboratory parameters included plasma low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), high-sensitivity C-reactive protein (hsCRP), the medulla metalloproteinase 9 (MMP9) and the lipoprotein-associated phospholipase A2 (Lp-PLA2). Correlation analysis was performed between the three groups. Results Baseline conditions Total 150 patients with essential hypertension were enrolled in, among them 78 (52.0%) were male and 72 (48.0%)were female. Thirty-nine patients complicated with diabetes mellitus, accounting for 26.0%. Thirty-six patients complicated with hyperlipidaemia, accounting for 16.0%. The mean age was 59.06 years and the mean blood pressure was 140.21/84.73 mm Hg. Comparison Analysis of Plasma Lipids and Inflammatory Parameters Level Compared with patients who were not treated with statins, patients treated with statins had lower total cholesterol and LDL-C levels. The plasma levels of Lp-PLA2, MMP9 and hsCRP were similar in patients treated with different drugs, the difference was not statistically significant. Correlation Analysis between Inflammatory Status and Carotid Atherosclerosis Pearman correlation analysis showed that Lp-PLA2 content was linearly correlated with hsCRP levels, the correlation coefficient was 0.282, p=0.001. But MMP9 content was not correlated with hsCRP levels, the correlation coefficient was 0.107, p=0.213. Compared with patients without carotid plaques, patients with soft carotid plaques had higher plasma content of hsCRP and Lp-PLA2, the difference was statistically significant showed by ANOVA analysis. MMP9 content was relatively lower in patients with soft carotid plaque, but the difference was not statistically significant. Conclusions 1. Plasma LP- PLA2 content, which was positively correlated with plasma hsCRP level, can reflect the bodys inflammatory state better than that of MMP9. 2. Patients with soft carotid plaques had higher plasma level of LP-PLA2, which suggested that the LP-PLA2 level can reflect the stability of plaques. 3. The difference of inflammatory parameters in different groups was not statistically significant.

e0352 Efficacy and safety of aliskiren in chinese patients with mild or moderate essential hypertension

To assess the antihypertensive efficacy and safety of aliskiren compared with ramipril in Chinese patients with mild or moderate essential hypertension. Methods This is a double-blind randomised, multicenter, parallel group, active-controlled study. Following washout and single-blind placebo run-in period, 1147 patients with essential hypertension (mean sitting diastolic blood pressure [msDBP] ≥95 and 110 mm Hg) were randomised to receive either aliskiren 300 mg (n=288), 150 mg (n=284), 75mg (n=289) or ramipril 5 mg (n=286) for 8 weeks. Efficacy and safety were assessed at Week 2, 4 and 8 in treatment duration. Results 994 (86.7%) completed the study. At week 8, aliskiren therapy produced greater mean blood pressure reductions compared with ramipril therapy. All aliskiren dose groups were statistically non-inferior (p<0.0001) to ramipril group in reducing msDBP. Aliskiren 300 mg group also showed statistically significantly superior reductions in msDBP and msSBP compared to ramipril 5 mg group (p=0.0002 and p=0.0073, respectively). Blood pressure control rates (target blood pressure 90 mm Hg) were higher for aliskiren groups (300 mg, 52.46%; 150 mg, 49.82% and 75 mg, 45.91%) compared to ramipril (5 mg, 44.44%); and aliskiren 300 mg group was significantly superior to ramipri l5 mg group (p=0.0359). The overall incidence of adverse effects (AEs) was similar among the treatment groups. The ramipril group had at least a four times higher incidence of cough (6.0%) compared with the three aliskiren treatments (ranging from 0.4% to 1.4%). Conclusion Aliskiren was well tolerated, and superior or non-inferior to ramipril in lowering BP in Chinese patients with essential hypertension.

e0086 Sinoaortic denervation disrupted the circadian rhythm of the oscillation of molecular clock and activity of RAS in cardiovascular

Objective To observe the profile of blood pressure in sinoaortic denervated (SAD) rats and investigate the expression of clock genes per2, BMAL1, clock output gene DBP, AT1 and PCNA in heart and thoracic aortic of SD and SAD rats, therefore to probe into the influences of the impairment of arterial baroreflex (ABR) on molecular clock and the activity of RAS in peripheral cardiovascular and their interaction. Methods 72 male Sprague-Dawley rats underwent SAD or sham operation at the age of 12 weeks. 24-h BP and BPV were measured in conscious and unrestrained rats 4 weeks after operation. Rats were housed in a 12 h light/12 h dark cycle (LD12:12) for at least 10 days. Heart and thoracic aorta were taken every 4 h throughout the day to investigate mRNA expression of clock genes (per2, BMAL1), clock output gene DBP, AT1 receptors and PCNA by RT-real time PCR and examine the abundance of Per2 protein in heart and vessel tissue by Western Blotting respectively. Results Compared with sham-operated rats, SBPV and DBPV over 24 h of SAD rats were enlarged (p<0.01). Clock genes (Per2 and BMAL1), clock output gene DBP, AT1 receptors and PCNA oscillated synchronously both in heart and vascular of SAD and sham-operated rats under light-dark cycle. After sinoaortic denervation, the total mRNA abundance of Per2 decreased significantly both in heart and aorta (p<0.05 or p<0.01). BMAL1, DBP, AT1 and PCNA in heart were up-regulated significantly (p<0.05 or p<0.01), while that of these genes in aortic remained unchanged. More importantly, after operation, the circadian rhythm of mRNA expression of all the above genes both in heart and aortic changed significantly, showing an abnormal expression level of these genes by a rough normal diurnal and nocturnal pattern in heart, or by diurnal oscillation patterns in aorta. Consistent with Per2 mRNA expression, its protein abundance in heart and aortic decreased simultaneously, and the circadian rhythm was also disturbed. Moreover, all the amplitude of the mentioned genes were significantly weakened or enlarged in SAD rats. Conclusions The impairment of arterial baroreflex leads to the abnormality in the circadian rhythm of the molecular clocks and the RAS activity was mediated by AT1 in peripheral cardiovascular. The abnormality of the total RAS activity, circadian rhythm of RAS activity in peripheral tissues, disorders of molecular clock as well as the abnormality of RAS activity may all contribute to the upset of molecular clock in peripheral cardiovascular following sinoaortic denervation. Therefore these abnormalities promote dysfunction of BP regulation and proliferation and remodelling of cardiovascular in SAD rats.