Plaque Progression In Patients Research Articles

7-year follow-up atherosclerotic plaque progression in patients with antiphospholipid syndrome versus diabetes mellitus and healthy controls.

Patients with antiphospholipid syndrome (APS) carry a substantial burden of cardiovascular disease and subclinical atherosclerosis. We aimed to assess a 7-year follow-up atherosclerotic plaque progression in APS patients vs diabetes mellitus (DM) and healthy controls (HC). Eighty-six patients with thrombotic APS, 86 with DM and 86 HC (all age- and sex-matched) who underwent a baseline ultrasound of carotid and femoral arteries were invited for a 7-year follow-up ultrasonography examination. We compared atherosclerosis progression among the three groups and examined determinants of plaque progression in APS patients. Sixty-four APS patients (75% females, 43.8% with primary APS), 58 patients with DM and 66 HC were included in the 7-year ultrasound re-evaluation. New plaque was detected in 51.6%, 36.2% and 25.8% of APS, DM and HC subjects, respectively. After adjusting for traditional cardiovascular risk factors (CVRFs) and baseline plaque presence, APS patients showed a 3-fold (OR = 3.07, p= 0.007) higher risk for atherosclerosis progression vs HC and 2-fold (OR = 2.25, p= 0.047) higher risk than DM patients. In multivariate analysis in the APS group, plaque progression was independently associated with systemic lupus erythematosus (SLE) co-existence (OR = 7.78, p= 0.005) and number of CVRFs (OR = 3.02, p= 0.002), after adjusting for disease-related parameters and CVRF-related medications. Sustained low-density lipoprotein target attainment reduced plaque progression risk (OR = 0.34, p= 0.021). Half of APS patients develop new atherosclerotic plaques over a 7-year follow-up, having a three-times higher risk vs HC. Concomitant SLE and number of traditional CVRFs are associated with plaque progression, supporting the need for thorough CVRF assessment and control.

Triglyceride levels predict high-risk coronary artery plaque progression in asymptomatic patients with type 2 diabetes and normal LDL cholesterol

Abstract Background Type 2 diabetes mellitus (T2D) is associated with an increased risk of coronary artery disease (CAD) and a significant residual risk remains despite management of conventional risk factors. Purpose The purpose of the present study was to assess the association of triglycerides and high-risk plaque progression in patients with asymptomatic T2D without known CAD. Methods Asymptomatic patients with T2D and no history of CAD were studied with serial computed tomography angiography with an inter-scan interval of 13 ± 0.8 months. The total atheroma volume (TAV), and plaque composition (dense calcium, fibrous, fibrous-fatty, and necrotic core plaque) were assessed at baseline and at follow-up. Lipid status was assessed at baseline and after a one-year follow-up. Patients were divided into two groups depending on progression in triglyceride (TG) levels (TG+) and regression of TG levels (TG-). Results Of the 261 patients who were enrolled, 209 patients (157 men and 52 women) were included in the final analysis. Based on changes in TG levels, 107 patients were categorized as (TG+) and 102 patients were categorized as (TG-). The mean age was 62 ± 10 years, and the mean diabetes duration was 11 ± 8 years. At baseline, 76 % of the patients received lipid-lowering treatment, and low-density lipoprotein (LDL) cholesterol was 2.0 ± 0.8 mmol/L. A significantly higher progression of TAV was observed in patients with TG+ compared to TG- (50.2 ± 144.3 vs. -28.5 ± 176.9 mm3, P<0.001). This observation was primarily driven by an increase of fibrous fatty plaque (8.6 ± 41.2 vs. -12.8 ± 39.2 mm3, P<0.001) and necrotic core plaque (-3.9 ± 51.4 vs. -23.7 ± 71.8 mm3, P=0.002). Furthermore, an increase in TG levels predicted rapid plaque progression independent of LDL and other risk factors (OR 1.36, 95% CI; 1.02 – 1.81, P=0.04). Conclusion Changes in TG levels are associated with the progression of total and high-risk plaque volumes in asymptomatic patients with T2D and well-controlled LDL cholesterol.Low attenuation plaque vs. triglycerides

Low HDL cholesterol and hyperglicemia are metabolic syndrome components associated with plaque progression in patients with chronic coronary syndrome: a PARADIGM study

