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BACKGROUND Homocysteine-lowering intervention with folate was recently shown to be able to increase day-night difference of blood pressure (BP) in humans indicating a potential relationship between homocysteine and circadian BP variation. We thus sought to investigate the association between plasma total homocysteine level (tHcy) and circadian BP variation in hypertensive adults. METHODS We enrolled 244 eligible dipping and 249 nondipping BP status adults from 560 adults who were randomly sampled from 5,233 Chinese hypertensive adults who received ambulatory BP monitoring (ABPM). We further enrolled 390 adults with CC/CT genotypes of the methylenetetrahydrofolate reductase (MTHFR) and 79 TT genotype who received ABPM at the same time from 1858 hypertensive adults with MTHFR polymorphisms detection. RESULTS Plasma tHcy in nondippers was significantly higher than dippers (P < 0.001). Simple linear analysis revealed that tHcy significantly correlated with nocturnal systolic BP fall (r = -0.145, P = 0.001) and diastolic BP fall (r = -0.141, P = 0.002). Multivariate logistic regression analysis further identified tHcy as an independent factor correlated with the presence of nondipping BP status in hypertensive adults (odds ratio: 1.873, 95% confidence interval: 1.171-2.996, P = 0.009). The percentage of dipping BP status was 19.49% or 8.86% and the percentage of nondipping BP status was 80.51% or 91.14% in CC/CT or TT genotypes, respectively. The above different between CC/CT and TT genotypes was significant (P = 0.024). CONCLUSIONS These results indicated that high homocysteine levels associate with disturbed circadian BP variation in Chinese hypertensive adults.

ZFAS1 is one of cardiac-specific or cardiac-related lncRNAs. This study was to explore the functional involvement of ZFAS1 and its regulatory role in AMI. In this study, the models of AMI rat and myocardial cell cultured under hypoxia were made. The expression of ZFAS1 and miR-150 of myocardial infarction tissue or cardiac myocytes was determined by quantitative real time PCR. The regulatory role of ZFAS1 on miR-150 was examined by RNA pull down assay. The effect of miR-150 or ZFAS1 expression on cell viability was analyzed by MTT assay. The relative expression of ZFAS1 in the myocardium infracted zone and border zone was significantly upregulated at 1-48 h of AMI rats, but it downregulated at 1 week and 2 weeks; miR-150 was significantly downregulated at AMI-1-48 h and upregulated at 1 and 2 weeks after model establishment. The result of RNA pull down assay indicated that ZFAS1 could interact directly with miR-150. C-reactive protein (CRP) was regulated by ZFAS1/miR-150 axis and negatively targeted by miR-150. Hypoxia caused the decrease of cell viability and the upregulation of CRP at mRNA and protein levels; whereas this upregulation could be attenuated by miR-150 mimic or si-ZFAS1 in H9C2 cells and cardiomyocytes. Knockdown of ZFAS1 or miR-150 overexpression effectively relieved AMI-induced myocardial infarction in AMI-1 week rats. The ZFAS1/miR-150 axis was involved in the molecular mechanism of AMI induced cardiomyocytes apoptosis via regulating CRP. J. Cell. Biochem. 118: 3281-3289, 2017. © 2017 Wiley Periodicals, Inc.

Vandetanib, a tyrosine kinase inhibitor used as an anticancer therapeutic agent, has adverse events associated with treatment resulting in noncompliance and withdrawal from the therapy. Here, we performed meta-analysis of published clinical trials to determine relative risk (RR) and incidence of gastrointestinal events during vandetanib therapy in patients with cancer. A comprehensive literature search was performed and summary incidence, RR, and 95% confidence intervals (CIs) were calculated employing fixed- or random-effects models, depending on the heterogeneity of trials. Twenty-two trials with 6382 patients were included summary incidences of all-grade gastrointestinal events in patients with cancer were anorexia 24% (95% CI, 20%-28%), constipation 17% (95% CI, 13%-20%), diarrhea 46% (95% CI, 40%-53%), nausea 29% (95% CI, 25%-33%), and vomiting 17% (95% CI, 14%-21%). Incidences of vandetanib-associated gastrointestinal events stratified by tumor histology were statistically insignificant. Vandetanib was associated with a significant risk of all-grade diarrhea (RR 1.75, 95% CI, 1.42-2.16) and high-grade diarrhea (RR 1.94, 95% CI, 1.43-2.64) and significantly decreased risk of all-grade constipation (RR 0.80, 95% CI, 0.71-0.91). Summary RR showed a significant risk of vandetanib-associated constipation (RR 0.82, 95% CI, 0.72-0.93) and diarrhea (all-grade: RR 1.68, 95% CI, 1.31-2.14 and high-grade: RR 1.57, 95% CI, 1.14-2.17) in patients with non-small-cell lung cancer. This study revealed a significantly increased risk of diarrhea and a reduced risk of constipation in patients with cancer receiving vandetanib, suggesting that appropriate and frequent clinical monitoring should be emphasized.

Background and Purpose— Elevated blood homocysteine concentration increases the risk of stroke, especially among hypertensive individuals. Homocysteine is largely affected by the methylenetetrahydrofolate reductase C677T polymorphism and folate status. Among hypertensive patients, we aimed to test the hypothesis that the association between homocysteine and stroke can be modified by the methylenetetrahydrofolate reductase C677T polymorphism and folic acid intervention. Methods— We analyzed the data of 20 424 hypertensive adults enrolled in the China Stroke Primary Prevention Trial. The participants, first stratified by methylenetetrahydrofolate reductase genotype, were randomly assigned to receive double-blind treatments of 10-mg enalapril and 0.8-mg folic acid or 10-mg enalapril only. The participants were followed up for a median of 4.5 years. Results— In the control group, baseline log-transformed homocysteine was associated with an increased risk of first stroke among participants with the CC/CT genotype (hazard ratio, 3.1; 1.1–9.2), but not among participants with the TT genotype (hazard ratio, 0.7; 0.2–2.1), indicating a significant gene–homocysteine interaction ( P =0.008). In the folic acid intervention group, homocysteine showed no significant effect on stroke regardless of genotype. Consistently, folic acid intervention significantly reduced stroke risk in participants with CC/CT genotypes and high homocysteine levels (tertile 3; hazard ratio, 0.73; 0.55–0.97). Conclusions— In Chinese hypertensive patients, the effect of homocysteine on the first stroke was significantly modified by the methylenetetrahydrofolate reductase C677T genotype and folic acid supplementation. Such information may help to more precisely predict stroke risk and develop folic acid interventions tailored to individual genetic background and nutritional status. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00794885.

Background: Diabetes is a known risk factor for stroke, but data on its prospective association with first stroke are limited. Folic acid supplementation has been shown to protect against first stroke, but its role in preventing first stroke in diabetes is unknown.Objectives: This post hoc analysis of the China Stroke Primary Prevention Trial tested the hypotheses that the fasting blood glucose (FBG) concentration is positively associated with first stroke risk and that folic acid treatment can reduce stroke risk associated with elevated fasting glucose concentrations.Design: This analysis included 20,327 hypertensive adults without a history of stroke or myocardial infarction, who were randomly assigned to a double-blind daily treatment with 10 mg enalapril and 0.8 mg folic acid (n = 10,160) or 10 mg enalapril alone (n = 10,167). Kaplan-Meier survival analysis and Cox proportionate hazard models were used to test the hypotheses with adjustment for pertinent covariables.Results: During a median treatment duration of 4.5 y, 616 participants developed a first stroke (497 ischemic strokes). A high FBG concentration (≥7.0 mmol/L) or diabetes, compared with a low FBG concentration (

Objective— We aimed to examine whether baseline homocysteine (Hcy) concentrations affect antihypertensive responses to enalapril treatment among previously untreated hypertensive patients (n=10 783) in the CSPPT (China Stroke Primary Prevention Trial). Approach and Results— After a 3-week run-in treatment with a daily dose of 10 mg enalapril, eligible hypertensive patients were randomly assigned to a double-blind daily treatment of a tablet of either enalapril (10 mg) and folic acid (0.8 mg) or enalapril (10 mg) alone for a median of 4.5 years. After the 3-week treatment period with enalapril alone, the systolic blood pressure–lowering effect was significantly reduced by 1.39 (95% confidence interval 0.40–2.37) and 3.25 (95% confidence interval 1.98–4.52) mm Hg, respectively, in those with baseline Hcy concentrations of 10 to 15 and ≥15 μmol/L ( P for trend P for trend Conclusions— Elevated Hcy concentrations significantly decreased the antihypertensive effect of the short-term and long-term enalapril-based antihypertensive treatment in previously untreated hypertensive patients.

