Icariin attenuates the enhanced prothrombotic state in atherosclerotic rabbits independently of its lipid-lowering effects.

Icariin is a major active component isolated from the traditional Chinese herb Epimedium brevicornum, with a wide range of pharmacological and biological activities. In this paper, we investigated the effects of icariin on hyperlipidemia, and further evaluated whether icariin could improve unfavorable hemorheological parameters, attenuate platelet activation and facilitate the balance between plasmic plasminogen activator inhibitor-1 and tissue-type plasminogen activator activities in rabbits fed a high-cholesterol diet. Icariin reduced the levels of serum total cholesterol and low-density lipoprotein cholesterol, as well as the atherosclerotic burden. In addition, this compound has been found to improve the imbalance between plasmic plasminogen activator inhibitor-1 and tissue-type plasminogen activator activities, reduce platelet adhesiveness and aggregation and modulate unfavorable hemorheological variables in hypercholesterolemia. In conclusion, icariin has lipid-lowering effects and may be used in the treatment and prevention of thrombosis in the atherosclerotic process.

Association of frailty index with congestive heart failure, all-cause and cardiovascular mortality among individuals with type 2 diabetes: a study from National Health and Nutrition Examination Surveys (NHANES), 1999-2018.

BACKGROUND: Both type 2 diabetes mellitus (T2DM) and frailty are strongly associated with congestive heart failure (CHF). Individuals with T2DM and CHF have a high frailty burden. The association of frailty with HF, all-cause, and cardiovascular mortality in patients with T2DM has not been thoroughly explored. METHODS: This study included 2894 adults with T2DM from the National Health and Nutrition Examination Survey (NHANES) database over ten cycles (1999-2018) and followed up for all-cause and cardiovascular mortality through 31 December 2019. The frailty index (FI) was calculated using a 46-item deficit model to assess frailty status. Weighted multivariable logistic regression was performed to explore the relationship between frailty and CHF in patients with T2DM. Weighted restricted cubic splines were used to evaluate the non-linear relationship between FI and outcome. All-cause mortality and cardiovascular mortality association with FI was assessed using the Kaplan-Meier curve and COX proportional hazards regression accounting for sampling weights. Subgroup and sensitivity analyses were performed to evaluate the robustness of the results. RESULTS: After the adjustment of essential confounders, a higher frailty index in T2DM was associated with increased odds of CHF (odds ratio [OR] for per 1-SD increase, 2.02, 95% confidence interval [CI] 1.67-2.45; P < 0.0001). The presence of frailty T2DM (OR, 3.60; 95% CI 2.34-5.54; P < 0.0001) was associated with a significant increase in the prevalence of CHF compared to non-frailty T2DM in a fully adjusted model. During the median follow-up of 6.75 years, per 1-SD increase in FI was associated with a 41% higher risk of all-cause mortality and a 30% higher risk of cardiovascular mortality after being adjusted for all confounders. Similar results were observed when sensitivity analyses were performed. There was also a non-linear relationship between FI and all-cause mortality. In a weighted multivariate COX proportional model adjusted for full confounders, frailty T2DM increased all-cause (HR, 1.86; 95% CI 1.55-2.24; P < 0.0001) and cardiovascular (HR 1.66; 95% CI 1.18-2.33; P = 0.003) mortality and compared to non-frailty T2DM. The positive association of frailty index and all-cause mortality was only in participants without CHF. The positive association of frailty index and cardiovascular mortality was only in non-anti-diabetic drug users. CONCLUSIONS: Frailty index in T2DM was positively associated with CHF in linear fashions. The Frailty index was positively correlated with all-cause and cardiovascular death in patients with T2DM. Frailty T2DM was positively associated with CHF, all-cause mortality, and cardiovascular mortality compared to non-frailty T2DM. Promoting frailty measurement and management in T2DM may be beneficial to reduce the burden of CHF and mortality.

Fibrosis-4 index is closely associated with clinical outcomes in acute cardioembolic stroke patients with nonvalvular atrial fibrillation.

