We investigated the effects of telmisartan, the blocker of angiotensin II receptor 1, on the regulation of systolic blood pressure (SBP) and oxidative stress through endothelial nitric oxide (NO) release in spontaneously hypertensive rats (SHRs). SHRs randomly received placebo, oral feeding of telmisartan (5 mg/kg or 10 mg/kg) every day and Wistar-Kyoto rats (WKYs) served as normotensive control. The SBP of rat was measured before and weekly thereafter. After a total of 8-week treatment, rats were killed for experimental measurements. Parameters that subject to measurements in isolated aorta endothelial cells include: NO concentration, protein expression levels of angiotensin II receptor 1, nitrotyrosine, 8-isoprostane, SOD, PI3K, Akt, AMPK and eNOS. In addition, L-NMMA, a general inhibitor of nitric oxide synthase, was also applied to test the inhibition of NO concentration. We found that SBPs were significantly lower in telmisartan therapy group than in placebo treated hypertensive rats and WKYs (p<0.05). The NO concentration was significantly higher in telmisartan-treated group with increased activity of the PI3K/Akt pathway and activated eNOS signaling. Blockade of Akt activity reversed such effects. Activation of AMPK also contributed to the phosphorylation of eNOS. L-NMMA treatment reduced less NO concentration in SHR rats than the telmisartan co-treated groups. Oxidative stress in SHRs was also attenuated by telmisartan administration, shown by reduced formation of nitrotyrosine, 8-isoprostane, and recovered SOD protein level. Telmisartan enhanced NO release by activating the PI3K/Akt system, AMPK phosphorylation and eNOS expression, which attenuated the blood pressure and oxidative stress in SHRs.

Background 1. Studies have found that gut microbiota is a new participant and potential therapeutic target for CVD and even MI. 2. No clinical study to date, however, has investigated whether the changes of gut microbiota associated with coronary lesion degree and prognosis in patients with acute coronary syndrome (ACS). Aim We prospectively investigated associations, of gut microbiota in their feces and coronary lesion degree, and long-term prognosis of patients with ACS. Methods 1. In prospective cohort study, a total 502 subjects including 402 ACS patients and 100 controls. Fecal specimens were used to extract bacterial genomic DNA 2. 16S rDNA sequence of bacteria were generated to analyse specific gut microbial taxa associated with ACS onset for 60 ACS patients and 30 healthy controls. 3. Specific primers were designed according to the 16S rDNA sequence of bacteria for real time PCR reaction to determine the number of different bacteria. 4. All ACS patients calculated SYNTAX score by coronary radiography results and followed up for one year. The correlation of gut microbiota with coronary angiographic severity and prognosis in the ACS patients was analyzed. Results 1. Compared with the control group,the number of bacteria in Escherichia coli, Streptococcus and Enterobacteriaceae increased significantly (P&lt;0.05) and Lactobacillus decreased significantly (P&lt;0.05) in patients with ACS. 2. Lactobacillus were independent predictors of coronary angiographic severity in patients with ACS (HR=0.953; 95% CI: 0.935–0.970, P&lt;0.001). 3. Decreased Lactobacillus levels were independent protection factors with all-cause death (HR=0.954; 95% CI: 0.913–0.997, P=0.038) and risk of major adverse cardiac events (HR=0.952; 95% CI: 0.929–0.976, P&lt;0.001),especially for heart failure in long-term prognosis(HR=0.960; 95% CI: 0.932–0.989, P=0.007). Conclusion 1. Number of Lactobacillus are significantly decreased in patients with ACS,and associated with SYNTAX score,suggesting that Lactobacillus is associated with severity of coronary artery disease, all-cause death and MACE. 2. It provides new ideas for the prevention and treatment of ACS. Real time PCR Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Major Science and Technology Projects of Tianjin Science and Technology Commission in 2016

Background Metabolic syndrome (MetS) is involved in the occurrence, development and prognosis of cardiovascular diseases, especially acute myocardial infarction (AMI). In recent years, the trend of AMI at a younger age has gradually attracted people's attention. Relevant studies have confirmed that MetS affects the prognosis of people aged ≥45 with AMI. However, there is still a lack of research on MetS in people with premature myocardial infarction (PMI). Purpose To explore the impact of MetS and its components on clinical severity and long-term prognosis in PMI patients. Methods 772 Patients with AMI who aged ≤45 years old from 2015 to 2020 in a hospital were enrolled. The patients were divided into MetS group (n=417) and non-MetS group (n=355) according to the criteria proposed by NCEP ATP III in 2005 (Any 3 of the following 5): 1) Hypertension: BP ≥130/85 mmHg or consistent hypertensive patients undergoing treatment; 2) Hypertriglyceridemia: fasting plasma triglyceride ≥1.7 mmol/L; 3) Fasting HDL-C &lt;1.0 mmol/L in men and &lt;1.3 mmol/L in women. 4) Hyperglycemia: fasting blood glucose level ≥6.1 mmol/L or known diabetic patients undergoing treatment; 5) Central obesity: BMI ≥28.0 kg/m2. Patients were followed for median of 42 months for major adverse cardiovascular events (MACE). The parameters of clinical severity were compared using logistic regression analysis. Cox regression were used to analyze the relationship between MetS and its components and prognosis. Results A total of 772 patients were included in the analysis. Hyperglycemia was associated with multi-vessel disease (OR=1.700, 95% CI 1.172–2.464, P=0.005) and Syntax score ≥33 (OR=2.736, 95% CI 1.241–6.032, P=0.013).Increased MACE were observed in the MetS group (17.9% vs 10.3%, P=0.004) after 42 months follow-up. The Kaplan-Meier curve also showed significant differences (P&lt;0.001). MetS was an independent risk factor for MACE (HR=2.181, 95% CI 1.392–3.418, P=0.001). Of each component of the definition, BMI ≥28.0 kg/m2 (HR=2.047, 95% CI 1.229–3.410, P=0.006) and hyperglycemia (HR=2.911, 95% CI 1.850–4.580, P&lt;0.001) were independent risk factors for MACE. Conclusions In patients with PMI, (1) hyperglycemia usually indicates more severe lesions; (2) MetS as a whole was an independent risk factor for MACE; (3) Of each component of the MetS, BMI ≥28.0 kg/m2 and hyperglycemia were associated with MACE. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): This research was supported by the Key Project of Scientific and Technological Support Plan of Tianjin in 2020

