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Background Dyslipidemia International Study II (DYSIS II)‐China was conducted to determine the low‐density lipoprotein cholesterol (LDL‐C) goal (

Study objective This study aimed to determine the safety and efficacy of a novel GP Ib receptor inhibitor in patients with non-ST segment elevation myocardial infarction (NSTEMI) undergoing percutaneous coronary intervention (PCI). Design and setting Multicenter, randomized, double-blind, placebo-controlled, dose-escalating, phase Ib-IIa clinical trial. Eligible patients were randomly assigned to the low-dose (n=20, 2 IU/60 kg), moderate-dose (n=20, 3 IU/60 kg), or high-dose anfibatide group (n=20, 5 IU/60 kg), or the placebo group (n=30). Anfibatide was administered for up to 48 hours along with standard aspirin and clopidogrel therapy. Patients Ninety patients with NSTEMI who underwent PCI at six academic hospitals in China. Measurements and main results All three doses of anfibatide showed dose-dependent antiplatelet activity as measured by ex vivo platelet aggregation at 5 minutes, 24 hours, and 48 hours during infusion, and 4 hours post-infusion compared with placebo. Higher inhibition of platelet aggregation occurred in all anfibatide groups compared with the placebo group. The post-procedural TIMI grade flow, myocardial blush grade, and corrected TIMI frame count were not significantly different among the four groups. Thirty-day mortality, non-fatal myocardial infarction, and major bleeding were rare and comparable between patients who received anfibatide and placebo. There was no significant difference in the platelet count among the groups during follow-up. Conclusions This study shows that intravenous administration of the platelet receptor GP Ib antagonist anfibatide is feasible and safe to inhibit platelet aggregation without increasing the risk of bleeding and thrombocytopenia in patients with NSTEMI undergoing PCI.

BACKGROUND Based on coronary angiography and mean aortic pressure, a specially designed computational flow dynamics (CFD) method is proposed to determine contrast fractional flow reserve (cFFR) without using invasive pressure wire. This substudy assessed diagnostic performance of coronary angiography-derived cFFR in catheterization laboratory, based on a previous multicenter trial for online assessment of coronary angiography-derived FFR (caFFR). METHODS Patients with diagnosis of stable angina pectoris or unstable angina pectoris were enrolled in six centers. Wire-based FFR was measured in coronary arteries with 30-90% diameter stenosis. Offline angiography-derived cFFR was computed in blinded fashion against the wire-based FFR and caFFR at an independent core laboratory. RESULTS A total of 330 patients were enrolled to fulfill inclusion/exclusion criteria from June 26 to December 18, 2018. Offline angiography-derived cFFR and wire-based FFR results were compared in 328 interrogated vessels. The statistical analysis showed the highest diagnostic accuracy of 89.0 and 86.6% for angiography-derived cFFR with a cutoff value of 0.94 and 0.93 against the wire-based FFR with a cutoff value of 0.80 and 0.75, respectively. The corresponding sensitivity and specificity were 92.2 and 87.3% for the cutoff value of 0.94 and 80.0 and 88.4% for the cutoff value of 0.93, which are similar to those against the caFFR. The receiver-operating curve has area under the curve of 0.951 and 0.972 for the wire-based FFR with the cutoff value of 0.80 and 0.75, respectively. CONCLUSIONS Coronary angiography-derived cFFR showed higher accuracy, sensitivity, and specificity against wired-based FFR and caFFR. Hence, angiography-derived cFFR could enhance the hemodynamic assessment of coronary lesions.

