Remote ischemic conditioning reduces adverse events in patients with acute ischemic stroke complicating acute myocardial infarction: a randomized controlled trial.

BACKGROUND: Acute ischemic stroke (AIS) complicating an acute myocardial infarction (AMI) is not uncommon, but can severely worsen the clinical prognosis. This study aimed to investigate whether remote ischemic conditioning (RIC) could provide clinical benefits to patients with AIS complicating AMI. METHODS: Subjects with AIS complicating AMI were recruited in this double-blind, randomized, controlled trial; assigned to the RIC and sham groups; and respectively underwent twice daily RIC and sham RIC for 2 weeks. All subjects received standard medical therapy. The primary endpoint was the rate of major adverse cardiac and cerebrovascular events (MACCEs) within 3 months after enrollment. MACCEs comprise of death from all causes, unstable anginas, AMI, acute ischemic strokes, and transient ischemic attacks. RESULTS: Eighty subjects were randomly assigned; 37 patients in the RIC group and 40 patients in the sham-RIC group completed the 3-month follow-up and were included in the final analysis. Both RIC and sham RIC procedures were well tolerated. At 3-month follow-up, 11 subjects (29.7%) in the RIC group experienced MACCEs compared to 21 (52.5%) in the sham group (hazard ratio [HR], 0.396; 95% confidence interval, 0.187-0.838; adjusted p < 0.05). Six subjects (16.2%) in the RIC group had died at the 3-month follow up, significantly lower than the 15 (37.5%) deaths in the sham group (adjusted HR 0.333; 95% CI 0.126-0.881; p = 0.027). Seventeen subjects (45.9%) in the RIC group and 6 subjects (15.0%) in the sham group achieved functional independence (mRS score ≤ 2) at 3-month follow-up (adjusted OR 12.75; 95% CI 2.104-77.21; p = 0.006). CONCLUSIONS: Among patients with acute ischemic stroke complicating acute myocardial infarction, treatment with remote ischemic conditioning decreased the major adverse cardiac and cerebrovascular events and improved functional outcomes at 90 days. TRIAL REGISTRATION: URL: www. CLINICALTRIALS: gov . Unique identifier: NCT03868007. Registered 8 March 2019.

Improving cardiac function of angiotensin receptor/neprilysin inhibitor in patients with acute myocardial infarction: a systematic review and meta-analysis.

AIM: As the impact of angiotensin receptor/neprilysin inhibitor (ARNI) on cardiac function in acute myocardial infarction (AMI) patients is unclear in clinical therapy, we conducted this research to investigate the actual effects of improving cardiac function with ARNI in AMI patients. METHODS: Publications were checked up to June 2022. Standardised mean differences (SMD) and 95% confidence intervals (CI) were utilised for assessing the size of the effect of continuous variables. To assess the magnitude of the effect of dichotomous variables, a relative risk (RR) with 95% CI was used. RESULTS: ARNI could improve left ventricular ejection fraction (SMD = 0.40; 95% CI: 0.23 - 0.58), while lowering left ventricular end-diastolic volume (SMD = -0.43, 95% CI: -0.78 to -0.08), left ventricular end-systolic volume (SMD = -0.39, 95% CI: -0.66 to -0.11) and left ventricular enddiastolic diameter (SMD = -0.49; 95% CI: -0.65 to -0.33). Besides, it could decrease the rates of major adverse cardiac events (RR = 0.55; 95% CI: 0.43 - 0.69) and heart failure (RR = 0.42; 95% CI: 0.31 - 0.58). CONCLUSION: ARNI could greatly improve cardiac function in AMI patients.

Role of activating the nuclear factor kappa B signaling pathway in the development of septic cardiomyopathy in rats with sepsis.

