Prognostic Value of Renal Function for Cardiac Events in Patients Without Significant Stenosis on Coronary Computed Tomography Angiography

This study was conducted to determine clinical parameters predicting future major adverse cardiovascular events (MACEs) in patients without significant stenosis on coronary computed tomographic angiography (CCTA). A total of 625 patients with suspected coronary artery disease (CAD) who underwent CCTA that revealed insignificant (< 50%) CAD was reviewed in three cardiac centers. The MACEs including cardiac death, non-fatal myocardial infarction (MI), unstable angina and late (> 90 days after CCTA) revascularization were assessed. During the mean follow-up period of 819 ± 529 days (median 837 days), there were 28 cases of MACEs (4.5%). In multivariable Cox regression analysis, independent predictors for MACEs were male sex (hazard ratio [HR], 2.40; 95% confidence interval [CI], 1.01-5.69; P = 0.046) and low estimated creatinine clearance (eCCr) (< 60 mL/min/1.73 m²) (HR, 3.07; 95% CI, 1.22-7.74; P = 0.017). Low eCCr was the only independent predictor for hard events including cardiac death and MI (HR, 17.6, 95% CI, 1.44-215.7; P = 0.025). In conclusion, renal function is an independent predictor for cardiovascular events among patients without significant CAD by CCTA. Careful monitoring and preventive strategy are warranted in patients with impaired renal function even without significant CAD.

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Absence of postprandial surge in coronary blood flow distal to significant stenosis: a possible mechanism of postprandial angina

OBJECTIVES: This study was designed to investigate a possible mechanism of postprandial angina. BACKGROUND: Postprandial angina has been recognized for more than two centuries; however, its mechanism is still controversial. The most widely accepted mechanism involves increased myocardial oxygen demand after food intake. Recently, the redistribution in coronary blood flow (CBF) was suggested as a possible mechanism. METHODS: Twenty young, healthy volunteer controls and 20 patients with significant stenosis in the left anterior descending (LAD) or left main coronary artery were enrolled in the study. Coronary blood flow was evaluated in the distal LAD by using transthoracic Doppler echocardiography before and 15, 30, 45, and 60 min after food intake. In the CBF curve, the time velocity integral of diastolic flow (Dtvi) and the product of Dtvi and heart rate (HR) were measured. In six patients, these measurements were repeated after successful coronary intervention. RESULTS: In the healthy volunteer controls, Dtvi and Dtvi x HR increased after food intake with a peak value at 15 min, which indicates the presence of postprandial surge in the CBF. Fasting values and peak values at 15 min were significantly different (Dtvi: 15.1 +/- 4.9 cm/s vs. 18.9 +/- 5.9 cm/s, p = 0.04, Dtvi x HR: 862.2 +/- 261.5 cm/min vs. 1,174.2 +/- 307.5, p = 0.002). In contrast with the controls, despite postprandial increase in double product (HR x blood pressure), Dtvi and Dtvi x HR in the patient group decreased after food intake, with a nadir value at 45 min. Fasting values and nadir values at 45 min were significantly different (Dtvi: 24.0 +/- 19.6 cm/s vs. 19.3 +/- 17.1 cm/s, p < 0.001, Dtvi x HR: 1,449.6 +/- 1,044.0 cm/min vs. 1,273.4 +/- 1,000.9 cm/min, p = 0.002). In six patients, the CBF pattern resumed the normal pattern of postprandial surge in the CBF after successful coronary intervention. CONCLUSIONS: Results of our study suggest that "steal phenomenon" may play a role in the mechanism of postprandial angina.     