Background and aims While folate is known for its importance in cardiovascular health, it is unknown whether folate status can modify the association between low-density lipoprotein cholesterol (LDL-C) and carotid intima-media thickness (CIMT). We aimed to investigate this question in a Chinese hypertensive population, who are at high-risk of low folate and atherosclerosis. Methods and results This report included 14,970 hypertensive adults (mean age 64.5 years; 40.3% male) from the China Stroke Primary Prevention Trial (CSPPT) and analyzed the fasting serum LDL-C and folate, and CIMT data obtained at the last follow-up visit. LDL-C was calculated using the Friedewald equation. Serum folate levels were measured by chemiluminescent immunoassay. CIMT was measured by ultrasound. Non-parametric smoothing plots, multivariate linear regression analysis, subgroup analyses and interaction testing were performed to examine the LDL-C–CIMI relationship and effect modification by folate. Consistent with graphic plots, multivariate linear regression showed that LDL-C levels were independently and positively associated with CIMT (β = 7.69, 95%CI: 5.76–9.62). More importantly, the relationship between LDL-C and CIMT was significantly attenuated with increasing serum folate levels (1st tertile: β = 10.06, 95%CI: 6.67–13.46; 2nd tertile: β = 6.81, 95%CI: 3.55–10.07; 3rd tertile: β = 5.96, 95%CI: 2.55–9.36; P-interaction = 0.045). Subgroup analyses showed the association between LDL-C and CIMT across serum folate tertiles was robust among various strata (all P-interaction >0.05). Conclusions Among Chinese hypertensive adults, the serum folate levels could modify the association between LDL-C and CIMT. Our findings, if further confirmed, have important clinical implications.

Background Numerous trials have investigated the effect of remote ischemic conditioning (RIC) in preventing contrast‐induced nephropathy (CIN) in patients receiving contrast medium (CM). This meta analysis aims to validate the role of RIC in preventing CIN. Methods We searched the PubMed, EMBASE, and Web of Science databases for eligible randomized controlled trials (RCTs) published before April 27, 2019. Two investigators independently extracted basic characteristics from each study. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to examine the treatment effect. Results A total of 18 studies comprising 2,503 patients were included in our meta‐analysis. Compared with conventional therapy, RIC significantly reduced the risk of CIN (OR = 0.43, 95% CI: 0.33, 0.56, p

Background This study aimed to test the feasibility and titration methods used to achieve specific blood pressure (BP) control targets in hypertensive patients of rural China. Methods A randomized, controlled, open-label trial was conducted in Rongcheng, China. We enrolled 105 hypertensive participants aged over 60 years, and who had no history of stroke or cardiovascular disease. The patients were randomly assigned to one of three systolic-BP target groups: standard: 140 to Discussion The optimal target for systolic blood pressure (SBP) lowering is still uncertain worldwide and such information is critically needed, especially in China. However, in China the rates of awareness, treatment and control are only 46.9%, 40.7%, and 15.3%, respectively. It is challenging to achieve BP control in the real world and it is very important to develop population-specific BP-control protocols that fully consider the population’s characteristics, such as age, sex, socio-economic status, compliance with medication, education level, and lifestyle. This randomized trial showed the feasibility and safety of the titration protocol to achieve desirable SBP targets ( Trial registration Feasibility Study of the Intensive Systolic Blood Pressure Control; ClinicalTrials.gov, ID: NCT02817503. Registered retrospectively on 29 June 2016.

We aimed to examine whether hypertension status modified the association between sleep duration and stroke among middle-aged and elderly population. This cross-sectional study included 10 516 participants aged ≥45 years from the China Hypertension Survey study. Sleep duration and history of stroke were assessed by questionnaires. Multivariate logistic regression analyses, a generalized additive model (GAM) and smooth curve fitting (penalized spline method) and a two-piecewise logistic regression models were performed to evaluate the association between sleep duration and stroke in different status of hypertension. 95% confidence interval (CI) for turning point was obtained by bootstrapping. Multiple logistic analyses showed that per 1 hour increase in sleep duration was associated with a 37% increased prevalence of stroke among participants without hypertension and associated with a 8% increased prevalence of stroke among hypertensive participants (without hypertension: odds ratio [OR] = 1.37, 95% CI 1.09-1.71; with hypertension: OR = 1.08, 95% CI 0.95-1.21; PInteraction = .029). The fully adjusted smooth curves presented a linear association between sleep duration and stroke among participants without hypertension, but a threshold, nonlinear association among hypertensive participants. The turning point for the curve was found at a sleep duration of 8 (95% CI 5-9) h among hypertensive patients. The ORs (95% CIs) for stroke were 0.92 (0.79, 1.06) and 1.60 (1.23, 2.08) to the left and right of the turning point, respectively. In conclusion, we found a linear association between sleep duration and stroke among middle-aged and elderly participants without hypertension, but a threshold, nonlinear association among hypertensive participants.

Background The efficacy of nifekalant in preexcited atrial fibrillation ( AF ) has not been assessed. Methods and Results The study populations consisted of patients with sustained preexcited AF (n=51), paroxysmal supraventricular tachycardia (n=201), and persistent AF (n=87). Effects of intravenous infusion of nifekalant were assessed on electrophysiological and clinical parameters. Nifekalant prolonged the shortest preexcited R‐R, the average preexcited R‐R, and the average R‐R intervals from 290±35 to 333±44 ms, 353±49 to 443±64 ms, and 356±53 to 467±75 ms, respectively, in patients with preexcited AF (all P QRS complexes, heart rate, and increased systolic pressure (all P AF in 33 of 51 patients (65%). Similar effects were also observed in a subgroup of 12 patients with preexcited AF and impaired left ventricular function. In patients with paroxysmal supraventricular tachycardia, nifekalant significantly prolonged the effective refractory period, the block cycle length of the antegrade accessory pathway, and the atrial effective refractory period (all P AF without an accessory pathway, nifekalant did not significantly decrease the ventricular rate of AF . One patient developed Torsades de Pointes. No other adverse effects were observed. Conclusions Nifekalant prolongs the effective refractory period of the antegrade accessory pathway and atrium without blocking antegrade conduction through the atrioventricular node, leading to slowing and/or to termination of preexcited AF . Thus, nifekalant might be an effective and a relatively safe drug in patients with preexcited AF .

In the treatment of resistant hypertension, physiologically individualized therapy based on phenotyping with plasma renin activity (PRA) and plasma aldosterone significantly improves blood pressure control. Patients with a low-renin/low aldosterone (Liddle) phenotype respond best to amiloride, while those with low-renin/high aldosterone respond best to aldosterone antagonists, and those with high renin/high aldosterone (renal phenotype) respond best to angiotensin receptor blockers (ARB). However, it is important to measure PRA in a stimulated condition to distinguish between low levels due to high salt intake, licorice or nonsteroidal inflammatory drugs and low levels due to suppression by excess aldosterone secretion or renal tubular genetic variants causing retention of salt and water (Liddle phenotype). In the past, both diuretics and angiotensin converting inhibitors (ACEi) have been used for this purpose, and it has been assumed that these classes of drugs are equivalent. In this study of 2896 patients with hypertension, we evaluated that assumption. We found important differences among diuretics alone, ACEi/ARB alone, and ACEi/ARB + diuretics, which all stimulated PRA. However, ACEi/ARB lowers plasma aldosterone, and beta blockers lower PRA. Among patients with systolic pressure ≥ 180 mmHg ± diastolic pressure ≥ 100 mmHg stimulated only by diuretics, the phenotypes were 25% Liddle, 38% IA, 8.7% renal, and 28.3% mixed. In choosing physiologically individualized therapy based on PRA and aldosterone, it is important to consider the classes of stimulating drugs. Phenotypes are best distinguished by taking into account the aldosterone/PRA ratio in addition to the levels of PRA and aldosterone.

