Coronary Atherosclerotic Plaque Activity and Risk of Myocardial Infarction.

BACKGROUND: Total coronary atherosclerotic plaque activity across the entire coronary arterial tree is associated with patient-level clinical outcomes. OBJECTIVES: We aimed to investigate whether vessel-level coronary atherosclerotic plaque activity is associated with vessel-level myocardial infarction. METHODS: In this secondary analysis of an international multicenter study of patients with recent myocardial infarction and multivessel coronary artery disease, we assessed vessel-level coronary atherosclerotic plaque activity using coronary 18F-sodium fluoride positron emission tomography to identify vessel-level myocardial infarction. RESULTS: Increased 18F-sodium fluoride uptake was found in 679 of 2,094 coronary arteries and 414 of 691 patients. Myocardial infarction occurred in 24 (4%) vessels with increased coronary atherosclerotic plaque activity and in 25 (2%) vessels without increased coronary atherosclerotic plaque activity (HR: 2.08; 95% CI: 1.16-3.72; P = 0.013). This association was not demonstrable in those treated with coronary revascularization (HR: 1.02; 95% CI: 0.47-2.25) but was notable in untreated vessels (HR: 3.86; 95% CI: 1.63-9.10; Pinteraction = 0.024). Increased coronary atherosclerotic plaque activity in multiple coronary arteries was associated with heightened patient-level risk of cardiac death or myocardial infarction (HR: 2.43; 95% CI: 1.37-4.30; P = 0.002) as well as first (HR: 2.19; 95% CI: 1.18-4.06; P = 0.013) and total (HR: 2.50; 95% CI: 1.42-4.39; P = 0.002) myocardial infarctions. CONCLUSIONS: In patients with recent myocardial infarction and multivessel coronary artery disease, coronary atherosclerotic plaque activity prognosticates individual coronary arteries and patients at risk for myocardial infarction.

Can proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors regress coronary atherosclerotic plaque? A systematic review and meta-analysis.

OBJECTIVE: Whether inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the regression of coronary atherosclerotic plaque in statin-treated individuals remains unclear. This study examined whether PCSK9 inhibitors combined with statin therapy could increase atherosclerotic plaque regression compared with statin therapy alone. METHODS: PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), the database Clinical trials, and the Web of Science were searched to report the coronary atherosclerotic plaque of PCSK9 inhibitors using intravascular ultrasonography (IVUS) or optical coherence tomography (OCT) in statin patients. The weighted mean difference (WMD) of the random-effects/fixed-effects model was used to pool data that satisfied our inclusion criteria obtained from the included studies. RESULTS: When compared with statin therapy alone, pooled studies revealed that PCSK9 inhibitors combined with statin therapy significantly decreased percent atheroma volume (PAV) (WMD: -1.06%, 95% confidence interval [CI]: -1.39 to -0.73; P<0.001) and total atheroma volume (TAV) (WMD: -6.38 mm3, 95% CI: -10.12 to -2.64; P=0.001). Moreover, the fibrous cap thickness (FCT) of the coronary atherosclerotic plaque increases to 21.31 um (WMD: 21.31, 95% CI: 7.08 to 35.53, P<0.001), and the maximum lipid arc decreases 10.9° (WMD: -10.9, 95% CI: -15.24 to -5.34, P<0.001). CONCLUSION: In our systematic review and meta-analysis, PCSK9 inhibitors combined with statin therapy were found to be more effective than statin therapy alone for slowing coronary plaque progression by decreasing PAV, TAV, and increasing FCT, maximum lipid arc.