Liver cirrhosis is a confirmed risk factor for poor prognosis of stroke; however, the contribution of clinically inapparent liver fibrosis to cardioembolic stroke (CES) and its outcomes are poorly understood. This study aimed to investigate the associations between liver fibrosis-measured by the Fibrosis-4 (FIB-4) score-and stroke severity and short-term clinical outcomes of patients with acute CES due to nonvalvular atrial fibrillation (NVAF). A total of 522 patients were followed for a median of 90 days. We calculated the FIB-4 score and defined liver fibrosis as follows: likely advanced fibrosis (FIB-4 > 3.25), indeterminate advanced fibrosis (FIB-4, 1.45-3.25), and unlikely advanced fibrosis (FIB-4 < 1.45). Logistic regression analysis and Cox regression analysis were used to investigate the relations between the FIB-4 score and stroke severity, major disability at discharge, and all-cause mortality. Among these 522 acute CES patients with NVAF, the mean FIB-4 score (2.28) on admission reflected intermediate fibrosis, whereas liver enzymes were largely normal. In multivariate regression analysis, patients with advanced liver fibrosis were more likely to have a higher risk of severe stroke (OR = 2.21, 95% CI 1.04-3.54), major disability at discharge (OR = 4.59, 95% CI 1.88-11.18), and all-cause mortality (HR = 1.25, 95% CI 1.10-1.56) than their counterparts. Regarding sex, these associations were stronger in males but not significant in females. In patients with acute CES due to NVAF, advanced liver fibrosis is associated with severe stroke, major disability, and all-cause death. Our findings indicate that early screening and management of liver fibrosis may decrease stroke severity and risk of death in patients with NVAF, especially for male patients. Consequently, FIB-4 > 3.25 of male patients should receive ultrasound elastography to further determine the degree of liver fibrosis.

Association between Phenotypic Age and Mortality in Patients with Multivessel Coronary Artery Disease.

BACKGROUND: Chronological age (CA) is not a perfect proxy for the true biological aging status of the body. A new biological aging measure, phenotypic age (PhenoAge), has been shown to capture morbidity and mortality risk in the general US population and diverse subpopulations. This study was aimed at evaluating the association between PhenoAge and long-term outcome of patients with multivessel coronary artery disease (CAD). METHODS: A total of 609 multivessel CAD patients who received PCI attempt and with follow-up were enrolled. The clinical outcome was all-cause mortality on follow-up. PhenoAge was calculated using an equation constructed from CA and 9 clinical biomarkers. Cox proportional hazards regression models and receiver operating characteristic (ROC) curves were performed to evaluate the association between PhenoAge and mortality. RESULTS: Overall, patients with more diseases had older PhenoAge and phenotypic age acceleration (PhenoAgeAccel). After a median follow-up of 33.5 months, those with positive PhenoAgeAccel had a significantly higher incidence of all-cause mortality (P = 0.001). After adjusting for CA, Cox proportional hazards models showed that both PhenoAge and PhenoAgeAccel were significantly associated with all-cause mortality. Even after further adjusting for confounding factors, each 10-year increase in PhenoAge was also associated with a 51% increased mortality risk. ROC curves revealed that PhenoAge, with an area under the curve of 0.705, significantly outperformed CA, the individual clinical chemistry measure, and other risk factors. When reexamining the ROC curves using various combinations of variables, we found that PhenoAge provides additional predictive power to all models. CONCLUSIONS: In conclusion, PhenoAge was strongly associated with all-cause mortality even after adjusting for CA. Our findings suggest that PhenoAge measure may be complementary in predicting mortality risk for patients with multivessel CAD.

Long-Term Outcomes of Percutaneous Coronary Intervention for Patients With In-Stent Chronic Total Occlusion Versus De Novo Chronic Total Occlusion.

Limited data are available on long-term outcomes and health status in the treatment of in-stent coronary chronic total occlusion (IS-CTO) and de novo coronary chronic total occlusion (de novo CTO). This study compared the long-term clinical outcomes and health status of percutaneous coronary intervention (PCI) for patients with IS-CTO versus patients with de novo CTO in the drug-eluting stent era. We screened 483 consecutive patients with 1 CTO lesion, including 81 patients with IS-CTO and 402 patients with de novo CTO. Propensity score matching was used to balance baseline characteristics between the 2 groups. The clinical end point was major adverse cardiac events (MACE). The success rates of CTO lesion revascularization were similar in both groups. In the propensity score-matched patients, after a median follow-up of 36 months, MACE was observed in 32.8% of patients with IS-CTO versus 13.5% of the patients with de novo CTO (P < .001), mainly driven by target-vessel revascularization (21.9% vs 6.7%; P < .01). Moreover, patients with IS-CTO had significantly worse Seattle Angina Questionnaire anginal stability scores than the patients with de novo CTO. In conclusion, patients with IS-CTO after PCI had a worse clinical outcome, mainly MACE, and a poorer anginal stability in the long term than patients with de novo CTO.

Cardiometabolic diseases, frailty, and healthcare utilization and expenditure in community-dwelling Chinese older adults.

