Endothelial function and 6-year outcomes following an acute coronary syndrome in patients with a history or presence of cancer

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y Matsuzawa ◽  
T.Y Yoshii ◽  
R.S Sato ◽  
H.N Nakahashi ◽  
E.A Akiyama ◽  
...  

Abstract Background It has been reported that in the primary prevention settings, patients with cancer are exposed to an increased risk of cardiovascular disease through multiple mechanisms. However, among patients with established coronary artery disease, it is unknown whether cancer is an additional risk for endothelial dysfunction, mortality, and subsequent cardiovascular events. Purpose To determine endothelial function, mortality and cardiovascular events following acute coronary syndrome according to history/presence of cancer on (ACS). Methods Patients who were admitted to our university medical center for ACS were enrolled, and were divided according to the history/presence of cancer. We measured reactive hyperemia index before discharge in all patients to evaluate endothelial function. The logarithmic value of RHI (LnRHI) was used in the analyses. All patients were followed for cardiovascular death, non-cardiovascular death, myocardial infarction (MI), and stroke. Results Six-hundred and ninety patients with ACS were enrolled (mean age [SD] was 66 [12] years, male was 78%), and 73 patients (10.6%) had a history or presence of cancer. Endothelial function was not significantly different between ACS patients with and without the history/presence of cancer (LnRHI 0.64 (0.26) versus 0.59 (0.26), p=0.10). During the follow up period (the median 6.1 years), cardiovascular death occurred in 48 patients, non-cardiovascular death in 36, MI in 46, and Stroke in 31, respectively. The composite outcomes with all cause death, MI, and stroke occurred more frequently in the patients with the history/presence of cancer than those without (Figure A). However, the risk for cardiovascular death, MI, and stroke was similar between the two groups, and only non-cardiovascular mortality was significantly higher in the patients with the history/presence of cancer than those without (Figure B and C). Conclusion Among patients with ACS, the history/presence of cancer is associated with the risk of non-cardiovascular death, but not the risk for endothelial dysfunction and subsequent cardiovascular events. Figure 1 Funding Acknowledgement Type of funding source: None

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Tatsuaki Murakami ◽  
Ikuo Moriuchi

Endothelial dysfunction is thought to contribute to atherothrombogenic process, however we identify little about practical relationship between clinical evolution of acute coronary syndrome (ACS) and endothelial dysfunction. This study investigated whether endothelial dysfunction has clinical impact on development of ACS. Endothelial dysfunction was graded by ultrasonic measured reactive changes in lumen diameter of right brachial artery following transient forearm occlusion for 5 minutes (FMD; flow-mediated endothelium-dependent vasodilation) in consecutive 518 patients with suspected coronary artery disease. The enrolled patients were categorized into three groups according to the values of FMD, and their cardiovascular events were prospectively followed-up for no less than 36 months. For a mean follow-up period of 60 months with 100% follow-up, the patients with severe endothelial dysfunction (FMD<4%; Group-L, n=174), more frequently developed ACS than Group-M with mild endothelial dysfunction (4%≤FMD<8%, n=171) plus Group-H with preserved endothelial function (FMD 8% or more, Group-H, n=173) (p<0.001, by Kaplan-Meier analysis] and majority of the patients with fatal cardiovascular events belonged to group-L. Cox proportional hazard model analysis showed that severe endothelial dysfunction was the most powerful predictor for future development of ACS (hazard ratio=5.77, 95%confidential interval; 2.52–13.22, p<0.001) and fatal cardiovascular events (hazard ratio=10.34, 95%confidential interval; 1.26 –72.25, p=0.022). These results suggest endothelial dysfunction plays important roles on development of ACS and fatal cardiovascular events in the near future, and strategies based on practical status of endothelial function are required to prevent ACS and fatal cardiovascular events. Cumulative Incidence


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Yoshii ◽  
T Matsuzawa ◽  
H Nakahashi ◽  
R Satou ◽  
E Akiyama ◽  
...  