Application of Biomechanical Stress from Coronary Computed Tomography Angiography in Coronary Plaque Assessment and Prediction of Adverse Cardiovascular Events / 医用生物力学

Long-term exposure to risk factors will lead to coronary atherosclerosis, which will lead to the formation and progression of coronary plaque. Early identification of high-risk plaque characteristics will help prevent plaque rupture or erosion, thus avoiding the occurrence of acute cardiovascular events. Biomechanical stress plays an important role in progression and rupture of atherosclerotic plaques. In recent years, non-invasive coronary computed tomography angiography (CCTA) computational fluid dynamics (CFD) modeling has made it possible to acquire the corresponding biomechanical stress parameters. These coronary biomechanical stress parameters, especially wall shear stress (WSS), will aid in the development of a more accurate clinical model for predicting plaque progression and major adverse cardiovascular events ( MACE ). In this review, the biomechanical stress and the role of WSS from CCTA in atherosclerosis were introduced, and the researches on the relationship between biomechanical stress from CCTA and coronary artery diseases were discussed.

The Role of Inflammation in Cardiovascular Disease.

Atherosclerosis is a chronic inflammatory disease, in which the immune system has a prominent role in its development and progression. Inflammation-induced endothelial dysfunction results in an increased permeability to lipoproteins and their subendothelial accumulation, leukocyte recruitment, and platelets activation. Recruited monocytes differentiate into macrophages which develop pro- or anti-inflammatory properties according to their microenvironment. Atheroma progression or healing is determined by the balance between these functional phenotypes. Macrophages and smooth muscle cells secrete inflammatory cytokines including interleukins IL-1ß, IL-12, and IL-6. Within the arterial wall, low-density lipoprotein cholesterol undergoes an oxidation. Additionally, triglyceride-rich lipoproteins and remnant lipoproteins exert pro-inflammatory effects. Macrophages catabolize the oxidized lipoproteins and coalesce into a lipid-rich necrotic core, encapsulated by a collagen fibrous cap, leading to the formation of fibro-atheroma. In the conditions of chronic inflammation, macrophages exert a catabolic effect on the fibrous cap, resulting in a thin-cap fibro-atheroma which makes the plaque vulnerable. However, their morphology may change over time, shifting from high-risk lesions to more stable calcified plaques. In addition to conventional cardiovascular risk factors, an exposure to acute and chronic psychological stress may increase the risk of cardiovascular disease through inflammation mediated by an increased sympathetic output which results in the release of inflammatory cytokines. Inflammation is also the link between ageing and cardiovascular disease through increased clones of leukocytes in peripheral blood. Anti-inflammatory interventions specifically blocking the cytokine pathways reduce the risk of myocardial infarction and stroke, although they increase the risk of infections.

Coronary Atherosclerosis, Cardiac Troponin, and Interleukin-6 in Patients With Chest Pain: The PROMISE Trial Results.

BACKGROUND: Increased inflammation and myocardial injury can be observed in the absence of myocardial infarction or obstructive coronary artery disease (CAD). OBJECTIVES: The authors determined whether biomarkers of inflammation and myocardial injury-interleukin (IL)-6 and high-sensitivity cardiac troponin (hs-cTn)-were associated with the presence and extent of CAD and were independent predictors of major adverse cardiovascular events (MACEs) in stable chest pain. METHODS: Using participants from the PROMISE trial, the authors measured hs-cTn I and IL-6 concentrations and analyzed computed tomography angiography (CTA) images in the core laboratory for CAD characteristics: significant stenosis (≥70%), high-risk plaque (HRP), Coronary Artery Disease Reporting and Data System (CAD-RADS) categories, segment involvement score (SIS), and coronary artery calcium (CAC) score. The primary endpoint was a composite MACE (death, myocardial infarction, or unstable angina). RESULTS: The authors included 1,796 participants (age 60.2 ± 8.0 years; 47.5% men, median follow-up 25 months). In multivariable linear regression adjusted for atherosclerotic cardiovascular disease (ASCVD) risk, hs-cTn was associated with HRP, stenosis, CAD-RADS, and SIS. IL-6 was only associated with stenosis and CAD-RADS. hs-cTn above median (1.5 ng/L) was associated with MACEs in univariable analysis (HR: 2.1 [95% CI: 1.3-3.6]; P = 0.006), but not in multivariable analysis adjusted for ASCVD and CAD. IL-6 above median (1.8 ng/L) was associated with MACEs in multivariable analysis adjusted for ASCVD and HRP (HR: 1.9 [95% CI: 1.1-3.3]; P = 0.03), CAC (HR: 1.9 [95% CI: 1.0-3.4]; P = 0.04), and SIS (HR: 1.8 [95% CI: 1.0-3.2]; P = 0.04), but not for stenosis or CAD-RADS. In participants with nonobstructive CAD (stenosis 1%-69%), the presence of both hs-cTn and IL-6 above median was strongly associated with MACEs (HR: 2.5-2.7 after adjustment for CAD characteristics). CONCLUSIONS: Concentrations of hs-cTn and IL-6 were associated with CAD characteristics and MACEs, indicating that myocardial injury and inflammation may each contribute to pathways in CAD pathophysiology. This association was most pronounced among participants with nonobstructive CAD representing an opportunity to tailor treatment in this at-risk group. (PROspective Multicenter Imaging Study for Evaluation of Chest Pain [PROMISE]; NCT01174550).