Role of asymmetric dimethylarginine in inflammatory reactions by angiotensin II

Previous investigations have demonstrated that angiotensin (Ang) II induces inflammatory reactions and asymmetric dimethylarginine (ADMA), an endogenous NOS inhibitor, might be a novel inflammatory factor. Endothelial cell activation was induced by incubation with Ang II or ADMA. Incubation with Ang II (10(-6) M) for 24 h elevated the levels of ADMA and decreased the levels of nitrite/nitrate concomitantly with a significant increase in the expression of protein arginine methyltransferase and a decrease in the activity of dimethylarginine dimethylaminohydrolase (DDAH). Exposure to Ang II (10(-6) M for 24 h) also enhanced intracellular ROS elaboration and the levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-8, upregulated chemokine receptor CXCR2 mRNA expression, increased adhesion of endothelial cells to monocytes and induced a significant increase in the activity of nuclear factor (NF)-kappaB, which was attenuated by pretreatment with the Ang II receptor blocker losartan (1, 3 and 10 muM). Exogenous ADMA (30 microM) also increased ROS generation and the levels of TNF-alpha and IL-8, decreased the levels of nitrite/nitrate, upregulated CXCR2 gene expression, increased endothelial cell binding with monocytes and activated the NF-kappaB pathway, which was inhibited by pretreatment with losartan or L-arginine. These data suggest that ADMA is a potential proinflammatory factor and may be involved in the inflammatory reaction induced by Ang II.     

江苏省恶性疟防治研究

为了解江苏省恶性疟的流行特点和媒介传疟作用，制定有效的防治对策以尽快控制和消灭恶性疟，我们通过多年大量的现场流行病学调查和实验研究，证实嗜人按蚊是江苏省传播恶性疟的主要媒介。根据调查和研究结果，在全省恶性疟流行区采取了大范围持续的室内滞留喷洒灭蚊，和药物浸泡蚊帐巩固灭蚊，同时抓好传染源和易感人群的综合防治措施，结果在较短时间内控制了恶性疟的流行，并大幅度降低了间日疟发病率。经多年疟疾监测证实，已连续８年未发生当地感染的恶性疟病例，达到基本消灭恶性疟的标准，取得了显著的防治效果。     

Incremental prognostic value of coronary computed tomographic angiography over coronary artery calcium score for risk prediction of major adverse cardiac events in asymptomatic diabetic individuals

Background

Coronary artery disease (CAD) diagnosis by coronary computed tomographic angiography (CCTA) is useful for identification of symptomatic diabetic individuals at heightened risk for death. Whether CCTA-detected CAD enables improved risk assessment of asymptomatic diabetic individuals beyond clinical risk factors and coronary artery calcium scoring (CACS) remains unexplored.

Methods

From a prospective 12-center international registry of 27,125 individuals undergoing CCTA, we identified 400 asymptomatic diabetic individuals without known CAD. Coronary stenosis by CCTA was graded as 0%, 1–49%, 50–69%, and ≥70%. CAD was judged on a per-patient, per-vessel and per-segment basis as maximal stenosis severity, number of vessels with ≥50% stenosis, and coronary segments weighted for stenosis severity (segment stenosis score), respectively. We assessed major adverse cardiovascular events (MACE) – inclusive of mortality, nonfatal myocardial infarction (MI), and late target vessel revascularization ≥90 days (REV) – and evaluated the incremental utility of CCTA for risk prediction, discrimination and reclassification.

Results

Mean age was 60.4 ± 9.9 years; 65.0% were male. At a mean follow-up 2.4 ± 1.1 years, 33 MACE occurred (13 deaths, 8 MI, 12 REV) [8.25%; annualized rate 3.4%]. By univariate analysis, per-patient maximal stenosis [hazards ratio (HR) 2.24 per stenosis grade, 95% confidence interval (CI) 1.61–3.10, p < 0.001], increasing numbers of obstructive vessels (HR 2.30 per vessel, 95% CI 1.75–3.03, p < 0.001) and segment stenosis score (HR 1.14 per segment, 95% CI 1.09–1.19, p < 0.001) were associated with increased MACE. After adjustment for CAD risk factors and CACS, maximal stenosis (HR 1.80 per grade, 95% CI 1.18–2.75, p = 0.006), number of obstructive vessels (HR 1.85 per vessel, 95% CI 1.29–2.65, p < 0.001) and segment stenosis score (HR 1.11 per segment, 95% CI 1.05–1.18, p < 0.001) were associated with increased risk of MACE. Beyond age, gender and CACS (C-index 0.64), CCTA improved discrimination by maximal stenosis, number of obstructive vessels and segment stenosis score (C-index 0.77, 0.77 and 0.78, respectively). Similarly, CCTA findings improved risk reclassification by per-patient maximal stenosis [integrated discrimination improvement (IDI) index 0.03, p = 0.03] and number of obstructive vessels (IDI index 0.06, p = 0.002), and by trend for segment stenosis score (IDI 0.03, p = 0.06).