Background Dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) prevents ischemic events while increasing bleeding risk. Real-world-based metrics to accurately predict postdischarge bleeding (PDB) occurrence and its potential impact on postdischarge major cardiovascular event (MACE) remain undefined. This study sought to evaluate the impact of PDB on MACE occurrence, and to develop a score to predict PDB risk among Chinese acute coronary syndrome (ACS) patients after PCI. Methods and results From May 2014 to January 2016, 2496 ACS patients who underwent PCI were recruited consecutively from 29 nationally representative Chinese tertiary hospitals. Among 2,381 patients (95.4%, 2,381/2,496) who completed 1-year follow-up, the cumulative incidence of PDB (bleeding academic research consortium type [BARC] ≥2) and postdischarge MACE (a composite of all-cause death, nonfatal myocardial infarction, ischemic stroke, or urgent revascularization) was 4.9% (n = 117) and 3.3% (n = 79), respectively. The association between PDB and MACE during 1-year follow-up, as well as the impact of DAPT with ticagrelor or clopidogrel on PDB were evaluated. PDB was associated with higher risk of postdischarge MACE (7.7 vs. 3.1%; adjusted hazard ratio: 2.59 [95% confidence interval: 1.17-5.74]; p = .02). For ticagrelor versus clopidogrel, PDB risk was higher (8.0 vs. 4.4%; 2.05 [1.17-3.60]; p = .01), while MACE risk was similar (2.0 vs. 3.4%; 0.70 [0.25-1.93]; p = .49). Based on identified PDB predictors, the constructed bleeding risk in real world Chinese acute coronary syndrome patients (BRIC-ACS) score for PDB was established. C-statistic for the score for PDB was 0.67 (95% CI: 0.62-0.73) in the overall cohort, and >0.70 in subgroups with non-ST- and ST-segment elevation myocardial infarction, diabetes and receiving more than two drug eluting stents. Conclusions In Chinese ACS patients, PDB with BARC ≥2 was associated with higher risk for MACE after PCI. The constructed BRIC-ACS risk score provides a useful tool for PDB discrimination, particularly among high ischemic and bleeding risk patients.

Uncertainty remains regarding the association between resting heart rate (RHR) with hypertension and stroke because of limited and inconsistent data. We assessed the association between RHR, hypertension, and stroke. In this cross-sectional study, 14 677 participants from the China Hypertension Survey study were analyzed. The history of stroke was conducted by questionnaires. RHR was measured by the standardized electronic monitors. Multivariate logistic regression analyses were performed to evaluate the association between RHR, hypertension, and stroke. Moreover, a generalized additive model (GAM) and smooth curve fitting (penalized spline method) were conducted to assess the association between RHR and stroke in different status of hypertension. Overall, each 10 beats per minute (bpm) increase in RHR was associated with an 18% increased prevalence of stroke (P = 0.017). Subjects with RHR > 80 bpm were associated with a higher prevalence of stroke (OR = 1.47; 95% CI, 1.08-2.01) compared with those with RHR ≤ 80 bpm. Similarly, hypertensives had a higher prevalence of stroke than normotensives (OR = 3.76; 95% CI, 2.39-5.92). Hypertensives with RHR > 80 bpm had the highest prevalence of stroke compared with their counterparts (OR = 5.47; 95% CI, 3.13-9.56). The fully adjusted smooth curve fitting presented a linear association between RHR and stroke among participants with hypertension, but almost horizontal association among participants without hypertension. In conclusion, elevated RHR and hypertension were independently and jointly associated with the increased prevalence of stroke. These findings suggested that elevated RHR was associated with increased prevalence of stroke especially among hypertensives.

The risk of thromboembolism in patients with CHA2DS2-VASc score of 0 to 1 was low, and the anticoagulant therapy was not recommended. Although the CHA2DS2-VASc score was low, there were still many patients suffered from thrombotic events and stroke. We aim to investigate the risk factors of thrombotic events in nonvalvular atrial fibrillation (NVAF) patients with low CHA2DS2-VASc score. We retrospectively enrolled 595 consecutive NVAF patients with low CHA2DS2-VASc score (male: CHA2DS2-VASc = 0, female: CHA2DS2-VASc = 1). The general clinical data, blood biochemical data, and echocardiography results of the 595 patients were collected. Multivariate logistic regression models were used to evaluate risk factors of thrombosis. Receiver operating characteristic curve was used to identify the optimal cut-off value of the independent risk factors. A P value of

Arterial stiffness plays a key role in the pathogenesis of cardiovascular disease. However, the relationship between lipid levels and arterial stiffness is controversial. We aimed to investigate the association between lipid parameters and brachial-ankle pulse-wave velocity (baPWV) in Chinese patients with hypertension. A total of 14 071 participants with hypertension in the China Stroke Primary Prevention Trial (CSPPT) were enrolled in the present study. Patients were assigned to 4 equal groups according to their baPWV. Participants in the highest baPWV group were older with a higher prevalence of stroke and diabetes mellitus as well as higher body mass index (BMI), blood pressure, fasting plasma glucose, uric acid, total cholesterol (TC), triglycerides (TG), homocysteine (Hcy), and vitamin B12 levels ( P < .001). After adjusting for age, sex, BMI, and other cardiovascular risks, high-density lipoprotein cholesterol (HDL-C) was negatively related to baPWV (β = -0.22, P = .012), TC (β = 0.08, P = 0.001), TG (β = 0.14, P = .001); non-HDL-C (β = 0.12, P = .001) and positively related to baPWV. The effect was not observed for low-density lipoprotein cholesterol (LDL-C; β = 0.12, P = .335).These results suggested that non-HDL-C, TG, and TC were associated with arterial stiffness in a Chinese population with hypertension. HDL-C was inversely associated with arterial stiffness.