Coronary CT Value in Quantitative Assessment of Intermediate Stenosis.

Background and Objectives: Cardiac computed tomography angiography (CCTA) is an excellent non-invasive imaging tool to evaluate coronary arteries and exclude coronary artery disease (CAD). Managing intermediate coronary artery stenosis with negative or inconclusive functional tests is still a challenge. A regular stenosis evaluation together with high-risk plaque features, using semi-automated programs, are becoming promising tools. This case-control study was designed to evaluate the intermediate lesion features' impact on CAD outcomes, using a semi-automated CCTA atherosclerotic plaque analysis program. Materials and Methods: We performed a single-center, prospective cohort study. A total of 133 patients with low to intermediate risk of CAD, older than 18 years with no previous history of CAD and good quality CCTA images were included in the study, and 194 intermediate stenosis (CAD-RADS 3) were analyzed. For more detailed morphological analysis, we used semi-automated CCTA-dedicated software. Enrolled patients were prospectively followed-up for 2 years. Results: Agatston score was significantly higher in the major adverse cardiovascular events (MACE) group (p = 0.025). Obstruction site analysis showed a significantly lower coronary artery remodeling index (RI) among patients with MACE (p = 0.037); nonetheless RI was negative in both groups. Plaque consistency analysis showed significantly bigger necrotic core area in the MACE group (p = 0.049). In addition, unadjusted multivariate analysis confirmed Agatston score and RI as significant MACE predictors. Conclusions: The Agatston score showes the total area of calcium deposits and higher values are linked to MACE. Higher plaque content of necrotic component is also associated with MACE. Additionally, negatively remodeled plaques are linked to MACE and could be a sign of advanced CAD. The Agatston score and RI are significant in risk stratification for the development of MACE.

Effects of different statins application methods on plaques in patients with coronary atherosclerosis.

BACKGROUND: Discontinued application of statins may be related to adverse cardiovascular events. However, it is unclear whether different statins administration methods have effects on coronary artery plaques. AIM: To evaluate the effects of different statins application methods on plaques in patients with coronary atherosclerosis. METHODS: A total of 100 patients diagnosed with atherosclerotic plaque by coronary artery computed tomography were continuously selected and divided into three groups according to different statins administration methods (discontinued application group, n = 32; intermittent application group, n = 39; sustained application group, n = 29). The effects of the different statins application methods on coronary atherosclerotic plaque were assessed. RESULTS: The volume change and rate of change of the most severe plaques were significantly reduced in the sustained application group (P ≤ 0.001). The volume change of the most severe plaques correlated positively with low-density lipoprotein (LDL-C) levels only in the sustained application group (R = 0.362, P = 0.013). There were no changes in plaques or LDL-C levels in the intermittent and discontinued application groups. CONCLUSION: Continuous application of statins is effective for controlling plaque progression, whereas discontinued or intermittent administration of statins is not conducive to controlling plaques. Only with continuous statins administration can a reduction in LDL-C levels result in plaque volume shrinkage.

