Atherosclerosis treatment with nanoagent: potential targets, stimulus signals and drug delivery mechanisms.

Cardiovascular disease (CVDs) is the first killer of human health, and it caused up at least 31% of global deaths. Atherosclerosis is one of the main reasons caused CVDs. Oral drug therapy with statins and other lipid-regulating drugs is the conventional treatment strategies for atherosclerosis. However, conventional therapeutic strategies are constrained by low drug utilization and non-target organ injury problems. Micro-nano materials, including particles, liposomes, micelles and bubbles, have been developed as the revolutionized tools for CVDs detection and drug delivery, specifically atherosclerotic targeting treatment. Furthermore, the micro-nano materials also could be designed to intelligently and responsive targeting drug delivering, and then become a promising tool to achieve atherosclerosis precision treatment. This work reviewed the advances in atherosclerosis nanotherapy, including the materials carriers, target sites, responsive model and treatment results. These nanoagents precisely delivery the therapeutic agents to the target atherosclerosis sites, and intelligent and precise release of drugs, which could minimize the potential adverse effects and be more effective in atherosclerosis lesion.

The stress hyperglycemia ratio improves the predictive ability of the GRACE score for in-hospital mortality in patients with acute myocardial infarction.

BACKGROUND: The Global Registry of Acute Coronary Events (GRACE) score is a powerful tool used to predict in-hospital mortality after acute myocardial infarction (AMI) and does not include a glycometabolism-related index. We investigated whether the addition of the stress hyperglycemia ratio (SHR) provides incremental prognostic value in addition to the GRACE score. METHODS: A retrospective cohort of 613 AMI patients was enrolled in the present analyses. The patients were stratified according to the primary endpoint (in-hospital mortality) and the tertiles of the SHR. RESULTS: During hospitalization, 40 patients reached the primary endpoint, which was more frequently observed in patients with a higher SHR. The SHR, but not admission blood glucose (ABG), adjusted for the GRACE score independently predicted in-hospital mortality [odds ratio 2.5861; 95% confidence interval (CI), 1.3910-4.8080; P = 0.0027]. The adjustment of the GRACE score by the SHR improved the predictive ability for in-hospital death (an increase in the C-statistic value from 0.787 to 0.814; net reclassification improvement, 0.6717, 95% CI 0.3665-0.977, P < 0.01; integrated discrimination improvement, 0.028, 95% CI 0.0066-0.0493, P = 0.01028). The likelihood ratio test showed that the SHR significantly improved the prognostic models, including the GRACE score. Adding the SHR to the GRACE score presented a larger net benefit across the range of in-hospital mortality risk than the GRACE score alone. CONCLUSION: The SHR, but not the ABG, is an independent predictor of in-hospital mortality after AMI even after adjusting for the GRACE score. The SHR improves the predictability and clinical usefulness of prognostic models containing the GRACE score.

Trimethylamine N-oxide and its precursors in relation to blood pressure: A mendelian randomization study.

Objective: Previous studies have demonstrated that trimethylamine N-oxide (TMAO) and its precursors, including choline, betaine, and carnitine, are closely associated with blood pressure (BP) changes. Nevertheless, with the limitation of reverse causality and confounder in observational studies, such a relationship remains unclear. We aimed to assess the causal relationship of TMAO and its precursors with BP by the Mendelian Randomization (MR) approach. Method: In this study, two-sample MR was used to reveal the causal effect of TMAO and its precursors on BP. Pooled data of TMAO and its precursors was from genome-wide association studies (GWAS) which includes summary data of human metabolome in 2,076 European participants from Framingham Heart Study. Summary-level data for BP was extracted from the International Consortium of Blood Pressure-Genome Wide Association Studies. Inverse variance weighted (IVW), MR Egger regression, Maximum likelihood, Weighted median, and MR pleiotropy residual sum and outlier test (MR-PRESSO) were used in this MR analysis. Results: A total of 160 independent SNP loci were associated with TMAO and three precursors, including 58 associated with TMAO, 29 associated with choline, 44 associated with betaine, and 29 associated with carnitine, were selected. MR results suggested that a 1 unit increase in TMAO should be associated with a 1SD increase in systolic BP mmHg (beta: 0.039, SE, 0.072, p = 0.020). Additionally, our findings also indicated that a 1 unit increase in carnitine should be associated with a 1SD increase in systolic BP mmHg (beta: 0.055, SE: 0.075, p = 0.039). This result was also confirmed by sensitivity analysis methods such as Maximum likelihood, MR-PRESSO, and Weighted median. No effects of betaine or choline on systolic or diastolic BP were observed in the present study. Conclusion: Our study provides evidence of a causal relationship of TMAO and its precursors with BP, suggesting that mediating the generation of TMAO would be beneficial for lowering BP.