Doi, Yasuji/0000-0002-8368-0827; galvani, marcello/0000-0001-5897-667X; Gislason, Gunnar H/0000-0002-0548-402X; Taskinen, Marja-Riitta/0000-0002-6229-3588; Sherwood, Matthew/0000-0002-4305-5883; Malynovsky, Yaroslav V/0000-0002-9118-1104; Viktorova, vic-inna@mail.ru I.A./0000-0001-8728-2722; bastos, jose/0000-0002-9526-3123; Yang, Eric H/0000-0003-4889-7454; Rudenko, Anatoliy Viktorovich/0000-0003-1099-1613; Novotny, Vojtech/0000-0003-3521-9945; Nikolaev, Konstantin/0000-0003-4601-6203; Reshetko, Olga/0000-0003-3107-7636; Leonardi, Sergio/0000-0002-4800-6132; Muenzel, Thomas/0000-0001-5503-4150; Ushakov, Alexei V/0000-0002-7020-4442; Tse, Hung Fat/0000-0002-9578-7808; Podoleanu, Cristian/0000-0001-9987-2519; Raffel, Owen C/0000-0001-5470-7050; Khasanov, Niiaz/0000-0002-7760-0763; Chumakova, Galina A/0000-0002-2810-6531; Ersanli, Murat/0000-0003-1847-3087; cornel, jan hein/0000-0002-1006-2112; Abbate, Antonio/0000-0002-1930-785X; Racca, Vittorio/0000-0002-4465-3789; Urina-Triana, Miguel A/0000-0001-6003-4622; Rasputina, Lesia/0000-0003-1230-4039; Racca, Vittorio/0000-0002-4465-3789; Reis, Gilmar/0000-0002-4847-1034; Sandhu, Manjinder/0000-0003-2538-2079; Keskin, Kudret/0000-0002-9049-1530; PAREPA, IRINEL/0000-0002-7571-9015; Manakshe, Gajendra/0000-0002-4983-4271; Nicolau, Jose C/0000-0002-9680-3689; Strelnieks, Aldis/0000-0003-3493-2562; Budaj, Andrzej/0000-0002-6395-2098; Marin, Francisco/0000-0001-7246-7708; Wongpraparut, Nattawut/0000-0002-1541-3313; Yuan, Zuyi/0000-0002-4141-0298; Jeong, Myung Ho/0000-0003-2424-810X; Mostovoy, Yuriy/0000-0002-7041-1230; Pepine, Carl/0000-0002-6011-681X; Lopez-Jaramillo, Patricio/0000-0002-9122-8742; Garcia-Lledo, Alberto/0000-0002-8986-2584; Tesloianu, Nicolae-Dan/0000-0002-1007-3022; Kosmacheva, Elena/0000-0001-8600-0199; Kunz Sebba Barroso Souza, Weimar/0000-0002-1265-1930; Katz, Amos/0000-0003-0422-934X; Tunon, Jose/0000-0002-1373-0999; Acevedo, Monica/0000-0002-7989-6633; Hove, Jens/0000-0002-5600-5623; Yakushin, Sergey/0000-0001-7202-742X; Gonzalez Juanatey, Jose Ramon/0000-0001-9681-3388; Lyamina, Nadezhda/0000-0001-6939-3234; Aylward, Philip/0000-0002-5358-8552; Apostolovic, Svetlana/0000-0001-9015-297X; Airaksinen, Juhani/0000-0002-0193-568X; Nahhas, Prof. Dr. Ahmed/0000-0002-2887-8187; Barbarash, Olga/0000-0002-4642-3610, WOS: 000475553300016, PubMed: 31272931, Background After acute coronary syndrome, diabetes conveys an excess risk of ischaemic cardiovascular events. A reduction in mean LDL cholesterol to 1.4-1.8 mmol/L with ezetimibe or statins reduces cardiovascular events in patients with an acute coronary syndrome and diabetes. However, the efficacy and safety of further reduction in LDL cholesterol with an inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) after acute coronary syndrome is unknown. We aimed to explore this issue in a prespecified analysis of the ODYSSEY OUTCOMES trial of the PCSK9 inhibitor alirocumab, assessing its effects on cardiovascular outcomes by baseline glycaemic status, while also assessing its effects on glycaemic measures including risk of new-onset diabetes. Methods ODYSSEY OUTCOMES was a randomised, double-blind, placebo-controlled trial, done at 1315 sites in 57 countries, that compared alirocumab with placebo in patients who had been admitted to hospital with an acute coronary syndrome (myocardial infarction or unstable angina) 1-12 months before randomisation and who had raised concentrations of atherogenic lipoproteins despite use of high-intensity statins. Patients were randomly assigned (1: 1) to receive alirocumab or placebo every 2 weeks; randomisation was stratified by country and was done centrally with an interactive voice-response or web-response system. Alirocumab was titrated to target LDL cholesterol concentrations of 0.65-1.30 mmol/L. in this prespecified analysis, we investigated the effect of alirocumab on cardiovascular events by glycaemic status at baseline (diabetes, prediabetes, or normoglycaemia)-defined on the basis of patient history, review of medical records, or baseline HbA(1c) or fasting serum glucose-and risk of new-onset diabetes among those without diabetes at baseline. the primary endpoint was a composite of death from coronary heart disease, non-fatal myocardial infarction, fatal or non-fatal ischaemic stroke, or unstable angina requiring hospital admission. ODYSSEY OUTCOMES is registered with ClinicalTrials. gov, number NCT01663402. Findings At study baseline, 5444 patients (28.8%) had diabetes, 8246 (43.6%) had prediabetes, and 5234 (27.7%) had normoglycaemia. There were no significant differences across glycaemic categories in median LDL cholesterol at baseline (2.20-2.28 mmol/L), after 4 months' treatment with alirocumab (0.80 mmol/L), or after 4 months' treatment with placebo (2.25-2.28 mmol/L). in the placebo group, the incidence of the primary endpoint over a median of 2.8 years was greater in patients with diabetes (16.4%) than in those with prediabetes (9.2%) or normoglycaemia (8.5%); hazard ratio (HR) for diabetes versus normoglycaemia 2.09 (95% CI 1.78-2.46, p, Sanofi; Regeneron Pharmaceuticals, Sanofi and Regeneron Pharmaceuticals.

Background. Association between age at menarche (AAM) and hypertension remains a controversial topic, and data in China were sparse. Therefore, we aimed to investigate the association between AAM and hypertension in Chinese female population. Methods. In this cross-sectional study, 5,102 females aged ≥15 years were enrolled. Self-reported AAM was assessed by the questionnaire. Multiple linear regression analysis was used to evaluate the association between systolic blood pressure (SBP), diastolic blood pressure (DBP), and AAM. Logistic regression analysis was performed to evaluate the association between hypertension and AAM. Generalized additive model (GAM) and smooth curve fitting (penalized spline method) were conducted to explore the exact shape of curve between them. Results. The overall mean of AAM was 15.5 years. Each additional year of AAM was associated with a 15% higher risk of hypertension (odds ratio (OR) = 1.15, 95% confidence interval (CI): 1.11–1.19). Among females with hypertension, there was a significant positive association between AAM and SBP (β = 0.88, 95% CI: 0.29–1.46) and DBP (β = 0.80, 95% CI: 0.47–1.13). A significantly higher risk of hypertension was found in younger subjects (15–44 y: OR = 1.37, 95% CI: 1.21–1.55; P for interaction = 0.009) compared with those aged between 62 and 97 y.Conclusions. AAM was positively associated with hypertension and blood pressure, especially among females in early adulthood from southern China.

Supplement_Table_1126 for Association Between Lipid Profiles and Arterial Stiffness in Chinese Patients With Hypertension: Insights From the CSPPT by Biming Zhan, Xiao Huang, Jiancheng Wang, Xianhui Qin, Jingping Zhang, Jingjing Cao, Yun Song, Lishun Liu, Ping Li, Renqiang Yang, Yanqing Wu, Qinghua Wu, Yan Zhang, Jianping Li, Yong Huo, Binyan Wang, Xiping Xu, Huihui Bao, and Xiaoshu Cheng in Angiology

We know that silencing Bim, a pro-apoptosis protein, significantly attenuates glucose and oxygen-deprived induced apoptosis in cardiomyocytes. However, the mechanisms underlying the regulation of the Bim activation in the heart have remained unknown. Pim-2 is one of three Pim serine/threonine kinase family members thought to be involved in cell survival and proliferation. H9c2 cardiomyocytes were subjected to a hypoxia/reoxygenation (H/R) condition in vitro, mimicking ischemic/reperfusion injury in vivo. H/R augmented the expression of Bim, Cyt C, and Pim-2 and induced H9c2 cell apoptosis. Overexpression of Pim-2 attenuated apoptosis which induced by H/R in H9c2 cells, via downregulation of Bim and Cyt C expression. Silencing of Pim-2 promoted H/R-induced apoptosis via upregulation of Bim and Cyt C expression. Co-IP revealed the interaction between Pim-2 and Bim protein, with Bim Ser65 phosphorylated by Pim-2. Furthermore, blocking proteasome activity by MG132 prevented Bim degradation, and Bim S65A mutation could reverse the anti-apoptotic role of Pim-2 which induced by H/R. These data demonstrated that Pim-2 is a novel Bim-interacting protein, which negatively regulates Bim degradation and protects H9c2 cardiomyocytes from H/R-induced apoptosis.