Aims/Introduction We aimed to investigate the relationship between glycemic status and coronary artery disease (CAD) extent and severity in ST‐elevation myocardial infarction (STEMI) patients, and further examine whether diabetes patients could benefit from glycosylated hemoglobin (HbA1c) below the recommended level. Materials and Methods Consecutive STEMI patients admitted in 2015–2017 across 244 hospitals were included in the China STEMI Care Project‐2. We carried out a cross‐sectional study comprising 8,370 participants with a record of HbA1c testing after admission. CAD extent and severity were assessed by admission heart rate, Killip classification and the number of stenosed vessels based on the coronary angiogram. Results Diabetes patients showed a greater risk for higher Killip class, admission tachycardia (admission heart rate ≥100 b.p.m.) and multivessel CAD (presence of left main and/or triple vessel disease). Likewise, HbA1c level was significantly associated with CAD extent and severity. While dividing diabetes patients according to general HbA1c targets (HbA1c ≤6.5, 6.5–7.0 and ≥7.0%), diabetes patients with HbA1c ≤6.5% showed a 1.30‐fold higher risk for multivessel CAD (adjusted odds ratio 1.30, 95% confidence interval 1.05–1.62). In stratified analysis, the association was even stronger in patients with hypertension (adjusted odds ratio 1.41, 95% confidence interval 1.08–1.86) or hyperlipidemia (adjusted odds ratio 1.57, 95% confidence interval 1.17–2.12). Conclusions HbA1c level is independently correlated with CAD extent and severity in STEMI patients. HbA1c below generally recommended levels might still increase the risk of CAD progression, especially for diabetes patients with hypertension or hyperlipidemia., The effect of type 2 diabetes and glycosylated hemoglobin level on the development of coronary artery disease was determined based on >8,000 patients admitted with a ST‐elevation myocardial infarction across China. Glycosylated hemoglobin below generally recommended levels might still increase the risk of coronary artery disease progression, especially for diabetes patients with hypertension or hyperlipidemia. For post‐myocardial infarction patients with diabetes and other comorbidities, physicians might use the number of stenosed vessels to improve cardiovascular risk assessment, and consider more intensive and individually tailored glycemic control.

Background Despite guideline recommendations, dual antiplatelet therapy (DAPT) is frequently used for longer than 1 year after an acute coronary syndrome (ACS) event. In Asia, information on antithrombotic management patterns (AMPs), including DAPT post discharge, is sparse. This analysis evaluated real‐world AMPs up to 2 years post discharge for ACS. Hypothesis There is wide variability in AMP use for ACS management in Asia. Methods EPICOR Asia (NCT01361386) is a prospective observational study of patients discharged after hospitalization for an ACS in eight countries/regions in Asia, followed up for 2 years. Here, we describe AMPs used and present an exploratory analysis of characteristics and outcomes in patients who received DAPT for ≤12 months post discharge compared with >12 months. Results Data were available for 12 922 patients; of 11 639 patients discharged on DAPT, 2364 (20.3%) received DAPT for ≤12 months and 9275 (79.7%) for >12 months, with approximately 60% still on DAPT at 2 years. Patients who received DAPT for >12 months were more likely to be younger, obese, lower Killip class, resident in India (vs China), and to have received invasive reperfusion. Clinical event rates during year 2 of follow‐up were lower in patients with DAPT >12 vs ≤12 months, but no causal association can be implied in this non‐randomized study. Conclusions Most ACS patients remained on DAPT up to 1 year, in accordance with current guidelines, and over half remained on DAPT at 2 years post discharge. Patients not on DAPT at 12 months are a higher risk group requiring careful monitoring.

To evaluate the association between plasma retinol levels with all‐cause mortality and investigate the possible effect modifiers in general hypertensive patients with no previous cardiovascular disease (CVD). This case‐control study was nested in the China Stroke Primary Prevention Trial (CSPPT), a randomized, double‐blind, controlled trial conducted in 32 communities in Anhui and Jiangsu provinces in China. The current study included 617 cases of all‐cause mortality and 617 controls matched on age (≤1 year), sex, treatment group, and study site. All‐cause mortality was the main outcome in this analysis, which included death due to any reason. The median follow‐up duration was 4.5 years. Overall, there was a U‐shaped relation of plasma retinol with all‐cause mortality. In the threshold effect analysis, the risk of all‐cause mortality significantly decreased with the increase in plasma retinol (per 10 μg/dL increments: OR, 0.73; 95% CI: 0.61‐0.87) in participants with plasma retinol