Conclusion

For asymptomatic diabetic individuals, CCTA measures of CAD severity confer incremental risk prediction, discrimination and reclassification on a per-patient, per-vessel and per-segment basis.     

氧化型极低密度脂蛋白诱导小鼠腹腔巨噬细胞凋亡

探讨氧化型极低密度脂蛋白诱导小鼠腹腔巨噬细胞凋亡的作用。应用低温超速离心法分离健康人血浆极低密度脂蛋白，用CuCl2氧化得到氧化型极低密度脂蛋白。琼脂糖凝胶电泳观察巨噬细胞凋亡DNA断裂“梯状”图谱；流式细胞仪和二苯胺法分别测定凋亡巨噬细胞百分率和：DNA片断百分率；光镜观察凋亡巨噬细胞形态变化。结果发现：①氧化型极低密度脂蛋白能诱导巨噬细胞发生凋亡及DNA断裂；②抗氧化剂二甲基硫脲能部分抑制氧化型极低密度脂蛋白诱导的：DNA断裂；③核转录因子核因子kB抑制剂吡咯烷二硫代氨基甲酸盐可完全抑制氧化型极低密度脂蛋白诱导的DNA断裂。提示氧化型极低密度脂蛋白诱导巨噬细胞凋亡可能是动脉粥样硬化形成机制之一；氧化型极低密度脂蛋白诱导巨噬细胞凋亡的作用可能与自由基和激活核因子kB有关。     

On the origin of Lake Malawi cichlid species: a population genetic analysis of divergence

The cichlid fishes of Lake Malawi are famously diverse. However, phylogenetic and population genetic studies of their history have been difficult because of the great amount of genetic variation that is shared between species. We apply a recently developed method for fitting the "isolation with migration" divergence model to a data set of specially designed compound loci to develop portraits of cichlid species divergence. Outgroup sequences from a cichlid from Lake Tanganyika permit model parameter estimates in units of years and effective population sizes. Estimated speciation times range from 1,000 to 17,000 years for species in the genus Tropheops. These exceptionally recent dates suggest that Malawi cichlids as a group experience a very active and dynamic diversification process. Current effective population size estimates range form 2,000 to near 40,000, and to >120,000 for estimates of ancestral population sizes. It appears that very recent speciation and gene flow are among the reasons why it has been difficult to discern the phylogenetic history of Malawi cichlids.     

Diagnostic yield of coronary angiography in patients with acute chest pain: role of noninvasive test

Objectives

This study investigated the diagnostic yield of invasive coronary angiography (CAG) and the impact of noninvasive test (NIV) in patients presented to emergency department (ED) with acute chest pain.

Methods

Patients 50 years or older who visited ED with acute chest pain and underwent CAG were identified retrospectively. Those with ischemic electrocardiogram, elevated cardiac enzyme, known coronary artery disease (CAD), history of cardiac surgery, renal failure, or allergy to radiocontrast were excluded. Diagnostic yields of CAG to detect significant CAD or differentiate the need for revascularization were analyzed according to whether NIV was performed and its result.

Results

Among the total 375 consecutive patients, significant CAD was observed in 244 (65.1%). Diagnostic yields of CAG were higher in patients who underwent NIV before CAG, but the discriminative effect was modest (59.7% vs 70.7% [P = .026] for detection of CAD; 45.0% vs 50.5% [P = .285] for revascularization). Positive results of NIV were significantly associated with the presence of CAD and the need for revascularization, when compared with patients without NIV or patients with negative results (P < .001, respectively).

Conclusion

The diagnostic yield of CAG was only 65% in low- to intermediate-risk ED patients with acute chest pain. Performing of NIV provided only modest improvement in diagnostic yield of CAG. The unexpectedly low diagnostic yield might be attributable to the underuse of NIV and misinterpretation of physicians. We suggest the use of NIV as a gatekeeper to discriminate patients who require CAG and/or revascularization, and for this, better risk stratification and appropriate application of NIV are required.