Purpose: Enhanced external counterpulsation (EECP) is a new non-drug treatment for coronary artery disease (CAD). However, the long-term effect of EECP on endothelial dysfunction and exercise tolerance, and the relationship between the changes in the endothelial dysfunction and exercise tolerance in the patients with coronary heart disease are still unclear.Methods: A total of 240 patients with CAD were randomly divided into EECP group (n = 120) and control group (n = 120). All patients received routine treatment of CAD as the basic therapy. Patients in the EECP group received 35 1-h daily sessions of EECP during 7 consecutive weeks while the control group received the same treatment course, but the cuff inflation pressure was 0–10 mmHg. Peak systolic velocity (PSV), end diastolic velocity (EDV), resistance index (RI), and inner diameter (ID) of the right carotid artery were examined using a Color Doppler Ultrasound and used to calculate the fluid shear stress (FSS). Serum levels of human vascular endothelial cell growth factor (VEGF), vascular endothelial cell growth factor receptor 2 (VEGFR₂), and human angiotensin 2 (Ang₂) were determined by enzyme-linked immunosorbent assay (ELISA). Exercise load time, maximal oxygen uptake (VO_2max), metabolic equivalent (METs), anaerobic threshold (AT), peak oxygen pulse (VO_2max/HR) were assessed using cardiopulmonary exercise tests.Results: After 1 year follow-up, the EDV, PSV, ID, and FSS were significantly increased in the EECP group (P < 0.05 and 0.01, respectively), whereas there were no significant changes in these parameters in the control group. The serum levels of VEGF and VEGFR₂ were elevated in the EECP and control groups (all P < 0.05). However, the changes in VEGF and VEGFR₂ were significantly higher in the EECP group than in the control group (P < 0.01). The serum level of Ang₂ was decreased in the EECP group (P < 0.05) and no obvious changes in the control group. As for exercise tolerance of patients, there were significant increases in the exercise load time, VO2_max, VO_2max/HR, AT and METs in the EECP group (all P < 0.05) and VO_2max and METs in the control group (all P < 0.05). Correlation analyses showed a significant and positive correlations of VEGF and VEGFR₂ levels with the changes in FSS (all P < 0.001). The correlations were still remained even after adjustment for confounders (all Padjustment < 0.001). Linear regression displays the age, the medication of ACEI (angiotensin-converting enzyme inhibitors) or ARB (angiotensin receptor blockers), the diabetes and the changes in VEGF and VEGFR₂ were positively and independently associated with the changes in METs after adjustment for confounders (all Padjustment < 0.05).Conclusion: The data of our study suggested that EECP is a useful therapeutic measurement for amelioration of endothelial dysfunction and long-term elevation of exercise tolerance for patients with coronary heart disease.Clinical trial registration: [http://www.chictr.org.cn/], identifier [ChiCTR1800020102].

Objective: To investigate the effect of telmisartan, rosuvastatin, or their combination on dementia and to understand the impact of Apolipoprotein E (APOE) genotype on the effect of the medications in older patients with hypertension. Methods: This is a double-blind, randomized, and placebo-controlled trial using a 2-by-2 factorial design. Between April 2008 and November 2010, 1244 hypertensive patients aged ≥60 years without cognitive impairment were recruited from communities in six cities in Shandong area, China. Patients were randomized into telmisartan and rosuvastatin administration after a 2-week washout period. APOE genotype was identified at the baseline. Possible dementia was determined using the combination of the global cognitive function and Assessment of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Results: Over an average follow-up of 7 (IQR: 6.7–7.2) years, telmisartan and rosuvastatin significantly reduced the cognitive impairment progression and the incidence of dementia. There was a synergistic interaction between telmisartan and rosuvastatin to reduce the cognitive impairment and the incidence of dementia (Padjusted <0.001). The cognitive impairment progression and the risk of dementia were higher in the hypertensive patients with APOE ε4 allele than in those without APOE ε4 allele. Rosuvastatin medication significantly alleviated the cognitive impairment progression and the risks of dementia in patients with APOE ε4 allele. Conclusion: The combination of telmisartan and rosuvastatin might be an effective prevention and/or treatment strategy for cognitive impairment and dementia, especially in the hypertensive patients with APOE ε4 allele.