[Age-related differences in the management and outcome of acute coronary syndrome under the chest pain center model: a multicenter retrospective study].

OBJECTIVE: To assess the age-related differences in the management strategies and outcomes of patients with acute coronary syndrome (ACS) under the chest pain center model. METHODS: Clinical data of 2 833 patients with ACS were enrolled in the retrospective observational registry between January 2017 and June 2019 at 11 hospitals with chest pain centers in Chengdu. The patients were divided into four groups according to their ages: < 55 years old group (n = 569), 55-64 years old group (n = 556), 65-74 years old group (n = 804), ≥ 75 years old group (n = 904). The collected data included the patients' demographic characteristics, cardiovascular risk factors, medical history, symptoms and signs of onset, experimental examination, types of ACS and the time from the symptom to the hospital (S-to-D), etc., and the clinical characteristics, management strategies, all-cause mortality in the hospital, and the incidence of major adverse cardiovascular and cerebrovascular events (MACCE) within 1 year after discharge were compared. The primary end point was the clinical outcome of ACS patients in different age groups, including all-cause deaths in the hospital and the incidence of MACCE within 1 year after discharge. The secondary end point was the proportion of ACS patients underwent percutaneous coronary intervention (PCI) in different age groups. Multivariate Logistic regression was used to analyze the risk factors of all-cause deaths in ACS patients. Kaplan-Meier curve was used to express the incidence of MACCE within 1 year after discharge in different age groups. Multivariate Cox regression was used to analyze the factors affecting the incidence of MACCE within 1 year after discharge of ACS patients. RESULTS: As age increased, the proportion of male patients gradually decreased, and the percentages of male patients aged < 55 years old, 55-64 years old, 65-74 years old, and ≥ 75 years old were 87.2% (496/569), 77.0% (428/556), 66.4% (534/804), and 60.1% (543/904), respectively; and ACS patients combined with hypertension, diabetes, coronary heart disease, and stroke history were more common [the percentages of patients with hypertension aged < 55 years old, 55-64 years old, 65-74 years old, ≥ 75 years old were 41.3% (235/569), 52.2% (290/556), 59.7% (480/804), and 66.9% (605/904); the percentages of diabetes were 18.6% (106/569), 25.5% (142/556), 27.0% (217/804), and 28.2% (255/904); the percentages of coronary heart disease were 10.1% (57/564), 13.9% (77/555), 17.6% (141/803), and 23.7% (213/899); the percentages of stroke were 0.7% (4/564), 4.0% (22/552), 4.5% (36/801), and 8.6% (77/894)]. But the percentages of patients with a history of active smoking, typical chest pain/chest tightness and dyslipidemia were significantly reduced [the percentages of smoking history were 60.2% (340/565), 48.0% (266/554), 33.7% (270/801), and 21.7% (195/899), typical chest pain/chest tightness were 96.9% (536/553), 96.4% (516/535), 91.8% (716/780), 90.2% (776/860); the percentages of dyslipidemia were 11.2% (63/565), 9.2% (51/553), 5.7% (46/802), and 4.9% (44/896)], the time of S-to-D was significantly prolonged [minutes: 176.0 (73.5, 557.0), 194.5 (89.3, 682.3), 221.0 (98.8, 940.5), and 270.0 (115.0, 867.0)], hemoglobin (Hb) level was significantly reduced (g/L: 145.44±17.43, 135.95±19.25, 129.75±19.03, 122.19±20.55), and the incidence of non-ST-segment elevation myocardial infarction (NSTEMI) increased significantly [18.6% (106/569), 20.5% (114/556), 26.6% (214/804), 26.5% (240/904)], and the differences were statistically significant (all P < 0.05). The proportion of Killip grade III-IV were the highest in patients aged ≥ 75 years old, 9.0% and 12.6%, respectively. Compared with the groups aged < 55 years old, 55-64 years old, and 65-74 years old, the proportion of patients aged ≥ 75 years old who underwent PCI was the lowest, and the all-cause mortality in the hospital and the incidence of 1-year MACCE of patients underwent PCI were significantly lower than those of patients underwent conservative treatment [6.0% (28/463) vs. 10.4% (45/434), 14.6% (43/294) vs. 24.3 % (55/226), both P < 0.05]. As age increased, the hospital all-cause mortality and the 1-year MACCE incidence increased (all-cause mortality rates in < 55 years old, 55-64 years old, 65-74 years old, ≥ 75 years old groups were 0.9%, 2.2%, 5.5%, 8.3%, and the 1-year MACCE incidences were 5.0%, 6.7%, 13.9%, 18.7%, both P < 0.01). The multivariate Logistic regression analysis showed that age, cardiogenic shock, ST-segment elevation myocardial infarction (STEMI), the number of vascular disease and underwent PCI were the independent risk factors of all-cause mortality [the odds ratio (OR) and 95% confidence interval (95%CI) were 1.644 (1.356-1.993), 11.794 (7.469-18.621), 2.449 (1.419-4.227), 1.334 (1.096-1.624), 0.391 (0.247-0.619), all P < 0.001]. Cox regression analysis showed that age, STEMI, the number of vascular disease and underwent PCI were independent risk factors of the occurrence of MACCE within 1 year after discharge [hazard ratio (HR) and 95%CI were 1.354 (1.205-1.521), 1.387 (1.003-1.916), 1.314 (1.155-1.495), 0.547 (0.402-0.745), all P < 0.05]. CONCLUSIONS: In the chest pain center model, compared with other age of ACS patients, the proportion of NSTEMI in elderly patients group aged ≥ 75 years old was higher, the proportion of PCI was lower, and the clinical outcome was worse. However, the prognosis of elderly patients receiving PCI treatment was better than the patients receiving conservative treatment.