Long-Term Prognostic Value of Coronary Atherosclerotic Plaque Characteristics Assessed by Computerized Tomographic Angiography.

We aimed to present the long-term prognostic role of coronary computed tomography angiography (CTA) in a cohort of patients with coronary artery disease (CAD) and noncritical stenosis. A total of 1138 patients who underwent coronary CTA for suspected CAD were included in the study. For the categorization of the coronary atherosclerotic plaque (CAP), the coronary system was divided into 16 segments. For each segment, CAPs were categorized as calcified, noncalcified, and mixed. All-cause and cardiovascular (CV) mortality data were collected for prognostic evaluation. Coronary CTA analyses showed that 34.5% of patients had noncalcified CAP, 14.5% of patients had calcified CAP, and 11% of patients had mixed CAP. During a median of 141.5 months follow-up, CV and all-cause mortality was observed in 57 (5%) and 149 (13.1%) patients, respectively. In multivariable Cox regression analysis, calcified CAP morphology and the extent of involved segments were significant predictors of both CV and all-cause mortality. The presence of calcified CAP morphology and the higher number of diseased coronary segments via coronary CTA might help stratify patients at risk for adverse CV outcomes during long-term follow-up. Patients with these features at index coronary CTA may be evaluated more closely with aggressive preventive measures.

The effect of combined ezetimibe and statin therapy versus statin therapy alone on coronary plaque volume assessed by intravascular ultrasound: A systematic review and meta-analysis.

BACKGROUND: Current guidelines recommend an intensive lipid-lowering therapy to achieve the low-density lipoprotein cholesterol (LDL-C) target in patients with high risk of cardiovascular disease. Former studies suggested adding ezetimibe to statin therapy in the above setting may promote plaque changes; however, this effect has not been consistently reported. METHODS: Electronic searches were performed in MEDLINE, EMBASE, and Cochrane library on November 30, 2017 to identify prospective trials assessing the effects of combined ezetimibe and statin therapy versus statin therapy alone on atheroma volume using intravascular ultrasound. The effect size between treatment groups within individual studies was assessed by weighted mean difference (MD) using a random-effects model. RESULTS: Eight studies were obtained for systematic review and 6 of them compromising total of 583 subjects that meet the criteria were meta-analyzed. There was a significant reduction from baseline to follow-up in total atheroma volume with an MD of -3.71 mm3 (95% confidence interval: -5.98 to -1.44, P < .001), whereas analysis for percent atheroma volume demonstrated weighted MD of - 0.77% (-1.68 to 0.14, P = .10). A substantial decrease in LDL-C was observed with MD -16.75 mg/dL (-20.89 to -12.60, P < .00001). CONCLUSION: The addition of ezetimibe to statin therapy is effective in reducing total atheroma volume assessed by intravascular ultrasound and also resulted in effective reduction of plasma LDL-C levels.

Low bone mineral density is associated with global coronary atherosclerotic plaque burden in stable angina patients.

BACKGROUND: Accelerated atherosclerosis is considered to be the linking factor between low bone mineral density (BMD) and increased cardiovascular events and mortality, while some coronary angiographic studies do not support this point. In this study, we attempt to provide a distinct comprehensive view of the relationship between BMD and the angiographically determined coronary atherosclerotic burden. METHODS: A total of 459 consecutive patients with stable chest pain suspected of coronary artery disease (CAD) underwent both dual-energy X-ray absorptiometry scan and selective coronary angiography. The association between BMD and global coronary atherosclerotic plaque burden as represented by the multivessel involvement and the modified Gensini score was analyzed. RESULTS: Multivariable analysis revealed that the low BMD at femoral neck and total hip was an independent correlate of multivessel CAD. The T-scores measured at femoral neck and total hip were both negatively and independently associated to the modified Gensini score. These inversely correlated relationships between BMD and CAD were not observed at lumbar spine 1-4. CONCLUSION: This cross-sectional study elucidated an inverse relationship between hip BMD and the modified Gensini score, and low hip BMD values (T-scores) were significantly and independently associated with increased risk of multivessel coronary disease in patients hospitalized for stable chest pain.

