Tafolecimab in Chinese Patients With Hypercholesterolemia (CREDIT-4): A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial.

Background: Tafolecimab is a novel fully human proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody, developed for the treatment of hypercholesterolemia. Objectives: The purpose of this study was to assess the efficacy and safety of tafolecimab in Chinese patients at high or very high cardiovascular risk with hypercholesterolemia. Methods: Patients with diagnoses of heterozygous familial hypercholesterolemia (HeFH) by the Simon Broome criteria or at high or very high cardiovascular risk with nonfamilial hypercholesterolemia, with screening low-density lipoprotein cholesterol (LDL-C) level ≥1.8 mmol/L, were randomized 2:1 to receive tafolecimab or placebo 450 mg every 4 weeks (Q4W) in the 12-week double-blind treatment period. The primary endpoint was the percent change from baseline to week 12 in LDL-C levels. Results: A total of 303 patients were enrolled and received at least 1 dose of tafolecimab (n = 205) or placebo (n = 98). The least squares mean percent change in LDL-C level from baseline to week 12 was -68.9% (SE 1.4%) in the tafolecimab group and -5.8% (1.8%) in the placebo group (difference: -63.0%; [95% CI: -66.5% to -59.6%]; P < 0.0001). More patients treated with tafolecimab achieved ≥50% LDL-C reductions, LDL-C <1.8 mmol/L, and LDL-C <1.4 mmol/L at week 12 than did those in the placebo group (all P < 0.0001). Furthermore, tafolecimab markedly reduced non-HDL-C, apolipoprotein B, and lipoprotein(a) levels. During the double-blind treatment period, the most commonly reported adverse events included urinary tract infection (5.9% with tafolecimab vs 4.1% with placebo) and hyperuricemia (3.4% vs 4.1%). Conclusions: Tafolecimab was safe and showed robust lipid-lowering efficacy in Chinese patients at high or very high cardiovascular risk with hypercholesterolemia. (A Study of IBI306 in Participants With Hypercholesterolemia; NCT04709536).

Association between basal septal hypertrophy and left ventricular geometry in a community population.

BACKGROUND: Left ventricular (LV) geometry is closely associated with cardiovascular disease; however, few studies have evaluated the relationship between basal septal hypertrophy (BSH) and LV geometry. In this study, we examined the relationship between BSH and LV geometry in a Beijing community population. METHODS: The clinical and echocardiographic data of 1032 participants from a community in Beijing were analyzed. BSH was defined as a basal interventricular septal thickness ≥ 14 mm and a basal septal thickness/mid-septal thickness ≥ 1.3. On the basis of their echocardiographic characteristics, patients were described as having a normal geometry, concentric remodeling, concentric hypertrophy, or eccentric hypertrophy. Multivariable logistic regression was used to analyze the relationship between BSH, LV mass index (LVMI), and relative wall thickness (RWT). RESULTS: The prevalence of BSH was 7.4% (95% confidence interval [CI] 5.8-9.0%). Basal and middle interventricular septal thickness, LV posterior wall thickness, and RWT were greater, while LVMI and LV end-diastolic dimension were lower in the BSH group than in the non-BSH group (p < 0.05). The BSH group accounted for the highest proportion of patients with concentric remodeling. A multivariable regression analysis showed that BSH increased by 3.99-times (odds ratio [OR] 3.99, 95% CI 2.05-7.78, p < 0.01) when RWT was > 0.42, but not when LVMI increased (OR 0.16, 95% CI 0.02-1.19, p = 0.07). There were no interactions between BSH and age, body mass index, sex, diabetes mellitus, coronary heart disease, stroke, and smoking in relation to an RWT > 0.42. CONCLUSION: BSH was independently associated with an RWT > 0.42.

Reduced left atrial contractile strain with speckle tracking analysis predicts abnormal plasma NTproBNP in an asymptomatic community population.

