Protective Effect of Pre-Infarction Angina on Microvascular Obstruction After Primary Percutaneous Coronary Intervention Is Blunted in Humans by Cardiovascular Risk Factors

Niccoli, Giampaolo; Scalone, Giancarla; Cosentino, Nicola; Fabretti, Alessandro; Mirizzi, A Mandurino; Gramegna, Mario; Panebianco, Mario; Roberto, Marco; Crea, Filippo

doi:10.1253/circj.cj-14-0194

Cited by 13 publications

(5 citation statements)

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“…Previous studies have shown that patients with PIA tend to have reduced infarct size and increased ejection fraction compared with patients without PIA [ 21 , 22 ]. Therefore, PIA was identified as a favorable prognosticator in patients with STEMI [ 23 ]. Mechanisms underlying this association are likely related to activation of ischemic preconditioning (IP) by PIA [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

The Value of Pre-Infarction Angina and Plasma D-Dimer in Predicting No-Reflow After Primary Percutaneous Coronary Intervention in ST-Segment Elevation Acute Myocardial Infarction Patients

et al. 2018

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BackgroundPrimary percutaneous coronary intervention (PCI) has improved outcomes greatly in patients with ST-elevation myocardial acute infarction (STEMI). However, the no-reflow phenomenon significantly reduces its efficacy.Material/MethodsIn this study, we investigated the value of combining plasma D-dimer level on admission and pre-infarction angina (PIA) in predicting no-reflow phenomenon in STEMI patients after primary PCI. A total of 926 STEMI patients who underwent primary PCI were included.ResultsThe average age was 52.6 years, 617 (66.6%) of them had experienced a PIA, and 435 (47.9%) showed no-reflow phenomenon after primary PCI. Both PIA and plasma D-dimer on admission were independent predictors of no-reflow, with a risk of 0.516 (95% CI: 0.380 to 0.701) and 2.563 (95% CI: 1.910 to 3.439), respectively. Plasma D-dimer level had an area under curve (AUC) of 0.604 (95% CI: 0.568~0.641) in predicting no-reflow phenomenon, and PIA had an AUC of 0.574 (95% CI: 0.537 to 0.611). Importantly, the new signature combining D-dimer level on admission and PIA showed an increased AUC (0.637, 95%CI: 0.601 to 0.673) in predicting the no-reflow phenomenon. Moreover, the patients with high D-dimer level on admission but without PIA had significantly increased ratio of no-reflow phenomenon and in-hospital mortality compared to the other patients (P<0.001 and P=0.041, respectively).ConclusionsBased on these solid results, we conclude that combining plasma D-dimer level on admission and PIA might create a good signature for use in predicting the no-reflow phenomenon after primary PCI in STEMI patients.

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Section: Discussionmentioning

confidence: 99%

The Value of Pre-Infarction Angina and Plasma D-Dimer in Predicting No-Reflow After Primary Percutaneous Coronary Intervention in ST-Segment Elevation Acute Myocardial Infarction Patients

et al. 2018

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“…The interval between prodromal angina and its impact in microvascular obstruction in previous reports is wide, ranging from 48 h 59 up to 3 months 60 before STEMI. Because it is arguable that those patients who have PIA more closely to the index event may benefit the most from the preconditioning stimulus, narrowing the definition of PIA to 24 to 72 h before STEMI could have had enhanced the effect.…”

Section: Discussionmentioning

confidence: 94%

Ticagrelor Loading on ST-Elevation Myocardial Infarction: Interaction With Prodromal Angina on Infarct Size and Clinical Events

Faria

Oliveira

Alexandre

et al. 2023

J Cardiovasc Pharmacol Ther

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Introduction: Ticagrelor might reduce infarct size by exerting a more potent antiplatelet effect or by promoting a potential conditioning stimulus in ST-elevation myocardial infarction (STEMI) patients. Pre-infarction angina (PIA) is an effective preconditioning stimulus that reduces ischemia-reperfusion injury. Because little is known on the interaction of PIA in STEMI-patients loaded with ticagrelor, we sought to determine if patients loaded with ticagrelor had improved clinical outcomes as compared to clopidogrel and to study if it is modulated by the presence of PIA. Methods: From 1272 STEMI patients submitted to primary percutaneous coronary intervention and treated with clopidogrel or ticagrelor from January 2008 to December 2018, 826 were analyzed after propensity score matching. Infarct size was estimated using peak creatine kinase (CK) and troponin T (TnT), and clinical impact was evaluated through cumulative major cardiac and cerebrovascular events (MACCE) at 1-year follow-up. Matched patients and their interaction with PIA were analyzed. Results: Patients loaded with ticagrelor had lower peak CK [1405.50 U/L (730.25-2491.00), P < .001] and TnT [3.58 ng/mL (1.73-6.59), P < .001)], regardless of PIA. The presence of PIA was associated with lower CK ( P = .030), but not TnT ( P = .097). There was no interaction between ticagrelor loading and PIA ( P = .788 for TnT and P = .555 for CK). There was no difference in MACCE incidence between clopidogrel or ticagrelor loading ( P = .129). Cumulative survival was also similar between clopidogrel or ticagrelor, regardless of PIA ( P = .103). Conclusion: Ticagrelor reduced infarct sizes independently and without a synergic effect with PIA. Despite reducing infarct size, clinical outcomes were similar across both groups.