Background Patients with non‐ST‐segment elevation myocardial infarction (NSTEMI) have a generally poor prognosis and antithrombotic management patterns (AMPs) used post‐acute coronary syndrome (ACS) remain unclear. Duration of dual antiplatelet therapy (DAPT) and patient characteristics was evaluated in NSTEMI patients enrolled in EPICOR Asia. Hypothesis Patients stopping DAPT early may benefit from more intensive monitoring. Methods EPICOR Asia was a prospective, real‐world, primary data collection, cohort study in adults with an ACS, conducted in eight countries/regions in Asia, with 2 year follow‐up. Eligible patients were hospitalized within 48 hours of symptom onset and survived to discharge. We describe AMPs and baseline characteristics in NSTEMI patients surviving ≥12 months with DAPT duration ≤12 and > 12 months post‐discharge. Clinical outcomes (composite of death, myocardial infarction, and stroke; and bleeding) were also explored. Results At discharge, 90.8% of patients were on DAPT (including clopidogrel, 99%). At 1‐ and 2‐year follow‐up, this was 79.2% and 60.0%. Patients who stopped DAPT ≤12 months post‐discharge tended to be older, female, less obese, have prior cardiovascular disease, and have renal dysfunction. While causality cannot be inferred, the incidence of the composite endpoint over the subsequent 12 months was 10.6% and 3.1% with shorter vs longer use of DAPT, and mortality risk over the same period was 8.4% and 1.6%. Conclusions Over 90% of NSTEMI patients were discharged on DAPT, with 60% on DAPT at 2 years. Patients stopping DAPT early were more likely to have higher baseline risk and may therefore benefit from more intensive monitoring during long‐term follow‐up.

Aims/Introduction To investigate the relationship between various glucose metabolic status and arterial stiffness, and further explore the threshold of blood glucose indices for the risk of arterial stiffness. Materials and Methods The present cross‐sectional study included 4,851 individuals from a Chinese community. Overnight fasting blood glucose and 2‐h post‐load glucose were sampled. Arterial stiffness was measured as brachial‐ankle pulse wave velocity. The association was examined using generalized linear regression models. The threshold effect was explored using two piecewise linear regression models by the smoothing plot. Results After adjustment for covariates, isolated impaired fasting glucose, isolated impaired glucose tolerance, combined glucose intolerance and newly diagnosed diabetes mellitus were associated with a greater risk of arterial stiffness compared with normal glucose tolerance (B = 18.09, 95% confidence interval [CI] 0.42–35.76, P = 0.045; B = 28.51, 95% CI: 3.40–53.62, P = 0.026; B = 60.70, 95% CI: 38.37–83.04, P < 0.001; B = 95.06, 95% CI: 71.88–118.25, P < 0.001, respectively). Furthermore, there was a non‐linear relationship between 2‐h post‐load glucose and arterial stiffness. A threshold for 2‐h post‐load glucose of 6.14 mmol/L was observed for the risk of arterial stiffness. Conclusions Impaired fasting glucose, impaired glucose tolerance, combined glucose intolerance and newly diagnosed diabetes mellitus were related to a greater risk of arterial stiffness compared with normal glucose levels. A threshold for 2‐h post‐load glucose of 6.14 mmol/L probably exists for the risk of arterial stiffness.

The relationship of folic acid supplementation with the risk of cancer remains inconclusive. We aimed to evaluate the effects of folic acid supplementation on cancer incidence among adults with hypertension without history of stroke or myocardial infarction (MI) in the China Stroke Primary Prevention Trial (CSPPT). A total of 20,702 hypertensive adults without history of stroke or MI, stratified by MTHFR C677T genotypes(CC, CT and TT), were randomly assigned to receive double-blind daily treatment with a single pill containing 10 mg enalapril and 0.8 mg folic acid(n = 10,348) or a pill containing 10 mg enalapril alone(n = 10,354). During a median treatment duration of 4.5 years, cancer occurred in 116 participants(1.12%) in the enalapril-folic acid group versus 116 participants(1.12%) in the enalapril group (HR, 1.00; 95%CI, 0.77-1.29). There was also no significant difference in the HRs for specific types of cancer(esophageal, gastric, breast, lung, colorectal, head and neck, liver and gynecologic cancer or lymphoma) or cancer mortality(HR, 1.05; 95%CI, 0.69-1.58). For participants not receiving folic acid treatment (enalapril only group), MTHFR 677 TT genotype was an independent predictor of total cancer risk compared to CC genotype (HR, 1.86; 95%CI, 1.07-3.22). Consistently, a beneficial effect was observed in participants with MTHFR TT genotype and low folate levels (