Abstract Background The metabolic syndrome (MetS), a cluster of dyslipidemia, hyperglicemia and hypertension predicts future cardiovascular disease and death in general populations. Purpose We aimed to assess whether MetS and its components may impact on coronary plaque progression (PP), at serial coronary computed tomography angiography (CCTA), and major adverse cardiovascular events (MACE) in patients with chronic coronary syndrome (CCS). Methods A total of 1200 CCS patients (aged 60.9±9.3 years, 55.4% male) who underwent serial CCTA (≥2 years apart) and had available data on glucose/lipid metabolism and outcome, were analysed from the Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry. MetS and its components were categorized according to NCEPT ATPIII definition. Plaque volumes were measured in coronary segments (≥ 2 mm in diameter) and summed to provide total plaque volume (PV, mm3) and percent atheroma volume (PV/vessel volume*100) (PAV, %) per patient at baseline and follow-up. Rapid PP was defined as annualized PAV increase (∆PAV) ≥1.0%/year. MACE included non-fatal myocardial infarction, any cause death and unplanned coronary revascularization (>30 days after first CCTA). Results MetS was present in 366 patients (31%). The median interscan period was 3.2 years (IQR 1.9) and rapid PP occurred in 341 patients (28%). MetS was associated with a higher total PV (133±183 vs 97±163, P<0.001) and PAV (7.1±9.3 vs 5.4±8.0, P<0.001) at baseline and a higher annual change in both PV (18.5±23.4 vs 13.9±22.5, P< 0.001) and PAV (0.9±1.1 vs 0.7±1.0, P<0.001) (Figure 1A). At a multivariable logistic regression analysis, MetS independently predicted rapid PP (OR 1.50, 95%CI 1.11-2.02, p<0.01) after adjustment for other risk factors not included among its components (age, gender, smoking habits, family history, hypercholesterolemia, previous CAD), statin treatment and baseline PAV. Among MetS components, diabetes under treatment or fasting plasma glucose >100 mg/dL (OR 1.37, 95%CI 1.02-1.84, p<0.05) and low HDL cholesterol (<40 mg/dL in males and < 50 mg/dL in females) (OR 1.76, 95%CI 1.29-2.39, p<0.001) were independently associated with rapid PP. They had an additive effect on baseline PAV and annualized PAV increase (Figure 1B). The median follow-up duration was 8.23 years (IQR 3.61). MACE occurred in 201 patients (16.8%) (17 death, 11 non-fatal MI, 173 unplanned revascularizations). At multivariable Cox regression analysis, rapid PP was a strong and independent predictor of events (HR 1.72, 95% CI 1.29-2.28, P<0.001) after correction for all risk factors including MeS or its components and baseline PAV. Conclusions Independently of other risk factors and treatment MetS is associated with a higher coronary atherosclerotic burden and rapid PP which are in turn strong predictors of MACE in patients with CCS. Among MetS components hyperglycemia and low HDL-C are major determinants of rapid PP.Figure 1

Abstract 18480: Type 2 Diabetic Patients Have Increased Coronary Plaque Burden and Plaque Progression During 10-Year Serial Coronary CT Angiography Follow-Up

Background Individuals diagnosed with type 2 diabetes are at high risk for coronary artery disease, however, data on long-term progression of coronary artery plaque burden is lacking. This study investigated atherosclerotic plaque characteristics and long-term plaque progression in patients with and without type 2 diabetes mellitus (T2DM). Methods: Per-protocol, patients from a coronary CT angiography (CCTA) cohort were invited for repeat CCTA imaging, regardless of symptoms. A total of 299 patients underwent follow-up CCTA imaging with a median scan interval of 10.2 [IQR 8.7-11.2] years. Patients who underwent coronary artery bypass grafting and vessels revascularized by percutaneous coronary intervention were excluded. Scans were analyzed using atherosclerosis imaging-quantitative CCTA (AI-QCT; Cleerly Inc.). The associations between diabetic status, baseline and follow-up plaque burden and characteristics were evaluated using multivariable regression adjusted for clinical risk factors, statin use and scanner settings. Results: In total, 274 patients were included, 43 (15.7%) had T2DM at baseline. The mean age was 57±7 years, 42% were women. At baseline, patients with T2DM had a median percent atheroma volume (PAV) of 6.80 (2.80, 17.70) at baseline; patients without T2DM had a median PAV of 3.20 (0.80, 9.55). Adjusted for clinical risk factors, patients with T2DM had a higher rate of plaque progression (Figure 1). The difference in PAV caused by T2DM was similar to the effect of a 13-year age difference. At baseline patients with T2DM had a higher prevalence of high-risk plaque (OR 2.11; p=0.025). After 10 years of follow-up, patients with T2DM had a higher prevalence of both high-risk plaque (OR 3.49; p<0.001) and low-density plaque (OR 3.74; p<0.001). Conclusion Patients with T2DM had a more than twofold higher coronary plaque burden, increased plaque progression during 10-year follow-up and had an increased prevalence of high-risk and low-density plaque.