Glucose metabolic disorder is associated with the risk of heart failure (HF). Adiposity is a comorbidity that is inextricably linked with abnormal glucose metabolism in older individuals. However, the effect of adiposity on the association between glucose metabolic disorder and HF risk, and the underlying mechanism remain unclear. A total of 13,251 participants aged ≥ 60 years from a cohort study were categorized into euglycemia, prediabetes, uncontrolled diabetes, and well-controlled diabetes. Adiposity was assessed using body mass index (BMI), waist-to-hip ratio (WHR), and visceral fat area (VFA). Adiposity-associated metabolic activities were evaluated using adiponectin-to-leptin ratio (ALR), homeostatic model assessment of insulin resistance (HOMA-IR), and triglyceride-glucose index (TyG). The first occurrence of HF served as the outcome during the follow-up period. A total of 1,138 participants developed HF over the course of an average follow-up period of 10.9 years. The rate of incident HF occurrence was higher in prediabetes, uncontrolled diabetes, and well-controlled diabetes participants compared to that in euglycemia participants. However, the high rates were significantly attenuated by BMI, VFA, and WHR. For WHR in particular, the hazard ratio for incident HF was 1.18 (95% confidence interval (CI): 1.03, 1.35, Padj.=0.017) in prediabetes, 1.59 (95% CI: 1.34, 1.90, Padj.<0.001) in uncontrolled diabetes, and 1.10 (95% CI: 0.85, 1.43, Padj.=0.466) in well-controlled diabetes. The population attributable risk percentage for central obesity classified by WHR for incident HF was 30.3% in euglycemia, 50.0% in prediabetes, 48.5% in uncontrolled diabetes, and 54.4% in well-controlled diabetes. Adiposity measures, especially WHR, showed a significant interaction with glucose metabolic disorder in incident HF (all Padj.<0.001). ALR was negatively associated and HOMA-IR and TyG were positively associated with BMI, WHR, VFA, and incident HF (all Padj.<0.05). ALR, HOMA-IR, and TyG mediated the associations for BMI, WHR and VFA with incident HF (all Padj.<0.05). Adiposity attenuated the association of glucose metabolic disorder with incident HF. The results also showed that WHR may be an appropriate indicator for evaluating adiposity in older individuals. Adiposity-associated metabolic activities may have a bridging role in the process of adiposity attenuating the association between glucose metabolic disorder and incident HF. retrospectively registered number: ChiCTR-EOC-17,013,598.

Skeletal muscle mass loss and insulin resistance (IR) are associated with cardiovascular diseases risk. However, it remains unclear whether the combination of skeletal muscle mass loss and elevated IR affects heart failure (HF) risk. Here, we investigate the association between a combination of appendicular skeletal muscle mass index (ASMI) with estimated glucose disposal rate (eGDR) and HF risk in older adults. A prospective analysis and a dual-trajectory analysis were carried out to investigate the association of the combined effect of ASMI and eGDR with HF risk. A total of 11,596 adults aged ≥ 60 years were enrolled from the community for prospective analysis. Among them, 10,489 were eligible for the dual-trajectory analysis. The temporal evolution of ASMI and eGDR was determined using a dual-trajectory model. In the prospective analysis, 1087 individuals developed HF. Restricted cubic splines analysis showed L-shaped associations between ASMI and eGDR and HF risk. HF risk decreased by 32.3% (hazard ratio (HR): 0.677, 95% confidence interval (CI): 0.623–0.734, Padj < 0.001) for female and 9.0% (HR 0.910, 95% CI 0.831–0.996, Padj = 0.003) for male patients per one standard deviation (SD) AMSI increment and 29.4% (HR 0.706, 95% CI 0.647–0.770, Padj < 0.001) for female and 26.8% (HR 0.732, 95% CI 0.668–0.803, Padj < 0.001) for male patients per one SD eGDR increment. There was a synergistic effect on HF risk per one SD ASMI and eGDR increment (Padj < 0.001). Five distinct dual ASMI and eGDR trajectories were identified in the dual-trajectory analysis. A total of 859 (8.85 per 1000 person-years) individuals developed HF. Compared to group 4 with moderate-stable ASMI and eGDR and the lowest incident HF, the HR in group 5 characterized by low-stable ASMI and eGDR was 1.908 (95% CI 1.482–2.457, Padj < 0.001), followed by 1.716 (95% CI 1.296–2.273, Padj < 0.001) in group 3 with low-decrease ASMI and high-decrease eGDR. Skeletal muscle mass loss and elevated IR act synergistically to increase the HF risk in older adults. Comprehensive management of muscle mass and IR might be a useful and effective strategy for preventing and controlling HF. Retrospectively registered number ChiCTREOC17013598.