Impact of smoking on young acute coronary syndrome patients evaluated by optical coherence tomography / 中国介入心脏病学杂志

Objective To explore the impact of smoking on coronary plaque characteristics on optical coherence tomography(OCT) in young patients with acute coronary disease(ACS).Methods We assessed the atherosclerotic plaque characteristics and vulnerability by OCT and coronary angiography in 60 ACS patients aged 45 years or younger in Beijing Anzhen Hospital, from June 2014 to June 2017. The patients were divided into the smoking group(n=33) and the non-smoking group(n=27) to compare the plaque characteristics and vulnerability.Results Smoking patients showed a less extent of fibrosis(48.55％vs. 77.8％,P=0.032)and microchannels(18.2％vs. 44.4％,P=0.033), and a greater extent of plaque rupture (24.2％vs. 3.7％,P=0.033) compared with non-smoking patients. In multivariate analysis, smoking was the only independent predictors of plaque rupture(OR 8.320, 95％CI 0.969-71.435,P=0.027) and less fibrosis (OR 0.269, 95％CI 0.086-0.837,P=0.020). Conclusions Patients who are smokers have less extensive fibrosis and a greater extent of plaque rupture, showing more extensive vulnerable plaque phenotype. Therefore, smoking is one of the major risk factors of advanced cardiovascular events in young patients.

Association between serum N-terminal pro-B-type natriuretic peptide levels and characteristics of coronary atherosclerotic plaque detected by coronary computed tomography angiography.

The aim of the present study was to explore the association between the levels of serum N-terminal pro-B-type natriuretic peptide (NT-pro BNP) and the characteristics of coronary atherosclerotic plaque detected by coronary computed tomography angiography (CCTA), in patients with unstable angina (UA). A total of 202 patients (age range, 47-82 years) were divided into the following three groups: Non-cardiac disease group (57 patients); stable angina pectoris (SAP) group (62 patients); and UA group (83 patients). There were significant differences between the serum NT-pro BNP levels among the three groups (P=0.007). However, in multivariant diagnoses, NT-pro BNP level was not an independent risk factor for UA. The levels of serum NT-pro BNP were observed to be positively correlated with the number of vessels involved (r=0.462; P<0.001), SIS (r=0.475; P<0.001), segment-stenosis score (r=0.453; P<0.001), coronary calcification score (r=0.412; P=0.001), number of obstructive diseases (r=0.346; P<0.001), and the number of segments with non-calcified plaque (r=0.235; P=0.017), mixed plaque (r=0.234; P=0.017) and calcified plaque (r=0.431; P<0.001). The levels of serum NT-pro BNP were significantly higher in patients with UA and left main-left anterior descending (LM-LAD) disease, compared with UA patients without LM-LAD disease (P<0.001). In addition, serum NT-pro BNP was significantly higher in patients with obstructive disease and UA than in those without obstructive disease (P<0.001). The area under the curve of log(NT-pro BNP) was 0.656 (P=0.006; optimal cut-off value, 1.74; sensitivity, 77.6%; specificity, 51.9%). In conclusion, the levels of serum NT-pro BNP are associated with the burden and severity of coronary artery atherosclerotic disease in patients with UA, and may be helpful in risk stratification of patients with UA.

Transcoronary gradients of vascular miRNAs and coronary atherosclerotic plaque characteristics.

