Abstract
Background
It is unclear if sex differences affect the efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors to improve cardiorenal outcomes in patients with increased risks of ...cardiovascular diseases.
Methods
A systematic review was performed by searching PubMed, Cochran Central, and Embase through February 2023 for randomized controlled trials (RCTs) of SGLT2 inhibitors that were performed in adults and large (≥500 participants per group). Hazard ratios (HRs) and relative risk estimates in subgroups stratified by sex were extracted from each study and were pooled using a random-effects meta-analysis. The primary outcome was a composite of cardiovascular death, myocardial infarction, or stroke. The secondary outcomes were heart failure exacerbation, adverse renal outcomes, and a composite outcome of cardiovascular death or heart failure exacerbation.
Results
This study included 10 RCTs. SGLT2 inhibitors were associated with decreased risks of the primary outcome (Female and male in total: HR, 0.80; 95% CI, 0.67-0.96, Female: HR, 0.71; 95% CI, 0.51-0.98, Male: HR, 0.90; 95% CI, 0.83-0.97). SGLT2 inhibitors were associated with decreased risks of heart failure exacerbation (Female: HR, 0.80; 95% CI, 0.69-0.94, Male: HR, 0.78; 95% CI, 0.69-0.87), adverse renal outcomes (Female: HR, 0.65; 95% CI, 0.48-0.88, Male: HR, 0.58; 95% CI, 0.46-0.72), and a composite outcome of cardiovascular death or heart failure exacerbation (Female: HR, 0.75; 95% CI, 0.67-0.84, Male: HR, 0.78; 95% CI, 0.72-0.85). There were no significant subgroup differences by sex for all outcomes (p>0.05).
Conclusions
SGLT2 inhibitor was associated with decreased risks of cardiorenal outcomes similarly in both sexes.
Abstract
Background
Recent randomized controlled trials (RCTs) showed that sodium-glucose cotransporter 2 (SGLT2) inhibitors improve cardiorenal outcomes in patients with increased risks of ...cardiovascular diseases. However, only limited data from subgroup analyses are available for older patients.
Methods
A systematic review was performed by searching PubMed, Cochran Central, and Embase through February 2023 for RCTs of SGLT2 inhibitors that were performed in adults and large (≥500 participants per group). Hazard ratios (HRs) and relative risk estimates in older subgroups ≥ 65 years were extracted from each study and were pooled using a random-effects meta-analysis. The primary outcome was a composite of cardiovascular death, myocardial infarction, or stroke. The secondary outcomes were heart failure exacerbation, adverse renal outcomes, and a composite outcome of cardiovascular death or heart failure exacerbation.
Results
This study included 10 RCTs. SGLT2 inhibitors decreased the primary outcome but it did not reach statistical significance in older subgroups (HR, 0.86; 95% CI, 0.73-0.1.00, p = 0.06). Whereas SGLT2 inhibitors were associated with decreased risks of heart failure exacerbation (HR, 0.76; 95% CI, 0.67-0.87), adverse renal outcome (HR, 0.58; 95% CI, 0.43-0.77), and a composite outcome of cardiovascular death or heart failure exacerbation (HR, 0.76; 95% CI, 0.70-0.83).
Conclusions
SGLT2 inhibitors were associated with improved cardiovascular outcomes in older patients. Further therapeutic data and sufficient long-term safety data are warranted in this population.
We examined 79 Japanese MNCs' R&D subsidiaries in the US from the knowledge-based view. We found: 1) subsidiaries' R&D strategies encouraged some types of knowledge flows, but discouraged other ...types; 2) autonomous R&D subsidiaries promoted knowledge flows from local environments to the subsidiary; 3) process-oriented incentives promoted technical knowledge flows between a subsidiary and its headquarters; 4) knowledge flows and R&D strategies contributed to a subsidiary's knowledge accumulation; 5) organizational factors such as autonomy and process-oriented incentives contributed more to a subsidiary's overall performance than the subsidiary's R&D strategies did
Abstract
Background
Despite of the development of endovascular therapy (EVT), the frequency of target lesion revascularization (TLR) after EVT in patients with critical limb ischemia (CLI) is still ...high. Recent histrogical study suggested the possibility of thromboembolic phenomenon in the development of CLI; however, there is few monitoring system of total thrombogenicity in perioperative period of EVT in CLI patients. The total thrombus-formation analysis system (T-TAS), a novel system for quantitatively analyzing thrombus formation using microchips with thrombogenic surfaces (collagen plus tissue factor, atheroma AR-chip), is validated and can evaluate the total thrombogenicity.