BACKGROUND: The left atrium (LA) is closely related to left ventricular diastolic function. Two-dimensional speckle tracking strain and strain rate (SR) imaging has been applied in the study of LA function. We intended to explore the relationship between global LA deformation parameters and plasma NTproBNP levels in asymptomatic community residents with normal ejection fraction and normal LA volume. METHODS: A cross-sectional sample of Beijing residents underwent comprehensive Doppler echocardiography and medical record review in 2009. Global LA longitudinal strain and SR indexes were obtained in the apical four-chamber view. LA stiffness index (LASI) was calculated as the ratio of early diastolic velocity of transmitral flow/early diastolic mitral annular motion velocity (E/E') to LA reservoir strain. RESULTS: A total of 620 individuals (mean age = 65.8 years, left ventricular ejection fraction = 70.8%, LA volume index = 17.9 ml/m2) were investigated in our study. 117 individuals had increased plasma NTproBNP (≥ 125 pg/ml). LA reservoir and contractile function by LA strain and SR indexes were significantly reduced in the abnormal NTproBNP group compared with the normal NTproBNP group. Multiple regression analysis indicated that LA contractile strain was a negative predictor of plasma NTproBNP in addition to indexed LA volume and E/E'. LASI was higher in the abnormal NTproBNP group and was significantly correlated with NTproBNP (r = 0.342, P < 0.001). The area under ROC analysis for LASI in predicting elevated plasma NTproBNP was 0.690, similar with LA contractile strain, E/E' and LAVI. The cut-off value of LASI was 0.612. CONCLUSIONS: LA reservoir and contractile functions demonstrated by LA strain and SR were significantly impaired in the community-based population with increased plasma NTproBNP levels. LA contractile strain adds incremental information in predicting abnormal NTproBNP levels. As a single index, LASI showed similar diagnostic value with LAVI and E/E' in predicting abnormal NTproBNP.

Efficacy and safety of hybutimibe in combination with atorvastatin for treatment of hypercholesteremia among patients with atherosclerotic cardiovascular disease risk equivalent: A multicenter, randomized, double-blinded phase III study.

Background: To evaluate the safety and efficacy of hybutimibe plus atorvastatin for lipid control in hypercholesterolemia patients with atherosclerotic cardiovascular disease risk equivalent. Methods: In this double-blind phase III study, we 1:1 randomly assigned 255 hypercholesterolemia patients with atherosclerotic cardiovascular disease to receive hybutimibe plus atorvastatin or placebo plus atorvastatin. The primary endpoint was the rate of change of plasma low-density lipoprotein-cholesterol (LDL-C) level at 12 weeks from baseline. The secondary endpoints were plasma total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C), non-HDL-C, apoprotein (Apo) B, and 2-, 4-, 8-, and 12-week Apo A1 levels change rate and rates of change of plasma LDL-C levels at 2, 4, and 8 weeks from baseline. Results: From April 2016 to January 2018, 128 in the hybutimibe plus atorvastatin group and 125 in the atorvastatin group were included in modified intention-to-treat (mITT) analysis. After 12 weeks of treatment, LDL-C level changed from 2.61 mmol/L (±0.30) at baseline to 2.18 mmol/L (±0.45) in the hybutimibe plus atorvastatin group and from 2.58 (±0.31) mmol/L to 2.40 (± 0.46) mmol/L in the atorvastatin group (P < 0.0001), in mITT. The change rate in the hybutimibe plus atorvastatin group was significantly higher than that in the atorvastatin group (P < 0.0001); the estimated mean rates of change were -16.39 (95% confidence interval: -19.04, -13.74) and -6.75 (-9.48, -4.02), respectively. Consistently, in per-protocol set (PPS) analysis, the rate of change of LDL-C in the hybutimibe plus atorvastatin group was significantly higher than that in atorvastatin group. Significant decreases in the change rates of non-HDL-C, TC, and Apo B at 2, 4, 8, and 12 weeks (all P < 0.05) were observed for hybutimibe plus atorvastatin, while the differences were not significant for HDL-C, TG, and Apo-A1 (all P > 0.05). During the study period, no additional side effects were reported. Conclusions: Hybutimibe combined with atorvastatin resulted in significant improvements in LDL-C, non-HDL-C, TC, and Apo B compared with atorvastatin alone. The safety and tolerability were also acceptable, although additional benefits of hybutimibe plus atorvastatin were not observed compared with atorvastatin alone in HDL-C, TG, and Apo-A1.

Left atrial phasic function remodeling during its enlargement: a two-dimensional speckle-tracking echocardiography study.

