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Aims Members of the chromogranin family play a role in angiogenesis. One such biologically active peptide, generated through the processing of chromogranin A, is vasostatin-2. This study aimed at assessing the association of serum vasostatin-2 levels with coronary collateral vessels (CCV) in diabetic patients with chronic total occlusions (CTO) and the effects of vasostatin-2 on angiogenesis in diabetic mice with hindlimb or myocardial ischemia. Methods and results Serum levels of vasostatin-2 in 452 diabetic CTO patients were evaluated. The status of CCV was categorized according to the Rentrop score. Vasostatin-2 recombinant protein or phosphate-buffered saline were then injected intraperitoneally in diabetic mouse models of hindlimb or myocardial ischemia, followed by laser Doppler imaging and molecular biology examinations. The effects of vasostatin-2 were also ascertained in endothelial cells and macrophages, with mechanisms clarified using ribonucleic acid (RNA) sequencing. Serum levels of vasostatin-2 were significantly different and progressively higher across Rentrop score 0, 1, 2, and 3 groups (P < .001), with significantly lower levels in patients with poor CCV (Rentrop score 0 and 1) than in those with good CCV (Rentrop score 2 and 3) (P < .05). Vasostatin-2 significantly promoted angiogenesis in diabetic mice with hindlimb or myocardial ischemia. RNA-seq analyzes verified an angiotensin-converting enzyme 2 (ACE2)-mediated vasostatin-2-induction of angiogenesis in ischemic tissues. Conclusion Lower serum levels of vasostatin-2 are associated with poor CCV in diabetic CTO patients compared with patients with good CCV. Vasostatin-2 significantly promotes angiogenesis in diabetic mice with hindlimb or myocardial ischemia. Such effects are mediated by ACE2.

Background Chromogranin B (CgB) is a member of granin family that can be cleaved into a number of bioactive peptides. Previous studies showed that CgB is produced in cardiomyocytes and is increased in heart failure animals and patients in proportion to disease severity. Chronic total occlusion (CTO) of coronary artery leads to sustained myocardial ischemia which predisposes to adverse cardiovascular outcomes including heart failure. Purpose In this study, we sought to investigate the association between CgB and coronary collateralization formation and heart failure in patients with stable angina and CTO. Methods A total of 720 subjects with stable angina and CTO of at least one major coronary artery were enrolled in this study. CgB was assayed using an ELISA kit and the degree of coronary collaterals supplying the distal aspect of a total occlusion from the contralateral vessel was graded according to Rentrop classification. Results These was a stepwise decrease in levels of CgB with increasing Rentrop grades of coronary collateralization (P=0.001). Compared with the good collateralization (Rentrop grade 2–3) group, CgB was significantly higher in subjects with poor coronary collateralization (Rentrop grade 0–1; 1222.95 [IQR 506.24–2710.24] pg/mL vs. 776.17 [IQR 276.24–2209.39] pg/mL, P Conclusions CgB is an independent predictor of poor coronary collateralization and is related to worse heart function in patients with stable angina and CTO. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Natural Science Foundation of China

