Associated factors and hemodynamic characteristics of resistant hypertension in the elderly.

The purpose of this study was to explore the associated factors and hemodynamic characteristics of resistant hypertension (RHTN) in the elderly. A total of 283 patients aged ≥60 years with hypertension were evaluated by the CNAP™ monitor. Among them, 240 patients were non-RHTN (controlled hypertension with use of three or fewer antihypertensive medications) and 43 patients were RHTN (uncontrolled hypertension despite the concurrent use of ≥3 antihypertensive drugs at optimized doses, including a diuretic, or achieving target blood pressure with the use of ≥4 antihypertensive medications). RHTN was associated with higher body mass index (BMI), longer hypertension duration, and coronary heart disease (p = .004, p < .001, and p = .042, respectively). The mean number of antihypertensive medications was greater in patients with RHTN (p < .001). Hemodynamic analysis revealed higher cardiac output in the RHTN group than in the non-RHTN group, while no difference was observed in systemic vascular resistance. Screening for secondary etiology showed that, among the 43 patients with RHTN, 8 (18.6%) had chronic kidney disease, 8 (18.6%) had obstructive sleep apnea, 4 (9.3%) had primary aldosteronism, 2 (4.7%) had renovascular disease. No significant differences were observed in the cardiac output and systemic vascular resistance values between different causes of RHTN. These findings suggest that higher body mass index, longer hypertension duration, and coronary heart disease emerged as the associated factors of RHTN in the elderly. RHTN is characterized by higher cardiac output. Screening for the possible secondary etiology of RHTN in the elderly patients is necessary and important.

Rationale and Design of LAPIS: A Multicenter Prospective Cohort Study to Investigate the Efficacy and Safety of Low-Dose Aspirin in Elderly Chinese Patients.

Purpose: Although aspirin can effectively reduce the occurrence of atherothrombosis, it is significantly associated with increased bleeding, with elderly individuals being at increased risk of cardiovascular diseases(CVDs) and hemorrhage. While the adverse effects of aspirin can be reduced by using the lowest effective dose, its optimal dose remains undetermined in the elderly Chinese population with both higher cardiovascular and bleeding risks. This study aims to assess the current status of aspirin therapy in real-world clinical settings as well as investigate the efficacy and safety of different doses of aspirin intake (≤ 50 mg/d and > 50 mg/d) for CVD prevention and management in elderly Chinese individuals. Patients and Methods: The Low-dose Aspirin for Primary and Secondary Prevention of Cardiovascular Disease in the Elderly Study (LAPIS) is a multicenter, prospective, observational cohort study. At least 10,000 people aged ≥ 60 years who require long-term aspirin therapy will be recruited. The effectiveness outcome is a composite of major cardiovascular events(MACEs), including nonfatal myocardial infarction, unstable angina, arteriosclerotic disease requiring surgery or intervention, nonfatal stroke, transient ischemic attack, or cardiovascular death (excluding intracranial hemorrhage). The safety outcome is a composite of the first occurrence of fatal bleeding, major bleeding and minor bleeding. Information on the incidence of aspirin-associated gastrointestinal adverse events will also be collected for safety analyses. Outcome measurements will be performed at intervals of 30 days, 3 months, 6 months and then every 6 months for the next 3 years. Conclusion: The results of the LAPIS study will ascertain the efficacy and safety of different doses of aspirin for the prevention and management of CVD, thereby providing evidence to determine the optimal evidence-based dose of aspirin therapy in Chinese elderly individuals. Trial Registration: ChiCTR1900021980 (chictr.org.cn). Registered on March 19, 2019.

Outcomes Associated with 50 mg/d and 100 mg/d Aspirin for the Prevention and Management of Cardiovascular Disease in Chinese Elderly: Single-Center Interim Analysis of a Multicenter, Prospective, Observational Study.