Time-varying effect of postoperative cholesterol profile on long-term outcomes of isolated coronary artery bypass graft surgery

BackgroundControlling cholesterol levels is one of the primary goals of preventing atherosclerotic plaque progression in patients undergoing coronary artery bypass graft (CABG) surgery. This study aimed to investigate the impact of serum cholesterol profile at multiple time points following isolated CABG surgery on long-term patient outcomes.MethodThis retrospective cohort study was conducted on the admission and follow-up data of isolated CABG patients from the Tehran Heart Center registry between 2009 and 2016. The association of low-density lipoprotein (LDL), high-density lipoprotein (HDL), and their ratio as an atherogenic index with major adverse cardiac and cerebrovascular events (MACCE) and all-cause mortality were evaluated using time-varying survival analysis methods.ResultA total of 18657 patients were included in this analysis. After adjusting for known confounding factors, no significant difference in all-cause mortality and MACCE was observed at different LDL levels. The incidence of acute coronary syndrome (ACS) in patients with LDL > 100 mg/dl and LDL < 50 mg/dl was significantly higher than in the control group (P-value = 0.004 and 0.04, respectively). The incidence of cerebrovascular accidents (CVA) at LDL > 100 mg/dl was also significantly higher compared to the control group (P -value = 0.033). Lower HDL levels were significantly associated with a higher MACCE (P -value < 0.001), all-cause mortality (P -value < 0.001), ACS (P -value = 0.00), and CVA (P -value = 0.014). The atherogenic index was also directly related to MACCE and all its components (all P-values < 0.001).ConclusionLDL/HDL ratio is suggested as a better marker for secondary prevention goals compared to LDL alone in patients undergoing CABG surgery.

279 LAYERED PLAQUES: NOT ALL ARE HEALED

Abstract Layered plaques are the effect of a previous plaque event. They are associated with coronary spasm and found in more than 50% of patients with stable angina and a quarter of those with an acute coronary syndrome. Nevertheless, it is not clear whether their presence is indicative of a healing process or rather is predictive of an increased risk of future events. A 71-year-old male, heavy smoker and hypertensive, presented with episodes of angina at rest that resolved spontaneously in less than 5 minutes, with evidence of ST-segment elevation (STE) in the lower leads during one of these episodes. Coronary angiography showed an intermediate stenosis at the end of the mid segment of the dominant right coronary artery (RCA) (Figure A). Optical coherence tomography (OCT) revealed a layered plaque, consisting of high backscattering layers alternated with low reflection layers (Figures A1-3). Given the minimum luminal area of 3.65 mm2 and the absence of other criteria for plaque instability (erosion, thin-cap, etc.), we treated the patient conservatively with medical therapy alone, consisting of a single antiplatelet agent and a high-dose statin with ezetimibe. A non-dihydropyridine calcium antagonist and a long-acting nitrate were started given the suspicion of coronary spasm. Four months later the patient returned to the emergency department for persistent oppressive chest pain unresponsive to sublingual nitrates with evidence of STE in the lower leads. Emergency coronary angiography showed an acute occlusion of RCA with TIMI 0 flow in correspondence to the layered plaque highlighted 4 months earlier on OCT (Figure B). Antegrade flow was restored with manual thrombus aspiration (Figure C) and OCT showed lesion progression with many new layers, together with a cavity suggestive of plaque rupture (Figures C1-3). A 3.5×38 mm everolimus eluting stent was deployed – based on OCT sizing – and post-dilated with a 4.0×8 mm non-compliant balloon, obtaining an excellent angiographic result with TIMI 3 flow (Figure D). Low-reflecting layers within layered plaques are generally considered to be lipid deposits, but they could also represent intraplaque haemorrhages, generated by coronary spasm. The haematoma can be reorganised within the plaque to create a new layer, leading to lesion progression without necessarily requiring a loss of endothelial integrity. The progressive increase of the haematoma may lead to plaque rupture when the pressure exceeds the resistance of superficial layers. This case reveals a new possible mechanism of plaque progression in patients with coronary spasm and explains how layered plaques can be ambivalently considered to be either stable or vulnerable. Their treatment should be meticulously tailored not only based on classical criteria of plaque instability but also according to the underlying trigger mechanism.