Background The role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in predicting major adverse cardiovascular events (MACEs) in Non-ST elevation myocardial infarction (NSTEMI) patients is still an open question and the PCSK9 concentration of clinical usefulness remains unknown in guiding treatment. Purpose To explore the role of PCSK9 in predicting major adverse cardiovascular events (MACEs) in Non-ST elevation myocardial infarction patients. Methods 272 patients with NSTEMI were included in our study, all patients received PCI therapy after admission. Patients were followed up for 1 year and MACEs were recored. Their baseline plasma PCSK9 levels were determined by ELISA. Patients were divided into high, medium and low PCSK9 groups and the associations of PCSK9 with other biomarkers and MACEs were evaluated. Results The results showed that PCSK9 levels was related to levels of lipoproteins, high-sensitivity C-reactive protein (r=0.162, P=0.008), platelet volume distribution width (r=0.299, P&lt;0.001) and D-dimer (r=0.285, P&lt;0.001). And the concentrations of PCSK9 was greater higher in people with MACEs (137.2ng/ml vs 243.6ng/ml) (Fig. 1A). The Kaplan-Meier curves showed patients with high PCSK9 level had lower event-free survival rate (Fig. 1B). Survival analysis indicated high level of PCSK9 predicted MACEs independently after adjusted for traditional cardiovascular risk factors and GRACE score (HR=2.646, 95CI%: 1.047–6.686, P=0.027) (Fig. 1C, Fig. 2). Subgroup analysis demonstrated the prognostic value of high PCSK9 level was greater for patients classified by the GRACE score as high risk (Fig. 1D). Conclusions In a NSTEMI setting, the concentration of PCSK9 is associated with hypercoagulability and hyper-inflammation. High levels of PCSK9 independently predict future MACEs in NSTEMI patients, particularly those classified by the GRACE score as high risk. FUNDunding Acknowledgement Type of funding sources: None.

Background Patient delay in seeking help has been reported to be a major factor that related to delay in care of acute myocardial infarction (AMI). Lack the knowledge of symptoms may translate to behavioral deficiencies which lead up to failing to seek medical assistant at early stage of AMI. Purpose The aim of present study is to investigate the awareness of AMI symptoms and the emergency responses among community residents over 35 years old. Methods The sample was proportionally distributed by age according to the national census data. The sex ratio was 1:1. The sample size is calculated according to the significance level of 0.05, the allowable error of 0.1, and the estimated Excellent awareness level of 10%. The final sample size is adjusted to 4200, considering non-response rate of 20%. Multi-stage stratified random sampling was used. On the first stage, two districts each in urban and rural regions were randomly selected. On the second stage, 3–10 community health service centers were randomly selected in each district. On the third stage, residents over 35 managed by the community health service center were proportionally sampled to be interviewed. A structured questionnaire was used and the survey was conducted in a face-to-face interview by clinical physicians. Logistic regression was applied to analyze factors related to Good knowledge. Results The top three symptom recognized by public is “pain or discomfort in the chest” (71.3%), followed by “difficulty breathing” (65.1%) and “pain or discomfort in the jaw, neck, or back” (60.9%). 85.0% chose to call an ambulance as first response when witness others having an AMI. Those who lives alone (OR=1.408; 95% CI, 1.005–1.972) and whose immediate family had been diagnosed with AMI (OR=1.510; 95% CI, 1.040–2.192) has better knowledge. A significant positive correlation was observed for those with hypertension (OR=1.199; 95% CI, 1.007–1.429), while a negative correlation was observed for those with diabetes (OR=0.788; 95% CI, 0.626–0.992). Public education could improve Good knowledge (OR=1.662; 95% CI, 1.388–1.990), while doctoral advise has been shown negative impact (OR=0.824; 95% CI, 0.691–0.984). Conclusions Our data provide first population-based estimates of public awareness in our country. Further promotional strategies to increase overall awareness in general public are seriously needed. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Major Science and Technology Projects of Tianjin Science and Technology Commission Multivariable logistic regression