Purpose
To investigate the utility of T-TAS parameters in predicting TLR after EVT in CLI patients.
Methods
We analyzed 27 CLI patients (45 lesions; aortoiliac 20%, femoropopliteal 40%, infrapopliteal 40%) who underwent EVT at our institution between January 2018 and December 2020. Patients undergoing hemodialysis were excluded. Blood sample was collected on the day of EVT and was used in T-TAS to compute the thrombus formation area under the curve (AUC; AUC for the first 30 minutes for AR tested at flow rate of 10 lL/min AR10-AUC30). We investigated the relationship between the AR10-AUC30 level and the occurrence of clinically-driven TLR, and the predictors of TLR among CLI patients.
Results
Study population had a mean age of 77 years, and 56% were male. During the follow-up period (mean 1.0±0.7 years), 11 lesions (24%) required clinically-driven TLR. The AR10-AUC30 level was significantly higher in patients requiring TLR than those without TLR (1783±121 vs. 1587±205; p<0.01). The frequency of TLR significantly increased in association with a tertile of the AR10-AUC30 level (Figure 1, p for trend=0.003). As shown in Figure 2, univariate logistic regression analysis demonstrated male sex and the third tertile of the AR10-AUC30 level compared to its first or second tertiles were significantly associated with TLR in patients with CLI, whereas platelet count, PT-INR, APTT, and atherosclerotic risk factors including glycated hemoglobin, low-density lipoprotein cholesterol, and renal function were not. Multivariate logistic regression analysis also revealed that the AR10-AUC30 level ≥1707 (=its third tertile) as an independent predictor for TLR, even after adjusted by age and sex (OR=6.28, 95% CI=1.18–33.3, p=0.03).
Conclusions
In patients with CLI, the AR10-AUC30 level measured by the T-TAS may be a potential predictor to identify the high-risk patients requiring TLR after EVT. This finding suggests the hypercoagulability in CLI patients and that an anticoagulant agent following EVT may be useful in preventing a restenosis in CLI patients. Further study with a larger sample size is warranted to validate this finding.
Funding Acknowledgement
Type of funding sources: None. Figure 1Figure 2
Abstract
Background
Immune checkpoint by programmed cell death (PD)-1 and its ligand (PD-L1) play crucial role in T cell tolerance toward vascular wall antigens. PD-L1 is widely expressed on a number ...of cells including immune cells and vascular endothelium. It was reported that increased expression of PD-L1 in dendritic cells implicates upregulated inflammation in atherosclerotic lesions that is associated with plaque instability. Although plaque rupture in coronary atherosclerosis is an important pathogenesis of acute coronary syndrome (ACS), the association between PD-L1 and ACS is still unknown.
Purpose
We hypothesize that circulating PD-L1 might be associated with ACS, reflecting endothelial damage and coronary plaque rupture. To elucidate this hypothesis, we compared serum levels of soluble PD-L1 (sPD-L1) in stable coronary artery disease (CAD) patients with those in ACS patients.
Methods
Serum levels of sPD-L1 were measured by using commercially available ELISA kit (Human PD-L1/B7-H1 DuoSet, R&D Systems) in consecutive patients with CAD admitted to our University Hospital from February 2016 to March 2017. Patients with any malignant disease or severe inflammatory disease were excluded from this study. Serum levels of sPD-L1 and clinical backgrounds were compared between stable-CAD and ACS patients.
Results
In total, 269 patients with CAD were enrolled (28 cases 10.4 % with ACS and 241 cases 89.6 % with stable-CAD). PD-L1 had no correlation to C-reactive protein, cardiac troponin, and classical atherosclerotic risks such as age, body mass index, estimated glomerular filtration rate, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol, and hemoglobin A1c. Although age, sex, history of smoking, and the prevalences of hypertension, diabetes mellitus and dyslipidemia were comparable between both groups, the level of LDL-C was significantly higher in patients with ACS compared with those with stable-CAD (94.0 77.0–112.0 mg/dL vs. 78.5 65.0–97.0 mg/dL, P = 0.008). Also serum level of sPD-L1 was significantly increased in patients with ACS compared with those with stable-CAD (106.1 60.9–157.7 pg/mL vs. 64.8 30.9–102.5 pg/mL, P = 0.003). Univariate logistic regression analysis identified that serum levels of both sPD-L1 and LDL-C were independently associated with ACS. Moreover, multivariable logistic regression analysis with factors from univariate analysis identified that serum level of sPD-L1 was significantly and independently associated with ACS (odds ratio: 1.006, 95 % confidence interval: 1.001–1.012, P = 0.03).