Purpose: Although aspirin can effectively reduce the occurrence of atherothrombosis, it is significantly associated with increased bleeding, with elderly individuals being at increased risk of cardiovascular diseases (CVD) and hemorrhage. This study aims to evaluate the efficacy and safety of aspirin 50 mg/d and 100 mg/d for the prevention and management of CVD in Chinese elderly. Patients and Methods: The Low-dose Aspirin for Primary and Secondary Prevention of Cardiovascular Disease in the Elderly Study (LAPIS) is a multicenter, prospective, observational cohort study, this study was a single-center interim analysis of LAPIS. Patients aged ≥60 and required long-term aspirin for primary and secondary prevention of CVD were eligible. From Apr 1, 2019 to Feb 28, 2022, 165 patients who received 50 mg/d aspirin and 261 patients who received 100 mg/d aspirin were included in the study. The incidence of major cardiovascular events (MACEs), bleeding events, and gastrointestinal adverse events were compared between two groups. Results: After adjusting for patient characteristics using propensity score matching, aspirin 100 mg/d was associated with increased incidence rates of total bleeding events (28.34 vs.17.25 events/100 patient-years, HR 1.671, 95% CI 1.024-2.712, P = 0.040) and minor bleeding events (27.63 vs.15.92 events/100 patient-years, HR 1.738, 95% CI 1.056-2.861, P = 0.031), whereas the incidence of MACE (6.35 vs 6.65 events/100 patient-years, HR 0.921, 95% CI 0.399-2.127, P = 0.848) and gastrointestinal adverse events (12.73 vs.10.42 events/100 patient-years, HR 1.206, 95% CI 0.623-2.337, P = 0.578) were similar between the two groups. Multivariate Cox analysis identified that aspirin dose (100 mg/d vs. 50 mg/d, HR 1.918, 95% CI 1.137-3.235, P = 0.015), concomitant use of other antiplatelets (HR 1.748, 95% CI 1.009-3.028, P = 0.046) and anticoagulants (HR 2.501, 95% CI 1.287-4.862, P = 0.007) were independently associated with bleeding events. Conclusion: 50 mg/d aspirin may be preferred to balance the safety and effectiveness in Chinese individuals over 60 years of age who need long-term aspirin for the prevention and management of CVD. Trial Registration: ChiCTR1900021980 (chictr.org.cn). Registered on 19 March 2019.

The Predictive Value of Combining Symptoms, Residual Syntax Score and Non-Invasive Tests in the Diagnosis of Significant Coronary Artery Disease in Elderly Post-PCI Patients.

Purpose: To assess the diagnostic efficiency of a combination of symptoms, residual Syntax score (rSS) and non-invasive tests in elderly post-PCI patients. Patients and Methods: This was a retrospective study that consecutively enrolled patients ≥60 years old with chronic coronary syndrome and previous stent implantation without lesions requiring further revascularization between March 2013 and June 2020. The patients were scheduled for exercise ECG, CCTA and invasive coronary angiography within 4 weeks. The study then calculated rSS and the sensitivity, specificity, positive and negative predictive values (PPV and NPV) and accuracy of symptoms, rSS, exercise ECG and CCTA, taking computational pressure-flow dynamics derived fractional flow reserve (caFFR) as the standard reference. Results: A total of 114 patients were enrolled in this study, including 75 patients with caFFR-positive and 39 patients with caFFR-negative. The caFFR-positive group had more patients with typical angina. Furthermore, the rSS in the caFFR-positive group was higher than that in the caFFR-negative category (7.33 ± 6.56 vs 3.34 ± 4.26, p < 0.001). There was no significant difference in exercise ECG results between the two groups. However, the rate of positive CCTA in the caFFR-positive group was higher than that in the caFFR-negative category (89.33% vs 46.15%, p < 0.001). In addition, after combining symptoms, rSS and CCTA, the sensitivity, specificity, PPV, NPV and accuracy for diagnose were 77.5%, 84.2%, 90.2%, 66.7% and 79.8%, respectively. Conclusion: The findings showed that exercise ECG had limited power to diagnose significant CAD in elderly post-PCI patients, but CCTA was more efficient. Moreover, combining symptoms, rSS and CCTA provided more accurate diagnostic performance with feasibility and safety.

Identification of Potential Key Biomarkers of Atrial Fibrillation and Their Correlation with Immune Infiltration in Atrial Tissue.

Objective: To identify potential key biomarkers and characterize immune infiltration in atrial tissue of patients with atrial fibrillation (AF) through bioinformatics analysis. Methods: Differentially expressed genes (DEGs) were identified by the LIMMA package in Bioconductor, and functional and pathway enrichment analyses were undertaken using GO and KEGG. The LASSO logistic regression and BORUTA algorithm were employed to screen for potential novel key markers of AF from all DEGs. Gene set variation analysis was also performed. Single-sample gene set enrichment analysis was employed to quantify the infiltration levels for each immune cell type, and the correlation between hub genes and infiltrating immune cells was analyzed. Results: A total of 52 DEGs were identified, including of 26 downregulated DEGs and 26 upregulated DEGs. DEGs were primarily enriched in the Major Histocompatibility Complex class II protein complex, glucose homeostasis, protein tetramerization, regulation of synapse organization, cytokine activity, heart morphogenesis, and blood circulation. Three downregulated genes and three upregulated genes were screened by LASSO logistic regression and the BORUTA algorithm. Finally, immune infiltration analysis indicated that the atrial tissue of AF patients contained significant infiltration of APC_co_inhibition, Mast_cell, neutrophils, pDCs, T_cell_costimulation, and Th1_cells compared with paired sinus rhythm (SR) atrial tissue, and the three downregulated genes were negatively correlated with the six kinds of immune cells mentioned above. Conclusion: The hub genes identified in this study and the differences in immune infiltration of atrial tissue observed between AF and SR tissue might help to characterize the occurrence and progression of AF.