Abstract Background Although the prognostic value of non-invasive endothelial function test has been reported in several populations including heart failure patients and angina pectoris patients, it is unknown in patients with acute coronary syndrome (ACS). Furthermore, the role of endothelial dysfunction in increased risk for specific causes of death has not been investigated. Purpose To study the relation between endothelial dysfunction and the risk of death in ACS patients, both overall and with regard to the main causes of death. Method Six hundred and ninety-two patients who were hospitalized for ACS from 2010 to 2014 were enrolled. Reactive hyoeremia index (RHI) was measured to assess endothelial function non-invasively in all patients using the peripheral arterial tonometry. RHI values below 1.67 were interpreted as signs of endothelial dysfunction in accordance with the manufacturer. Patients were followed up for a median of 6.5 years. Result A mean age (standard deviation) was 66 (12) years, and 542 patients (78%) were male. The patients in this study consist of 377 ST-elevation myocardial infarction (54%), and 263 non ST-elevation myocardial infarction (38%), and 52 unstable angina (8%). Endothelial dysfunction was detected in 276 patients (40%). During the follow-up period, 84 patients (12%) died (48 from cardiovascular disease, 36 from other causes). Patients with endothelial dysfunction had an increased risk of death (hazard ratio (HR) 1.83, 95% confidence interval (95% CI): 1.19–2.83, p=0.006) compared with those without endothelial dysfunction. Analyses for specific causes of death showed that patients with endothelial dysfunction had a 2.4-fold higher increased risk of cardiovascular death (HR: 2.44, 95% CI: 1.35 ro 4.59, p=0.003) after multivariate adjustment. However there was no significant relation between endothelial dysfunction and non-cardiovascular mortality (HR: 0.69, 95% CI: 0.34 to 1.36, p=0.29). Conclusion Endothelial dysfunction is strongly associated with an increased risk of cardiovascular mortality in ACS patients. Figure 1 Funding Acknowledgement Type of funding source: None


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Tatsuaki Murakami ◽  
Kazuo Ohsato

Introduction: Although coronary endothelial dysfunction is thought to affect coronary atherothrombogenic processes, there has been little practical evidence for the relationship between clinical evolution of fatal or non-fatal acute coronary syndrome (ACS) and coronary endothelial dysfunction. Hypothesis: We assessed hypothesis that coronary endothelial dysfunction has clinical impacts on development of ACS and fatal cardiovascular events. Methods: Coronary endothelial dysfunction was practically graded by the flow-mediated endothelium-dependent reactive changes in coronary artery diameter (CFMD) to infusion of adenosine triphosphate (ATP ; 50μg) into the normal left coronary artery using quantitative coronary arteriography in 150 patients with stable coronary artery disease. The enrolled patients were categorized into tertile groups according to the values of CFMD, and we prospectively followed-up major adverse clinical cardiac events including ACS and cardiovascular death. Results: For a mean follow-up period of 132 months (range; 120 to 144) with complete follow-up, the patients in the lower third with severe coronary endothelial dysfunction (Group-L) more frequently developed ACS than those in the middle third with mild coronary endothelial dysfunction (Group-M) plus those in the higher third without coronary endothelial dysfunction (Group-H) [Group-L versus Group-M plus Group-H: 15(30%) versus 5(10%) plus 0(0%), p<0.001, by Kaplan-Meier analysis]. Majority of the patients who resulted in cardiovascular death belonged to Group-L, [6(12%) versus 1(2%) plus 0(0%), p=0.014]. Cox hazard proportional model analyses indicated that severe coronary endothelial dysfunction was the strong predictor for future ACS (hazard ratio=7.53, 95%confidential interval; 1.78-12.25, p<0.001) and future cardiovascular death (hazard ratio=13.50, 95%confidential interval; 1.55-25.25, p=0.005). Conclusions: This is the novel and longest follow-up investigation that demonstrates coronary endothelial dysfunction plays important roles on development of ACS and fatal cardiovascular events and therefore the strategies based on status of coronary endothelial dysfunction are required to prevent major adverse ischemic cardiac events.


2021 ◽  
Author(s):  
Marco G Del Buono ◽  
Rocco A Montone ◽  
Giulia Iannaccone ◽  
Riccardo Rinaldi ◽  
Giulia La Vecchia ◽  
...  

Over the last decades, inflammation proved to play a pivotal role in atherosclerotic plaque formation, progression and destabilization. Several studies showed that the patients presenting with acute coronary syndrome are at increased risk of adverse cardiovascular events at both short- and long-term follow-up. Results from different clinical trials highlighted that a residual inflammatory risk exist and targeting inflammation is a successful strategy in selected cases associated to an increased inflammatory burden. Recently, the optimization of intracoronary and multimodality imaging allowed to also assess the entity of local inflammation, thus encouraging the individuation of plaque characteristics that portend a higher risk of future cardiovascular events. In this short review, we aim to highlight the role of systemic and local inflammation in acute coronary syndromes, to provide a summarized overview of the possible medical strategies applicable in selected cases and to underline the diagnostic and prognostic potential of multimodality imaging.


Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1710 ◽  
Author(s):  
Diego Estrada-Luna ◽  
Elizabeth Carreón-Torres ◽  
Rocío Bautista-Pérez ◽  
Gabriel Betanzos-Cabrera ◽  
Alan Dorantes-Morales ◽  
...  