Several large prospective studies show an association between serum uric acid (SUA) and cancer, however there is a lack of evidence in China. We aimed to investigate the effects of SUA levels on cancer incidence and mortality in China. This study included 20,577 adult hypertensive patients with valid SUA measurements who participated in the China Stroke Primary Prevention Trial where subjects were randomly assigned to receive a double-blind treatment of either 10 mg enalapril (n = 10,286) or 10.8 mg enalapril-folic acid (n = 10,291). Subjects were prospectively followed for a median of 4.5 years. Cox proportional hazards models were used to calculate hazards ratios (HR) of cancer risk associated with SUA. A total of 232 participants developed cancer. SUA was independently associated with increased cancer risk in the enalapril group [HR: 1.12, (95% CI: 1.03-1.22)]. Compared to the lowest tertile, combined subjects with SUA levels from the upper two tertiles had a higher risk of cancer in the enalapril group [T2 + T3: HR: 1.58, (95% CI: 1.02-2.47)]. In cancer site-specific analyses, a positive association of SUA levels with digestive cancer and all fatal cancer was also observed [HR: 1.18, (95% CI: 1.09-1.27); HR: 1.15, (95% CI: 1.03-1.28), respectively] in the enalapril group. Interestingly, SUA levels were not associated with the risk of cancer or related mortality in the enalapril folic acid group. Our results suggest that elevated SUA is independently and positively associated with the risk of total cancer incidence, digestive cancer incidence and cancer mortality among hypertensive Chinese.

Background The aim of the present post hoc analysis of the China Stroke Primary Prevention Trial (CSPPT) was to evaluate the effect of folic acid supplementation on the risk of new-onset diabetes in hypertensive adults in China. Methods In all, 20 702 hypertensive adults with no history of stroke and/or myocardial infarction (MI) were randomly assigned to receive double-blind daily treatment with tablets containing either: (i) 10 mg enalapril and 0.8 mg folic acid (n = 10 348); or (ii) 10 mg enalapril alone (n = 10 354). New-onset diabetes was defined as either self-reported physician-diagnosed diabetes or the use of glucose-lowering drugs during the follow-up period of the CSPPT. Results Over a median treatment duration of 4.5 years, new-onset diabetes occurred in 198 (2.0%) and 214 (2.1%) subjects in the enalapril–folic acid and enalapril groups, respectively (hazard ratio [HR] 0.92; 95% confidence interval [CI] 0.76–1.12). Similar results were observed when analyses were limited to subjects with baseline fasting glucose (FG)

Background In-hospital and postdischarge mortality for acute coronary syndromes (ACS) vary across Asia and remain generally poorer than globally. The relationship between real-life antithrombotic management patterns (AMPs) and ACS-related outcomes in Asia is unclear. Methods EPICOR Asia (Long-tErm follow-uP of antithrombotic management patterns In acute CORonary syndrome patients in Asia) (NCT01361386) is a prospective, multinational, observational study of patients discharged after hospitalization for an ACS, with 2-year follow-up. The aim is to describe short- and long-term (up to 2 years post–index event) AMPs in patients hospitalized for ACS and to record clinical outcomes, healthcare resource use, and self-reported health status. Pre- and in-hospital management, AMPs, and associated outcomes, with particular focus on ischemic and bleeding events, will be recorded during the 2-year follow up. Results Between June 2011 and May 2012, 13 005 patients were enrolled. From these, 12 922 patients surviving an ACS (6616 with STEMI, 2570 with NSTEMI, and 3736 with UA) were eligible for inclusion from 219 hospitals across 8 countries and regions in Asia: China (n = 8214), Hong Kong (n = 177), India (n = 2468), Malaysia (n = 100), Singapore (n = 93), South Korea (n = 705), Thailand (n = 957), and Vietnam (n = 208). Conclusions EPICOR Asia will provide information regarding clinical management and AMPs for ACS patients in Asia. Impact of AMPs on clinical outcomes, healthcare resource use, and self-reported health status both during hospitalization and up to 2 years after discharge will also be described.