Serum MPO levels and activities are associated with angiographic coronary atherosclerotic plaque progression in type 2 diabetic patients

BackgroundThe uncontrolled production of MPO promotes inflammation, oxidative stress and atherosclerosis. Serum MPO levels are increased in patients with diabetes compared with patients without diabetes.ObjectivesThis study aimed to investigate whether the serum levels and activities of MPO are related to coronary plaque progression in patients with type 2 diabetes mellitus (T2DM).Material and methodsSerum MPO levels and activities were measured in 161 patients with diabetes with plaque progression (plaque progression group) and 87 patients with diabetes with no plaque progression (no plaque progression group). These patients were eligible based on the inclusion criteria and received quantitative coronary angiography at baseline and after approximately 1 year of follow-up. The characteristics and parameters of the participants at baseline were documented.ResultsSerum MPO levels and activities were significantly higher in plaque progression group than in no plaque progression group (P < 0.001). We categorized these patients with diabetes into MPO level or activity tertile subgroups. Significant differences in the plaque progression ratio and prominent changes in the minimal lumen diameter, stenosis diameter and coronary artery stenosis score were observed across the tertile subgroups of MPO levels and activities (all P < 0.01). Moreover, serum MPO levels and activities correlated significantly with these indices of coronary artery disease severity after adjustment for other risk factors. Multivariable regression analyses revealed that serum MPO levels and activities remained independently associated with plaque progression, in addition to smoking, hypertension and CRP levels (all P < 0.05).ConclusionsSerum MPO levels and activities are significantly associated with coronary atherosclerotic plaque progression in patients with type 2 diabetes.

Abstract 10905: Relationship of Eicosapentaenoic Acid and Docosahexaenoic Acid Dosage to Plaque Progression in Patients With Coronary Atherosclerosis Receiving Statin and Polyunsaturated Fatty Acid Therapy

Introduction: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are omega-3 polyunsaturated fatty acids (PUFAs) extensively studied in atherosclerosis. Clinical endpoint and imaging studies have yielded convergent findings favoring pure EPA over mixed EPA/DHA formulations. The effects of EPA and DHA dose on coronary plaque dynamics, however, remain unknown, and could yield insights into the utility of these PUFAs in coronary artery disease. Methods: We considered longitudinal studies that compared coronary plaque change in patients receiving statin versus statin+PUFA therapy. Outcomes were % change in total and lipid plaque volume. Treatment effects were calculated as standardized mean difference (SMD), the mean % plaque volume change between statin and statin+PUFA cohorts divided by their pooled standard error. To isolate effects of EPA or DHA dose respectively, treatment arms were pooled by dosage of the PUFA of interest. To account for dependent samples, we fit hierarchical mixed effects models using robust variance estimation, assuming a correlation of 0.5 among treatment effects within multi-arm studies. Results: Among 555 screened articles, 11 studies met inclusion criteria. Among 1,070 patients, there were 14 treatment arms stratified by EPA dose, and 15 treatment arms stratified by DHA dose. Meta-regression revealed that EPA dose (g/day) correlated positively with treatment effect (β = 0.3 [0.1, 0.6], P = 0.02), while daily DHA dose correlated negatively with treatment effect (β = -0.4 [-0.7, -0.1], P = 0.01). We found no associations between EPA (β = 0.1 [-0.2, 0.4], P = 0.44) or DHA (β = -0.1 [-0.3, 0.2], P = 0.59) dose and treatment effects for lipid volume (Figure 1). Conclusions: Among cohorts receiving statin+PUFA therapy, we found a dose-dependent benefit of administered EPA on coronary plaque volume; the opposite was true for DHA. This adds to a growing body of evidence suggesting DHA may blunt beneficial effects of EPA in atherosclerosis.

Association of serum MMP9 with adverse features of plaque progression in patients with chronic coronary syndrome (CCS)

Abstract Background Previous studies have demonstrated that MMP-9 may be a predictor of atherosclerotic plaque instability and future adverse cardiovascular events, but longitudinal data on the association between MMP9 and coronary disease progression are lacking. Purpose This study is aimed at investigating whether MMP9 is associated with atherosclerotic plaque progression. Methods MMP9 serum levels were measured in stable patients with chronic coronary syndrome (CCS) undergoing coronary computed tomography angiography at baseline and after a period of 6.5±1.1 years of follow up to assess progression of Total, Fibrous, Fibro-fatty, Necrotic Core, and Dense Calcium plaque volume (PV). The relationship of serum MMP9 with plaque progression was assessed using linear regression analysis, adjusting for clinical variables including, age, sex, risk factors, medical therapy, LDL-C, TG/HDL-C ratio, hs-CRP, and the presence of obstructive CAD (&amp;gt;50% coronary stenosis in at least one major coronary vessels). Results A total of 157 patients (58±8 years of age; 66% males) were included in the analysis, with median MMP9 values of 135±186 mg/dL (mean ± SD). Annual changes of Total, Fibrous-Fatty and Necrotic Core PV were significantly different across MMP9 tertiles (Figure 1). Multivariable linear regression analysis demonstrated a positive association between serum levels of MMP9 and annual change of Total and Necrotic Core PV (Figure 1). Conclusion Among patients with CCS, MMP9 serum levels were an independent predictor of progression of coronary plaque burden and, in particular, of adverse plaque features, such as Necrotic Core PV. This association was robust and independent from baseline traditional cardiovascular risk factors and medications, supporting for MMP9 a role as a novel marker of residual coronary risk. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Horizon 2020 - Project “Simulation Modeling of coronary ARTery disease: a tool for clinical decision support–SMARTool”

