Statins and Vulnerable Plaque

2018 ◽  
Vol 23 (46) ◽  
pp. 7069-7085 ◽  
Author(s):  
Maria Drakopoulou ◽  
Konstantinos Toutouzas ◽  
Archontoula Michelongona ◽  
Dimitrios Tousoulis
Keyword(s):  
Statin Therapy ◽  
Vulnerable Plaque ◽  
Vascular Wall ◽  
Statin Treatment ◽  
Duration Of Treatment ◽  
Fibrous Cap ◽  
Plaque Development ◽  
Plaque Stabilization ◽  
Inflammatory Activation ◽  
The One

Background: Atherosclerosis is a systemic, progressive lipid-driven inflammatory disease of the arterial vascular wall leading progressively to plaque development. The vulnerable plaque, the one considered to be the leading cause of cardiovascular events seems to exhibit a large and soft lipid-rich necrotic core covered by a thin and inflamed fibrous cap. Statin treatment is considered as one of the most effective methods for vulnerable plaque stabilization, currently being the principal drug in primary and secondary prevention of cardiovascular disease. </P><P> Objective: We sought to evaluate the beneficial effect of statins on biological processes involved in the evolution of vulnerable plaques </P><P> Method: We performed a systematic review of the literature searching MEDLINE via Pubmed for all experimental and human studies implementing statins in vulnerable plaque. </P><P> Results: Statins seem to have a beneficial role in plaque stabilization and patient outcome. It seems that this effect is mediated by improving endothelial function, decreasing oxidative stress and inflammation, reducing inflammatory activation and inhibiting thrombogenic response. Although these data are quite promising, it remains to be determined the extent of a potent benefit of the pleiotropic effects of statin therapy in clinical setting. </P><P> Conclusion: Prospective randomized trials should be conducted in order to further elucidate differences among type and dose of statin therapy, duration of treatment and association with LDL levels and clinical outcome.

Abstract 15389: Effect of Icosapent Ethyl on Changes in Coronary Plaque Characteristics at 9 Months in Patients With Elevated Triglycerides on Statin Therapy: Insights From EVAPORATE

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Suvasini Lakshmanan ◽  
Andrew Buckler ◽  
Deepak L Bhatt ◽  
April Kinninger ◽  
Ilana Golub ◽  
...  
Keyword(s):  
Statin Therapy ◽  
Vulnerable Plaque ◽  
Statistical Significance ◽  
Coronary Plaque ◽  
Intraplaque Hemorrhage ◽  
Icosapent Ethyl ◽  
Fibrous Cap ◽  
Stable Plaque ◽  
Plaque Phenotype ◽  
Fibrous Cap Thickness

Background: Residual cardiovascular (CV) risk persists despite statin therapy. In REDUCE-IT, icosapent ethyl (IPE) reduced total CV events by 30%, but the mechanisms of benefit are not fully understood. The EVAPORATE trial evaluated the effects of IPE as adjunct to statins on adverse atherosclerotic plaque characteristics by CCTA. Here we use a novel software validated using histology to evaluate the effect of IPE on vulnerable plaque features. Methods: The EVAPORATE trial randomized statin-treated patients, with high TG (135-499 mg/dL), and known atherosclerosis to IPE 4 g/d or placebo. Plaque characteristics including lipid rich necrotic core (LRNC), fibrous cap thickness, and intraplaque hemorrhage (IPH) were assessed using vascuCAP ® (Elucid Bioimaging Inc., Boston, MA). Per-patient multivariable models robust with respect to physiological variation were used to evaluate plaque progression. Results: A total of 60 patients had interpretable images. Relative to placebo, patients on IPE demonstrated decreased wall volume (-7.2 vs. +28.4 mm 3 ), LRNC (-1.4 vs. +9.7 mm 3 ), and IPH (-0.02 vs. +0.3 mm 3 ), as well as increased cap thickness (+100 vs. -290 microns), indicating a migration to more stable phenotypes (p>0.05).Statistical significance was achieved when incorporated into an optimized neural network model of lipid-rich phenotype (p = 0.04), AUROC=0.7[0.63,0.77], sensitivity=0.66[0.59,0.74], specificity=0.64 [0.56,0.72], and Cohen’s kappa=0.3 [0.19,0.41]. Operating points when used as a per-patient measure of response are presented in Figure 1. Conclusions: This study demonstrated that IPE, when added to statin therapy, is associated with reduction in vulnerable plaque, moving patients to a more stable plaque phenotype.