1969年,McCully 首次发现同型半胱氨酸水平即使轻度升高也可加速动脉粥样硬化的发展,由此提出“同型半胱氨酸-动脉粥样硬化学说”1。接下来的一些前瞻性队列研究提出,同型半胱氨酸水平每降低3 µmol/L可以使脑卒中风险下降24%2。然而,考察降低同型半胱氨酸治疗对脑卒中影响的一些随机、对照临床研究并未观察到明确的结果3。需要注意的是,流行病学研究与临床试验存在诸多重要的不同之处。一般队列研究多关注相对健康人群,而大多数临床研究入组的则是患有心脑血管疾病的受试者;此外,很多临床研究入组的是本身叶酸摄入较多或已经在食物中强化补充叶酸的人群3,因而缺乏足够的效能检测出补充叶酸的明显疗效。因此,在血同型半胱氨酸水平升高且未经食物强化补充叶酸的人群中降低同型半胱氨酸是否可以获益目前尚不明确。鉴别出可以显著受益于降低同型半胱氨酸治疗的人群不仅可以进一步解释疾病的发病机理,同时具有非常重要的临床和公共卫生价值。 既往研究表明高血压是脑卒中的重要可干预危险因素4。更为重要的是,高血压和同型半胱氨酸升高对脑卒中风险升高显示出了交互效应。与无高血压且同型半胱氨酸水平正常人群相比,同时有高血压和同型半胱氨酸水平升高(≥ 10 µmol/L)的人群(我们将该人群定义为“H型高血压”)的脑卒中风险显著升高(男性:OR,12,95% CI:6-23;女性:OR,17,95% CI:10-29)5。同型半胱氨酸水平升高多源于叶酸摄入不足,或叶酸及同型半胱氨酸代谢过程中关键酶的基因缺陷6,7。有研究表明,使用降压药,尤其是血管紧张素转化酶抑制剂与叶酸联合,可以有效控制H型高血压的风险8,9。例如,Albert等研究发现ACEI与补充叶酸疗法在降低心脑血管疾病方面具有显著的交互作用(P = 0.03)9。 同型半胱氨酸升高对血管有多重不良效应,包括损伤内皮细胞、促进氧化应激及改变DNA甲基化等10。同时,同型半胱氨酸水平升高是叶酸缺乏的重要指标;除了降低同型半胱氨酸外,叶酸具有直接抗氧化及内皮细胞保护效应(作用于内皮细胞一氧化氮合成酶)11。 我们前期一项meta分析表明,降低同型半胱氨酸的治疗(主要是补充叶酸)能够显著降低脑卒中风险3;另一项meta分析则发现补充叶酸可以显著降低慢性肾脏病患者的心脑血管疾病风险12;同时,补充叶酸可以降低颈动脉内膜中膜厚度的进展(CIMT;加权平均差异:-0.04 mm;95%可信区间:-0.07至-0.02;P < 0.001),且同型半胱氨酸的降低程度与CIMT的降低呈现剂量效应关系(P < 0.001)13。然而,尽管有这些令人兴奋的结果,在中国脑卒中一级预防研究(China Stroke Primary Trial,CSPPT;ClinicalTrials.gov ID NCT00794885)8之前,只有Supplementation en Folates et Omega-3(SU.FOL.OM3)研究和Heart Outcomes Prevention Evaluation(HOPE)2研究14,15提示补充叶酸对降低脑卒中有积极作用,并且脑卒中的发生在这两项研究中仅为次要终点。 从2008年5月19日至2013年8月24日,我们在中国高血压人群中组织进行了CSPPT研究。我们预期中国高血压人群可以最大程度受益于降压和补充叶酸降低同型半胱氨酸的同时治疗。中国未进行食物强化补充叶酸的措施,未广泛使用叶酸补充剂,同时具有极高的脑卒中疾病负担。脑卒中是目前中国人群的首位死因;从1984年至2004年,年龄标化的缺血性脑卒中的发病率仍以每年8.7%(95% CI:4.3-8.9,P < 0.05)的速率逐年上升16。中国人群同时具有很高的高血压患病率;基于一项全国调查,2009-2010年中国高血压患病率为29.6%,男性(31.2%)高于女性(28.0%)17。非常值得关注的是,约75%的高血压人群伴有血同型半胱氨酸水平的升高(H型高血压)18。H型高血压的高发可能是我国高血压人群的脑卒中患病即使在良好控制血压后依然居高不下的重要原因之一。 可以预期,同时干预脑卒中的这两项主要危险因素(高血压和高同型半胱氨酸血症)将比单独干预其中一项更加有效。CSPPT研究希望证实上述假设,其主要研究目的是考察与单独使用依那普利片相比,依那普利叶酸片(单片复方制剂)治疗是否可以进一步有效降低不伴脑卒中或心肌梗死病史的原发性高血压患者的脑卒中发生风险。 CSPPT研究总共纳入20702例高血压患者,是目前评估降压药物合并降低同型半胱氨酸治疗对脑卒中一级预防疗效的样本量最大的一项随机、对照临床试验。研究结果发现,在不伴脑卒中或心肌梗死病史的高血压患者中,与单用依那普利治疗相比,依那普利联合叶酸治疗(叶酸0.8 mg/天)能够显著降低脑卒中的发病率达21%(HR,0.79;95% CI:0.68-0.93)8。更重要的是,校正年龄、性别、研究中心、基线收缩压、舒张压和过程收缩压、舒张压后,H型高血压患者(占本研究人群的80.3%,HR,0.78;95% CI:0.66-0.93)较非H型高血压患者获益更为充分(HR,0.94;95% CI:0.62-1.42)。 越来越多的证据表明,高同型半胱氨酸血症和2型糖尿病的发生密切相关。2010年中国2型糖尿病的患病率约为11.6%(95% CI:11.3%-11.8%)19。近期一项对病例对照研究的meta分析报道,2型糖尿病患者的同型半胱氨酸水平显著高于非2型糖尿病患者(平均差异为0.94 µmol/L;95% CI:0.40-1.48)20。同型半胱氨酸水平升高可能促进2型糖尿病患者的胰岛素抵抗,增加死亡风险21。然而,尚有很多关键问题有待解决。 首先,补充叶酸是否能够预防2型糖尿病的发生或发展?Women's Antioxidant and Folic Acid Cardiovascular Study(WAFACS)研究发现,在有心脑血管疾病病史或3项以上心血管危险因素的40岁及以上女性,经过7年的治疗,每日补充叶酸和维生素B6、B12并不能够降低2型糖尿病的发生风险22。然而,WAFACS的所有受试者均来自食物中强化补充叶酸的国家。强化叶酸很可能降低了最可能受益的人群的比例,即同型半胱氨酸水平升高或叶酸水平较低的患者数量大幅减少。 其次,之前一项meta分析表明,补充叶酸降低同型半胱氨酸能够有效预防慢性肾脏病患者的心血管疾病风险;然而,其疗效受到基线糖尿病患者比例的显著影响(P = 0.007)12。需要更多的研究去评估基线空腹血糖和/或糖化血红蛋白水平对补充叶酸一级预防2型糖尿病及血管性并发症的疗效的影响程度。 总之,CSPPT研究以其大样本及独特的设计,为补充叶酸合并降压治疗对脑卒中一级预防作用的有效性提供了确切的答案。补充叶酸合并降压治疗对2型糖尿病的发生发展及其血管性并发症的作用尚需更多的研究来进行探讨;目前尤其缺乏在未强化补充叶酸的人群中的相关证据。如果能够阐明这些关系及其相关的机制,将对临床和公共卫生实践产生巨大的影响。