Activin a inhibits foam cell formation and up-regulates ABCA1 and ABCG1 expression through Alk4-Smad signaling pathway in RAW 264.7 macrophages.

BACKGROUND: Activin A has been reported to play important roles in the pathogenesis of atherosclerosis. The purpose of this study is to investigate the effects of activin A on oxidized low-density lipoprotein (ox-LDL)-induced foam cell formation and explore the underlying molecular mechanisms in murine macrophage-like cell line RAW 264.7. METHODS: The effects of activin A on Dil-labeled ox-LDL uptake were examined by confocal microscopy and flow cytometry analysis. The mRNA and protein levels of cholesterol receptors were analyzed by RT-qPCR and western blot analysis, respectively. To investigate whether activin receptor-like kinase 4 (Alk4) is required for activin A-mediated cellular effects, cells were pre-treated with SB-431542. The involvement of Smad2, Smad3 and Smad4 was confirmed by transfection with specific small interfering RNAs (siRNAs). RESULTS: Activin A inhibits ox-ldl-induced foam cell formation and class A scavenger receptors (SR-A) expression, while up-regulates ATP-binding cassette transporter A1 (ABCA1) and ABCG1 expression in RAW 264.7 macrophages. Pre-treatment with SB-431542 abolished activin A-mediated anti-atherogenic effect. Knockdown of Smad2 reversed activin A-induced inhibition of ox-LDL uptake and SR-A expression. However, knockdown of Smad3 or Smad4 did not have such effect. Meanwhile, knockdown of either Smad2, Smad3 or Smad4 reversed the activin A-induced up-regulation of ABCA1 and ABCG1. CONCLUSIONS: Our study provides novel evidence that activin A may exert anti-atherogenic effects through Alk4-Smad signaling pathway in RAW 264.7 macrophages.

Evaluation of Extended-Interval Dabigatran Dosing in Older Patients With Non-Valvular Atrial Fibrillation.

OBJECTIVE: To evaluate the safety and efficacy of extended-interval dabigatran dosing in older Chinese patients with non-valvular atrial fibrillation. METHODS: We conducted an observational study on non-valvular atrial fibrillation patients administered dabigatran at different dosing intervals at the Department of Geriatrics, Peking University First Hospital, China. We enrolled 121 consecutive non-valvular atrial fibrillation patients aged ≥60 years on dabigatran therapy (mean age, 79.6 ± 7.4 years); they were administered conventional low-dose dabigatran (110 mg twice daily) or extended-interval dosing with dabigatran (110 mg every 16 h or every 24 h). All patients received follow-up care, and we evaluated the presence of bleeding and thromboembolic events. RESULTS: All patients exhibited creatinine clearance greater than 30 mL/min with an average of 56.6 ± 17.3 mL/min. Sixty-two patients received extended-interval dosing with dabigatran at a mean dose of 117.1 ± 18.6 mg daily. Patients on extended-interval dosing were older; they exhibited lower creatinine clearance and bodyweight and higher CHA2DS2-VASc and HAS-BLED scores. The mean follow-up time was 25.8 ± 15.6 months. No significant differences were observed in the trough and peak values of the activated partial thromboplastin time and in thromboembolic or bleeding events between the 2 groups. CONCLUSION: Extended-interval dabigatran dosing in older patients with non-valvular atrial fibrillation and lower creatinine clearance can maintain activated partial thromboplastin time trough and peak values comparable to the conventional low dose. Physician-prescribed practices regarding dabigatran dosing intervals do not lead to worse outcomes in the above-mentioned population.

Serum ω-3 Polyunsaturated Fatty Acids and Potential Influence Factors in Elderly Patients with Multiple Cardiovascular Risk Factors.