BACKGROUND: Left atrial (LA) size is often used as a surrogate marker of LA function in clinical practice, with larger atrial thought to represent a "dysfunctioning" atrium, since there is no accepted 'gold' standard to evaluate LA function. The exact relationship between LA size and phasic function, and whether LA dysfunction occur before LA enlargement (LAE) may be of clinical interest while have not been fully studied. Two-dimensional speckle-tracking echocardiography (2D STE) was showed a promising method in measuring LA physical deformation. MATERIALS AND METHODS: A community cohort of 715 subjects at cardiovascular disease high risk accepted comprehensive echocardiography. LA longitudinal phasic strain Sa (absolute peak strain during atrial contraction), Se (peak strain at early diastole) and Stot (total atrial strain = Sa + Se), representing contractile, conduit, and reservoir function respectively, were measured using off-line 2D STE software in apical 4 chamber view, and data were compared among groups at different LA size and between subgroups in normal LA size with and without hypertension (HT). RESULTS: With LAE (from normal size, mild, moderate to severe LAE), the Stot (21.74 ± 5.97, 20.75 ± 4.99, 20.49 ± 5.27, 17.75 ± 4.71, respectively, ANOVA P = 0.003) and Sa (11.84 ± 3.92, 11.00 ± 3.29, 10.11 ± 2.57, 8.55 ± 2.88, respectively, ANOVA P < 0.001) reduced while Se had no change. Stot of Severe LAE group was significantly lower than that of Normal LA size group (P = 0.002). Sa of the three LAE groups were all significantly lower than that of Normal LA size group (P = 0.024, P = 0.002, P < 0.001, respectively). In normal sized LA subgroups, Stot (21.35 ± 5.91 vs. 23.01 ± 6.02, P = 0.008) and Se (9.51 ± 4.41 vs. 11.17 ± 4.89, P < 0.001) reduced in subjects with HT comparing with those without. CONCLUSION: LA phasic function remodeling occurs before LAE and continues with LAE, with reservoir, conduit and contractile function being affected unparalleled.

Treatment of Chinese Patients with Hypertriglyceridemia with a Pharmaceutical-Grade Preparation of Highly Purified Omega-3 Polyunsaturated Fatty Acid Ethyl Esters: Main Results of a Randomized, Double-Blind, Controlled Trial.

INTRODUCTION: The lipid-modifying potential of omega-3 polyunsaturated fatty acids in Chinese patients is under-researched. We conducted a multicenter, randomized, placebo-controlled, double-blind, parallel-group study of twice-daily treatment with OMACOR (OM3EE), a prescription-only formulation of highly purified ethyl esters of omega-3 polyunsaturated fatty acids in Chinese adult patients (≥18 years) who had elevated baseline fasting serum triglycerides (TG). METHODS: Patients were stratified according to the severity of their hypertriglyceridemia (severe HTG, with baseline TG ≥500 and <1000 mg/dL or moderate HTG, with baseline TG >200 and <500 mg/dL) or use of statins. Patients randomized to OM3EE therapy received 2 g/day for 4 weeks, then 4 g/day for 8 weeks. The primary efficacy endpoint was the percentage change in fasting serum TG between baseline and the end of treatment in patients with severe HTG. The study was concluded after a planned interim analysis demonstrated a significant TG-lowering effect of OM3EE in that contingent (p=0.0019). RESULTS: The mean TG end-of-treatment effect of OM3EE was -29.46% (standard deviation 40.60%) in the severe HTG contingent compared with +0.26% (standard deviation 54.68%) in the placebo group. Corresponding changes were -12.12% and -23.25% in the moderate HTG and combination cohorts (vs +55.45% and +6.24% in relevant placebo groups). A dose-dependent reduction in TG was evident in all patient contingents. Safety and tolerability of OM3EE were in line with previous experience. DISCUSSION: These data indicate that OMACOR therapy at a dose of 2-4 g/day is an effective treatment for Chinese patients with raised TG levels and is well tolerated.

Association of epicardial fat thickness with left ventricular diastolic function parameters in a community population.

BACKGROUND: We examined the relationship between epicardial fat thickness (EFT) measured by echocardiography and left ventricular diastolic function parameters in a Beijing community population. METHODS: We included 1004 participants in this study. Echocardiographic parameters including E and A peak velocity, the early diastolic velocities (e') of the septal and lateral mitral annulus using tissue doppler imaging, E/e', and EFT were measured. EFT1 was measured perpendicularly on the right ventricular free wall at end diastole in the extension line of the aortic root. EFT2 was the maximum thickness measured perpendicularly on the right ventricular free wall at end diastole. Multivariable linear regression was used to analyze the relationship between EFT and the mean e' and E/e'. RESULTS: The mean age of the participants was 63.91 ± 9.02 years, and 51.4% were men. EFT1 and EFT2 were negatively correlated with lateral e', septal e', and mean e' (p < 0.05), and the correlation coefficient for EFT1 and EFT2 and mean e' was - 0.138 and - 0.180, respectively. EFT1 and EFT2 were positively correlated with lateral E/e', septal E/e', and mean E/e' (p < 0.05), and the correlation coefficient for EFT1 and EFT2 and mean e' was 0.100 and 0.090, respectively. Multivariable egression analysis showed that EFT2 was independently and negatively associated with e' mean (ß = - 0.078 [95% confidence interval = - 0.143, - 0.012, p = 0.020]). There were no interactions between EFT2 and any covariates, including age or heart groups, sex, BMI, or presence of hypertension, diabetes, or coronary heart disease, in relation to left ventricular diastolic dysfunction. CONCLUSIONS: EFT2 was negatively and independently associated with e' mean, which suggests that more attention to this type of adipose fat is required for cardiovascular disease therapy.