There are growing data and a continuing controversy over the effect of folic acid supplementation on cancer risk. We conducted a meta-analysis based on up-to-date published relevant randomized trials to further examine this issue. Relative risk (RR) was used to measure the effect of folic acid supplementation on risk of cancer using a random-effects model. Overall, folic acid supplementation had no significant effect on total cancer incidence (13 trials, n = 49,406, RR = 1.05; 95% CI: 0.99–1.11, p = 0.13), colorectal cancer (seven trials, n = 33,824, 1.01; 0.82–1.23, p = 0.95), other gastrointestinal cancer (two trials, n = 20,228, 1.00; 0.75–1.33, p = 0.99), prostate cancer (five trials, n = 27,065, 1.17; 0.84–1.62, p = 0.35), other genitourinary cancer (two trials, n = 20,228, 0.97; 0.75–1.27, p = 0.84), lung cancer (five trials, n = 31,864, 1.00; 0.84–1.21, p = 0.97), breast cancer (four trials, n = 19,800, 0.82; 0.63–1.07, p = 0.15), hematological malignancy (three trials, n = 25,670, 0.87; 0.64–1.17, p = 0.35) and total cancer mortality (six trials, n = 31,930, 1.02; 0.90–1.15, p = 0.81). However, a significantly reduced risk was observed for melanoma (three trials, n = 19,128, 0.47; 0.23–0.94, p = 0.03). Furthermore, higher total cancer incidence risk was observed among those trials with a higher percent use of lipid-lowering drugs (>60%, 1.10; 1.00–1.20, p = 0.04), or with lower percent baseline hypertension (≤70%, 1.08; 1.00–1.16, p = 0.057).Consistently, meta-regression analyses suggested that the similar trend between percent use of lipid-lowering drugs (p = 0.084) or percent baseline hypertension (p = 0.056) and log-RR for total cancer incidence associated with folic acid supplementation. Our findings indicate that folic acid supplementation has no significant effect on total cancer incidence, colorectal cancer, prostate cancer, lung cancer, breast cancer or hematological malignancy, but reduces the risk of melanoma.