520 Predictors Of Coronary Atherosclerotic Plaque Progression Assessed By Serial Coronary Ct Angiography In Patients With Diabetes: From Proceed Study

Introduction: Natural history of coronary plaque progression in patients with diabetes mellitus (DM) remains unclear. We sought to explore the predictors of plaque progression according to plaque subtypes, as measured by serial coronary computed tomographic angiography (CCTA), in patients with DM.

Ten years follow-up under atorvastatin therapy of patients with carotid artery stenosis: the prognostic impact of oxidised low-density lipoprotein on carotid plaque progression and restenosis.

Background: Atorvastatin reduces oxidized low-density lipoprotein (oxLDL) levels and reduces the rate of plaque progression in patients with and without prior carotid angioplasty. The aim of our study was to investigate the durability of this effect and to explore possible prognostic impact of oxLDL levels on carotid stenosis and plaque stability. Methods: 106 patients (71 males, mean age 64.82±7.26 years) were studied. They were divided into two groups. Group 1 including patients with carotid stenosis &gt;70% (n=50) who underwent carotid angioplasty prior to enrolment. Group 2 included those with &lt;70% stenosis who were treated medically and were given atorvastatin with dose adjusted to maintain LDL cholesterol &lt;100mg/dl. Anthropometrics, complete lipid profile, oxLDL and ultrasonography were performed at baseline, 1, 3, 6, 12 months and yearly thereafter for 10 years. Results: oxLDL levels significantly decreased from 53.3±10.91 mg/dl at baseline to 8.31±2.08 mg/dl at 12 months (p&lt;0.001) and remained stable until the 10th year. In group 1, restenosis (&gt;70%) was noticed in four patients, yet no further intervention was needed due to plaque morphology (echo-grade IV). In group 2, carotid stenosis was initially reduced (6th month – 4th year) and later relapsed (5th – 10th year), yet plaque morphology was recorded as type III or IV in almost all patients of group 2 (53=95%), indicating a significantly lower risk for stroke. Conclusion: Atorvastatin treatment to a target of LDL &lt;100 mg/dl in patients with carotid stenosis is associated with marked and durable reduction of lipid levels, especially oxLDL and LDL and reduction in the rate of stenosis progression, improved plaque stability and decreased stroke risk.

Soluble lectin-like oxidized low-density lipoprotein receptor-1 predicts premature death in acute coronary syndromes.

The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and its shedding product [soluble LOX-1 (sLOX-1)] are implicated in atherosclerotic cardiovascular disease (ASCVD) pathogenesis. Herein, we examined the relationship of sLOX-1 with both fatal events and plaque progression in patients with acute coronary syndromes (ACS). Plasma sLOX-1 was assessed at baseline in ACS and chronic coronary syndrome (CCS) patients prospectively recruited in the multicentre SPUM-ACS study, with sex- and age-matched healthy subjects serving as additional controls (n = 2924). Compared with both CCS and controls, ACS patients showed markedly elevated sLOX-1 levels (median, 2.00 and 2.00 vs. 35.08 pg/mL; P < 0.0001) which were independently associated with increased mortality risk over 30-day [tertile (T)3: adjusted hazard ratio (HR), 3.11; 95% confidence interval (CI), 1.44-10.61; P = 0.0055] and 1-year intervals (T3: adjusted HR, 2.04; 95% CI, 1.19-3.92; P = 0.0098). Results remained consistent after adjustment for GRACE 2.0 (T3: adjusted HR, 1.86; 95% CI, 1.04-3.74; P = 0.0391) and were primarily driven by the pronounced relationship of sLOX-1 with cardiovascular mortality at 30 days (T3: adjusted HR, 3.81; 95% CI, 1.62-19.62; P = 0.0036) and at 1 year (T3: adjusted HR, 2.29; 95% CI, 1.19-5.34; P = 0.0148). In ACS patients undergoing serial intracoronary imaging and statin therapy, sLOX-1 dropped significantly in those with coronary plaque regression at 1 year (ΔsLOX-1: -4.64 ± 1.80; P = 0.0057), and showed a good discrimination for predicting plaque progression (area under the curve = 0.74; 95% CI, 0.59-0.86; P = 0.0031). Plasma sLOX-1 levels are increased during ACS and predict fatal events beyond traditional and emerging risk factors. Persistently high sLOX-1 associates with coronary plaque progression in patients with established ASCVD. NCT01000701.