Recent clinical trials failed to demonstrate that ω-3 polyunsaturated fatty acid (PUFA) supplement reduced cardiovascular events, which contradicted previous evidence. However, serum ω-3 PUFA concentrations of participants remained unclear in those studies. We aimed to investigate the definite relationship between serum concentrations of ω-3 PUFAs and coronary artery disease (CAD), and to explore the potential influence factors of ω-3 PUFAs. We selected Chinese in-patients (n = 460) with multiple cardiovascular risk factors or an established diagnosis of CAD. Serum ω-3 PUFAs, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were measured by liquid chromatography mass spectrometry. Serum concentrations of ω-3 PUFAs in CAD patients were lower than that in patients with cardiovascular risk factors. Furthermore, high serum DHA concentration was an independent protective factor of CAD after adjustment for confounding factors (OR: 0.52, p = 0.014). Alcohol intake (p = 0.036) and proton pump inhibitor (PPI) usage (p = 0.027) were associated with a decreased serum ω-3 PUFA concentration. We conclude that serum concentrations of ω-3 PUFAs may associate with a decreased CAD proportion, and DHA may serve as a protective factor of CAD. Serum ω-3 PUFA concentrations may be reduced by alcohol intake and certain drugs like PPIs.

[Association between CMTM5 gene rs723840 single nucleotide polymorphism and high on asprin platelet reactivity].

OBJECTIVE: To elucidate the correlation between the single nucleotide polymorphism of CKLF-like MARVEL transmembrane member 5 (CMTM5) gene rs723840 and the occurrence of high on aspirin platelet reactivity (HAPR). METHODS: The present study is a case-control study. A total of 210 hospitalized patients in Peking University First Hospital were enrolled. Aspirin response was assessed by 0.5 g/L arachidonic acid (AA)-induced platelet aggregation ratio (PR), and ≥ 3/4 quartile of PR of the population was defined as HAPR. Accordingly all the enrolled 210 coronary artery diseases (CAD) patients were divided into HAPR group and No-HAPR group. The genotypes were determined by polymerase chain reaction (PCR) and sequencing analysis for rs723840 of CMTM5 gene. RESULTS: The genotype frequencies in rs723840 C>T of CMTM5 gene conformed well to the Hardy-Weinberg equilibrium in both HAPR group and No-HAPR group. Between the two groups, the genotypes frequencies in HAPR and No-HAPR groups were 48.4%, 51.6%, 0.0% and 73.7%, 22.9%, 0.034%, respectively (P=0.004). The C, T allele frequencies were significantly different in the two groups (P=0.031,OR=0.501, 95% CI: 0.264-0.947). CONCLUSION: Our study finds a significant correlation between CMTM5 gene rs723840 polymorphism and high on aspirin platelet reactivity.

[Correlation between the level of the urinary 11-dehydrothromboxane B2 and the clinical efficacy of aspirin in patients with type 2 diabetes and coronary artery disease].

OBJECTIVE: To elucidate the correlation between urinary 11-dehydro-thromboxane B2 (11dhTxB2) and clinical efficacy of aspirin treatment in patients with type 2 diabete and coronary artery disease (CAD). METHODS: In this prospective cohort study, 169 aged patients with type 2 diabete accompanying CAD in Peking University First Hospital were enrolled. The level of urinary 11dhTxB2 was detected using enzyme-linked immuno-sorbent assay. Low aspirin response or high on aspirin platelet reactivity (HAPR) was defined as urinary 11dhTxB2>1 500 ng/g. All the included patients were divided into two groups based on the results, HAPR group and No-HAPR group. RESULTS: Baseline urinary 11dhTxB2 of the patients with type 2 diabete accompanying CAD was (3 687±3 052) ng/g, while the urinary 11dhTxB2 was (1 954±859) ng/g in patients after 100 mg/d aspirin treatment (P<0.001). Prevalence of HAPR in patients with type 2 diabete accompanying CAD were 32.5%. Within a mean follow-up time of 12 months, the outcomes occurred more frequently in HAPR group than in No-HAPR group (P<0.05). CONCLUSION: Urinary 11dhTxB2 can be recognized as an effective indicator in evaluating aspirin clinical efficacy of patients with type 2 diabete accompanying CAD.

Comparison between urinary 11-dehydrothromboxane B2 detection and platelet Light Transmission Aggregometry (LTA) assays for evaluating aspirin response in elderly patients with coronary artery disease.