(1) Background: the composition of high-density lipoproteins (HDL) becomes altered during the postprandial state, probably affecting their functionality vis-à-vis the endothelium. Since acute coronary syndrome (ACS) in women is frequently associated with endothelial dysfunction, it is likely that HDL are unable to improve artery vasodilation in these patients. Therefore, we characterized HDL from women with ACS in fasting and postprandial conditions. We also determined whether microencapsulated pomegranate (MiPo) reverts the HDL abnormalities, since previous studies have suggested that this fruit improves HDL functionality. (2) Methods: Eleven women with a history of ACS were supplemented daily with 20 g of MiPo, for 30 days. Plasma samples were obtained during fasting and at different times, after a lipid load test to determine the lipid profile and paraoxonase–1 (PON1) activity. HDL were isolated by sequential ultracentrifugation to determine their size distribution and to assess their effect on endothelial function, by using an in vitro model of rat aorta rings. (3) Results: MiPo improved the lipid profile and increased PON1 activity, as previously reported, with fresh pomegranate juice. After supplementation with MiPo, the incremental area under the curve of triglycerides decreased to half of the initial values. The HDL distribution shifted from large HDL to intermediate and small-size particles during the postprandial period in the basal conditions, whereas such a shift was no longer observed after MiPo supplementation. Consistently, HDL isolated from postprandial plasma samples hindered the vasodilation of aorta rings, and this endothelial dysfunction was reverted after MiPo consumption. (4) Conclusions: MiPo exhibited the same beneficial effects on the lipid profile and PON1 activity as the previously reported fresh pomegranate. In addition, MiPo supplementation reverted the negative effects of HDL on endothelial function generated during the postprandial period in women with ACS.


2019 ◽  
Vol 40 (24) ◽  
pp. 1942-1951 ◽  
Author(s):  
Dániel Aradi ◽  
Lisa Gross ◽  
Dietmar Trenk ◽  
Tobias Geisler ◽  
Béla Merkely ◽  
...  

Abstract Aims The value of platelet function testing (PFT) in predicting clinical outcomes and guiding P2Y12-inhibitor treatment is uncertain. In a pre-specified sub-study of the TROPICAL-ACS trial, we assessed ischaemic and bleeding risks according to high platelet reactivity (HPR) and low platelet reactivity (LPR) to ADP in patients receiving uniform prasugrel vs. PFT-guided clopidogrel or prasugrel. Methods and results Acute coronary syndrome patients with PFT done 14 days after hospital discharge were included with prior randomization to uniform prasugrel for 12 months (control group, no treatment modification) vs. early de-escalation from prasugrel to clopidogrel and PFT-guided maintenance treatment (HPR: switch-back to prasugrel, non-HPR: clopidogrel). The composite ischaemic endpoint included cardiovascular death, myocardial infarction, or stroke, while key safety outcome was Bleeding Academic Research Consortium (BARC) 2–5 bleeding, from PFT until 12 months. We identified 2527 patients with PFT results available: 1266 were randomized to the guided and 1261 to the control group. Before treatment adjustment, HPR was more prevalent in the guided group (40% vs. 15%), while LPR was more common in control patients (27% vs. 11%). Compared to control patients without HPR on prasugrel (n = 1073), similar outcomes were observed in guided patients kept on clopidogrel [n = 755, hazard ratio (HR): 1.06 (0.57–1.95), P = 0.86] and also in patients with HPR on clopidogrel switched to prasugrel [n = 511, HR: 0.96 (0.47–1.96), P = 0.91]. In contrast, HPR on prasugrel was associated with a higher risk for ischaemic events in control patients [n = 188, HR: 2.16 (1.01–4.65), P = 0.049]. Low platelet reactivity was an independent predictor of bleeding [HR: 1.74 (1.18–2.56), P = 0.005], without interaction (Pint = 0.76) between study groups. Conclusion Based on this substudy of a randomized trial, selecting prasugrel or clopidogrel based on PFT resulted in similar ischaemic outcomes as uniform prasugrel therapy without HPR. Although infrequent, HPR on prasugrel was associated with increased risk of ischaemic events. Low platelet reactivity was a strong and independent predictor of bleeding both on prasugrel and clopidogrel.


2012 ◽  
Vol 58 (1) ◽  
pp. 257-266 ◽  
Author(s):  
Payal Kohli ◽  
Marc P Bonaca ◽  
Rahul Kakkar ◽  
Anastacia Y Kudinova ◽  
Benjamin M Scirica ◽  
...  