To evaluate whether the mean pulse rate (PR) from three oscillometric blood pressure (BP) measurements provides an accurate estimation of electrocardiogram ventricular rate (HR) in patients with permanent atrial fibrillation (AF).BP and PR were measured with an oscillometric BP device for three times with one-minute interval. Simultaneously, one-minute electrocardiogram was also recorded for three times. The first PR and HR values were recorded as PR1 and HR1, and the averages of three PR and HR values as mean PR (mPR) and mean HR (mHR). Meanwhile, the differences between the highest and lowest values among the three PR and HR were calculated as ΔPR and ΔHR. Furthermore, the patients were stratified on ΔPR into the 0-15 and15 subgroups.A moderate positive correlation existed between PR1 and HR1 or mPR and mHR, and Bland-Altman plot also showed quite wide 95% limits between them. Meanwhile, ΔPR was significantly higher than ΔHR (12.1±8.6 vs 3.6±2.5bpm, P0.001). However, in the 0-15 subgroup, the correlation between mPR and mHR was high (R2=0.800), and the 95% limits were only from -11.3 to 14.2bpm with a difference of 1.4bpm. The coincidence (mPR-mHR10bpm) rate was 93.9% when PR≤80bpm, 96.3% when PR 81-100bpm, and 88.9% when PR over 100bpm.The average of three PR values reported by an oscillometric BP device could provide a clinically accepted estimation of mean HR of 3min in AF patients with ΔPR 0-15bpm and mean PR ≤100bpm.

Background Caspase-1 is present in the cytosol as an inactive zymogen and requires the protein complexes named “inflammasomes” for proteolytic activation. However, it remains unclear whether the proteolytic activity of caspase-1 is confined only to the cytosol where inflammasomes are assembled to convert inactive pro-caspase-1 to active caspase-1. Methods We conducted meticulous data analysis method s on proteomic, protein interaction, protein intracellular localization, and gene expressions of 114 experimentally identified caspase-1 substrates and 38 caspase-1 interaction proteins in normal physiological conditions and in various pathologies. Results We made the following important findings: (1) Caspase-1 substrates and interaction proteins are localized in various intracellular organelles including nucleus and secreted extracellularly; (2) Caspase-1 may get activated in situ in the nucleus in response to intra-nuclear danger signals; (3) Caspase-1 cleaves its substrates in exocytotic secretory pathways including exosomes to propagate inflammation to neighboring and remote cells; (4) Most of caspase-1 substrates are upregulated in coronary artery disease regardless of their subcellular localization but the majority of metabolic diseases cause no significant expression changes in caspase-1 nuclear substrates; and (5) In coronary artery disease, majority of upregulated caspase-1 extracellular substrate-related pathways are involved in induction of inflammation; and in contrast, upregulated caspase-1 nuclear substrate-related pathways are more involved in regulating cell death and chromatin regulation. Conclusions Our identification of novel caspase-1 trafficking sites, nuclear and extracellular inflammasomes, and extracellular caspase-1-based inflammation propagation model provides a list of targets for the future development of new therapeutics to treat cardiovascular diseases, inflammatory diseases, and inflammatory cancers. Electronic supplementary material The online version of this article (doi:10.1186/s13045-016-0351-5) contains supplementary material, which is available to authorized users.

Objective To explore the effect and mechanism of angiotensin II receptor blockers – Irbesartan on occurrence of ventricular arrhythmias in rats with myocardial ischemia. Methods Rats with embryonic cardiomyocytes-H9c2 were randomly divided into control group, ischemia group, Irbesartan group and Irbesartan + ischemia group. The cell viability of rats in each group was tested using MTT. Real-time PCR was employed to detect the expression of connexin43 (Cx43) mRNA and western blot to detect the expression of Cx43 and phosphorylated Cx43. SD rats were randomly divided into the sham-operation group (SO), myocardial infarction group (MI), Irbesartan group and MI + Irbesartan group, with 10 rats in each group. HE staining was employed to observe the change in the pathomorphology of left ventricular tissue and TUNEL method to analyze the cell apoptosis in the tissue. The immunofluorescence was adopted to observe the expression and distribution of Cx43 in the left ventricular myocardium and study the change in the expression of Cx43 in the cardiac muscular tissue at mRNA and protein level. Results The intervention of Irbesartan in the condition of ischemia indicated the significant decrease in the number of necrotic cells. The expression of Cx43 was significantly decreased under the culture of ischemia (P

Background At present, the estimation of rest heart rate (HR) in atrial fibrillation (AF) is obtained by apical auscultation for 1min or on the surface electrocardiogram (ECG) by multiplying the number of RR intervals on the 10second recording by six. But the reasonability of 10second ECG recording is controversial. Methods ECG was continuously recorded at rest for 60s to calculate the real rest HR (HR60s). Meanwhile, the first 10s and 30s ECG recordings were used for calculating HR10s (sixfold) and HR30s (twofold). The differences of HR10s or HR30s with the HR60s were compared. The patients were divided into three sub-groups on the HR60s 100bpm. Results No significant difference among the mean HR10s, HR30s and HR60s was found. A positive correlation existed between HR10s and HR60s or HR30s and HR60s. Bland–Altman plot showed that the 95% reference limits were high as −11.0 to 16.0bpm for HR10s, but for HR30s these values were only −4.5 to 5.2bpm. Among the three subgroups with HR60s 100bpm, the 95% reference limits with HR60s were −8.9 to 10.6, −10.5 to 14.0 and −11.3 to 21.7bpm for HR10s, but these values were −3.9 to 4.3, −4.1 to 4.6 and −5.3 to 6.7bpm for HR30s. Conclusion As 10s ECG recording could not provide clinically accepted estimation HR, ECG should be recorded at least for 30s in the patients with AF. It is better to record ECG for 60s when the HR is rapid.

Pulse wave velocity (PWV) has been shown to influence the effects of antihypertensive drugs in the prevention of cardiovascular diseases. Data are limited on whether PWV is an independent predictor of stroke above and beyond hypertension control. This longitudinal analysis examined the independent and joint effect of brachial-ankle PWV (baPWV) with hypertension control on the risk of first stroke. This report included 3310 hypertensive adults, a subset of the China Stroke Primary Prevention Trial (CSPPT) with baseline measurements for baPWV. During a median follow-up of 4.5 years, 111 participants developed first stroke. The risk of stroke was higher among participants with baPWV in the highest quartile than among those in the lower quartiles (6.3% versus 2.4%; hazard ratio, 1.66; 95% confidence interval, 1.06–2.60). Similarly, the participants with inadequate hypertension control had a higher risk of stroke than those with adequate control (5.1% versus 1.8%; hazard ratio, 2.32; 95% confidence interval, 1.49–3.61). When baPWV and hypertension control were examined jointly, participants in the highest baPWV quartile and with inadequate hypertension control had the highest risk of stroke compared with their counterparts (7.5% versus 1.3%; hazard ratio, 3.57; 95% confidence interval, 1.88–6.77). There was a significant and independent effect of high baPWV on stroke as shown among participants with adequate hypertension control (4.2% versus 1.3%; hazard ratio, 2.29, 95% confidence interval, 1.09–4.81). In summary, among hypertensive patients, baPWV and hypertension control were found to independently and jointly affect the risk of first stroke. Participants with high baPWV and inadequate hypertension control had the highest risk of stroke compared with other groups.