Serum cholesterol efflux capacity is associated with coronary plaque progression in patients with coronary heart disease

Abstract Background Coronary plaque progression is a major risk factor of adverse cardiac events in patients with coronary heart disease (CHD). Emerging evidence showed that attenuated high-density lipoprotein (HDL) function measured by cholesterol efflux capacity (CEC) was associated with development of atherosclerosis independent of HDL cholesterol level. In this study, we sought to investigate whether CEC is a predictor for coronary plaque progression in CHD patients. Methods We consecutively enrolled CHD patients from January 2017 to August 2019 in our Hospital who underwent elective percutaneous coronary intervention and had at least one non-target coronary lesion. Follow-up coronary angiography were performed at around 12 months. Fluorescence-labeled cholesterol and J774 macrophages were used to measure the CEC of ApoB-depleted serum sample from all patients. Quantitative coronary angiography (QCA) was performed both at baseline and follow-up to analyze the plaque progression. Results A total of 430 CHD patients with 586 non-target coronary lesions were included in the final analysis. During a mean follow-up time of 381.04±59.52 days, patients with decreased CEC presented more severe plaque progression (net luminal loss in highest to lowest CEC quartile: 0.22±0.42mm vs 0.20±0.41mm vs 0.13±0.36mm vs 0.11±0.34mm, p=0.035). In multivariate analysis, baseline CEC was independently associated with coronary plaque progression after adjustment for traditional risk factors including HDL cholesterol and ApoA-I, no matter treated as categorical variable (OR: 0.382 [95% CI 0.180–0.781] for highest to lowest quartile) or continuous variable (OR: 0.522 [95% CI 0.373–0.714] for per SD increase]. Furthermore, CEC demonstrated a better power in predicting coronary plaque progression compared with HDL cholesterol concentration (AUC=0.644 vs 0.514). Conclusions This study suggests that HDL function reflected by serum CEC is an independent predictor for coronary plaque progression in CHD patients. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Natural Science Foundation of China, Shanghai Municipal Commission of Health and Family Planning

Effect of diabetes mellitus on coronary plaque characteristics and progression by serial Coronary Computed Tomography Angiography (CCTA)

Abstract Background Diabetes Mellitus (DM) is a major risk factor for coronary artery disease (CAD) and associated poor outcomes. There is a higher incidence of major adverse cardiac events in patients with DM than those without DM. Coronary plaque characteristics measured by CCTA are correlated with adverse cardiovascular (CV) outcomes. Purpose We sought to evaluate coronary plaque characteristics as well as rates of progression of coronary plaque burden as measured by serial CCTA in patients with DM and those without DM. Methods The study population included a total of 403 participants (mean age 61.4±11.4 years, 53% men; median scan interval 1.5 years) who were prospectively enrolled in serial CCTA trials. We identified 212 participants with DM and 191 participants without DM, who had undergone serial CCTA. Coronary Plaque volumes were measured and characterized as low attenuation plaque (LAP), total non-calcified plaque (TNCP) and total plaque (TP) using semi-automated plaque analysis software (Qangio medis). Multivariate linear regression was used to examine the effect of DM on coronary plaque progression. Results Patients with DM had greater rates of progression of normalized TP volume (median change in annualized plaque (IQR): 39.1 (9.9–114.4) in DM vs 23.5 (4.1–63.8) mm3 in non-DM, p=0.001), TNCP volume (21.6 (3.3–60.8) in DM vs 8.7 (0.1–35.6) mm3 in non-DM, p=0.003) and LAP volumes (0.7 (−0.6 to 7.8) in DM vs 0.1 (−0.4 to 1.9) mm3 in non-DM, p=0.04). After adjusting for relevant risk factors and baseline plaque, the annualized rates of progression were higher in patients with DM by 28% for TP (p=0.004), 27% for TNCP (p=0.011), 23% for fibrous plaque (p=0.026) and by 42% LAP (p=0.050), compared to those without DM. Conclusion Patients with DM have significantly higher rates of coronary plaque progression, including vulnerable LAP, than those without DM. Our findings reveal differences in rates, burden and characteristics of coronary plaque progression in patients with DM vs those without DM. These results provide mechanistic understanding of natural history of coronary atherosclerosis in this vulnerable population, that could explain the increased risk of CV events among patients with DM. Coronary atherosclerotic phenotyping by CCTA could serve as a potential surrogate measure for risk stratification and evaluation in clinical trials to examine therapeutic strategies in this vulnerable population. Funding Acknowledgement Type of funding sources: None.