AIMS: Circulating microRNAs (miRs) may reflect pathophysiologically relevant processes in the atherosclerotically diseased coronary arterial wall. Given the unmet medical need to identify patients with an unstable plaque phenotype, we determined the relation of circulating atherosclerosis-regulatory miRs with plaque phenotypes. METHODS AND RESULTS: We assessed coronary atherosclerotic plaque burden and phenotype by optical coherence tomography in 52 patients and measured the levels of circulating miRs across the transcoronary gradient. The overall plaque load was significantly correlated with transcoronary concentration gradients of miR-126-3p (P = 0.04), miR-145-5p (P = 0.01), miR-155-5p (P < 0.01), and miR-29b-3p (P = 0.02), but not with other miRs such as miR-92a-3p. In patients with a high extent of vulnerable plaques as assessed by the presence of thin-cap fibroatheromas (TCFAs), significantly higher transcoronary gradients were observed, particularly for miR-126-3p, miR-126-5p, and miR-145-5p (all P < 0.02). Transcoronary gradients of miR-126-3p (P < 0.01), miR-126-5p (P < 0.01), miR-145-5p (P = 0.01), miR-29b-3p (P = 0.03), and miR-155-5p (P = 0.02) demonstrated a significant discriminatory power to predict the presence of TCFAs (AUC > 0.7 for all). Moreover, aortic and venous coronary sinus levels of miR-29b-3p were inversely correlated with plaque fibrosis, a finding that is consistent with the anti-fibrotic activity of miR-29b-3p. CONCLUSION: The overall plaque burden and plaque phenotypes are associated with changes in the kinetics of miR-concentrations across the transcoronary passage. Transcoronary gradients of the anti-atherosclerotic miR-126-3p and miR-145-5p correlated with the extent of TCFAs, suggesting that instable plaques may affect the local uptake or degradation of these miRs.

Computed tomography-based high-risk coronary plaque score to predict acute coronary syndrome among patients with acute chest pain--Results from the ROMICAT II trial.

BACKGROUND: Coronary computed tomography angiography (CTA) can be used to detect and quantitatively assess high-risk plaque features. OBJECTIVE: To validate the ROMICAT score, which was derived using semi-automated quantitative measurements of high-risk plaque features, for the prediction of ACS. MATERIAL AND METHODS: We performed quantitative plaque analysis in 260 patients who presented to the emergency department with suspected ACS in the ROMICAT II trial. The readers used a semi-automated software (QAngio, Medis medical imaging systems BV) to measure high-risk plaque features (volume of <60HU plaque, remodeling index, spotty calcium, plaque length) and diameter stenosis in all plaques. We calculated a ROMICAT score, which was derived from the ROMICAT I study and applied to the ROMICAT II trial. The primary outcome of the study was diagnosis of an ACS during the index hospitalization. RESULTS: Patient characteristics (age 57 ± 8 vs. 56 ± 8 years, cardiovascular risk factors) were not different between those with and without ACS (prevalence of ACS 7.8%). There were more men in the ACS group (84% vs. 59%, p = 0.005). When applying the ROMICAT score derived from the ROMICAT I trial to the patient population of the ROMICAT II trial, the ROMICAT score (OR 2.9, 95% CI 1.4-6.0, p = 0.003) was a predictor of ACS after adjusting for gender and ≥ 50% stenosis. The AUC of the model containing ROMICAT score, gender, and ≥ 50% stenosis was 0.91 (95% CI 0.86-0.96) and was better than with a model that included only gender and ≥ 50% stenosis (AUC 0.85, 95%CI 0.77-0.92; p = 0.002). CONCLUSIONS: The ROMICAT score derived from semi-automated quantitative measurements of high-risk plaque features was an independent predictor of ACS during the index hospitalization and was incremental to gender and presence of ≥ 50% stenosis.

Correlation of concentrations of high-sensitivity troponin T and high-sensitivity C-reactive protein with plaque progression as measured by CT coronary angiography.