Background Left ventricular aneurysm (LVA), a serious complication of transmural myocardial infarction, is generally related to poor cardiovascular outcomes. The formation of LVA is essentially an inflammatory remodeling process regulated by multiple systemic and local factors. Epicardial adipose tissue (EAT), a depot of visceral adipose tissue directly overlying the myocardium, is increasingly recognized as an important immune organ by secreting a variety of bioactive adipocytokines. However, the relation of EAT to the development of LVA is still unclear. Purpose In this study, we sought to investigate the association between EAT volume and the formation of LVA in subjects with previous myocardial infarction (MI). Methods A total of 55 subjects with previous MI and the presence of LVA, and age- and sex-matched 50 subjects with previous MI but without LVA were enrolled between October 2011 and June 2019. EAT was quantified and the presence of LVA was ascertained by cardiac magnetic resonance (CMR). EAT volume was indexed to body surface area. Results In the overall population, EAT volume index was correlated positively to log-transformed N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (Pearson's r=0.332, P=0.002), and inversely to left ventricular ejection fraction (LVEF; Pearson's r=−0.240, P=0.031). The indexed EAT volume was significantly higher in subjects with than without LVA (41.10±11.73 vs. 33.25/11.70 mL/m2, P=0.003). In subjects with LVA, EAT volume index was further increased in those at older age (43.59±13.09 mL/m2 vs. 37.29±8.26 mL/m2, P=0.029) or with type 2 diabetes (43.38±12.32 mL/m2 vs. 35.20±7.67 mL/m2, P=0.013). After adjusting for sex, age and the presence of diabetes in the multivariate analysis, tertiles of EAT volume index remained significantly associated with the presence of LVA (P for trend=0. 003). Strikingly, compared to the lowest tertile (≤30.80 mL/m2), the intermediate (30.80–44.13 mL/m2) and highest (>44.13 mL/m2) tertiles of EAT volume index corresponded to 4.869– (95% CI 1.792–14.155, P=0.003) and 4.876– (95% CI, 1.787–14.206, P=0.003) increased risk for LVA. Conclusion Our study suggests that EAT volume is independently associated with the formation of LVA and reduced cardiac function after myocardial infarction. EAT in patients with or without LVA Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Natural Science Foundation of China

Aims We investigated the association of the adipokine C1q/TNF-related protein (CTRP) 1 with coronary artery disease (CAD), and the biological vascular effects of CTRP1. Methods and results We analysed CTRP1 levels in sera of CAD patients ( n = 451) and non-CAD controls ( n = 686), and in coronary endarterectomy specimens ( n = 32), non-atherosclerotic internal mammary arteries ( n = 26), aortic atherosclerotic plaques ( n = 15), and non-atherosclerotic aortic samples ( n = 10). C1q/TNF-related protein-levels were higher in sera, endarterectomy specimens, aortic atherosclerotic plaques, and peripheral blood mononuclear cells (PBMCs) from CAD patients compared with controls, and were related to CAD severity. The production of CTRP1 was profusely induced by inflammatory cytokines and itself caused a concentration-dependent expression of adhesion molecules and inflammatory markers in human endothelial cells, human peripheral blood monocytes, and THP-1 cells. C1q/TNF-related protein-1 induced p38-dependent monocyte-endothelium adhesion in vitro and the recruitment of leucocytes to mesenteric venules in C57BL/6 mice. Immunohistochemistry of atherosclerotic femoral arteries exhibited CD68 and VE-cadherin loci-associated increased CTRP1 expression in plaques. Compared with saline, intraperitoneal injection of recombinant CTRP1 protein (200 μg/kg) every other day promoted atherogenesis in apoE−/− mice at 24 weeks. However, pro-atherogenic effects were significantly attenuated in CTRP1−/−/apoE−/− double-knockout mice compared with apoE−/− mice, with a consistent decrease in vascular adhesion molecule, phospho-p38 and TNF-α expression and macrophage infiltration in plaque in CTRP1−/− and double-knockout mice. Tumour necrosis factor-α-induced expression of adhesion molecules and cytokines were lower in primary endothelial cells and macrophages from CTRP−/− mice than in those from C57BL/6 mice. Conclusion C1q/TNF-related protein-1 is a marker of atherosclerosis in humans and promotes atherogenesis in mice.