Objective To investigate the impact of talking with doctors on blood pressure (BP) in outpatients. Patients and methods This study included 122 hypertensive and 78 normotensive outpatients. BP was measured initially in silence with oscillometric BP monitors three times at 1-min intervals as follows: pre-1, pre-2, and pre-3. BP was then measured with the same device immediately, at 3 min, and at 5 min after talking commenced as follows: during-1, during-3, and during-5. When talking stopped, BP was measured again as post-1, post-3, and post-5. The increments in BP and heart rate (HR) were the differences during and pre-3 values. Results Systolic blood pressure/diastolic blood pressure (SBP/DBP) increased significantly at 1 min during talking compared with pre-3 values. The maximum increment of SBP was 9.1 mmHg, occurring at 3 min and continuing up to 5 min during the talking stage. The maximum increment of DBP was 4.5 mmHg and that of HR was 2.7 bpm, both occurring at 1 min. When talking stopped, the SBP and DBP significantly decreased immediately. SBP at 5 min, DBP at 3 min, and HR at 1 min were similar to their pre-3 values. Logistic multifactor analysis showed that pre-SBP3 level (R=0.141, P=0.023) was an independent factor, but anxiety scale, age, sex, BMI, and hypertension history were not independent factors. Conclusion The maximum SBP increment is 9.1 mmHg and DBP increment is 4.5 mmHg during 5 min of talking with doctor. Meanwhile, the increased SBP needs about 5 min to return to the baseline level.

Previous studies have demonstrated that targeting inflammation is a promising strategy for treating lipopolysaccharide (LPS)-induced sepsis and related heart injury. Interleukin-35 (IL-35), which consists of two subunits, Epstein–Barr virus-induced gene 3 (EBI3) and p35, is an immunosuppressive cytokine of the IL-12 family and exhibits strong anti-inflammatory activity. However, the role of IL-35 in LPS-induced heart injury reains obscure. In this study, we explored the role of IL-35 in heart injury induced by LPS and its potential mechanisms. Mice were treated with a plasmid encoding IL-35 (pIL-35) and then injected intraperitoneally (ip) with LPS (10 mg/kg). Cardiac function was assessed by echocardiography 12 h later. LPS apparently decreased the expression of EBI3 and p35 and caused cardiac dysfunction and pathological changes, which were significantly improved by pIL-35 pretreatment. Moreover, pIL-35 pretreatment significantly decreased the levels of cardiac proinflammatory cytokines including TNF-α, IL-6, and IL-1β, and the NLRP3 inflammasome. Furthermore, decreased number of apoptotic myocardial cells, increased BCL-2 levels and decreased BAX levels inhibited apoptosis, and LPS-induced upregulation of the expression of cardiac pro-fibrotic genes (MMP2 and MMP9) and fibrotic factor (Collagen type I) was inhibited. Further investigation indicated that pIL-35 pretreatment might suppressed the activation of the cardiac NF-κBp65 and TGF-β1/Smad2/3 signaling pathways in LPS-treated mice. Similar cardioprotective effects of IL-35 pretreatment were observed in mouse myocardial fibroblasts challenged with LPS in vitro. In summary, IL-35 pretreatment can attenuate cardiac inflammation, apoptosis, and fibrotic reactions induced by LPS, implicating IL-35 as a promising therapeutic target in sepsis-related cardiac injury.

Background: Accumulating evidence has reported that physical activity (PA) is effective in reducing stroke and mortality. However, whether PA levels are associated with stroke in middle-aged and elderly people in Jiangxi Province of China remains unclear. In the present study, we evaluated the association between PA and the risk of stroke in Jiangxi Province of China. Methods: A cross-sectional survey was conducted in Jiangxi Province of China from November 2013 to August 2014, using standardized questionnaire forms and physical measurements. Self-reported PA was assessed using the international PA questionnaire. A history of stroke was self-reported by answering the questionnaire. Multivariate logistic regression analysis was performed to evaluate the association between PA levels and the risk of stroke after adjustment for sociodemographic characteristics, lifestyle factors, and disease-related risk factors. Results: A total of 10,398 participants (4240 men and 6158 women, aged 45 to 97 years) completed the International Physical Activity Questionnaire (IPAQ). Compared with low-intensity PA, vigorous PA was associated with graded reduction in the risk of stroke (odds ratio [OR] of 0.763, 95% confidence interval [CI] 0.717–0.812, P 0.05). Conclusions: Compared with low PA, vigorous PA, but not moderate PA, was associated with a lower risk of stroke in middle aged and elderly people in southern China, specifically among men. These findings suggested that increasing PA is beneficial.

Background: Pacemaker lead–related thrombosis is a rare but severe complication in patients with pacing lead implantation in the right ventricle. We present a case with recurrent syncope after single-chamber implantable cardioverter defibrillator (ICD) implantation. Pacing lead–related thrombosis was observed during open-heart surgery. This induced intermittent pacemaker dysfunction and recurrent syncope. Case Presentation: A 67-year-old male patient presented with frequent episodes of syncope and a history of dilated cardiomyopathy and paroxysmal ventricular tachycardia. Normal coronary angiography was found, and therefore a single-chamber ICD was implanted into the right ventricle to prevent cardiac events in 2013. However, he was referred to our hospital because of recurrent syncope 3 to 4 years after ICD implantation. A comprehensive investigation was performed to find out the etiology for the recurrent syncope. Pacing lead thrombosis was finally observed during open-heart surgery, which can introduce intermittent pacemaker dysfunction. After the thrombus was removed and the lead was separated from the posterior leaflet of the tricuspid valve, the ICD functioned normally after reprogramming. Oral anticoagulant was prescribed after discharging. During the 1-year follow-up period, this patient was free of syncope. Conclusions: This case illustrated that pacemaker lead–associated thrombosis should be considered when the cardiac implantable electronic device fails to prevent patients from having cardiac events. Oral anticoagulant might be important for preventing thrombosis among patients with ICD implantation into the right ventricle.

BACKGROUND VSMC proliferation plays a key role in atherosclerosis, but the role of XPD in VSMC proliferation remains unknown. We investigated the expression of XPD, which is involved in cell cycle regulation, and its role in VSMC proliferation response to atherogenic stimuli. MATERIAL AND METHODS Human umbilical vein VSMCs were transfected with recombinant plasmid pEGFP-N2/XPD and pEGFP-N2 and incubated with PDGF-BB in vitro. Cell viability was determined by MTT assay. The expressions of XPD, GSK3β, p-GSK3β, CDK4, and cyclin D1 protein were detected by Western blot analysis. Cell cycle was examined by flow cytometry. RESULTS PDGF inhibited the expression of XPD in VSMCs and promoted VSMC proliferation. Overexpression of XPD significantly augmented cell cycle arrest, and attenuated protein expression levels of CDK4 and cyclin D1 in VSMCs. XPD overexpression suppressed the effects of PDGF-BB in promoting G1/S transition and accelerating protein expression levels of CDK4 and cyclin D1. XPD diminished the phosphorylation of GSK3β, and SB216763 inhibited the reduction effect of XPD on CDK4 and cyclin D1. CONCLUSIONS XPD induces VSMC cell cycle arrest, and the activation of GSK3β plays a crucial role in inhibitory effect of XPD on VSMC proliferation.

Long-term heart rate (HR) control is a management strategy for patients with chronic atrial fibrillation (AF). Nevertheless, the optimal target HR of AF patients is debatable. Our aim was to study HR at rest, during, and after a 6-minute walk test (6MWT) in AF patients, compared with controls with sinus rhythm (SR). Consecutive matched patients with AF (n = 186) or SR (n = 172) were recruited, and 6MWT was performed. HRs at rest, during 6MWT, and recovery periods were recorded. All subjects were divided into 5 subgroups (90 beats/min. Unlike the SR patients, the 4 AF subgroups with HR >80 beats/min at the fifth minute after 6MWT did not recover to at rest levels. In conclusion, HR increased excessively during 6MWT and HR recovery was delayed after 6MWT in AF patients, especially when HR at rest is >90 beats/min. The optimal initial HR at rest for AF patients should perhaps be