Conclusions
This is the first study to elucidate that the increased serum levels of sPD-L1 was associated with ACS. This study suggests that sPD-L1 could be a risk marker and therapeutic target for ACS.
Abstract
Background
While it is clear that device technology of percutaneous coronary intervention (PCI) has advanced over the course of the last 40 years and the evidence for improvements in the ...efficacy of PCI is clear, it is less clear whether the prognosis following PCI continues to improve year by year.
Methods
The Kumamoto Intervention Conference Study Real-World Registry is a multi-center registry that enrolls consecutive patients undergoing PCI in 17 centers in Kyushu area, Japan. To elucidate the clinical impact of recent changes in treatment strategies, 8,841 consecutive participants (historical PCI: n=4,038, enrolled between January 2013 and December 2014, and current PCI: n=4,803, between January 2015 and March 2017) with 1-year follow-up data were analysed. Baseline demographic data, cardiovascular risk factors, and the medication being taken at discharge were documented. The primary endpoint was defined as a major adverse cardiac event (MACE), comprising cardiovascular death or non-fatal MI, including stent thrombosis (ST), occurring within 1 year of PCI.
Results
Regarding the relationships between presenting symptoms and PCI status, ACS, STEMI, NSTEMI, and UAP were similarly common, but the proportion of patients with multi-vessel disease was lower and the proportion with type B2/C lesions was higher in the current PCI group (p=0.004 and p<0.001, respectively). The prevalences of left main trunk lesions and Killip classes III or IV were comparable between the groups, but in-stent restenotic lesions were significantly more frequent in the historical PCI group (p<0.001). In addition to the change in the DAPT regimen, more optimal medical therapy was introduced during this time period, including the use of β-blockers, ACE-Is, and statins.
The incidences of MACE were comparable between historical PCI and current PCI (2.2% vs. 2.1%, p=0.693), even though complex lesions were more frequent during the more recent period. During this period, the use of radial approaches, drug eluting stents, and coronary imaging increased, but the use of intra-aortic balloon pumping (IABP) or thromboaspiration decreased. The incidences of major adverse cardiac or cerebrovascular events (MACCE), cardiac death, non-fatal MI, and stent thrombosis were similar between the historical and current periods (Figure). Multivariate analysis for overall patients, after adjustment, showed that multi-vessel disease, type B2/C lesions, ACS, and DES use were significant independent predictors of MACE.
Figure 1. Comparison of Clinical Events
Conclusion
An improvement in the prognosis associated with PCI has not occurred in recent years. However, the lesions being treated are becoming more complex, and the selection of evidence-based approaches, the use of coronary imaging, and the optimal medication treatments may have contributed to comparable outcomes being maintained.
Acknowledgement/Funding
Daiichi Sankyo Co., Ltd. Japan.
Abstract
Background
Inflammation, characterized by early leukocyte recruitment, is known to be associated with vascular endothelial dysfunction and atherosclerosis. Previous studies have reported ...that an increased leukocyte count is a risk factor for the progression of atherosclerosis in cardiovascular diseases, and we previously reported that a high monocyte count was an independent and incremental of cardiovascular events in patients with coronary artery disease. Furthermore, previous study also reported that inflammation play a role in the pathophysiology of heart failure (HF), but few studies have evaluated the prognostic role of monocyte in patients with HF.
Purpose
To elucidate the prognostic value of monocyte in HF, we investigated the association of monocyte counts in patients with HF with their future cardiovascular events, and compared them among new categories of HF in this study.
Methods
Consecutive HF patients referred for hospitalization at Kumamoto University Hospital between 2006 and 2015 were registered. Finally, a total of 678 HF patients were enrolled in the study, and were followed prospectively until 2016 or until the occurrence of cardiovascular events. We defined high monocyte group as monocyte counts ≥360/mm3 according to previous clinical reports. We further divided HF patients into three types according to left ventricular ejection fraction (LVEF) (HF with reduced LVEF (HFrEF), HF with mid-range LVEF (HFmrEF), and HF with preserved LVEF (HFpEF)).
