The association of coronary non-calcified plaque loading based on coronary computed tomography angiogram and adverse cardiovascular events in patients with unstable coronary heart disease-a retrospective cohort study.

Background: Coronary computed tomography angiogram (CCTA) has the characteristics of non-invasive, high resolution, and can accurately determine the characteristics of tubular wall plaques. The non-calcified plaque loading of the coronary arteries is unstable and prone to shedding, leading to adverse cardiovascular events. However, few studies focused on the predictive value of non-calcified plaque loading for adverse cardiovascular events in patients with unstable coronary heart disease (CHD). The present study was conducted to investigate the association of coronary non-calcified plaque loading based on CCTA and adverse cardiovascular events in patients with unstable CHD. Methods: A total of 206 patients with unstable CHD were collected and followed up for 1 year. The patients were divided into an observation group (n=56) and a control group (n=150) according to whether adverse cardiovascular events occurred or not. We analyzed the predictive value of coronary artery non-calcified plaque loading for adverse cardiovascular events in unstable CHD using receiver operating characteristic and multivariate logistics regression analysis. Results: Compared with the control group, the non-calcified plaque volume in the observation group was increased (160.10±44.02 vs. 128.06±42.22 mm3, P=0.000); non-calcified plaque loading increased (26.93%±7.98% vs. 21.46%±7.62%, P=0.000); carotid intima-media thickness increased (1.49±0.17 vs. 1.40%±0.18 mm, P=0.001); and left ventricular ejection fraction (LVEF) was significantly reduced (53.28%±7.39% vs. 58.02%±7.91%, P=0.000). Non-calcified plaque volume and non-calcified plaque loading have certain diagnostic value for recurrence of adverse cardiovascular events within 1 year (P<0.05). A non-calcified plaque volume >145.58 mm3 is a risk factor for recurrence of adverse cardiovascular events (P<0.05). Conclusions: Increased non-calcified plaque volume in patients with unstable CHD is associated with the development of adverse cardiovascular events in patients with unstable CHD.

HDL-C is associated with mortality from all causes, cardiovascular disease and cancer in a J-shaped dose-response fashion: a pooled analysis of 37 prospective cohort studies.

OBJECTIVE: The association between high-density lipoprotein cholesterol (HDL-C) levels and mortality remains controversial. We aimed to investigate the potential dose-response associations between HDL-C levels and mortality from all causes, cardiovascular disease and cancer in the general population. METHODS: PubMed and Embase were searched through April 2019. Prospective cohort studies reporting risk estimates of HDL-C levels and mortality were included. Linear and non-linear dose-response analyses were conducted. A random-effects model was employed to calculate pooled hazard ratio. RESULTS: Thirty-seven studies, involving 3,524,505 participants and more than 612,027 deaths, were included. HDL-C level was found to be associated with mortality from all causes, cardiovascular disease and cancer in a J-shaped dose-response pattern, with the lowest risk observed at HDL-C levels of 54-58 mg/dL, 68-71 mg/dL and 64-68 mg/dL, respectively. Compared with HDL-C level of 56 mg/dL, the pooled hazard ratios for all-cause mortality were 1.03 (95% confidence interval (CI) 1.01, 1.05) and 1.10 (95% CI 1.09, 1.12) for each 10-mg/dL increase and decrease in HDL-C levels, respectively; furthermore, compared with the reference category, the pooled hazard ratios for all-cause mortality were 1.21 (95% CI 1.09, 1.36) and 1.36 (95% CI 1.21, 1.53) for the highest and the lowest categories of HDL-C levels, respectively. Similar results were obtained for cardiovascular and cancer mortality. CONCLUSIONS: In the general population, HDL-C level is associated with mortality from all causes, cardiovascular disease and cancer in a J-shaped dose-response manner; both extremely high and low HDL-C levels are associated with an increased risk of mortality.

Soyasaponin Bb inhibits the recruitment of toll-like receptor 4 (TLR4) into lipid rafts and its signaling pathway by suppressing the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent generation of reactive oxygen species.

SCOPE: We and others recently showed that soyasaponin Bb (SSBb ) inhibited lipopolysaccharide (LPS)-induced inflammation in macrophages. Since the recruitment of toll-like receptor 4 (TLR4) into lipid rafts is vital for LPS-initiated signaling, we investigated whether this process would be modulated by SSBb . METHODS AND RESULTS: By using sucrose gradient ultracentrifuge, we found that pretreatment of macrophages with SSBb inhibited LPS-induced recruitments of TLR4, myeloid differentiation primary response protein 88 (MyD88) and Toll/IL-1 receptor domain-containing adaptor inducing interferon-ß (TRIF) into fractions enriched with lipid rafts marker flotillin-1. We also found SSBb decreased co-localization of TLR4 and lipid rafts by utilizing confocal immunofluorescence microscopy. Additionally, we observed that SSBb suppressed LPS-induced formation of TLR4/MyD88 and TLR4/TRIF complexes, production of pro-inflammatory molecules, and activation of nuclear factor kappa B (NF-κB). Furthermore, we found that these inhibitory effects of SSBb were associated with reduced reactive oxygen species (ROS) because pretreating cells with N-acetyl-L-cysteine and NADPH oxidase inhibitor diphenyleneiodonium (DPI) inhibited LPS-induced TLR4 recruitment into lipid rafts and NF-κB activation. SSBb also inhibited NADPH oxidase activation by blocking interaction between gp91(phox) and p47(phox) similarly as DPI. CONCLUSION: SSBb can inhibit TLR4 recruitment into lipid rafts and its signaling by suppressing the NADPH oxidase-dependent ROS generation.