Background: Myocardial necrosis is related to higher incidence of cardiovascular events and higher mortality rates during follow-up. Statins have been demonstrated to lower the risk of periprocedural myocardial infarction. The aim of this study is to evaluate the safety and efficacy of intensive statin therapy and the long-term outcome of patients in the Asian population. Study design: Approximately 1,100 patients with stable angina or non-ST elevation acute coronary syndrome undergoing selective percutaneous coronary intervention (PCI) are enrolled in this study. Patients are randomized either to the experimental group (80 mg atorvastatin 80 mg/day × 2 days before and 40 mg/day × 30 days after PCI) or to the control group (usual care). Creatine kinase-MB (CK-MB), troponin I (cTnI), and serum creatine are measured at 24 hours after the procedure. The total follow-up period is 6 months. The primary objective is to evaluate the efficacy of intensive atorvastatin treatment compared with usual care in reducing 30-day primary cardiovascular endpoints in patients undergoing selective PCI. Secondary endpoints are changes in myocardial biomarkers (cTnI, CK-MB) and hs-CRP, CIN morbidity, 6-month clinical outcomes, and safety. Conclusion: The result of the ISCAP study will provide important evidence on the efficacy and safety of periprocedural serial intensive statin treatment in Asian patients with coronary artery disease undergoing selective PCI. © 2011 Wiley Periodicals, Inc.

Background: Osteoprotegerin (OPG) is a member of the tumor necrosis factor superfamily and plays an important regulatory role in the skeletal, immune, and vascular systems. Intermediate coronary artery lesions that have a diameter stenosis of approximately 20%–70% might cause serious consequences. However, the prognostic value of plasma OPG levels in patients with intermediate coronary artery lesions has been less reported. Hypothesis: We hypothesized that OPG is a predictive marker of prognosis of intermediate coronary artery lesions. Methods: A prospective study was performed on 890 patients with intermediate (20%–70%) coronary lesions. The median age was 62 years (25th and 75th percentiles, 55 and 70 years, respectively) and 67.2% were male. Fasting blood was sampled at baseline. The primary clinical endpoint was a composite of readmission due to angina pectoris, nonfatal myocardial infarction, revascularization, and cardiovascular death. Results: During a median follow-up of 24 months, events occurred in 11.1% of the patients. Of these patients, 7.9% were readmitted for angina pectoris, 1.5% received revascularization, 0.7% suffered nonfatal myocardial infarction, and 1.0% died. The plasma levels of OPG (median, 5304.7 pg/mL vs 2993.4 pg/mL, P

OBJECTIVE In a subgroup analysis of the China Stroke Primary Prevention Trial, we aimed to explore the impact of folic acid supplementation on arterial stiffness and assess the modifying effect of the methylenetetrahydrofolate reductase (MTHFR) gene in Chinese patients with hypertension. METHODS This prospective study enrolled 2529 hypertensive Chinese patients. Participants were randomized to receive treatment with either a combination of enalapril and folic acid or enalapril. Brachial-ankle pulse wave velocity (PWV) was measured by trained medical staff using PWV instruments at both baseline and exit visits, approximately 5 years after enrollment. This trial was registered with clinicaltrials.gov (NCT00794885). RESULTS During the follow-up, change in folate was significantly and independently correlated with change in ba-PWV in study patients (β = -1.31, P