This study investigated associations between cardiometabolic diseases, frailty, and healthcare utilization and expenditure among Chinese older adults. The participants were 5204 community-dwelling adults aged at least 60 years from the China Health and Retirement Longitudinal Study. Five cardiometabolic diseases were assessed including hypertension, dyslipidemia, diabetes, cardiac diseases and stroke. Frailty status was based on five criteria: slowness, weakness, exhaustion, inactivity, and shrinking. Participants were deemed frailty if they met at least three criteria. As the number of cardiometabolic diseases increased, so did the prevalence of frailty, and the proportion of healthcare utilization, including outpatient visit and inpatient visit. Moreover, the total healthcare expenditure and the odds of catastrophic health expenditure were increased with the number of cardiometabolic disorders. After adjusting for covariates, cardiometabolic diseases were positively associated with higher odds of frailty, incurring outpatient and inpatient visit. And individuals with 2 or more cardiometabolic diseases had a higher odds of catastrophic health expenditure than persons with non-cardiometabolic disease. Participants who were frailty were more likely to report higher odds of healthcare utilization. These findings suggest that both cardiometabolic diseases and frailty assessment may improve identification of older adults likely to require costly, extensive healthcare.

Migration of intravenously grafted mesenchymal stem cells to injured heart in rats.

The present study aimed to determine the role of tissue injury in migration of mesenchymal stem cells (MSCs) intravenously transplanted into heart and to establish experimental basis for improving stem cell therapy in its targeting and effectiveness. MSCs were isolated from bone marrow of male Sprague-Dawley rats and purified by density centrifuge and adhered to the culture plate in vitro. Female rats were divided randomly into four groups. Myocardial ischemia (MI) transplanted group received MSCs infusion through tail vein 3 h after MI and compared with sham-operated group or normal group with MSCs infusion, or control group received culture medium infusion. MI was created in female rats by ligating the left anterior descending coronary artery. The heart was harvested 1 week and 8 weeks after transplantation. The characteristics of migration of MSCs to heart were detected with expression of sry gene of Y chromosome by using fluorescence in situ hybridization (FISH). Ultrastructural changes of the ischemic myocardium of the recipient rats were observed by transmission electron microscope (TEM). One week or 8 weeks after transplantation, sry positive cells were observed in the cardiac tissue in both of MI transplanted group and sham-operated group, the number of sry positive cells being significantly higher in MI transplanted group (P<0.01). No significant difference was found in the number of sry positive cells between 1 week and 8 weeks after transplantation. No sry positive cells were observed in the hearts of control and normal group. In addition, the ultrastructure of some cells located in the peri-infarct area of MI rats with MSCs transplantation was similar to that of MSCs cultured in vitro. These results indicate that MSCs are capable of migrating towards ischemic myocardium in vivo and the fastigium of migration might appear around 1 week after MI. The tissue injury and its degree play an important role in the migration of MSCs.

[Ultrastructural changes of rat ischemic myocardium after bone marrow mesenchymal stem cell transplantation].

OBJECTIVE: To observe the ultrastructural changes of ischemic myocardium of rats after bone marrow mesenchymal stem cells (MSCs) transplantation. METHODS: Rat models of myocardial ischemia were established by ligating the descending anterior branch of the left coronary artery. The isolated and in vitro cultured MSCs labeled with 4' 6-diamidine-2-phenylindole (DAPI) were injected into the rats via the tail vein and the hearts of the rats were taken 1 week and 8 weeks after transplantation, respectively, for observation under fluorescence microscopy. The ultrastructural changes of the ischemic myocardium of the recipient rats were observed by transmission electron microscope. RESULTS: The third passage of cultured MSCs growing in colonies possessed good homogeneity. One week and 8 weeks after transplantation, DAPI-labeled cells were observed in the heart of the recipient rats, but not in the hearts of control rats. One week after transplantation, ultrastructural observation identified a small number of cells in the peripherals of the infarct area of the recipient rats with similar morphology to that of MSCs cultured in vitro. At 8 weeks,a large number of capillaries were seen in the ischemic myocardium on the peripheral of the infarct area. Ultrastructural observation also revealed some immature myocytes surviving in the ischemic region. CONCLUSION: MSCs is capable in vivo of homing to the ischemic myocardium via the blood circulation, and promote regeneration of the myocardium and blood vessels.

Oestradiol supplement minimises coronary occlusion-induced myocardial infarction and ventricular dysfunction in oophorectomised female rats.