Relation between Blood Pressure Variability within a Single Visit and Stroke.

Blood pressure variability (BPV) has been identified as an important risk factor for cardiovascular events. The white coat effect (WCE), which is measured as the first systolic blood pressure (SBP) measurement minus the mean of the second and third measurements, is a BPV indicator within a single visit. In total, 2,972 participants who had three measurements of BP within a single visit were included. The participants were divided into three groups based on their WCE percentiles: Group 1 (WCE2.5-97.5, 2.5-97.5th percentiles of WCE), Group 2 (WCE2.5, 0-2.4th percentiles of WCE), and Group 3 (WCE97.5, 97.6-100th percentiles of WCE). A multiple logistic regression model was used to analyze the relationship between WCE and stroke after adjusting for cardiovascular disease risk factors. Compared with the WCE2.5-97.5 group, the OR for stroke in the WCE2.5 group was 2.78 (95% CI: 1.22, 6.36, p=0.015). After adjusting for cardiovascular factors, OR increased to 3.12 (95% CI: 1.22, 7.96, p=0.017). The OR of WCE for stroke was 0.93 (95%CI: 0.87, 0.99, p=0.036). BPV within a single visit is associated with stroke. The value and direction of the change may be important as well.

A Potential Long-Acting LDL-Cholesterol-Lowering PCSK9 Monoclonal Antibody: Randomized, Placebo-Controlled Phase 1 Studies.

The aim of the studies was to evaluate the safety, tolerability, and efficacy of tafolecimab, a novel proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody, in Chinese healthy volunteers and patients with hypercholesterolemia. Fifty-eight healthy volunteers (phase 1a) were randomized to receive a single dose of 25, 75, 150, 300, 450, or 600 mg tafolecimab subcutaneously, 75 or 450 mg intravenously, or placebo. Sixty patients with hypercholesterolemia (phase 1b) were randomized to receive 75 or 140 mg tafolecimab every 2 weeks, 300 or 420 mg every 4 weeks, or 450 or 600 mg every 6 weeks subcutaneously or placebo for 12 weeks. Tafolecimab was well tolerated. Adverse events in both studies were either mild or moderate. In the phase 1a study, a single dose of tafolecimab reduced low-density lipoprotein-cholesterol (LDL-C) levels up to 72% in healthy volunteers. In the phase 1b study, tafolecimab reduced LDL-C levels up to 71.6% and by more than 50% consistently to week 12 for all tafolecimab dose regimens. Tafolecimab is a safe PCSK9 monoclonal antibody with significant and potential long-acting LDL-C-lowering effect. (Single Ascending Dose Study of PCSK-9 Inhibitor [IBI306] in Healthy Subjects; NCT03366688) (Multiple Ascending Dose Study of PCSK-9 Inhibitor [IBI306] in Chinese Patients With Hypercholesterolemia; NCT03815812).

Association between inter-arm difference in SBP and central blood pressure in a Beijing community cohort.

OBJECTIVE: The inter-arm SBP difference (IASBPD) can serve as a predictor of cardiovascular disease (CVD). In this study, we aimed to determine the relationship between IASBPD and central blood pressure (CBP). METHODS: The study cohort comprised of 7842 eligible individuals. Their BPs were assessed simultaneously in both arms using an Omron BP-203RPEIII vascular profiler, and the IASBPD was measured as the absolute difference in these values (absolute value of left minus right). The CBP was noninvasively measured using an Omron HEM-9000AI device. Multivariate regression analysis was used to assess the association between the central SBP (cSBP) and the IASBPD. RESULTS: An IASBPD of ≥10 mmHg was positively associated with the cSBP (ß = 2.26; 95% confidence interval, 1.04-3.48; P < 0.001). The interaction test showed no significant interactions between the IASBPD and any of the assessed covariates (age group; sex; BMI; smoking status; heart rate group; the presence of hypertension, diabetes, or CVD; and antihypertensive drug use) when the cSBP was used as the outcome in the subgroup analysis. CONCLUSION: The mechanism underlying the ability of the IASBPD to predict CVD may partly involve an increase in the CBP.

Efficacy and Safety of PCSK9 Monoclonal Antibodies in Patients at High Cardiovascular Risk: An Updated Systematic Review and Meta-Analysis of 32 Randomized Controlled Trials.