BACKGROUND: Despite advances in the treatment of sepsis over time, this condition remains both a serious threat and a cause of death among critical patients. OBJECTIVE: This study aimed to explore the role of the nuclear factor kappa B (NF-κB) signaling pathway in the development of septic cardiomyopathy in rats with sepsis. METHOD: A total of 32 Sprague Dawley rats were randomized into a sham operation group and three groups with sepsis, which were tested at one of the following time-points: 3, 6, or 12 h. Each group included eight rats. Sepsis models were created via cecal ligation and puncture procedures. All the study rats had the following cardiac parameters and serum levels measured at either 3, 6, or 12 h after the operation (according to their assigned group): heart rate, left ventricular systolic pressure (LVSP), maximum rate of left ventricular pressure rise (+dP/dtmax) and fall (-dP/dtmax), tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), and cardiac troponin I (cTnI). The myocardium of the left ventricle was collected and subjected to hematoxylin and eosin staining to observe the changes in pathological morphology. The expression of toll-like receptor 4 (TLR4) and NF-κB in the myocardium were detected by western blot analysis. RESULTS: Compared with the sham operation group, the rats in the sepsis subgroups exhibited significantly lower values for all the cardiac parameters measured, including the heart rate (sham operation group = 386.63 ± 18.62 beats per minute [bpm], sepsis 3-h group = 368.38 ± 12.55 bpm, sepsis 6-h group = 341.75 ± 17.05 bpm, sepsis 12-h group = 302.13 ± 21.15 bpm), LVSP (sham operation group = 125.50 ± 11.45 mmHg, sepsis 3-h group = 110.88 ± 7.51 mmHg, sepsis 6-h group = 100.00 ± 15.06 mmHg, sepsis 12-h group = 91.38 ± 14.73 mmHg), +dp/dtmax (sham operation group = 7137.50 ± 276.44 mm Hg/sec, sepsis 3-h group = 5745.00 ± 346.16 mm Hg/sec, sepsis 6-h group = 4360.00 ± 312.04 mm Hg/sec, sepsis 12-h group = 2871.25 ± 443.99 mm Hg/sec), and -dp/dtmax (sham operation group = 6363.75 ± 123.86 mm Hg/sec, sepsis 3-h group = 6018.75 ± 173.49 mm Hg/sec, sepsis 6-h group = 5350.00 ± 337.89 mm Hg/sec, sepsis 12-h group = 4085.00 ± 326.76 mm Hg/sec). They also displayed significantly higher levels of serum cytokines, including TNF-α (sham operation group = 14.72 ± 2.90 pg/mL, sepsis 3-h group = 34.90 ± 4.79 pg/mL, sepsis 6-h group = 24.91 ± 2.57 pg/mL, sepsis 12-h group 22.06 ± 3.11 pg/mL), IL-1ß (sham operation group = 42.25 ± 16.91, 3-h group = 112.25 ± 13.77, sepsis 6-h group = 207.90 ± 22.64, sepsis 12-h group = 157.18 ± 23.06), IL-6 (sham operation group = 39.89 ± 5.74, sepsis 3-h group = 78.27 ± 9.31, sepsis 6-h group = 123.75 ± 13.11, sepsis 12-h group = 93.21 ± 8.96), and cTnI (sham operation group = 0.07 ± 0.03 ng/mL, sepsis 3-h group = 0.18 ± 0.06 ng/mL, sepsis 6-h group = 0.67 ± 0.19 ng/mL, sepsis = 12-h group 1.28 ± 0.10 ng/mL). The rats in the sepsis groups exhibited pathological changes in the myocardium, which deteriorated gradually over time. The animals in all the sepsis groups exhibited significantly higher levels of TLR4 and NF-κB protein expression compared with the sham group. The TLR4 protein expressions were 0.376 in the sham operation group, 0.534 in the sepsis 3-h group, 0.551 in the sepsis 6-h group, and 0.719 in the sepsis 12-h group. The NF-κB protein expressions were 0.299 in the sham operation group, 0.488 in the sepsis 3-h group, 0.516 in the sepsis 6-h group, and 0.636 in the sepsis 12-h group. CONCLUSION: Sepsis can lead to myocardial injury and cardiac dysfunction. This may be related to the activation of the NF-κB intracellular signal transduction pathway and the release of inflammatory factors as a result of lipopolysaccharides acting on TLR4 during the onset of sepsis.

Triage Nurse-Activated Emergency Evaluation Reduced Door-to-Needle Time in Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis.

Methods: This was a retrospective analysis in a general hospital emergency department in Beijing, China. 212 adult AIS patients treated with thrombolysis who failed to use EMSs were included. In addition to DNT, door-to-vein open time (DVT), door-to-blood sample deliver time (DBT), and 7-day NIHSS scores were evaluated. Results: 137 (64.6%) patients were in the triage nurse-activated group and 75 (35.4%) patients were in the doctor-activated group. The DNT of the triage nurse-activated group was significantly reduced compared with the doctor-activated group (28 (26, 32.5) min vs. 30 (28, 40) min, p=0.001). DNT less than 45 min was seen in 95.6% of patients in the triage nurse-activated group and 84% of patients in the doctor-activated group (p=0.011, OR 3.972, 95% CI 1.375-11.477). In addition, DVT (7 (4, 10) min vs. 8 (5, 12) min, P=0.025) and DBT (15 (13, 21) min vs. 19 (15, 26) min, p=0.001) of the triage nurse-activated group were also shorter than those of the doctor-activated group (p < 0.05). The 7-day NIHSS scores were not statistically different between the two groups. Conclusions: Triage nurse-activated urgent emergency evaluation could reduce the door-to-needle time, which provides a feasible opportunity to optimize the emergency department service for AIS patients who failed to use emergency medical services.