Background The present study performed a meta-analysis of randomized and prospective trials to compare the outcomes of percutaneous coronary intervention (PCI) with stents versus coronary artery bypass graft surgery (CABG) for unprotected left main coronary artery (UPLM) stenosis. Methods The Cochrane Library, PubMed and EMBASE databases were systematically searched until July 2017. The Newcastle-Ottawa scale was used for quality assessment. Results A total of 19 studies with 16,900 participants were included. Pooled analysis showed no significant differences in all-cause mortality (odds ratio [OR] 0.94; 95% CI 0.74-1.20) and cardiac death (OR 1.04; 95% CI 0.74-1.47). However, subgroup analysis showed that PCI was associated with a low all-cause mortality rate at 30-day follow up (OR 0.48; 95% CI 0.26-0.89). The stroke rate in PCI was lower in short-term follow up (OR 0.45; 95% CI 0.23-0.88) and long-term follow up (OR 0.36; 95% CI 0.27-0.47). On the other hand, PCI was associated with higher risk of myocardial infarction (OR 1.59; 95% CI 1.34-1.88), repeat revascularization (OR 2.47; 95% CI 1.80-3.37) and target vessel revascularization (OR 2.10; 95% CI 1.72-2.57) compared to CABG in the pooled analysis. Conclusions The current evidence suggests that the risk of stroke was significantly reduced in PCI compared to that in CABG. Therefore, PCI is the preferred treatment for patients with a high risk of stroke. Additionally, in short-term follow up, PCI was reported to be safe and effective for UPLM patients compared to CABG. However, CABG caused fewer complications long term.

Objectives To examine the association between sleep duration on workdays or non-workdays and unsatisfactory blood pressure (BP) control in Southern China. Methods We analyzed 4370 hypertensive patients, including their self-reported sleep duration on workdays or non-workdays and their BP. Unsatisfactory BP control was defined as systolic BP of ≥140 mm Hg or diastolic BP of ≥90 mm Hg. Multivariate logistic regression analyses were performed to evaluate the association between sleep duration and unsatisfactory BP control. Results Overall, the multivariable-adjusted odds ratios of unsatisfactory BP control risk were 1.59 (95% confidence interval, 1.14–2.22) for 9–10 hours of sleep on workdays and 1.47 (95% confidence interval, 1.07–2.03) for ≥10 hours of sleep on non-workdays compared with a sleep duration of 5–9 hours. No association between a short sleep duration and unsatisfactory BP control was noted. The association between a longer sleep duration (≥10 hours) and unsatisfactory BP control was more pronounced among women aged 65–70 years, with a body mass index ≥ 24 kg/m2. Conclusion People with hypertension who slept 9–10 hours on workdays and ≥10 hours on non-workdays were more likely to have unsatisfactory BP control compared with those with a sleep duration of 5–9 hours; these associations tended to vary by age, sex, and body mass index. These findings indicate that a longer sleep duration might be a way to predict uncontrolled BP in hypertensive adults.

OBJECTIVE To investigate the influence of arm circumference (AC) on the brachial blood pressure (BP) measured with an adult cuff. PARTICIPANTS AND METHODS This study included 208 patients (150 men, 61.0±8.0 years) for coronary angiography. Intra-aortic BP and noninvasive right brachial oscillometric BP (noninvasive BP) were measured simultaneously before coronary angiography. The noninvasive BP was measured using an electronic oscillometric device with an adult cuff (12×22 cm). The mid-ACs were measured. Thus, proper cuff-arm (≤26 cm) and small cuff (>26 cm) groups were created. The difference in intra-aortic and noninvasive BP was calculated as BPi-n. RESULTS The correlation coefficients (r) between noninvasive and invasive systolic blood pressure (SBP), mean artery pressure, and diastolic blood pressure (DBP) were 0.88, 0.76, and 0.58, respectively. The SBPi-n was higher (7.9±1.6 vs. 5.2±1.1 mmHg), but the DBPi-n (3.9±1.4 vs. 6.1±1.0 mmHg, P 26 cm. Among the four subgroups divided by 20-23, 24-26, 27-30, and 31-37 cm of AC, as the AC increased, the SBPi-n increased, but DBP decreased, resulting in noninvasive SBP 4.6 mmHg higher and noninvasive DBP 4.6 mmHg lower in the 31-37 cm group in comparison with the 20-23 cm group. CONCLUSION When an adult cuff was used, the noninvasive oscillometric SBP was overestimated, but DBP was underestimated in the individuals with large arms against the intra-aortic BP.

Background Sorafenib is a relatively new multi-kinase inhibitor used to treat a wide range of cancers. As fatal adverse events from sorafenib therapy are rare, their investigation requires a meta-analysis. Aim of the review To provide a meta-analysis of sorafenib-associated fatal adverse events with the most expansive and current data. Method We searched Medline, EMBASE, Web of Science and Cochrane Library databases. We also searched abstracts from a number of conferences. Twenty trials of sorafenib were found in 9434 cancer patients, tested against placebos and against other drugs. We calculated relative risks and incidences for sorafenib-associated mortality. Results Overall incidence of sorafenib-associated mortality was 3.3 %. Patients with renal cell carcinoma (RCC) and thyroid cancer had treatment-related mortality ≥5 %. Patients treated with sorafenib had a significantly greater risk of mortality than those in placebo/control groups, with an RR of 1.75. Subgroup analyses also showed significant differences in sorafenib versus placebo (RR 1.87, 95 % CI 1.23–2.86; I 2 = 0.0 %, P = 0.865); and sorafenib + platinum-based chemotherapy (RR 2.03, 95 % CI 1.15–3.59; I 2 = 0.0 %, P = 0.654). However, sorafenib had lower risk than other multi-targeted antiangiogenic tyrosine kinase inhibitors. Patients with RCC and non-small-cell lung carcinoma were significantly more vulnerable. Conclusion Sorafenib presents a significant risk of fatal adverse events (FAEs) in patients with cancer, especially for RCC or non-small-cell lung carcinoma, and in patients treated with sorafenib + platinum-based chemotherapy. However, compared with other multi-targeted antiangiogenic tyrosine kinase inhibitors, sorafenib has a lower risk of FAEs.

In this study, we analyzed two cases of pure cerebral fat embolism and reviewed related literatures to explore the pathogenesis, clinical manifestations, diagnosis and treatment of cerebral fat embolism, improve the treatment efficiency and reduce the misdiagnosis rate. In our cases, patients fully returned to consciousness at the different times with good prognosis, normal vital signs and without obvious sequelae. For patients with the limb fractures, who developed coma without chest distress, dyspnea or other pulmonary symptoms 12 or 24 h post injury, cerebral fat embolism should be highly suspected, except for those with intracranial lesions, such as delayed traumatic intracerebral hemorrhage, etc. The early diagnosis and comprehensive treatment can improve prognosis.

Sleep apnoea is associated with chronic kidney diseases. A high obstructive sleep apnoea (OSA) prevalence is shown in patients with hypertrophic cardiomyopathy (HCM). Whether the presence of OSA would affect the renal function of patients with HCM is unknown. Forty-five consecutive patients with HCM were divided into the HCM OSA− and OSA+ groups. Forty-three patients with OSA without HCM were recruited as controls. Clinical indices, including estimated glomerular filtration rate (eGFR) and urine 8-hydroxy-2-deoxyguanosine (8-OHdG), were measured. The eGFR was significantly lower in the HCM OSA+ group than in the HCM OSA− (P

Adropin is a secreted protein that regulates endothelial function. However, adropin levels in obese adolescent patients are currently uncertain. Therefore, we evaluated the association between plasma adropin levels and vascular endothelial function and investigated the effect of aerobic exercise in obese adolescents. A total of 45 obese adolescents and 20 controls (age 16–19 years) were included in our study. The obese adolescents received 12 weeks of aerobic exercise training. Serum adropin was detected using enzyme-linked immunosorbent assay. Vascular reactive hyperemia indexes (RHIs) were obtained using Endo-PAT2000. Adropin levels and RHI were significantly lower in obese adolescents than in normal-weight adolescents. Adropin levels and RHI increased significantly independently of changes in body weight after an exercise intervention (P