scholarly journals Optical coherent tomography in patients with unstable angina

2019 ◽  
Vol 26 (1) ◽  
pp. 79-88
Author(s):  
M. Yu. Sokolov ◽  
O. O. Lazarenko
Keyword(s):  
Vulnerable Plaque ◽  
Clinical Case ◽  
Vascular Wall ◽  
Drug Eluting Stents ◽  
Atherosclerotic Plaques ◽  
Additional Method ◽  
Optical Coherent Tomography ◽  
Fibrous Cap ◽  
Before And After ◽  
Drug Eluting

The article describes modern approaches to the study of atherosclerotic plaques characteristics using invasive imaging methods of the coronary arteries. We briefly highlighted the features of the so-called «vulnerable» atheroma. The features of the method of optical coherent tomography (OCT) in determining the thickness of the fibrous cap of a vulnerable plaque are considered. Factors limiting the possibilities of OCT and advantages over intravascular ultrasound before and after stenting are described. The clinical case is presented as a complex and uncertain one for the further tactics of treating a patient with non-Q myocardial infarction and a destroyed plaque in the LAD. The objective of this clinical case was to show the advantages of OCT as an additional method for assessing the structure of the vascular wall at the site of the destroyed plaque, the extent of the affected area, to assess the adequacy of stent implantation and the degree of pressure of stent branches, the possible dissection with an angio-graphically adequate result, which made it possible to identify malposition earlier. Also, the OCT method can be used in the remote period to visualize the degree of stent endothelization and determine the duration of double antiplatelet therapy in patients after stenting with drug-eluting stents.

Abstract 18525: Effects of Statin Therapy on Ascending Aorta Aneurysms Growth: a Propensity-matched Analysis of 828 Patients

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Emiliano Angeloni ◽  
Simone Refice ◽  
Angelo Vitaterna ◽  
Paola Lombardo ◽  
Michele Pirelli ◽  
...  
Keyword(s):  
Growth Rate ◽  
Statin Therapy ◽  
Vascular Wall ◽  
Statin Treatment ◽  
Ascending Aorta ◽  
Maximum Diameter ◽  
C Statistic ◽  
Group A ◽  
Group B ◽  
Model C

Introduction: Pleiotropic effects of statins have been advocated for remodelling of the vascular wall. Hypothesis: Whether statin therapy influences the growth rate of ascending aorta (AA) aneurysms. Methods: A total of 1348 patients was referred to our outpatient clinic for initial AA ectasia from September 2005 to December 2010. A propensity score was built to perfectly match (1:1) patients administered (Group A) or not (Group B) with statin therapy. Clinical and echocardiographic follow-up was 100% completed at 3 years after the first visit. Treatment groups were investigated for differences in AA maximum diameter, furthermore rates of survival free from death and/or complications were assessed by Kaplan-Meyer analysis. Results: Finally, two fairly-comparable groups of 414 patients each were obtained (Propensity model c-statistic 0.84, p<0.0001). No significant differences were noted in baseline characteristics, mean AA diameters were 40.9±2.6 mm and 40.7±2.5 mm in Group A and B, respectively. At 3-years, similar rates of hypertension control (84±9% vs. 83±11%) were found, whilst growth rate of AA diameter was +22.3±9.4 mm in Group A (+7.4 mm/year) and +26.5±8.4 mm (+8.8 mm/year) in Group B (p=0.0001). Three-year survival free from the composite outcome (death, dissection/rupture, need for operative repair) was found to be significantly improved in Group A (64±4%) rather than in Group B (53±5%), with a log-rank p=0.002 (HR 0.41, 95%CI 0.37 to 0.48). Conclusions: In this study, statin treatment is associated with reduced growth rate of ascending aorta aneurysms. The latter resulted in better survival free from complications for patients receiving statins.