Daily Remote Ischemic Conditioning Can Improve Cerebral Perfusion and Slow Arterial Progression of Adult Moyamoya Disease-A Randomized Controlled Study.

BACKGROUND AND PURPOSE: Moyamoya disease (MMD) is a complicated cerebrovascular disease with recurrent ischemic or hemorrhagic events. This study aimed to prove the safety and efficacy of remote ischemic conditioning (RIC) on MMD. METHODS: In total, 34 patients with MMD participated in this pilot, prospective randomized controlled study for 1 year. 18 patients were allocated into the RIC group, and 16 patients accepted routine medical treatment only. RIC-related adverse events were recorded. The primary outcome was the improvement ratio of mean cerebral blood flow (mCBF) in middle cerebral artery territory measured by multidelay pseudocontinuous arterial spin labeling, and the secondary outcomes were the cumulative incidence of major adverse cerebrovascular events (MACEs), the prevalence of stenotic-occlusive progression, and periventricular anastomosis at 1-year follow-up. RESULTS: In total, 30 of the 34 patients with MMD completed the final follow-up (17 in the RIC group and 13 in the control group). No adverse events of RIC were observed. The mCBF improvement ratio of the RIC group was distinctively higher compared with the control group (mCBF-whole-brain : 0.16 ± 0.15 vs. -0.03 ± 0.13, p = 0.001). Stenotic-occlusive progression occurred in 11.8% hemispheres in the RIC group and 38.5% in the control group (p = 0.021). The incidence of MACE was 5.9% in the RIC group and 30.8% in the control group (hazard ratio with RIC, 0.174; 95% CI, 0.019-1.557; p = 0.118). No statistical difference was documented in the periventricular anastomosis between the two groups after treatment. CONCLUSIONS: Remote ischemic conditioning has the potential to be a safe and effective adjunctive therapy for patients with MMD largely due to improving cerebral blood flow and slowing the arterial progression of the stenotic-occlusive lesions. These findings warrant future studies in larger trials.

miRNA-10a-5p Alleviates Insulin Resistance and Maintains Diurnal Patterns of Triglycerides and Gut Microbiota in High-Fat Diet-Fed Mice.

miRNA-10a is rhythmically expressed and regulates genes involved in lipid and glucose metabolism. However, the effects of miRNA-10a on obesity and glucose intolerance, as well as on the diurnal pattern of expression of circadian clock genes, remain unknown. We explored the effects of miRNA-10a-5p on insulin resistance and on the diurnal patterns of serum triglycerides and gut microbiota in high-fat diet- (HFD-) fed mice. The results showed that oral administration of miRNA-10a-5p significantly prevented body weight gain and improved glucose tolerance and insulin sensitivity in HFD-fed mice. Administration of miRNA-10a-5p also maintained the diurnal rhythm of Clock, Per2, and Cry1 expression, as well as serum glucose and triglyceride levels. Surprisingly, the diurnal oscillations of three genera of microbes, Oscillospira, Ruminococcus, and Lachnospiraceae, disrupted by HFD feeding, maintained by administration of miRNA-10a-5p. Moreover, a strong positive correlation was found between hepatic Clock expression and relative abundance of Lachnospiraceae, both in control mice (r = 0.877) and in mice administered miRNA-10a-5p (r = 0.853). Furthermore, we found that along with changes in Lachnospiraceae abundance, butyrate content in the feces maintained a diurnal rhythm after miRNA-10a-5p administration in HFD-fed mice. In conclusion, we suggest that miRNA-10a-5p may improve HFD-induced glucose intolerance and insulin resistance through the modulation of the diurnal rhythm of Lachnospiraceae and its metabolite butyrate. Therefore, miRNA-10a-5p may have preventative properties in subjects with metabolic disorders.

Aortic pulse wave velocity is associated with measures of subclinical target organ damage in patients with mild hypertension.

We evaluated the temporal association between aortic arterial stiffness and subclinical target organ damage, including renal function decline, left ventricular geometric remodeling, and left ventricular diastolic dysfunction in patients with mild hypertension. Automatic pulse wave velocity (PWV) measuring system was applied to examine carotid-femoral PWV (CFPWV) reflecting aortic arterial stiffness in 644 essential hypertensive patients. Clinical data were collected, and cardiac structure and function were assessed by echocardiography. CFPWV was significantly and positively associated with left ventricular mass index (r = 0.153, P = 0.018), relative wall thickness (r = 0.235, P < 0.001), and left atrial diameter (r = 0.192, P = 0.003), and negatively with E/A ratio (r = -0.361, P < 0.001) and creatinine clearance (r = -0.248, P < 0.001). Logistic regression analysis demonstrated that CFPWV remained significantly correlated with renal function decline (P = 0.011), left ventricular diastolic dysfunction (P = 0.009) and left ventricular geometric remodeling (P = 0.020). Higher CFPWV was independently associated with greater burden of subclinical disease in renal impairment, left ventricular geometric remodeling and diastolic dysfunction.