Abstract OBJECTIVE We investigated the prognostic performance of ST2 with respect to cardiovascular death (CVD) and heart failure (HF) in patients with non–ST-elevation acute coronary syndrome (NSTE-ACS) in a large multinational trial. BACKGROUND Myocytes that are subjected to mechanical stress secrete ST2, a soluble interleukin-1 receptor family member that is associated with HF after STE-ACS. METHODS We measured ST2 with a high-sensitivity assay in all available baseline samples (N = 4426) in patients enrolled in the Metabolic Efficiency With Ranolazine for Less Ischemia in the Non–ST-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36), a placebo-controlled trial of ranolazine in NSTE-ACS. All events, including cardiovascular death and new or worsening HF, were adjudicated by an independent events committee. RESULTS Patients with ST2 concentrations in the top quartile (&gt;35 μg/L) were more likely to be older and male and have diabetes and renal dysfunction. ST2 was only weakly correlated with troponin and B-type natriuretic peptide. High ST2 was associated with increased risk for CVD/HF at 30 days (6.6% vs 1.6%, P &lt; 0.0001) and 1 year (12.2% vs 5.2%, P &lt; 0.0001). The risk associated with ST2 was significant after adjustment for clinical covariates and biomarkers (adjusted hazard ratio CVD/HF 1.90, 95% CI 1.15–3.13 at 30 days, P = 0.012; 1.51, 95% CI 1.15–1.98 at 1 year, P = 0.003), with a significant integrated discrimination improvement (P &lt; 0.0001). No significant interaction was found between ST2 and ranolazine (Pinteraction = 0.15). CONCLUSIONS ST2 correlates weakly with biomarkers of acute injury and hemodynamic stress but is strongly associated with the risk of HF after NSTE-ACS. This biomarker and related pathway merit further investigation as potential therapeutic targets for patients with ACS at risk for cardiac remodeling.


2019 ◽  
Vol 27 (7) ◽  
pp. 696-705 ◽  
Author(s):  
Fabrizio D'Ascenzo ◽  
Maurizio Bertaina ◽  
Francesco Fioravanti ◽  
Federica Bongiovanni ◽  
Sergio Raposeiras-Roubin ◽  
...  

Introduction The benefits of short versus long-term dual antiplatelet therapy (DAPT) based on the third generation P2Y12 antagonists prasugrel or ticagrelor, in patients with acute coronary syndromes treated with percutaneous coronary intervention remain to be clearly defined due to current evidences limited to patients treated with clopidogrel. Methods All acute coronary syndrome patients from the REgistry of New Antiplatelets in patients with Myocardial Infarction (RENAMI) undergoing percutaneous coronary intervention and treated with aspirin, prasugrel or ticagrelor were stratified according to DAPT duration, that is, shorter than 12 months (D1 group), 12 months (D2 group) and longer than 12 months (D3 group). The three groups were compared before and after propensity score matching. Net adverse clinical events (NACEs), defined as a combination of major adverse cardiac events (MACEs) and major bleedings (including therefore all cause death, myocardial infarction and Bleeding Academic Research Consortium (BARC) 3–5 bleeding), were the primary end points, MACEs (a composite of all cause death and myocardial infarction) the secondary one. Single components of NACEs were co-secondary end points, along with BARC 2–5 bleeding, cardiovascular death and stent thrombosis. Results A total of 4424 patients from the RENAMI registry with available data on DAPT duration were included in the model. After propensity score matching, 628 patients from each group were selected. After 20 months of follow up, DAPT for 12 months and DAPT for longer than 12 months significantly reduced the risk of NACE (D1 11.6% vs. D2 6.7% vs. D3 7.2%, p = 0.003) and MACE (10% vs. 6.2% vs. 2.4%, p < 0.001) compared with DAPT for less than 12 months. These differences were driven by a reduced risk of all cause death (7.8% vs. 1.3% vs. 1.6%, p < 0.001), cardiovascular death (5.1% vs. 1.0% vs. 1.2%, p < 0.0001) and recurrent myocardial infarction (8.3% vs. 5.2% vs. 3.5%, p = 0.002). NACEs were lower with longer DAPT despite a higher risk of BARC 2–5 bleedings (4.6% vs. 5.7% vs. 6.2%, p = 0.04) and a trend towards a higher risk of BARC 3–5 bleedings (2.4% vs. 3.3% vs. 3.9%, p = 0.06). These results were not consistent for female patients and those older than 75 years old, due to an increased risk of bleedings which exceeded the reduction in myocardial infarction. Conclusion In unselected real world acute coronary syndrome patients treated with percutaneous coronary intervention, DAPT with prasugrel or ticagrelor prolonged beyond 12 months markedly reduces fatal and non-fatal ischaemic events, offsetting the increased risk deriving from the higher bleeding risk. On the contrary, patients >75 years old and female ones showed a less favourable risk–benefit ratio for longer DAPT due to excess of bleedings.


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