Macrophage infiltrates in coronary plaque erosion portend a worse cardiovascular outcome in patients with acute coronary syndrome

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R.A Montone ◽  
V Vetrugno ◽  
M Camilli ◽  
M Russo ◽  
M.G Del Buono ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Vulnerable Plaque ◽  
Cardiac Death ◽  
Cox Regression ◽  
Plaque Rupture ◽  
Culprit Lesion ◽  
Coronary Syndrome ◽  
Fibrous Cap ◽  
Plaque Erosion

Abstract Background Plaque erosion (PE) is responsible for at least one-third of acute coronary syndrome (ACS). Inflammatory activation is considered a key mechanism of plaque instability in patients with plaque rupture through the release of metalloproteinases and the inhibition of collagen synthesis that in turns lead to fibrous cap degradation. However, the clinical relevance of macrophage infiltration has never been investigated in patients with PE. Purpose In our study, we aimed at assessing the presence of optical coherence tomography (OCT)-defined macrophage infiltrates (MØI) at the culprit site in ACS patients with PE, evaluating their clinical and OCT correlates, along with their prognostic value. Methods ACS patients undergoing OCT imaging and presenting PE as culprit lesion were retrospectively selected. Presence of MØI at culprit site and in non-culprit segments along the culprit vessel was assessed. The incidence of major adverse cardiac events (MACEs), defined as the composite of cardiac death, recurrent myocardial infarction and target vessel revascularization (TVR), was assessed [follow-up median (interquartile range, IQR) time 2.5 (2.03–2.58) years]. Results We included 153 patients [median age (IQR) 64 (53–75) years, 99 (64.7%) males]. Fifty-one (33.3%) patients presented PE with MØI and 102 (66.7%) PE without MØI. Patients having PE with MØI compared with PE patients without MØI had more vulnerable plaque features both at culprit site and at non-culprit segments. In particular, culprit lesion analysis demonstrated that patients with PE with MØI had a significantly thinner fibrous cap [median (IQR) 100 (60–120) μm vs. 160 (95–190) μm, p&lt;0.001], higher prevalence of thrombus [41 (80.4%) vs. 64 (62.7%), p=0.028], lipid plaque [39 (76.5%) vs. 50 (49.0%), p&lt;0.001], TCFA [20 (39.2%) vs. 14 (13.7%), p=0.001], and a higher maximum lipid arc [median [IQR] 250.0° (177.5°-290.0°) vs. 190.0° (150.0°-260.0°), p=0.018) at the culprit lesion compared with PE without MØI. MACEs were significantly more frequent in PE with MØI patients compared with PE without MØI [11 (21.6%) vs. 6 (5.9%), p=0.008], mainly driven by a higher risk of cardiac death and TVR. At multivariable Cox regression model, PE with MØI [HR=2.95, 95% CI (1.09–8.02), p=0.034] was an independent predictor of MACEs. Conclusion Our study demonstrates that among ACS patients with PE the presence of MØI at culprit lesion is associated with a more aggressive phenotype of coronary atherosclerosis with more vulnerable plaque features, along with a worse prognosis at a long-term follow-up. These findings are of the utmost importance in the era of precision medicine because clearly show that macrophage infiltrates may identify patients with a higher cardiovascular risk requiring more aggressive secondary prevention therapies and a closer clinical follow-up. Prognosis Funding Acknowledgement Type of funding source: None

Phenothiazine Treatment and Electrocardiographic Abnormalities

1969 ◽  
Vol 14 (5) ◽  
pp. 517-523 ◽  
Author(s):  
Y. D. Lapierre ◽  
L. Lapointe ◽  
J. M. Bordeleau ◽  
L. Tetreault
Keyword(s):  
Dosage Level ◽  
The Other ◽  
Duration Of Treatment ◽  
Other Hand ◽  
The One ◽  
Treatment Dosage ◽  
Ecg Abnormalities ◽  
Electrocardiographic Abnormalities

We have received the literature on ECG. abnormalities found in patients treated with phenothiazines. A survey of 106 electrocardiograms of patients receiving thioridazine as the only neuroleptic has been made. Fifty-nine patients (55.6%) had ECG. abnormalities considered ‘specific' to thioridazine. No statistically significant correlation could be made on the one hand with the sex of the patient, his age, duration of treatment, dosage level, use of antiparkinsonian medication and on the other hand the presence or absence of ECG. abnormalities. It is suggested that the ECG. abnormalities represent a disturbance in many patients with a particular susceptibility to the drug which is unpredictable at present.

