scholarly journals Atherosclerotic Plaque Fissuration and Clinical Outcomes in Pre-Diabetics vs. Normoglycemics Patients Affected by Asymptomatic Significant Carotid Artery Stenosis at 2 Years of Follow-Up: Role of MIcRoRNAs Modulation. The ATIMIR Study

Author(s):  
Celestino Sardu ◽  
Piero Modugno ◽  
Gaetano Castellano ◽  
Lucia Scisciola ◽  
Michelangela Barbieri ◽  
...  

BACKGROUND AND PURPOSE—Atherosclerotic plaque instability and rupture in patients with asymptomatic carotid artery stenosis (ACAS) is a leading cause of major adverse cardiac events (MACE). This could be mainly evidenced in patients with pre-diabetes. Indeed, the altered glucose homeostasis and insulin resistance could cause over-inflammation of atherosclerotic plaque, favoring its conversion to unstable phenotype with rupture and MACE. Notably, the metformin therapy reducing the metabolic distress and the inflammatory burden, could lead to reduction of MACE in ACAS patients with pre-diabetes. In this setting, microRNAs (miRs) could be used as molecular biomarkers of atherosclerosis progression, plaque rupture and worse prognosis in normoglycemics (NG) vs. pre-diabetics metformin users (PDMU) vs. pre-diabetics non metformin users (PDNMU). However, the aim of our study was to investigate a wide miRNA panel in peripheral blood exosomes from patients with ACAS divided in NG vs. PDMU vs. PDNMU, and to associate the circulating miRNA expression profiles with MACE at 2 years of follow-up after endarterectomy. METHODS—The study included 234 patients with ACAS divided in NG (n 125), PDNMU (n 73) and PDMU (n 36). The miRs’ expression profiles of circulating exosomes were determined at baseline and at 2 years of follow-up by Affymetrix microarrays from plasma samples of the patients from any study cohort. Then we collected and analyzed MACE at 2 years of follow-up in NG vs. PDMU vs. PDNMU. RESULTS—prediabetics vs. NG had over-inflammation (p<0.05) and over expressed miR 24 and miR 27 at baseline. At 2 years of follow-up PDNMU vs. NG, PDMU vs. NG and PDNMU vs. PDMU over-expressed inflammatory markers and miR 24, miR 27, miR 100, miR 126 and miR 133 (p<0.05). Finally, at follow-up end we observed a significant difference about MACE comparing PDNMU vs. NG (n 27 (36.9%) vs. n 8 (6.4%); p<0.05), PDNMU vs. PDMU (n 27 (36.9%) vs. n 6 (16.6%); p <0.05), and PDMU vs. NG (n 6 (16.6%) vs. n 8 (6.4%); p<0.05). Admission glucose values (HR 1.020, CI 95% [1.001-1.038], p 0.029), atheromatous carotid plaque (HR 5.373, CI 95% [1.251-11.079], p 0.024), and miR 24 (HR 3.842, CI 95% [1.768-19.222], p 0.011) predicted MACE at 2 years of follow-up. CONCLUSIONS—Specific circulating miRs could be over-expressed in pre-diabetics and specifically in PDNMU vs. PDMU after endarterectomy. MiR24, hyperglycemia and atheromatous plaque could predict MACE at 2 years of follow-up.

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 401
Author(s):  
Celestino Sardu ◽  
Pietro Modugno ◽  
Gaetano Castellano ◽  
Lucia Scisciola ◽  
Michelangela Barbieri ◽  
...  