BACKGROUND: Elevated levels of inflammatory biomarkers are associated with increased cardiovascular morbidity and mortality. OBJECTIVE: We sought to determine whether elevated concentrations of high-sensitivity troponin T (hs-TnT) and high-sensitivity C-reactive protein (hs-CRP) predict progression of coronary artery disease (CAD) as determined by coronary CT angiography (coronary CTA). METHODS: Patients presenting to the emergency department with acute chest pain who initially showed no evidence of an acute coronary syndrome underwent baseline and follow-up coronary CTA (median follow-up, 23.9 months) using identical acquisition and reconstruction parameters. Coronary CTA data of each major coronary artery were co-registered. Cross-sections were assessed for the presence of calcified and noncalcified plaques. Progression of atherosclerotic plaque and change of plaque composition from noncalcified to calcified plaque was evaluated and correlated to levels of hs-TnT and hs-CRP at the time of the baseline CT. RESULTS: Fifty-four patients (mean age, 54.1 years; 59% male) were included, and 6775 cross-sections were compared. CAD was detected in 12.2 ± 21.2 cross-sections per patient at baseline. Prevalence of calcified plaque increased by 1.5 ± 2.4 slices per patient (P < .0001) over the follow-up period. On average, 1.6 ± 3.6 slices with new noncalcified plaque were found per patient (P < .0001) and 0.7 ± 1.7 slices with pre-existing noncalcified plaque had progressed to calcified plaque (P < .0001). After multivariate adjustment, change of overall CAD burden was predicted by baseline hs-TnT and hs-CRP (r = 0.29; P = .039 and r = 0.40; P = .004). Change of plaque composition was associated with baseline hs-TnT (r = 0.29; P = .03). CONCLUSION: Concentrations of hs-TnT and hs-CRP are weakly associated with a significant increase in CAD burden and change in plaque composition over 24 months independent of baseline risk factors.

Impact of abdominal and epicardial fat on the association between plasma adipocytokine levels and coronary atherosclerosis in non-obese patients.

OBJECTIVE: Ectopic fat accumulation is associated with coronary artery disease. Visceral adipose tissue has paracrine and systemic effects and is a source of adipocytokines. It has been implicated in the pathogenesis of coronary atherosclerosis; however, nothing is known about whether increases in epicardial fat have the same effect on coronary atherosclerosis as increases in abdominal visceral fat. METHODS: We examined 216 consecutive patients suspected to have coronary artery disease. Individuals with acute coronary syndrome and inadequate computed tomography (CT) imaging were excluded. We enrolled 164 patients (65 ± 10 years old; 70% men; body mass index [BMI], 23.8 ± 3.6 kg/m(2)). The plasma concentrations of adiponectin, interleukin-6 (IL-6), plasminogen activator inhibitor-1, and vascular endothelial growth factor were measured. The characteristics of coronary plaque, abdominal visceral fat area, and epicardial fat volume (EFV) were determined by 64-slice CT imaging. RESULTS: EFV was greater in subjects with noncalcified plaque than in those with no plaque or with calcified plaque (126 ± 39 mL vs. 98 ± 34 mL and 97 ± 45 mL, respectively; P = 0.010). EFV was significantly correlated with BMI, triglycerides, and the triglyceride/high-density lipoprotein cholesterol ratio (r = 0.51, 0.19, and 0.20, respectively) but not with plasma levels of adipocytokines. The plasma adiponectin and IL-6 concentration was significantly correlated with abdominal visceral fat area in coronary plaque patients (r = -0.49 and 0.20). CONCLUSIONS: In non-obese Japanese patients, epicardial fat may have unique mechanisms affecting the development of coronary atherosclerosis, which is different from abdominal visceral fat.

Lipoprotein-associated phospholipase A2 is related to plaque stability and is a potential biomarker for acute coronary syndrome.