The utilization of an inhibitor of spermidine and spermine synthesis as a tool for the study of the determination of cavitation in the preimplantation mouse embryo

Development ◽  
1979 ◽  
Vol 53 (1) ◽  
pp. 145-162
Author(s):  
H. Alexandre
Keyword(s):  
Biological Clock ◽  
Duration Of Treatment ◽  
Experimental Conditions ◽  
Cell Stage ◽  
Cytoplasmic Factor ◽  
Average Cell ◽  
Length Of Treatment ◽  
Preimplantation Mouse ◽  
The One

The inhibition of spermidine and spermine synthesis by methylglyoxal-Bis(guanylhydrazone) (MeGAG) at concentrations of 5, 10 and 20 µM, induces a reversible metabolic quiescence of mouse embryos, cultured in vitro from the 2-cell stage, at an average of 10·2, 8·5 and 6·9 cell stages respectively. In contrast, the inhibition of putrescine synthesis by α-methylornithine (α-MeOrn) at concentrations up to 10 mM fails to inhibit blastocyst formation, as shown previously. Complete reversibility of this induced arrest of development is observed for treatments up to 31 h with MeGAG at 10 µM. In agreement with the biological clock theory of Smith & MacLaren's hypothesis, the delay in cavitation is proportional to the length of treatment. However, the average cell numbers of the ‘delayed nascent blastocysts’ of all treated embryos (21·8–24·2) are consistently lower than that of control embryos (33·6) irrespective of the duration of treatment. It seems therefore that under some experimental conditions, DNA and chromosome replication on the one hand and cytoplasmic maturation on the other may be desynchronized. This suggests a role for a cytoplasmic factor in the induction of cavitation.

Abstract P297: Long-Term Benefit Comparison of Absolute Risk Reduction versus Absolute Risk to Prioritize Statin Therapy

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Ciaran N Kohli-Lynch ◽  
Andrew E Moran ◽  
George Thanassoulis ◽  
Allan D Sniderman ◽  
Yiyi Zhang ◽  
...  
Keyword(s):  
Risk Factor ◽  
Statin Therapy ◽  
Risk Reduction ◽  
Treatment Initiation ◽  
Absolute Risk ◽  
Treatment Strategies ◽  
Absolute Risk Reduction ◽  
Statin Treatment ◽  
Policy Model

Introduction: Individuals with no established cardiovascular disease (CVD) are currently recommended preventive statin therapy based on 10-year absolute risk (AR) of CVD, and individuals with a 10-year AR ≥7.5% are recommended statins. However, individuals with elevated LDL cholesterol experience greater absolute CVD absolute risk reduction (ARR) from statin therapy compared with those with the same 10-year AR but with lower LDL. A previous study showed that ARR-based statin treatment would prevent more CVD events than AR-based treatment in the 10 years following treatment initiation. Objective: This study aimed to quantify the long-term benefits of treating patients based on ARR rather than AR. Methods: A microsimulation version of the CVD Policy Model, a decision-analytic state transition model, simulated intermediate-strength statin therapy in 40,000 CVD-free US adults (50% female) under a variety of treatment strategies. The model predicts health outcomes for individuals based on their age, sex, and risk factor profile, accounting for the competing risk of non-CVD mortality. Individuals entered the model aged 40 years, and a time horizon of 40 years was employed. Life year gains and CVD events prevented compared to no treatment were estimated for a range of 10-year ARR and AR treatment initiation thresholds. Results: At the same numbers of patient-years of treatment (PYoT), ARR consistently produced more life year gains than AR (Figure). A 10-year ARR threshold of ≥2.62% would lead to approximately the same PYoT as standard of care (10-year AR ≥7.5%) while preventing 60 additional CVD events and producing 421 additional life year gains in the cohort. Conclusion: Treating patients with statins based on ARR would yield significant health gains in the U.S. population compared to standard AR-based treatment strategies. The ARR strategy may also achieve greater adherence and uptake as it focuses on individuals with elevated levels of a modifiable risk factor.

scholarly journals Optical Coherence Tomography Predictors for a Favorable Vascular Response to Statin Therapy

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Akihiro Nakajima ◽  
Yoshiyasu Minami ◽  
Makoto Araki ◽  
Osamu Kurihara ◽  
Tsunenari Soeda ◽  
...  
Keyword(s):  
Optical Coherence Tomography ◽  
Statin Therapy ◽  
Optical Coherence ◽  
Vascular Response ◽  
Unique Identifier ◽  
Tomography Imaging ◽  
3 Dimensional ◽  
Fibrous Cap ◽  
Optical Coherence Tomography Imaging ◽  
Fibrous Cap Thickness