Both increased arterial stiffness and higher total homocysteine (tHcy) are associated with an elevated risk for cardiovascular disease. However, the relationship between tHcy and arterial stiffness is still inconclusive. The authors aimed to test the relationship of tHcy with carotid‐femoral pulse wave velocity (cfPWV) and examine the possible effect modifiers in adults. A study was conducted from July to September 2016 in Jiangsu Province, China. A total of 16 644 participants were enrolled in the final analysis. Increased arterial stiffness is defined as a cfPWV ≥10 m/s. Overall, there was a positive association between tHcy and cfPWV levels (per 5‐μmol/L tHcy increase: β = 0.10; 95% confidence interval [CI], 0.08–0.13) and increased arterial stiffness (per 5‐μmol/L tHcy increase: odds ratio, 1.11; 95% CI, 1.07–1.14). Compared with participants with tHcy

Several studies have investigated the effect of nicorandil on contrast-induced nephropathy (CIN) in patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI). However, the final results of these trials are not identical. This meta-analysis evaluated the role of nicorandil administration on CIN prevention. We searched databases to find randomized controlled trial (RCT) comparing nicorandil with hydration versus conventional hydration therapy on preventing CIN. Finally, 5 articles (805 patients) were included in our meta-analysis; the data showed that nicorandil was related to significant reduction in the risk of CIN (risk ratio = 0.37, 95% confidence interval [CI]: 0.22-0.61, P = .0001). We found not only the cystatin C level after operation was nonsignificant between 2 groups at the first 24 hours ( P = .65, 95% CI = −0.06 to 0.04) and 48 hours ( P = .19, 95% CI = −0.11 to 0.02) but also the serum creatinine level was nonsignificantly elevated, at 24 hours ( P = .46, 95% CI = −5.19 to 1.88) and 72 hours ( P = .49, 95% CI = −0.49 to 0.34). Our analysis suggested that the nicorandil treatment compared with conventional hydration can significantly reduce the risk of CIN.

This study aimed to assess the relationship between sleep duration on work or nonworkdays and myocardial infarction (MI) and stroke in Southern China.A cross-sectional survey was conducted among 15,364 participants of age ≥15 years in Southern China from November 2013 to August 2014. Data on self-reported duration of sleep on workdays or nonworkdays as well as history of MI and stroke were collected in the questionnaire. The subjects were examined for weight, height, waist circumference, and blood pressure. Multivariate logistic regression analyses were performed to evaluate the association of sleep duration with MI and stroke.Overall, compared with a sleep duration of 6-8 h, individuals who slept6 h on workdays and nonworkdays were associated with increased risk for MI (odds ratio [OR] = 3.17, 2.04). Furthermore, individuals who slept8 h on workdays and nonworkdays were associated with an increased risk for stroke (OR = 1.86, 1.54). Although this association persisted in men and subjects aged65 years, we also observed that long sleep duration on workdays was associated with MI, especially among women, and short sleep duration on nonworkdays was associated with stroke among those aged 65 years or older. Participants with abnormal sleep duration and hypertension had higher risk of MI and stroke. Sleep debt was independently associated with MI risk, but not stroke (OR = 1.40; 95% confidence interval [CI]: 1.06-1.86), specifically among men aged65 years.Compared with a sleep duration of 6-8 h, both short and long sleep duration were associated with the prevalence of MI and stroke and these associations were more pronounced among hypertensive persons, and tended to vary by age and sex. Moreover, sleep debt was linked to greater MI risk among men aged65 years. These findings suggest that we should develop a healthy biological clock.

This study aimed to provide insights into the relationship between lipid levels and new-onset diabetes (NOD) in 14,864 Chinese hypertensive patients without diabetes (6056 men and 8808 women) aged 45–75 years from the China Stroke Primary Prevention Trial (CSPPT, led by Nanfang Hospital, Guangzhou, China). NOD (defined as fasting plasma glucose (FPG) ≥ 7.0 mmol/L at the end of study or self-reported physician diagnosis of diabetes or self-reported use of hypoglycemic agents during follow-up) was analyzed using multivariate analysis. Follow-up was censored on August 24, 2014. Among the 14,864 subjects, 1615 developed NOD (10.9%, men = 10.8% and women = 10.9%). Increased triglycerides (TG) [odds ratio (OR) = 1.18; 95% confidence interval (CI): 1.13–1.25, P

Background The optimal range of blood pressure variability remains unclear. We aimed to stratify the degree of risk of stroke based on visit‐to‐visit systolic blood pressure (SBP) variability in a large Chinese hypertensive population in 32 communities. Methods and Results We retrospectively analyzed the data of 20 702 hypertensive patients from the China Stroke Primary Prevention Trial. The participants were randomized into 2 treatment groups to receive either enalapril or enalapril plus folic acid. Their blood pressures were measured every 3 months. The outcome was the first stroke. Three parameters of SBP variability were calculated: standard deviation, coefficient of variation, and average real variability. The records of first 4, 6, 8, 10 and 12 visits at which SBP was measured were used to calculate SBP variability and to predict subsequent stroke risk in adjusted Cox regression models. After median follow‐up of 4.5 years, 597 patients had experienced stroke. Visit‐to‐visit SBP variability was an independent predictor of subsequent stroke (eg, the hazard ratio for the highest quintile of average real variability [22.67–61.07 mm Hg] over 6 visits was 1.55, 95% CI 1.07–2.25, P =0.021), independent of mean SBP over the follow‐up period. Its value was more predictive when more blood pressure records were used. Conclusions Visit‐to‐visit SBP variability is an independent predictor of primary stroke in Chinese hypertensive patients. This predictive value depends on the number of blood pressure measurements used to calculate variability but is independent of mean SBP. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00794885.

Endocytosis is a cellular process mostly responsible for membrane receptor internalization. Cell membrane receptors bind to their ligands and form a complex which can be internalized. We previously proposed that F-BAR protein initiates membrane curvature and mediates endocytosis via their binding partners. However, F-BAR protein partners involved in membrane receptor endocytosis and the regulatory mechanism remain unknown. In this study, we established a group of database mining strategies to explore mechanisms underlying receptor-related endocytosis. We identified 34 endocytic membrane receptors and 10 regulating proteins for vesicle formation in clathrin-dependent endocytosis (CDE), a major process of membrane receptor internalization. We found that F-BAR protein FCHSD2 (Carom) may facilitate endocytosis via 9 endocytic partners. Carom is highly expressed, along with highly expressed endocytic membrane receptors and partners, in endothelial cells and macrophages. We established 3 models of Carom-receptor complex and their intracellular trafficking based on protein-protein interaction and subcellular localization. We conclude that Carom may mediate receptor endocytosis and transport endocytic receptors to the cytoplasm for receptor signaling and lysosome/proteasome degradation, or to the nucleus for RNA processing, gene transcription and DNA repair.

The relationship between clinical phenotypes and desmosomal gene mutations in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) is poorly characterized. Therefore, we performed a meta-analysis to explore the genotype-phenotype relationship in patients with ARVC. Any studies reporting this genotype-phenotype relationship were included. In total, 11 studies involving 1,113 patients were included. The presence of desmosomal gene mutations was associated with a younger onset age of ARVC (32.7 ± 15.2 versus 43.2 ± 13.3 years; P = 0.001), a higher incidence of T wave inversion in V1–3 leads (78.5% versus 51.6%; P = 0.0002) or a family history of ARVC (39.5% versus 27.1%; P = 0.03). There was no difference in the proportion of males between desmosomal-positive and desmosomal-negative patients (68.3% versus 68.9%; P = 0.60). The presence of desmosomal gene mutations was not associated with global or regional structural and functional alterations (63.5% versus 60.5%; P = 0.37), epsilon wave (29.4% versus 26.2%; P = 0.51) or ventricular tachycardia of left bundle-branch morphology (62.6% versus 57.2%; P = 0.30). Overall, patients with desmosomal gene mutations are characterized by an earlier onset age, a higher incidence of T wave inversion in V1–3 leads and a strong family history of ARVC.