BACKGROUND In a meta-analysis, we investigated effects of β-blockers on central hemodynamic measurements and explored the impact of heart rate (HR) on central hemodynamics and the risk of stroke. METHODS We searched randomized controlled trials that compared β-blockers with other classes of antihypertensive drugs in reducing central systolic blood pressure (cSBP) and augmentation index (cAI) and in preventing stroke. A random-effects model was used to compute pooled estimates. RESULTS In 9 trials (n = 754), β-blockers were less efficacious in reducing cAI than all the other classes of drugs (8.6%, P < 0.001). β-blockers were also less efficacious in reducing cSBP than angiotensin converting enzyme inhibitors (7.7 mm Hg, P = 0.02) and angiotensin receptor blockers (3.6 mm Hg, P = 0.005) but not the other classes of drugs (P ≥ 0.50). In a meta-regression analysis of these 9 trials, the baseline-adjusted difference in HR between randomized groups was associated with cAI (7.0% increase for each 10 bpm decrease in HR, P = 0.02), which was associated with cSBP (1.2 mm Hg increase for each 1% increase in cAI, P = 0.009). In 5 outcome trials, the pooled OR of stroke was 1.23 (P < 0.001), which would be accounted for by the difference in cSBP derived from the above meta-regression analysis. CONCLUSIONS Slowing HR with β-blockers may increase cAI and in turn may decrease cSBP less than with other classes of drugs. This mechanism might account for a smaller reduction in the risk of stroke when using β-blockers to treat hypertension.

BACKGROUND To investigate the accuracy of the SphygmoCor and Omron HEM9000-AI devices in the estimation of central blood pressure (BP) in comparison with the simultaneous invasive catheter measurement. METHODS The radial arterial pulse was sequentially recorded by the use of the Omron and SphygmoCor devices in 33 patients, with the calibration of the brachial oscillometric BP, to derive central BPs, which were also measured simultaneously with a catheter-based fluid-filled manometer system. The procedure was repeated three times to obtain 99 pairs of noninvasive and invasive measurements. RESULTS The noninvasive central systolic BP estimations were significantly (P < 0.001) associated with the invasive measurement at the ascending aorta, with a correlation coefficient of 0.91 and 0.90 for the SphygmoCor and Omron devices, respectively. However, both devices underestimated central systolic BP with a difference of -15 mm Hg (95% confidence interval (CI), -17 to -13 mm Hg, P < 0.001) for SphygmoCor and -2 mm Hg (95% CI, -4 to 0 mm Hg, P < 0.05) for Omron. In comparison with the invasive catheter measurement at the brachial artery, the oscillometric Omron device underestimated brachial systolic BP by -19 mm Hg (95% CI, -23 to -15 mm Hg, P < 0.001). CONCLUSIONS Both devices underestimated central systolic BP, with a larger deviation by SphygmoCor. Nonetheless, these noninvasive estimations of central BP closely correlate with the invasive measurements, and can still be properly used, on the condition that device specific diagnostic thresholds become available.

Background: Sirolimus-eluting stents (SES) with biodegradable polymer coating showed promising results in registry studies. We investigated whether their efficacy and safety were noninferior to those of durable polymer-coated SES in primary percutaneous coronary intervention (PCI) for patients with acute ST-segment elevation myocardial infarction (STEMI). Methods: A total of 1192 STEMI patients within 12 hours of symptom-onset were randomly assigned, in an open-label fashion with 1:1 ratio, to receive SES coated with biodegradable (n=596) or durable polymer (n=596) during primary PCI. Primary endpoint was composite major adverse cardiac events (MACE) at one-year follow-up, including all-cause mortality, recurrent myocardial infarction, and target lesion revascularization. Secondary endpoint included individual components of primary endpoint and stent thrombosis according to the ARC definition. Results: Compared with durable polymer coated SES, the non-inferiority of SES with biodegradable polymer coating was established by an absolute risk difference of -0.9% in primary endpoint (12.4% vs. 13.3%, p=0.67) and an upper limit of one-sided 95% CI at 2.96% (one-sided p value for non-inferiority=0.001). And the finding of non-inferiority of SES with biodegradable polymer coating was consistent across the subgroups of patients with left ventricular dysfunction, door-to-balloon time 65 years in age. Despite similar occurrence of acute and subacute stent thrombosis (definite or probable), late stent thrombosis was lower after implantation of biodegradable polymer coated SES (0.7% vs. 2.2%, p=0.03). Conclusions: Our results indicate that a stent eluting sirolimus from a biodegradable polymer represents an effective and safer alternative to a stent eluting sirolimus from a durable polymer in STEMI patients treated by primary PCI.