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“…In patients, pre-infarction angina is a prototypic event that is protective per se in that 1 or several episodes of myocardial ischemia in the presence of epicardial coronary atherosclerosis are precipitated by sympathetic activation such as stress or exercise and then exert an ischemic PreC effect on the myocardium for a limited period of time ( Heusch, 2001 ; Rezkalla and Kloner, 2004 ). Pre-infarction angina in patients decreases IS ( Andreotti et al, 1996 ; Iglesias-Garriz et al, 2001 ; Kloner et al, 1998 ; Lønborg, Kelbæk, Vejlstrup, Bøtker, Kim, Holmvang, Jørgensen, Helqvist, Saunamäki, Thuesen, et al, 2012 ; Reiter et al, 2013 ) and no-reflow ( Karila-Cohen et al, 1999 ; Colonna et al, 2002 ; Niccoli et al, 2014 ), and it improves patients’ prognosis ( Lorgis et al, 2012 ; Herrett et al, 2014 ; Schmidt et al, 2015 ). However, the protection by pre-infarction angina is attenuated by nonmodifiable risk factors, such as age ( Ishihara et al, 2000 ); modifiable risk factors, such as smoking; and comorbidities, such as dyslipidemia ( Niccoli et al, 2014 ).…”

Section: Effects Of Nonmodifiable Risk Factors and Comorbidities On I...mentioning

confidence: 99%

“…Pre-infarction angina in patients decreases IS ( Andreotti et al, 1996 ; Iglesias-Garriz et al, 2001 ; Kloner et al, 1998 ; Lønborg, Kelbæk, Vejlstrup, Bøtker, Kim, Holmvang, Jørgensen, Helqvist, Saunamäki, Thuesen, et al, 2012 ; Reiter et al, 2013 ) and no-reflow ( Karila-Cohen et al, 1999 ; Colonna et al, 2002 ; Niccoli et al, 2014 ), and it improves patients’ prognosis ( Lorgis et al, 2012 ; Herrett et al, 2014 ; Schmidt et al, 2015 ). However, the protection by pre-infarction angina is attenuated by nonmodifiable risk factors, such as age ( Ishihara et al, 2000 ); modifiable risk factors, such as smoking; and comorbidities, such as dyslipidemia ( Niccoli et al, 2014 ). Also, the time interval between the prodromal angina and the onset of AMI is decisive and was between 1 ( Kloner et al, 1998 ; Ishihara et al, 2000 ; Iglesias-Garriz et al, 2001 ; Reiter et al, 2013 ) and 7 ( Karila-Cohen et al, 1999 ; Colonna et al, 2002 ; Lønborg Kelbæk, Vejlstrup, Bøtker, Kim, Holmvang, Jørgensen, Helqvist, Saunamäki, Thuesen, et al, 2012 ; Herrett et al, 2014 ) or 14 days ( Schmidt et al, 2015 ) when resulting in a clinical benefit.…”

Section: Effects Of Nonmodifiable Risk Factors and Comorbidities On I...mentioning

confidence: 99%

Interaction of Cardiovascular Nonmodifiable Risk Factors, Comorbidities and Comedications With Ischemia/Reperfusion Injury and Cardioprotection by Pharmacological Treatments and Ischemic Conditioning

et al. 2022

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Preconditioning, postconditioning, and remote conditioning of the myocardium enhance the ability of the heart to withstand a prolonged ischemia/reperfusion insult and the potential to provide novel therapeutic paradigms for cardioprotection. While many signaling pathways leading to endogenous cardioprotection have been elucidated in experimental studies over the past 30 years, no cardioprotective drug is on the market yet for that indication. One likely major reason for this failure to translate cardioprotection into patient benefit is the lack of rigorous and systematic preclinical evaluation of promising cardioprotective therapies prior to their clinical evaluation, since ischemic heart disease in humans is a complex disorder caused by or associated with cardiovascular risk factors and comorbidities. These risk factors and comorbidities induce fundamental alterations in cellular signaling cascades that affect the development of ischemia/reperfusion injury and responses to cardioprotective interventions. Moreover, some of the medications used to treat these comorbidities may impact on cardioprotection by again modifying cellular signaling pathways. The aim of this article is to review the recent evidence that cardiovascular risk factors as well as comorbidities and their medications may modify the response to cardioprotective interventions. We emphasize the critical need for taking into account the presence of cardiovascular risk factors as well as comorbidities and their concomitant medications when designing preclinical studies for the identification and validation of cardioprotective drug targets and clinical studies. This will hopefully maximize the success rate of developing rational approaches to effective cardioprotective therapies for the majority of patients with multiple comorbidities. Significance Statement Ischemic heart disease is a major cause of mortality; however, there are still no cardioprotective drugs on the market. Most studies on cardioprotection have been undertaken in animal models of ischemia/reperfusion in the absence of comorbidities; however, ischemic heart disease develops with other systemic disorders (e.g., hypertension, hyperlipidemia, diabetes, atherosclerosis). Here we focus on the preclinical and clinical evidence showing how these comorbidities and their routine medications affect ischemia/reperfusion injury and interfere with cardioprotective strategies.

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Protective Effect of Pre-Infarction Angina on Microvascular Obstruction After Primary Percutaneous Coronary Intervention Is Blunted in Humans by Cardiovascular Risk Factors

Cited by 13 publications

References 63 publications

The Value of Pre-Infarction Angina and Plasma D-Dimer in Predicting No-Reflow After Primary Percutaneous Coronary Intervention in ST-Segment Elevation Acute Myocardial Infarction Patients

The Value of Pre-Infarction Angina and Plasma D-Dimer in Predicting No-Reflow After Primary Percutaneous Coronary Intervention in ST-Segment Elevation Acute Myocardial Infarction Patients

Ticagrelor Loading on ST-Elevation Myocardial Infarction: Interaction With Prodromal Angina on Infarct Size and Clinical Events

Interaction of Cardiovascular Nonmodifiable Risk Factors, Comorbidities and Comedications With Ischemia/Reperfusion Injury and Cardioprotection by Pharmacological Treatments and Ischemic Conditioning

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