Atherosclerotic plaque instability and rupture in patients with asymptomatic carotid artery stenosis (ACAS) is a leading cause of major adverse cardiac events (MACE). This could be mainly evidenced in patients with pre-diabetes. Indeed, the altered glucose homeostasis and insulin resistance could cause over-inflammation of atherosclerotic plaque, favoring its conversion to unstable phenotype with rupture and MACE. Notably, metformin therapy reducing the metabolic distress and the inflammatory burden could reduce MACE in ACAS patients with pre-diabetes. In this setting, the microRNAs (miRs) could be used as molecular biomarkers of atherosclerosis progression, plaque rupture, and worse prognosis in normoglycemics (NG) versus pre-diabetics metformin users (PDMU) versus pre-diabetics non-metformin users (PDNMU). However, our study aimed to investigate a wide miRNA panel in peripheral blood exosomes from patients with ACAS divided in NG versus PDMU versus PDNMU, and to associate the circulating miRNA expression profiles with MACE at 2 years of follow-up after endarterectomy. The study included 234 patients with ACAS divided into NG (n = 125), PDNMU (n = 73), and PDMU (n = 36). The miRs’ expression profiles of circulating exosomes were determined at baseline and at 2 years of follow-up by Affymetrix microarrays from the patients’ plasma samples from any study cohort. Then we collected and analyzed MACE at 2 years of follow-up in NG versus PDMU versus PDNMU. Prediabetics versus NG had over-inflammation (p < 0.05) and over expressed miR-24 and miR-27 at baseline. At 2 years of follow-up, PDNMU versus NG, PDMU versus NG, and PDNMU versus PDMU over-expressed inflammatory markers and miR-24, miR-27, miR-100, miR-126, and miR-133 (p < 0.05). Finally, at the end of follow-up, we observed a significant difference about MACE comparing PDNMU versus NG (n = 27 (36.9%) versus n = 8 (6.4%); p < 0.05), PDNMU versus PDMU (n = 27 (36.9%) versus n = 6 (16.6%); p < 0.05); and PDMU versus NG (n = 6 (16.6%) versus n = 8 (6.4%); p < 0.05). Admission glucose values (HR (hazard ratio) 1.020, CI (confidence of interval) 95% (1.001–1.038), p = 0.029), atheromatous carotid plaque (HR 5.373, CI 95% (1.251–11.079), p = 0.024), and miR-24 (HR 3.842, CI 95% (1.768–19.222), p = 0.011) predicted MACE at 2 years of follow-up. Specific circulating miRs could be over-expressed in pre-diabetics and specifically in PDNMU versus PDMU after endarterectomy. MiR24, hyperglycemia, and atheromatous plaque could predict MACE at 2 years of follow-up.


2021 ◽  
Vol 5 (1) ◽  
pp. 2514183X2110016
Author(s):  
Mandy D Müller ◽  
Leo H Bonati

Background: Carotid artery stenosis is an important cause for stroke. Carotid endarterectomy (CEA) reduces the risk of stroke in patients with symptomatic carotid stenosis and to some extent in patients with asymptomatic carotid stenosis. More than 20 years ago, carotid artery stenting (CAS) emerged as an endovascular treatment alternative to CEA. Objective and Methods: This review summarises the available evidence from randomised clinical trials in patients with symptomatic as well as in patients with asymptomatic carotid stenosis. Results: CAS is associated with a higher risk of death or any stroke between randomisation and 30 days after treatment than CEA (odds ratio (OR) = 1.74, 95% CI 1.3 to 2.33, p < 0.0001). In a pre-defined subgroup analysis, the OR for stroke or death within 30 days after treatment was 1.11 (95% CI 0.74 to 1.64) in patients <70 years old and 2.23 (95% CI 1.61 to 3.08) in patients ≥70 years old, resulting in a significant interaction between patient age and treatment modality (interaction p = 0.007). The combination of death or any stroke up to 30 days after treatment or ipsilateral stroke during follow-up also favoured CEA (OR = 1.51, 95% CI 1.24 to 1.85, p < 0.0001). In asymptomatic patients, there is a non-significant increase in death or stroke occurring within 30 days of treatment with CAS compared to CEA (OR = 1.72, 95% CI 1.00 to 2.97, p = 0.05). The risk of peri-procedural death or stroke or ipsilateral stroke during follow-up did not differ significantly between treatments (OR = 1.27, 95% CI 0.87 to 1.84, p = 0.22). Discussion and Conclusion: In symptomatic patients, randomised evidence has consistently shown CAS to be associated with a higher risk of stroke or death within 30 days of treatment than CEA. This extra risk is mostly attributed to an increase in strokes occurring on the day of the procedure in patients ≥70 years. In asymptomatic patients, there may be a small increase in the risk of stroke or death within 30 days of treatment with CAS compared to CEA, but the currently available evidence is insufficient and further data from ongoing randomised trials are needed.


1998 ◽  
Vol 5 (6) ◽  
pp. E7
Author(s):  
Giuseppe Lanzino ◽  
Robert A. Mericle ◽  
Demetrius K. Lopes ◽  
Ajay K. Wakhloo ◽  
Lee R. Guterman ◽  
...  