BACKGROUND: Endogenous oestrogen deficiency after menopause is associated with high risk of acute cardiac events and the protection of exogenous oestrogen supplements remains uncertain. This study investigates whether oestrogen therapy protects the heart from ischemic injury in oophorectomised rats. METHODS: Sexually mature female Sprague-Dawley rats (6 for each group) with bilateral oophorectomy underwent selective ligation (occlusion) of left coronary artery for 4 weeks. 17ß-oestradiol (E2) supplements (10 µg, i.m., every other day) were started before (preventive-therapeutic supplement) or after coronary occlusion (therapeutic supplement). RESULTS: In oophorectomised rats plasma levels of E2 declined from 1301 ± 80 to 196 ± 48 pmol/L (p<0.01) and cardiac expression of oestrogen receptors (ER) decreased by ∼60%. E2 supplements recovered the ER expression. Selective ligation of left coronary led myocardial infarction in the left ventricle, with an increase in plasma cardiac troponin I (cTn-I), decrease in systolic blood pressure (SBP), and reduction of left ventricular pressures. Preventive-therapeutic but not therapeutic E2 supplement reduced cTn-I levels (from 21.9 ± 2.0 to 6.0 ± 0.3 ng/mL, p<0.01), minimised infarction (from 37.0 ± 1.2% to 18.1 ± 2.3%, p<0.05), increased SBP (from 82 ± 4.2 to 97 ± 4.4mm Hg, p<0.05), and improved left ventricular end pressures in the oophorectomised rats following coronary occlusion. CONCLUSION: Postmenopausal (ooporectomised) oestrogen supplement commenced before establishment of myocardial ischemia minimises myocardial infarction and ventricular dysfunction following the coronary artery occlusion. Cellular and molecular mechanisms underlying the cardiac protection of oestrogen therapy remain unclear, in which activation of cardiac ER expression and increasing in circulating CD90(+) stem cells may be involved.

[Correlation of changes in circulating bone marrow stem cells in pregnant rabbits after acute myocardial infarction with serum estradiol].

OBJECTIVE: To investigate the changes in circulating bone marrow stem cells in pregnant rabbits after AMI (AMI) and their relationship with estradiol. METHODS: Three groups of rabbits were used, namely pregnancy and AMI group, AMI group without pregnancy, and sham operation group with pregnancy. The ratio of CD90(+) cells in the peripheral blood was determined with flow cytometry in all the rabbits, and serum estradiol level measured. Four weeks after AMI, hemodynamic measurements were carried out. The morphological changes of the myocardial tissues were examined with ImageJ 1.31. RESULTS AND CONCLUSION: Four weeks after AMI, the two pregnancy groups showed a higher Left ventricular end systolic pressure(LVESP) and+dp/dtmax, lower left ventricular end-diastolic pressure (LVEDP) and -dp/dtmax and high levels of CD90(+) cells in peripheral blood than AMI group without pregnancy (P<0.01). The ratio of circulating CD90(+) cells increased gradually with gestational age and peaked at the end stage of pregnancy. After delivery the circulating CD90+ cell ratio decreased sharply, showing a significant correlation with serum estradiol level (r=0.725, P<0.01). Four weeks after AMI, the pregnancy group had smaller myocardial infarction (MI) volume than the non-pregnant group (22.17+/-6.34% vs 38.86+/-5.97%, P<0.05). Circulating bone marrow stem cells increased during pregnancy with gestational age and peaked at the end stage of pregnancy. Ten days after delivery, the stem cells resumed basically the normal level. The proportion of circulating bone marrow stem cells was significantly correlated with the level of serum estradiol during pregnancy, and mobilization of the bone marrow stem cells induced by acute ischemic event in pregnant rabbits was advanced. 4 weeks after AMI, the pregnant rabbits showed better heart contraction and diastolic function than the non-pregnant ones.

[Effects of estradiol intervention on peripheral blood CD90+ cells and cardiac function in de-ovary rats before and after myocardial infarction].

AIM: To investigate the effects of estradiol intervention on peripheral blood CD90+ cells and cardiac function in de-ovary rats before and after myocardial infarction. METHODS: Thirty SD female rats were divided into the control group, acute myocardial infarction group, de-ovary myocardial infarction group, de-ovary replacement group with estradiol, and de-ovary therapy group with estradiol. CD90+ cell percentage was determined with flow cytometry. The left ventricle end systolic pressure (LVESP), left ventricle end diastolic pressure (LVEDP), +dp/dt(max) and -dp/dt(max) were also measured with the POWERLAB4.12 system. RESULTS: The percentage of peripheral blood CD90+ cells in the de-ovary myocardial infarction group was remarkably lower than that in the acute myocardial infarction group and the de-ovary replacement group with estradiol (P<0.01). In the de-ovary replacement group with estradiol, the percentage of peripheral blood CD90+ cells was remarkably elevated following the first day of operation (P<0.05), reaching the peak value at day 3. In the de-ovary therapy group with estradiol, it started to elevate at day 7 after the operation, much lower than that in the de-ovary replacement group with estradiol. LVESP in each operation group decreased, especially in the acute myocardial infarction group, whereas LVEDP increased in the de-ovary group and de-ovary therapy group with estradiol (P<0.01). CONCLUSION: Replacement with estradiol before myocardial infarction exerts more beneficial effects than estradiol replacement after myocardial infarction in de-ovary rats.