High baseline fetuin-A levels are associated with lower atherosclerotic plaque progression as measured by 3D ultrasound

Background and aimsThe glycoprotein fetuin-A has anti-inflammatory effects, increases insulin resistance and plays an important role in calcium metabolism. The aim of our study was to assess the predictive value of fetuin-A on atherosclerotic plaque progression in comparison to the established cardiovascular biomarker high sensitivity C-reactive protein (hsCRP). MethodsIn this prospective, single center-, cohort study, we included 194 patients with at least one cardiovascular risk factor or established cardiovascular disease (CVD). Over a period of 4 years, each patient underwent 3D plaque volumetry of the carotid and femoral arteries on a yearly basis. To evaluate the predictive value of biomarkers in terms of plaque progression, the baseline values of fetuin-A and hsCRP were correlated with the plaque progression from baseline to the last follow up visit. Results171 patients were included in the final analysis. Baseline fetuin-A levels showed a significant negative correlation with plaque progression (r = −0.244; p = 0.001). In contrast, baseline hsCRP levels showed no correlation with plaque progression (r = 0.096, p = 0.20). In the ROC-analysis, fetuin-A had a significantly better predictive value than hsCRP (fetuin-A AUC 0.67; p = 0.001 vs hsCRP AUC 0.49; p = 0.88) with an optimal cut-off value at 712 μg/ml. In patients with high fetuin A levels (>712 μg/ml), a significantly lower plaque progression was observed compared to the group with low fetuin-A levels <712 μg/ml (high fetuin-A 197 mm3 vs. low fetuin-A 279 mm3; p = 0.01) ConclusionsHigher fetuin-A levels appear to predict lower atherosclerotic plaque progression in patients with or at risk of cardiovascular disease.

Predictors of atherosclerotic plaque progression in patients with non-obstructive coronary artery disease

Background and Aims: Progressive coronary artery disease (CAD) is defined as atherosclerotic obstructive lesion in a previously disease-free segment, or new obstruction in a previously nonobstructive coronary artery disease (NOCAD). The aim of this study is to describe the predictive factors of atherosclerotic lesions progression related to specific period of time in a patient with NOCAD previously.

Serial coronary CT angiography-derived fractional flow reserve and plaque progression can predict long-term outcomes of coronary artery disease.

To investigate the utility of coronary CT angiography-derived fractional flow reserve (FFRCT) and plaque progression in patients undergoing serial coronary CT angiography for predicting major adverse cardiovascular events (MACE). This retrospective study evaluated patients suspected or known coronary artery disease who underwent serial coronary CT angiography examinations between January 2006 and December 2017 and followed up until June 2019. The primary endpoint was MACE, defined as acute coronary syndrome, rehospitalization due to progressive angina, percutaneous coronary intervention, or cardiac death. FFRCT and plaque parameters were analyzed on a per-vessel and per-patient basis. Univariable and multivariable COX regression analysis determined predictors of MACE. The prognostic value of FFRCT and plaque progression were assessed in nested models. Two hundred eighty-four patients (median age, 61 years (interquartile range, 54-70); 202 males) were evaluated. MACE was observed in 45 patients (15.8%, 45/284). By Cox multivariable regression modeling, vessel-specific FFRCT ≤ 0.80 was associated with a 2.4-fold increased risk of MACE (HR (95% CI): 2.4 (1.3-4.4); p = 0.005) and plaque progression was associated with a 9-fold increased risk of MACE (HR (95% CI): 9 (3.5-23); p < 0.001) after adjusting for clinical and imaging risk factors. FFRCT and plaque progression improved the prediction of events over coronary artery calcium (CAC) score and high-risk plaques (HRP) in the receiver operating characteristics analysis (area under the curve: 0.70 to 0.86; p = 0.002). Fractional flow reserve and plaque progression assessed by serial coronary CT angiography predicted the risk of future MACE. • Vessel-specific CT angiography-derived fractional flow reserve (FFRCT) ≤ 0.80 and plaque progression improved the prediction of events over current risk factors. • Major adverse cardiovascular events (MACE) significantly increased with the presence of plaque progression at follow-up stratified by the FFRCT change group.

Application of machine learning in understanding atherosclerosis: Emerging insights.