INTRODUCTION: Proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies are powerful lipid-lowering drugs which have been shown to improve clinical endpoints in patients with hypercholesterolemia. However, it is not clear how effective PCSK9 monoclonal antibodies are for patients at high cardiovascular risk. Also, whether the effectiveness of PCSK9 monoclonal antibodies varies between different drug types, dosages, race, and indications for PCSK9 monoclonal antibodies remains unclear. Therefore, we used recently published studies to systematically evaluate the efficacy and safety of PCSK9 monoclonal antibodies by analyzing the lipid profiles, adverse events, and clinical endpoints in patients at high cardiovascular risk. METHODS: Randomized controlled trials (RCTs) comparing PCSK9 monoclonal antibodies with placebos or active drugs in patients at high cardiovascular risk were retrieved from electronic databases from their inception until November 2019. Efficacy and safety outcomes included low-density lipoprotein cholesterol (LDL-C) and other lipid profiles, treatment-emergent adverse events (TEAEs) and adverse events of interests, and clinical endpoints. Subgroup analyses based on drug types, dosing, and race were conducted. Statistical analysis was performed using STATA 15.1 and RevMan 5.0. RESULTS: Thirty-two RCTs were included in the systematic review, and 25 of them (57,090 individuals) were included in the meta-analysis. PCSK9 monoclonal antibodies significantly improved LDL-C and other lipid profiles (P < 0.05), and no racial differences were found. A recommended dose of 140 mg of evolocumab every 2 weeks was likely to produce a relatively stronger effect than 150 mg of alirocumab every 2 weeks in terms of the absolute change (weighted mean differences (WMD) - 0.36; 95% confidence interval (CI) - 0.71 to - 0.01; P = 0.041) and percent change (WMD - 19.53; 95% CI - 32.02 to - 7.04; P = 0.002) in LDL-C levels. Overall, PCSK9 monoclonal antibodies were safe, except for the significantly increased risk of injection site reactions (relative risks (RR) 1.54; 95% CI 1.38-1.71; P < 0.001). Both alirocumab (RR 0.89; 95% CI 0.83-0.95; P < 0.001) and evolocumab (RR 0.86; 95% CI 0.80-0.92; P < 0.001) were associated with a lower risk of major cardiovascular events (MACEs), especially in secondary preventive patients (alirocumab group: RR 0.88; 95% CI 0.82-0.95; P < 0.001; evolocumab group: RR 0.86; 95% CI 0.80-0.92; P < 0.001). The reduction in MACEs was observed in White but not in Asian subjects. No significant reduction of all-cause mortality was found (RR 0.88; 95% CI 0.72-1.07; P = 0.182). CONCLUSION: Both alirocumab and evolocumab are well tolerated and can greatly improve lipid profiles for patients at high cardiovascular risk. Both PCSK9 monoclonal antibodies significantly reduce the risk of nonfatal MACEs in patients with previous cardiovascular events, but the effect on all-cause mortality remains uncertain.

The relationship between carotid intima-media thickness and carotid plaque: a cohort study in China.

Both carotid intima-media thickness (cIMT) and carotid plaque (CP) quantified by B-mode ultrasound have been proposed as surrogate imaging biomarkers of subclinical atherosclerosis, while the relationship between cIMT and CP, whether cIMT evaluation in a given patient might allow for predicting the development of a carotid plaque, is still discussed controversially. We investigated the cross-sectional relationship between cIMT and CP, and the predictive value of cIMT for incident CP formation in 1078 subjects with mean age of 52 ± 5 years in a community based atherosclerosis cohort in Beijing. Participants underwent ultrasonography of bilateral carotid arteries and received vascular risk factor assessment at baseline and after a mean of 2.35 years follow-up. The prevalence of plaque was increased by 3.75-fold for upper quartile cIMT compare with the lower quartile even after adjustments for traditional risk factors at baseline. Among the 746 plaque-free subjects at baseline, 230 (31.0%) developed new CP. After adjusted for demographics and vascular risk factors, neither baseline cIMT nor the cIMT change from baseline to follow-up predicted incident CP. In conclusion, although cIMT associates with CP cross-sectionally, increased cIMT dose not independently predict future plaque development. Our data suggest that paying attention to the traditional risk factors might prevent subjects from developing carotid plaques regardless from IMT changes.

The association between carotid intima-media thickness and new-onset hypertension in a Chinese community-based population.