PURPOSE: Plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) binds to low-density lipoprotein. The levels of Lp-PLA2 reflect the plaque burden, and are upregulated in acute coronary syndrome (ACS). We investigated the diagnostic value of Lp-PLA2 levels and found that it might be a potential biomarker for ACS. MATERIALS AND METHODS: We classified 226 study participants into three groups: patients without significant stenosis (control group), patients with significant stenosis with stable angina (SA group), and patients with ACS (ACS group). RESULTS: Lp-PLA2 and high-sensitivity C-reactive protein (hs-CRP) levels were significantly greater in the ACS group than in the SA group (p=0.044 and p=0.029, respectively). Multivariate logistic regression analysis revealed that Lp-PLA2 levels are significantly associated with ACS (odds ratio=1.047, p=0.013). The addition of Lp-PLA2 to the ACS model significantly increased the global χ² value over traditional risk factors (28.14 to 35.602, p=0.006). The area under the receiver operating characteristic curve for Lp-PLA2 was 0.624 (p=0.004). The addition of Lp-PLA2 level to serum hs-CRP concentration yielded an integrated discrimination improvement of 0.0368 (p=0.0093, standard error: 0.0142) and improved the ability to diagnose ACS. CONCLUSION: Lp-PLA2 levels are related to plaque stability and might be a diagnostic biomarker for ACS.

High-risk plaque detected on coronary CT angiography predicts acute coronary syndromes independent of significant stenosis in acute chest pain: results from the ROMICAT-II trial.

BACKGROUND: It is not known whether high-risk plaque, as detected by coronary computed tomography angiography (CTA), permits improved early diagnosis of acute coronary syndromes (ACS) independently to the presence of significant coronary artery disease (CAD) in patients with acute chest pain. OBJECTIVES: The primary aim of this study was to determine whether high-risk plaque features, as detected by CTA in the emergency department (ED), may improve diagnostic certainty of ACS independently and incrementally to the presence of significant CAD and clinical risk assessment in patients with acute chest pain but without objective evidence of myocardial ischemia or myocardial infarction (MI). METHODS: We included patients randomized to the coronary CTA arm of the ROMICAT-II (Rule Out Myocardial Infarction/Ischemia Using Computer-Assisted Tomography II) trial. Readers assessed coronary CTA qualitatively for the presence of nonobstructive CAD (1% to 49% stenosis), significant CAD (≥50% or ≥70% stenosis), and the presence of at least 1 of the high-risk plaque features (positive remodeling, low <30 Hounsfield units plaque, napkin-ring sign, spotty calcium). In logistic regression analysis, we determined the association of high-risk plaque with ACS (MI or unstable angina pectoris) during the index hospitalization and whether this was independent of significant CAD and clinical risk assessment. RESULTS: Overall, 37 of 472 patients who underwent coronary CTA with diagnostic image quality (mean age 53.9 ± 8.0 years; 52.8% men) had ACS (7.8%; MI n = 5; unstable angina pectoris n = 32). CAD was present in 262 patients (55.5%; nonobstructive CAD in 217 patients [46.0%] and significant CAD with ≥50% stenosis in 45 patients [9.5%]). High-risk plaques were more frequent in patients with ACS and remained a significant predictor of ACS (odds ratio [OR]: 8.9; 95% CI: 1.8 to 43.3; p = 0.006) after adjustment for ≥50% stenosis (OR: 38.6; 95% CI: 14.2 to 104.7; p < 0.001) and clinical risk assessment (age, sex, number of cardiovascular risk factors). Similar results were observed after adjustment for ≥70% stenosis. CONCLUSIONS: In patients presenting to the ED with acute chest pain but negative initial electrocardiogram and troponin, presence of high-risk plaques on coronary CTA increased the likelihood of ACS independent of significant CAD and clinical risk assessment (age, sex, and number of cardiovascular risk factors). (Multicenter Study to Rule Out Myocardial Infarction by Cardiac Computed Tomography [ROMICAT-II]; NCT01084239).