[Percutaneous transcather closure of atrial septal defect guided by transthoracic echocardiography and transesophageal echocardiography].

OBJECTIVE: To evaluate the reliability of the combined use of TTE and TEE in guiding percutaneous closure of atrial septal defect. METHODS: A total of 120 patients were recruited, all accepting TTE and TEE examinations before surgery. The release of ASD occluders was guided by TTE. The patients were divided into two groups. Patients in Group A received ASD occluders with > or = 24 mm diameter. Group B received ASD occluders with < 24 mm diameter. Each group comprised patients with and without retroaortic rim. The patients were followed up with TTE and ECG examinations 24 h, 1, 3 and 6 months after the procedure. RESULTS: ASD closure was successful for 94% and 100% of the patients in group A and group B, respectively. The difference of the ASD diameter measured by TEE and TTE was (2.7 +/- 2.8) mm in group A and (1.7 +/- 2) mm in group B, P < 0.05. The ASD diameter measured by TEE had a (4.87 +/- 1.10) mm and (4.2 +/- 0.80) mm difference with the diameter of ASD occluders for patients in Group A and Group B, respectively (P < 0.05). The ASD diameter measured by TTE had a (7.51 +/- 2.72) mm and (5.89 +/- 2.26) mm difference with the diameter of ASD occluders for patients in Group A and Group B, respectively (P < 0.05). The ASD diameter measured by TEE had a greater correlation coefficient with the ASD occluder diameter than that measured by TTE. The ASD diameters measured by TEE(x1) and TTE(x2) were both linearly correlated with the ASD occluder diameter(y). There was no difference in the successful rate of ASD closure between the patients with and without deficient retroaortic rim. In group A, the procedure failed in 4 patients; misalignment of the ASD occlude occurred in one patient; one patient suffered from second degree type II atrio-ventricular block; one patient had ischemic cerebral stroke. No such complications occurred in group B. CONCLUSION: The combined use of TTE and TEE before the intervention procedure and the release of ASD occluder guided by TTE enables high successful closure rate with little complication. It is an effective and safe method. It can be performed in patients with deficient retroaortic rim.

Does the E/e' index predict the maintenance of sinus rhythm after catheter ablation of atrial fibrillation?

INTRODUCTION: The role of left ventricular (LV) diastolic dysfunction in recurrent atrial fibrillation (AF) after catheter ablation remains unknown. We investigated LV diastolic function using the ratio of early transmitral flow velocity (E) to early diastolic mitral annular velocity (e') and evaluated its predictive value for AF recurrence. METHODS: One hundred three AF patients underwent transthoracic echocardiography before ablation and during 3 months of follow-up. Clinical and echocardiographic parameters of patients with maintained sinus rhythm were compared with those with recurrent AF. RESULTS: Of 103 patients, 26 had recurrent AF during follow-up. The E/e' index was the best independent predictor of AF recurrence in a multivariate logistic regression model. A cutoff value of 11.2 for the E/e' measured before ablation was associated with a sensitivity of 80.8% and specificity of 81.8% (area under ROC curve, 0.840; 95% CI, 0.754-0.926) for AF recurrence. E/e' measured in sinus rhythm after ablation had an even better predictive power (area under ROC curve, 0.917; 95% CI, 0.850-0.983). CONCLUSION: LV diastolic function was closely associated with AF recurrence after catheter ablation. The E/e' index can be used as an incremental predictor for AF recurrence after catheter ablation.