BACKGROUND: Hypertension and arterial vasculopathy may be mutual causes and effects. It is unknown whether carotid intima-media thickness (cIMT) is reliably predictive of the presence of newly developed hypertension in the Chinese population. This study evaluated the impacts of cIMT on new-onset hypertension in a community-based population without hypertension at baseline in China. METHODS: A total of 672 Chinese subjects who had complete data for demographics, baseline and follow-up blood pressure measurements, and cIMT measurements at baseline were included in our study. Baseline cIMT was obtained under standardized procedures using the GE Vivid 7 ultrasound system equipped with an 8-MHz linear array vascular probe (GE Medical Systems, Milwaukee, Wl, USA). The outcome was the incidence of hypertension at follow-up. Multivariate regression models were used to access the association between baseline cIMT and the risk of new-onset hypertension. RESULTS: Subjects were 51.5 ± 4.7 years old, and 32.0% were male. The mean baseline systolic blood pressure (SBP) was 122.5 ± 10.0 mmHg. The mean baseline diastolic blood pressure (DBP) was 72.4 ± 7.5 mmHg. The number of subjects with thickened cIMT (maximum ≥0.9 mm) at baseline was 198 (29.5%). After 2.3 years of follow-up, the rate of new-onset hypertension was 12.6%. The incidence rates of hypertension in the groups with thickened cIMT and normal cIMT were 19.2 and 9.9%, respectively. In the multivariable logistic regression analyses, both the average (OR = 1.69, 95% CI: 1.30-2.19, P = 0.0001) and maximum (OR = 1.55, 95% CI: 1.23-1.95, P = 0.0002) cIMT were significantly associated with new-onset hypertension after adjustment for various confounders. The group with thickened cIMT showed a higher risk for the incidence of hypertension, with an OR of 1.82 (95% CI: 1.07-3.10, P = 0.0270), compared to the normal group. CONCLUSION: Thickened cIMT has a strong association with incident hypertension risk in a community-based population without hypertension at baseline in China.

Noninvasive central systolic blood pressure, not peripheral systolic blood pressure, independently predicts the progression of carotid intima-media thickness in a Chinese community-based population.

This study aimed to investigate the predictive values of central systolic blood pressure (cSBP) and peripheral systolic blood pressure (pSBP) for the progression of carotid intima-media thickness (cIMT). A total of 953 Chinese participants from an atherosclerosis cohort with complete information, including baseline cSBP, questionnaire information, biochemical examination, baseline, and follow-up carotid ultrasonography quantitative data, were included in this study. A multilinear regression model, adjusted for possible covariates, was used to investigate the predictive values of cSBP and pSBP for rate of cIMT change. The average age of all participants was (52.11 ± 4.74 years). The baseline levels of cSBP, pSBP, max cIMT, and mean cIMT were (132.55 ± 18.18)mmHg, (130.76 ± 15.40)mmHg, (813.52 ± 118.49)µm and (681.11 ± 99.90)µm, respectively Those with hypertension, diabetes and dyslipidemia accounted for 40.71% (388), 18.05% (172), and 70.41% (671), respectively. After 2.3 years of follow-up, the average rates of max and mean cIMT change were 8.70 (-0.49-19.43)% and 2.59 (-4.72-10.81)%, respectively. Per standard deviation increase of cSBP, but not pSBP, was associated with increases of max (for cSBP, ß 1.07, 95%CI 0.18-1.96, p = 0.018; for pSBP, ß 0.48, 95%CI -0.45-1.41, p = 0.315) and mean (for cSBP, ß 0.84%, 95%CI 0.10-1.58, p = 0.027; for pSBP, ß 0.59%, 95%CI -0.18-1.37, p = 0.135) cIMT change rate after adjusting for possible covariates. In conclusion, cSBP, but not pSBP, is independently associated with cIMT progression in our community-based Chinese population. cSBP should be considered for the purpose of CVD primary prevention.

Joint Effect of Non-invasive Central Systolic Blood Pressure and Peripheral Systolic Blood Pressure on Incident Hypertension in a Chinese Community-based Population.