TZDs (thiazolidinediones) are prescribed as anti-Type II diabetes drugs, but little is known regarding whether TZDs regulate the expression of sPLA2 (secretory phospholipase A2) in macrophages. We have investigated the effects of pioglitazone on LPS (lipopolysaccharide)-induced production of TNF-alpha (tumour necrosis factor alpha), sPLA2-V and -X (groups V and X sPLA2) in RAW 264.7 macrophages. TNF-alpha, sPLA2-V and -X mRNA and protein expression were determined by RT-PCR (reverse transcriptase-PCR) and Western blot analysis, respectively. The activity of NF-kappaB (nuclear factor kappaB) was determined by Western blot and confocal microscopy. LPS induced TNF-alpha, sPLA2-V and sPLA2-X mRNA and protein expression. Pretreatment with 10 mumol/l pioglitazone significantly suppressed LPS-induced TNF-alpha, sPLA2-V and sPLA2-X mRNA and protein expression. LPS induced NF-kappaB expression and translocation in the nucleus, but the inductive effects were inhibited by pioglitazone. Our findings indicate that pioglitazone inhibits production of inflammatory factors induced by LPS in murine macrophage cells by inactivating NF-kappaB. Pioglitazone appears to play an anti-inflammatory role in the atherosclerotic process.

Background: Estimates of the genetic influences on electrocardiographic (ECG) parameters are inconsistent in previous reports, and no such studies have been performed in China. So we estimated genetic contributions to PR and QRS intervals and the rate-adjusted QT interval (Bazett's QTc) in a Chinese rural population. Methods: A total of 2909 subjects from 847 families were enrolled in the current study. Genetic contributions to ECG parameters were estimated in two ways: correlation coefficients among family members (father-mother, parent-offspring, first sibling-other sibling) and the heritability of each of the ECG parameters. Results: Our results showed significant correlations among family members on theses parameters: the correlation coefficients for PR interval, QRS duration, QTc interval, and HR, between parent-sibling, and sibling-sibling were 0.17 and 0.13, 0.18 and 0.23, 0.22 and 0.28, 0.19 and 0.18, respectively. The heritability for PR interval, QRS duration, QTc interval, and HR were estimated as 0.34, 0.43, 0.40, and 0.34, respectively. Conclusion: Genetic factors, together with the environmental and other cofactors contribute no more than 60% to the variance of the ECG intervals, supporting the concept that multiple factors, including gene-gene and gene-environment interactions could influence ECG interval phenotypes, and genetic factors play a major role.

Objectives: Obesity is a complex trait that is affected by both environmental and genetic risk factors. The β3 adrenergic receptor (ADRB3) is expressed in adipose tissue and plays a role in energy metabolism. A missense mutation on codon 64 of this gene (W64R) is associated with receptor malfunction. Previous studies examining the relation between this polymorphism and obesity produced inconsistent findings. The current study assessed the association between the W64R genotype and obesity-related phenotypes, including body weight, BMI, and serum triglycerides, cholesterol, and glucose. Research Methods and Procedures: We determined the ADRB3 W64R genotypes and fasting serum lipid and glucose concentrations for 695 hypertensive adults (336 men, 359 women) from a rural county in Anhui Province, China. Multivariate linear regression models were fit to detect associations between the genetic polymorphism and obesity-related phenotypes. Results: The ADRB3 W64R polymorphism was significantly associated with body weight and BMI in men but not in women. After controlling for potential confounding variables, men who were homozygous for the R64 allele were 11.8 kg heavier (p < 0.001) and had a BMI that was 3.7 kg/m2 greater (p = 0.001) than men who were homozygous for the W64 allele. Serum concentrations of lipids and glucose were found not associated with the genetic polymorphism. Discussion: The ADRB3 R64 allele was associated with increased body weight and BMI in men but not in women. The genetic association was not modified by triglyceride, cholesterol, blood glucose, or blood pressure levels of the subjects.

Background: Cholesterol crystal embolism (CCE) is a complication of atherosclerosis. Vascular surgery, vascular angiography, and anticoagulation have been identified as inciting factors. Hypothesis: This paper sought to analyze the clinical characteristics of patients with CCE after percutaneous coronary intervention. Methods: Six patients with atherosclerosis presenting with simultaneous occurrence of acute renal failure and peripheral ischemic changes were diagnosed with CCE and their clinical data were analyzed. Results: The average age of the patients was 72 years. Most had risk factors of atherosclerosis such as hypertension, diabetes, and smoking. The levels of serum creatinine increased progressively after coronary angiography. All patients had concomitant skin lesions, including blue toes. Cholesterol crystal emboli were found in arterioles by cutaneous biopsy in one patient. All patients received statins and two of these received dialysis therapy. Three patients died and three remained in chronic renal failure. Conclusion: Since CCE is a severe complication of coronary intervention, special attention should be paid to this disease.