Background Specific plaque phenotypes that predict a favorable response to statin therapy have not been systematically studied. This study aimed to identify optical coherence tomography predictors for a favorable vascular response to statin therapy. Methods and Results Patients who had serial optical coherence tomography imaging at baseline and at 6 months were included. Thin‐cap area (defined as an area with fibrous cap thickness <200 μm) was measured using a 3‐dimensional computer‐aided algorithm, and changes in the thin‐cap area at 6 months were calculated. A favorable vascular response was defined as the highest tertile in the degree of reduction of the thin‐cap area. Macrophage index was defined as the product of the average macrophage arc and length of the lesion with macrophage infiltration. Layered plaque was defined as a plaque with 1 or more layers of different optical density. In 84 patients, 140 nonculprit lipid plaques were identified. In multivariable analysis, baseline thin‐cap area (odds ratio [OR] 1.442; 95% CI, 1.024–2.031, P =0.036), macrophage index (OR, 1.031; 95% CI, 1.002–1.061, P =0.036), and layered plaque (OR, 2.767; 95% CI, 1.024–7.479, P =0.045) were identified as the significant predictors for a favorable vascular response. Favorable vascular response was associated with a decrease in the macrophage index. Conclusions Three optical coherence tomography predictors for a favorable vascular response to statin therapy have been identified: large thin‐cap area, high macrophage index, and layered plaque. Favorable vascular response to statin was correlated with signs of decreased inflammation. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01110538.

Animal models of vulnerable plaque

2003 ◽  
Vol 90 (11) ◽  
pp. 774-780 ◽  
Author(s):  
Ik-Kyung Jang ◽  
Levon Khachigian ◽  
Harry Lowe
Keyword(s):  
Animal Models ◽  
Vulnerable Plaque ◽  
Acute Coronary Syndromes ◽  
Plaque Rupture ◽  
Plaque Vulnerability ◽  
Plaque Stabilization ◽  
Apo E ◽  
Recent Developments ◽  
Coronary Syndromes ◽  
Apo E Knockout Mice

SummaryThere is increasing recognition of the importance of vulnerable plaque and acute plaque rupture leading to thrombosis, in the pathogenesis of acute coronary syndromes. This is fueling a number of developments, including novel imaging modalities and potential plaque stabilization therapies. However, to date, no animal model of vulnerable plaque or plaque rupture has been established. Recent developments, particularly using Apo E knockout mice, appear set to provide key breakthroughs. The present status of our understanding of plaque vulnerability is therefore discussed, with a discussion of these current advances in animal models.

THUR 116 Vascular prevention in patients with parkinson’s disease

2018 ◽  
Vol 89 (10) ◽  
pp. A12.3-A12
Author(s):  
Kempe Isla ◽  
Grosset Katherine A ◽  
Grosset Donald G
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Primary Prevention ◽  
Statin Therapy ◽  
Statin Treatment ◽  
Vascular Risk ◽  
Vascular Events ◽  
Cross Sectional ◽  
Increased Risk ◽  
Cognitive Problems

BackgroundVascular prevention is appropriate for patients with a vascular history (secondary prevention) and increased risk (primary prevention). Cerebrovascular disease adds to gait and cognitive problems in patients with Parkinson’s disease (PD).MethodsA convenience cross-sectional sample of consecutive PD patients attending the Neurology Movement Disorder clinic was assessed, and QRISK3 scored when appropriate (cases without vascular events, age <85 years).ResultsOf 100 cases, mean age 66.5 (SD 9.0) years, 52.0% male, with PD duration 8.3 (SD 5.5) years, 15 had a vascular history meriting statin therapy, of whom 12 (80.0%) were prescribed statins. 22 had a high vascular risk (QRISK3 >20%), mean QRISK3 28.6 (SD 7.7) of whom 2 (9.1%) were prescribed statins. We are now actively assessing QRISK3 and recommending statin therapy where appropriate.ConclusionsSecondary vascular prevention with statins is more commonly implemented than primary prevention, in patients with PD. In patients without a vascular diagnosis, vascular risk should be assessed and statin therapy offered where appropriate, noting that around one-fifth of patients have a high vascular risk and are not on statin treatment.

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