Central blood pressure level is not always consistent with peripheral blood pressure level, and especially their joint effect on incident hypertension is not well established. A total of 1607 non-hypertensive subjects from an atherosclerosis cohort in Beijing, China were included. Central systolic blood pressure (cSBP) was obtained using Omron HEM-9000AI machine and peripheral systolic blood pressure (pSBP) was measured using Omron HEM-7117 electronic sphygmomanometer, separately. Hypertension was defined as BP ≥ 140/90 mmHg or self-reported hypertension or taking any antihypertension drugs at the follow-up survey. After a median follow-up of 2.3 years, incident hypertension was 13.1%. Every 1 standard deviation increase of cSBP and pSBP was associated with 1.98 (95%CI: 1.69-2.33) and 2.84 (95%CI: 2.30-3.52) times of incident hypertension after adjustment for confounders. Moreover, hypertension risk in single pSBP ≥ 120 mmHg group, single cSBP ≥ 120 mmHg group, and both pSBP and cSBP ≥ 120 mmHg group was 2.83 (95%CI: 0.98-8.16), 3.28 (95%CI: 1.24-8.70), and 11.47 (95%CI: 4.97-26.46) times higher than both pSBP and cSBP < 120 mmHg group, respectively. The joint effect of cSBP and pSBP is superior to either cSBP or pSBP to predict incident hypertension in a Chinese community-based population. Screening of central blood pressure should be considered in non-hypertensive population for the purpose of primary intervention, especially for subjects with pSBP ≥ 120 mmHg.

Associations of plasma homocysteine levels with peripheral systolic blood pressure and noninvasive central systolic blood pressure in a community-based Chinese population.

Previous studies indicated that homocysteine (Hcy) is associated with higher peripheral systolic blood pressure (pSBP). There have been few data on the relationship between Hcy and central SBP (cSBP). A total of 4,364 Chinese subjects from the Shijingshan community in Beijing were included. cSBP and pSBP were measured with an Omron HEM-9000AI device. Subjects were 57.20 ± 8.9 years old, 37.9% were male. The median of Hcy was 11.96 µmol/L. The mean of cSBP and pSBP was 129.94 ± 18.03 mmHg and 133.25 ± 18.58 mmHg. lnHcy was associated with cSBP (adjusted ß = 2.17, SE = 0.80, P = 0.007) and pSBP (adjusted ß = 2.42, SE = 0.75, P = 0.001). With increasing Hcy, there were enhanced correlations of Hcy with pSBP and cSBP (p for trend between quartiles <0.01). Using Q1 for reference, the Q4 was associated with cSBP (adjusted ß = 1.77, SE = 0.89, P = 0.047) and pSBP (adjusted ß = 2.15, SE = 0.84, P = 0.011). The correlations were more significant in non-obese subjects than in obese subjects (cSBP: ß = 4.30 vs 0.46, pSBP: ß = 5.04 vs 1.18, P for interaction <0.001). Our study showed that Hcy was associated with higher cSBP and pSBP, especially in non-obese subjects.

Efficacy and tolerability of once-daily 160 mg valsartan in Chinese patients with mild to moderate hypertension.

The present multicentre, prospective, open-label, single treatment arm study (Val-Perfect) examined the efficacy and tolerability of once-daily valsartan monotherapy (80 mg for two weeks, followed by 160 mg for eight weeks) in 195 Chinese patients with mild to moderate hypertension, using office, home, and ambulatory blood pressure (BP) monitoring. Significant mean reductions (P<0.0001) were observed in office BP from baseline to week 10, with mean sitting systolic BP (MSSBP) and mean sitting diastolic BP (MSDBP) values of 15.6±12.3 and 11.1±8.6 mmHg, respectively. The office BP control rate at week 10 was 56.9% (target MSSBP/MSDBP <130/80 mmHg for patients with type 2 diabetes or chronic kidney disease, <140/90 mmHg for others). Valsartan treatment significantly reduced mean 24-h SBP/DBP (-6.1/-4.4 mmHg; both P<0.0001) and mean home-monitored SBP/DBP (-13.3/-9.1 mmHg; both P<0.0001) at week 10. The incidence of adverse events (AEs) leading to discontinuation (1.5%) or drug-related AEs (3.1%) was low, with no instances of mortality or drug-related serious AEs. These results indicate that 160 mg valsartan is safe and effective at lowering BP in Chinese patients with mild to moderate hypertension. The significant reductions in office-based and out-of-office BP measures support the clinical relevance of moderate-dose valsartan monotherapy for effective 24-h BP control.

Correlating the relationship between interarm systolic blood pressure and cardiovascular disease risk factors.

Interarm systolic blood pressure difference (IASBPD) can predict cardiovascular disease. To investigate the relationship between IASBPD and cardiovascular disease risk factors, a total of 1426 individuals were studied. Blood pressure was assessed simultaneously and IASBPD was expressed as the absolute difference value (|R-L|). Cardiovascular disease risk factors were compared between the high IASBPD group (IASBPD ≥10 mm Hg) and the normal IASBPD group (IASBPD <10 mm Hg). An increased prevalence of hypertension, body mass index, and systolic and diastolic blood pressure were observed in the high IASBPD group (P<.05), associated with the enhanced mean values of intima-media thickness and maximum intima-media thickness (P<.05). Brachial-ankle pulse wave velocity was increased, while ankle-brachial index was lower in the high IASBPD group (P<.05). Multivariate logistic regression analysis revealed that IASBPD ≥10 mm Hg was positively associated with body mass index (odds ratio, 1.077; P=.002) and systolic blood pressure (odds ratio, 1.032; P<.001), and negatively associated with ankle-brachial index (odds ratio, 0.038; P<.001).