Results
In this study, HFrEF was 82 patients, HFmrEF was 118 patients and HFpEF was 478 patients, respectively. The average of total monocyte counts were 397±136 in HFrEF and 375±172 in HFmrEF, and 341±138 in HFpEF patients. Kaplan-Meier analysis revealed that both HFrEF and HFmrEF patients with high monocyte group (≥360 /mm3) had a significant higher risk of HF-related events (P=0.03 and P=0.02, respectively) but not of total cardiovascular events compared with those with low monocyte groups (<360/mm3) (P=0.001). By contrast, high and low monocyte groups in HFpEF patients had no significant difference in both total cardiovascular and HF-related events. Multivariate Cox hazard analysis identified a high monocyte count as an independent and significant predictor of future HF-related events in HFrEF and HFmrEF patients (hazard ratio: 3.02, 95% confidence interval: 1.20–7.59, p=0.018).
Next, by whether they had ischemic heart disease (IHD), we divided HFrEF and HFmrEF patients into two groups. Non-ischemic HF group with high monocyte counts had a significant higher risk of HF-related events compared to those with low monocyte counts (P=0.014). By contrast, there was no statistically significant difference of the occurrences of future HF-related events between in ischemic HF group with high and low monocyte counts.
Conclusion
A high monocyte count was an independent and incremental predictor of HF-related events in HFrEF and HFmrEF especially with IHD, but not in HFpEF patients.
Abstract
Background
In heart failure (HF) patients, various factors, such as hyperactivity of the renin-angiotensin system, influence of drug therapy such as loop and thiazide diuretics, ...undernutrition and others, can causes hypokalemia and hypomagnesemia. Although serum magnesium (Mg) levels are closely associated with the prognosis of HF patients, the clinical significance of serum Mg levels in cardiovascular outcomes of HF with preserved ejection fraction (HFpEF) patients is not fully understood.
Purpose
We examined the relationship between serum Mg and future HF-related events in patients with HFpEF.
Methods
This study was a retrospective, single-center, observational study. We enrolled 452 consecutive HFpEF patients admitted to our university hospital between January 2007 and September 2013 and followed them for 4 years or until occurrence of HF-related events. We defined lower serum Mg as <2.0 mg/dL (=0.8 mmol/L) and higher serum Mg as ≥2.0 mg/dL based on recent clinical evidences and compared their clinical characteristics and prognosis.
Results
The mean serum Mg level was 2.12 mg/dL (median, 2.1 mg/dL; interquartile range, 2.0–2.28 mg/dL). The follow-up period was 0–50 months (median, 47.3 months) and 48 HF-related events (10.6%) were recorded. The frequency of HF-related events was significantly higher in the lower serum Mg group compared with the higher serum Mg group (n=16, 17.4% vs. n=32, 8.9%; P=0.018). There were no significant differences between groups in the use of all drugs (loop diuretics, mineralcorticoid receptor antagonists, renin-angiotensin-aldosterone system inhibitors, calcium channel blockers, β-blockers, statins and Mg preparations). The lower serum Mg group (n=92) showed significantly higher prevalence of diabetes mellitus (DM), uric acid levels and B-type natriuretic peptide (BNP)levels compared with the higher serum Mg group (n=360). Kaplan-Meier curve revealed a significantly higher probability of HF-related events in the lower serum Mg group compared with the higher serum Mg group (log-rank test, P=0.012, Figure). Multivariate Cox proportional hazard analysis revealed that the lower serum Mg group had significantly and independently higher probabilities of HF-related events compared with those in the higher serum Mg group (hazard ratio: 2.37, 95% confidence intervals: 1.27–4.41, P=0.007). We reclassified the risk of a HF-related events after adding the lower serum Mg to the prognostic factors (age, previous hospitalization for HF, DM, ln-BNP); the continuous net reclassification improvement was 29.0% (p=0.041).
Conclusion
We first demonstrated that serum Mg was significantly correlated with the occurrence of future HF-related events in HFpEF patients. Lower serum Mg is able to successfully predict future HF-related events, and management of serum Mg in HFpEF patients is thus important.
Acknowledgement/Funding
None
An innovation model providing a solution for climate change and sustainable economic growth is required. In this scenario, renewable energy is one of the most promising technologies. Its research ...-requires a considerable amount of R&D expenditure and various core technologies. Therefore, international research collaboration is effective for prompt and efficient development. With countries and organizations contributing to the rapid growth of knowledge, the meta-structure of international research and collaboration has become ambiguous. This paper aims to establish a knowledgebase that can help prepare international research collaboration policies. This paper demonstrates research capacity and international research collaboration in solar and fuel cell technologies, using MAPs gathered from 68,000 research papers. The two technologies are compared and international research collaboration is analyzed. A valley of research collaboration in Asia and a gap between the research collaboration structures of the two technologies are identified, and the context of this gap is discussed.
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