Percutaneous transluminal angioplasty (PTA) and stenting has recently been proposed as an alternative to surgical reexploration in patients with recurrent carotid artery stenosis following endarterectomy. The authors retrospectively reviewed their experience after performing 25 procedures in 21 patients to assess the safety and efficacy of PTA with or without stenting for carotid artery restenosis. The mean interval between endarterectomy and the endovascular procedure was 57 months (range 8-220 months). Seven arteries in five patients were treated by PTA alone (including bilateral procedures in one patient and repeated angioplasty in the same vessel in another). Early suboptimum results and recurrent stenosis in some of these initial cases prompted the authors to combine PTA with stenting in the treatment of 18 arteries over the past 3 years. No major periprocedural deficits (neurological or cardiac complications) or death occurred. There was one periprocedural transient neurological event. A pseudoaneurysm of the femoral artery (at the access site) required surgical repair. In the 16 patients who each underwent at least 6 months of follow-up review, no neurological events ipsilateral to the treated artery had occurred after a mean follow-up period of 27 months (range 6-57 months). Three of five patients who underwent PTA alone developed significant (> 50%) asymptomatic restenoses that required repeated angioplasty in one and PTA with stenting in two patients. Significant restenosis (55%) was observed in only one of the vessels treated by combined angioplasty with stenting. Endovascular PTA and stenting of recurrent carotid artery stenosis is both technically feasible and safe and has a satisfactory midterm patency. This procedure can be considered a viable alternative to surgical reexploration in patients with recurrent carotid artery stenosis.


Stroke ◽  
2000 ◽  
Vol 31 (12) ◽  
pp. 2930-2935 ◽  
Author(s):  
R. G. J. Gibbs ◽  
M. Sian ◽  
A. W. M. Mitchell ◽  
R. M. Greenhalgh ◽  
A. H. Davies ◽  
...  

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Aditya Singh ◽  
Tom Stys ◽  
Valerie Bares ◽  
Jeffrey Wilson ◽  
Adam Stys

Introduction: Coronary artery calcium (CAC) has been found to be associated with coronary artery plaque burden and is a major predictor of coronary heart disease (CHD) events. The data on its role in predicting carotid artery stenosis (CAS) is limited. Methods: Participants age ≥ 18 years with heart screen done from Nov 2008- Feb 2019 were selected and were assessed for documented diagnosis of carotid artery stenosis after their heart screen. Only the most recent heart screen per person and earliest documented CAS was considered. The chi-squared test and Welch’s 2-sample t-test was used to test for significant association between CAS and the nominal variables and mean calcium score respectively. Results: A total of 35,084 patient were screened for CAC score and 1439 (4.1%), were recorded to have a diagnosis of carotid artery stenosis. 53.5% being females and mean age of 63.69±9.31 years. The mean time between heart screen and documented diagnosis of CAS was 1529.4 ± 1211.0 days. The presence of CAS was significantly higher in patients ≥ 60 years (8.5%) as compared to those age <60 years (2%). There was a significant difference in mean CAC score between those with CAS as compared to non- carotid stenosis group (324.2, vs 107.27, p<.0001). In patient with elevated CAC ≥ 100, 9.98% had diagnosis of CAS, as compared to 2.82% in patients with CAC <100, however among patients with diagnosis of CAS 46.6% had elevated CAC ≥ 100. Conclusions: The presence of carotid artery stenosis (CAS) was significantly associated with elevated coronary artery calcium score (≥100) and was significantly higher in patients with age ≥ 60 years, which in correct clinical context is helpful in suspecting CAS.


2017 ◽  
Vol 65 (2) ◽  
pp. 279 ◽  
Author(s):  
Subhash Kaul ◽  
Suvarna Alladi ◽  
KRukmini Mridula ◽  
V C SSrinivasarao Bandaru ◽  
Matapathi Umamashesh ◽  
...  

Author(s):  
Clint S. Schoolfield ◽  
Wayne W. Zhang ◽  
Tze-Woei Tan

This chapter provides a summary of the landmark CREST study that compared carotid endarterectomy (CEA) and carotid artery stenting (CAS) for patients with symptomatic or asymptomatic carotid artery stenosis. The study found that the combined overall rate of stroke, myocardial infarction (MI) or death between CEA and CAS did not differ significantly in symptomatic or asymptomatic patients. However, during the perioperative period, CAS was associated with an increased risk of stroke and CEA was associated with an increased risk of MI. The chapter describes the basics of the study, including funding, year study began, year study was published, study location, who was studied, who was excluded, how many patients, study design, study intervention, follow-up, endpoints, results, and criticism and limitations. The chapter briefly reviews other relevant studies and information, gives a summary and discusses implications, and concludes with a relevant clinical case.


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