Impact of the metalloproteinase-9/tissue inhibitor of metalloproteinase-1 system on large arterial stiffness in patients with essential hypertension.

The extracellular matrix is vital for maintaining tissue integrity, and the matrix metalloproteinases/tissue inhibitors of metalloproteinases (MMPs/TIMPs) system is involved in the regulation of extracellular matrix metabolism. Extracellular matrix turnover plays an important role in the change of large arterial mechanical properties in hypertension. However, the association of the metalloproteinase-9/tissue inhibitor of metalloproteinase-1 (MMP-9/TIMP-1) system and arterial stiffness is not straightforward and existing data are rather limited. Our objective is to explore the impact of the MMP-9/TIMP-1 system on large arterial stiffness in patients with essential hypertension. An automatic pulse wave velocity (PWV) measuring system was used to examine carotid-femoral PWV (CFPWV) and carotid-radial PWV (CRPWV) as the parameters reflecting central elastic large arterial and peripheral muscular medium-sized arterial elasticity, respectively; and serum MMP-9 and TIMP-1 levels, along with a number of other established biomarkers, were measured by enzyme-linked immunosorbent assay (ELISA) in 202 essential hypertensive patients and 54 age and gender-matched control subjects. Compared with the control subjects, hypertensive patients exhibited higher levels of MMP-9 (p=0.001) and TIMP-1 (p=0.002). Spearman's correlation analysis showed that serum levels of MMP-9 (p=0.014) and TIMP-1 (p=0.005) were significantly and positively correlated with CFPWV in hypertensive patients. A stepwise multiple regressive analysis demonstrated that age, systolic blood pressure, heart rate and TIMP-1 were independent predictors of CFPWV in patients with essential hypertension (adjusted r2=0.458). In conclusion, our results imply that the MMP-9/TIMP-1 system may play an important role in the determination of arterial function, and these findings may have implications for the involvement of MMP-9/TIMP-1 system in the pathophysiology of cardiovascular disease.

[A study on the risk factors of cardiovascular between hypertensive patients and normal subjects in the same family].

OBJECTIVE: Through studying the difference between the hypertensive patients and those with normal blood pressure who all from the same hypertensive pedigree, we tried to find the factors which would decrease the risk of hypertension. METHODS: Hypertensive patients, when coming to the cardiovascular clinic of Xuan Wu Hospital from 2003 to 2004, were defined as the members of the hypertensive pedigrees through inquiry. 84 families including 368 persons, with 192 syblings were involved. Metabolic syndrome could be defined by the criterion of adult treatment panel III. RESULTS: When compared with normal blood pressure persons, clinical examinations of the hypertensive patients had an higher levels of triglyceride, total cholesterol, glucose and body mass index (BMI). The hypertensive group showed higher ratios among male patients, smokers, alcohol drinkers, having irritable personality and high-salt-intake. Through logistic regression, overweight, smoking and irritable temperament showed positive relations with hypertension. The rate of metabolic syndrome was higher in hypertension group. CONCLUSION: It is important that either persons with normal blood pressure or hypertension should control their body weights (BMI) since the rate of metabolic syndrome in hypertension group was high.

[The changes and impact factors of carotid-femoral and carotid-radial pulse wave velocity in patients with essential hypertension].

OBJECTIVE: To analyze the changes of carotid-femoral and carotid-radial pulse wave velocity in patients with essential hypertension, and effects of age and levels blood pressure levels on these changes. METHODS: Automatic pulse wave velocity (PWV) measuring system was applied to examine carotid-femoral PWV (CFPWV) and carotid-radial PWV (CRPWV) as the parameters reflecting central elastic large arterial and peripheral muscular medium-sized arterial elasticity respectively. 517 hypertensive patients aged 17-82 years (272 males and 245 females, mean age 52.0 +/- 13.0 years) and 118 healthy subjects aged 19-82 years (52 males and 66 females, mean age 54.2 +/- 13.8 years) were recruited in the study. RESULTS: CFPWV increased with age in both groups (P < 0.001), whereas CRPWV did not change significantly. CFPWV and CRPWV both increased with blood pressure. A stepwise multiple regression analysis demonstrated that age and systolic blood pressure were positively related to CFPWV independently, while diastolic blood pressure was significantly associated with CRPWV. CONCLUSIONS: Age and components of blood pressure exert different effects on elasticity of central elastic large artery and peripheral muscular medium-sized artery. Examining the change of large arterial elasticity has important clinical value in hypertensive patients.