Aspirin is widely used in the primary and secondary prevention of cardiovascular diseases. The aim of our study was to compare between two established methods of aspirin response, urinary 11-dehydrothromboxane B2 (11dhTXB2) and platelet Light Transmission Aggregometry (LTA) assays in elderly Chinese patients with coronary artery disease (CAD), and to investigate the clinical significance of both methods in predicting cardiovascular events. Urinary 11dhTxB2 assay and arachidonic acid-induced (AA, 0.5mg/ml) platelet aggregation by Light Transmission Aggregometry (LTAAA) assay were measured to evaluate aspirin responses. High-on aspirin platelet reactivity (HAPR) was defined as urinary 11dhTxB2>1500pg/mg or AA-induced platelet aggregation≥15.22%-the upper quartile of our enrolled population. The two tests showed a poor correlation for aspirin inhibition (r=0.063) and a poor agreement in classifying HAPR (kappa=0.053). With a mean follow-up time of 12months, cardiovascular events occurred more frequently in HAPR patients who were diagnosed by LTA assay as compared with no-HAPR patients (22.5% versus 10.6%, P=0.039, OR=2.45, 95% CI=1.06-5.63). However, the HAPR status, as determined by urinary 11dTXB2 measurement, did not show a significant correlation with outcomes.

Effects of different types of antihypertensive agents on arterial stiffness: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: This system review and meta-analysis was conducted to systematically review and analyze the clinical benefits of different antihypertensive agents in improving arterial stiffness in hypertensive patients. METHODS: PubMed database was searched for randomized controlled trials (RCTs) evaluating the effects of angiotensin receptor blockers (ARB) or other types of antihypertensive agents on pulse wave velocity (PWV). The main indicators were the improvements of PWV and augmentation index (AI) before and after randomized treatments with antihypertensive agents. For the studies that only provided the mean and standard deviation of the indicators before and after randomization, the standardized mean difference (SMD) method was directly applied to combine the mean and standard deviation of various indicators after the treatment. For the studies provided the mean and standard deviation of the changes of the indicators, the weighted mean difference (MD) method was applied to combine the mean and standard deviation of the therapeutic effect. RESULTS: Ten RCT studies were included and the sample sizes range from 40 to 201 (total: 938). Four studies provided the changes of PWV before and after randomization, the pooled analysis showed that the changes of PWV in ARB group were not significantly higher than other antihypertensive agents [MD: 125.76, 95% confidence interval (CI): -78.70 to 330.23, P=0.23]; 4 studies provided the PWV values before and after randomization, the PWV values in ARB group were not significantly superior (SMD: 0.04, 95% CI: -0.16 to 0.24, P=0.71). Three studies provided the changes of AI before and after randomization, the ability of ARB to lower the level of the AI was superior to other antihypertensive agents (MD: 8.94, 95% CI: 2.18-5.71, P=0.01); 2 studies provided the AI value after randomization, the abilities of ARB and other anti-hypertensive agents to improve the AI were similar (SMD: 0.03, 95% CI: -1.20 to 1.26, P=0.06). CONCLUSIONS: The effect of ARB on the improvement of the PWV level is not superior to other types of antihypertensive agents, but ARB is superior to other types of antihypertensive agents for improving the AI level. Overall, to improve of arterial stiffness, ARB maybe is superior to other antihypertensive agents.

[Effects of mixed-tocopherols and eicosapentaenoic acid on oxidized LDL-induced oxidative damage and inflammatory cytokine secretion in human umbilical vein endothelial cells].

OBJECTIVE: To observe the influence of either alone or combined mixed-tocopherols combined with eicosapentaenoic acid (EPA) and α-Tocopherol use on oxidized LDL (oxLDL) induced 8-hydroxy-2'-deoxyguanosine (8-OHDG) and interleukin-6 (IL-6) secretion by human umbilical vein endothelial cells (HUVECs) and to explore the potential mechanism. METHOD: Cultured HUVECs in vitro were incubated with oxLDL, oxLDL + α-tocopherol, oxLDL + mixed-tocopherols, oxLDL + EPA, oxLDL + α-tocopherol + EPA, oxLDL + mixed-tocopherols + EPA for 24 hours, respectively. Secretion of 8-OHDG and IL-6 were detected by cell enzyme linked immunosorbent assay (ELISA). The expressions of superoxide dismutase (SOD), protein kinase C-δ (PKC-δ), phosphorylated PKC-δ (p-PKC-δ) were analyzed by Western blot. RESULTS: 8-OHDG and IL-6 secretion of HUVECs was significantly increased significantly after incubated with oxLDL for 24 hours which could be significantly attenuated in the presence of tocopherols and EPA (alone or in combination, all P < 0.05) while the strongest inhibition effects were seen with combined use of mixed-tocopherols and EPA. Moreover, combination of mixed-tocopherols and EPA could also significantly increase SOD activity and decrease PKC activity (all P < 0.05). However, the protein expression of SOD and PKC-was similar among groups. CONCLUSION: Combined mixed-tocopherols + EPA use enhanced the inhibiting effects on the secretion of 8-OHDG and IL-6 in oxLDL stimulated HUVECs which might be linked with increased SOD activity and reduced p-PKC activity.