Noninvasive Central Systolic Blood Pressure Is More Strongly Related to Kidney Function Decline Than Peripheral Systolic Blood Pressure in a Chinese Community-Based Population.

This study aimed to investigate the association of noninvasive central aortic blood pressure with kidney function decline in a Chinese community-based population with normal kidney function at baseline. A total of 3153 Chinese participants from an atherosclerosis cohort were included in our analysis. The primary outcome was renal function decline defined as a drop in estimated glomerular filtration rate (eGFR) category accompanied by a ≥25% drop in eGFR from baseline; or a sustained decline in eGFR of >5 mL/min per 1.73 m(2)/y. The secondary outcomes were rapid eGFR decline (a decline in eGFR of >3 mL/min per 1.73 m(2)/y) and new incidence of chronic kidney disease. Participants were 56.6±8.5 years old, 36.0% were males, and 48.8% had hypertension. Mean (SD) baseline eGFR was 101.2±10.6 mL/min per 1.73 m(2) After a mean 2.35-year follow-up, the incidence of renal function decline, rapid eGFR decline and chronic kidney disease were 7.3%, 19.7%, and 0.7%, respectively. In multivariate logistic-regression analyses, central and peripheral systolic blood pressure (SBP) were both independently associated with all outcomes after adjustment for various confounders. When peripheral SBP was forced into the model with central SBP simultaneously, its significant association with the 3 outcomes all disappeared; however, central SBP was still significantly related with all outcomes even after further adjusting peripheral SBP. In conclusion, central SBP is a stronger predictor compared with peripheral SBP for early kidney function decline in a Chinese community-based population with normal kidney function at baseline.

[Efficacy comparison between 5 mg perindopril arginine salt and 4 mg perindopril tert-butylamine salt for patients with mild to moderate essential hypertension].

OBJECTIVE: To compare the efficacy and safety of 5 mg perindopril arginine salt and 4 mg perindopril tert-butylamine salt for patients with mild to moderate essential hypertension. METHODS: The study was designed as multicenter, randomized, double-blind, active controlled trial with two parallel groups enrolling 524 participants with mild to moderate essential hypertension. After 2-week run-in period, 186 patients were enrolled and randomly treated with 5 mg perindopril arginine salt and 183 patients were enrolled and randomly treated with 4 mg perindopril tert-butylamine salt. The random sequence was generated by the I.R.I.S., and a balance was made in each center. After double-blind treatment for 8 weeks, the dose could be doubled for patients with uncontrolled BP ((SBP) ≥ 140 mmHg (1 mmHg = 0.133 kPa) or diastolic blood pressure (DBP) ≥ 90 mmHg) and patients were treated for another 4 weeks. RESULTS: The sitting SBP was similarly decreased by (19.9 ± 17.2) mmHg in perindopril arginine group and (18.5 ± 14.7) mmHg (P = 0.000 5) in perindopril tert-butylamine group post 8 weeks treatment. Dose was doubled in 109 patients (59.9%) in perindopril arginine group and 116 patients (63.7%) in perindopril tert-butylamine group. At 12 weeks post therapy, the sitting SBP decreased by (19.8 ± 16.2) and (19.6 ± 16.3) mmHg respectively in the 2 groups. The decrease of sitting DBP was also similar in both groups (-12.0 ± 10.0) mmHg and (-11.0 ± 8.9) mmHg (P < 0.000 1), respectively. The control rate or response rate was also similar between the two groups (control rate over 8 weeks was 38.5% vs. 31.3%, 95% CI (-2.6-16.9), control rate over 12 weeks was 36.3% vs. 35.7%, 95% CI (-9.3-10.4), response rate over 8 weeks was 64.3% vs. 63.2%, 95% CI (-8.8-11.0), response rate over 12 weeks was 65.9% vs. 64.8%, 95% CI (-8.7-10.9)). Incidence of adverse events was low and similar in both therapy groups. CONCLUSIONS: The results show that perindopril arginine salt 5 mg is as efficient as perindopril tert-butylamine 4 mg on lowering BP for patients with mild to moderate essential hypertension. Both drugs have good safety profile and are well tolerated by patients in this cohort.