Biological processes are incredibly complex—integrating molecular signaling networks involved in multicellular communication and function, thus maintaining homeostasis. Dysfunction of these processes can result in the disruption of homeostasis, leading to the development of several disease processes including atherosclerosis. We have significantly advanced our understanding of bioprocesses in atherosclerosis, and in doing so, we are beginning to appreciate the complexities, intricacies, and heterogeneity atherosclerosi. We are also now better equipped to acquire, store, and process the vast amount of biological data needed to shed light on the biological circuitry involved. Such data can be analyzed within machine learning frameworks to better tease out such complex relationships. Indeed, there has been an increasing number of studies applying machine learning methods for patient risk stratification based on comorbidities, multi-modality image processing, and biomarker discovery pertaining to atherosclerotic plaque formation. Here, we focus on current applications of machine learning to provide insight into atherosclerotic plaque formation and better understand atherosclerotic plaque progression in patients with cardiovascular disease.

Clinical Predictors of Coronary Artery Plaque Progression by Quantitative Serial Assessment Using 320-Row Computed Tomography Coronary Angiography in Asymptomatic Patients with Type 2 Diabetes Mellitus

BackgroundNatural history of coronary plaque progression (PP) in patients with diabetes mellitus (DM) remains unclear. This study aimed to investigate the clinical predictors of coronary PP in patients with DM. MethodsIn this prospective observational study, we analyzed 70 asymptomatic patients (age, 64.4 years; male, 67%) with type 2 DM without prior history of coronary artery disease who underwent serial 320-row computed tomography coronary angiography with an interscan interval of more than 24 months (median 37.7 months). Study endpoint was PP, which was defined if coronary plaque volumes (PVs) at follow-up minus PVs at baseline was >0. We evaluated plaque composition using the Hounsfield Unit thresholds and insulin resistance estimated by the homeostasis model assessment of insulin resistance (HOMA-IR). ResultsThirty-nine patients who showed PP had a higher increase in hemoglobin A1c (⊿HbA1c) from baseline to follow-up than those without PP (0.3% ± 0.8% vs −0.4% ± 1.1%; p = 0.01), although there was no statistical difference in HbA1c at baseline (7.1 ± 0.5% vs. 7.3 ± 1.4%; p = 0.24). In multivariable analysis, ⊿HbA1c [odds ratio (OR): 3.05; 95% confidence interval (CI): 1.39–6.67; p = 0.001] was an independent predictor for PP.Increase in low-density lipoprotein cholesterol (⊿LDL-C), not ⊿HbA1c, was significantly correlated to percent change in necrotic core (NC) volume (β-coefficients: 0.04; 95% CI: 0.004 - 0.08; p = 0.03). Among 48 patients without insulin therapy, patients with PP (n = 28) had a higher increase in HOMA-IR than those without PP (n = 20) (0.95 ± 2.00 vs. −0.63 ± 1.31; p = 0.003). ConclusionsIncrease in HbA1c and HOMA-IR was associated with PP in asymptomatic patients with type 2 DM, whereas increase in LDL-C was correlated to increase in NC.

Aged garlic extract reduces low attenuation plaque in coronary arteries of patients with diabetes: A randomized, double-blind, placebo-controlled study.

Several previous studies have demonstrated that aged garlic extract (AGE) inhibits the progression of coronary artery calcification and non-calcified plaque (NCP) in the general population. However, its effects on plaque progression in patients with diabetes have not yet been investigated, at least to the best of our knowledge. This study investigated whether AGE reduces the coronary plaque volume measured by cardiac computed tomography angiography (CCTA) in patients with diabetes mellitus (DM). A total of 80 participants with DM with a median age of 57 years were prospectively assigned to consume 2,400 mg AGE/day (after completion, 37 participants) or placebo (after completion, 29 participants) orally. Both groups underwent CCTA at baseline and follow-up 365 days apart. In total, 66 participants completed the study. Coronary plaque volume, including total plaque (TP), dense calcium (DC), fibrous, fibro-fatty and low-attenuation plaque (LAP) volumes were measured based upon pre-defined intensity cut-off values using semi-automated software (QAngio CT). Changes in various plaque types were normalized to the total coronary artery length. The non-parametric Wilcoxon rank-sum test was performed to examine the differences in plaque formation between the 2 groups. No significant differences were found in the baseline characteristics between the AGE and placebo groups. Compared with the placebo group, the AGE group exhibited a statistically significant regression in normalized LAP [median and standard deviation (SD) −0.2 (18.8) vs. 2.5 (69.3), P=0.0415]. No differences were observed in TP, fibrous, or fibrofatty plaque volumes between the AGE and placebo group. On the whole, this study indicated that the %LAP change in the AGE group was significantly greater than that in the placebo group in patients with diabetes. However, further studies are warranted to evaluate whether AGE has the ability to stabilize vulnerable plaque and decrease adverse cardiovascular events.