Majority Of Acute Coronary Events Research Articles

Acute coronary event (ACE) prediction following breast radiotherapy by features extracted from 3D CT, dose, and cardiac structures.

Heart toxicity, such as major acute coronary events (ACE), following breast radiation therapy (RT) is of utmost concern. Thus, many studies have been investigating the effect of mean heart dose (MHD) and dose received in heart sub-structures on toxicity. Most studies focused on the dose thresholds in the heart and its sub-structures, while few studies adopted such computational methods as deep neural networks (DNN) and radiomics. This work aims to construct a feature-driven predictive model for ACE after breast RT. A recently proposed two-step predictive model that extracts a number of features from a deep auto-segmentation network and processes the selected features for prediction was adopted. This work refined the auto-segmenting network and feature processing algorithms to enhance performance in cardiac toxicity prediction. In the predictive model, the deep convolutional neural network (CNN) extracted features from 3D computed tomography (CT) images and dose distributions in three automatically segmented heart sub-structures, including the left anterior descending artery (LAD), right coronary artery (RCA), and left ventricle (LV). The optimal feature processing workflow for the extracted features was explored to enhance the prediction accuracy. The regions associated with toxicity were visualized using a class activation map (CAM)-based technique. Our proposed model was validated against a conventional DNN (convolutional and fully connected layers) and radiomics with a patient cohort of 84 cases, including 29 and 55 patient cases with and without ACE. Of the entire 84 cases, 12 randomly chosen cases (5 toxicity and 7 non-toxicity cases) were set aside for independent test, and the remaining 72 cases were applied to 4-fold stratified cross-validation. Our predictive model outperformed the conventional DNN by 38% and 10% and radiomics-based predictive models by 9% and 10% in AUC for 4-fold cross-validations and independent test, respectively. The degree of enhancement was greater when incorporating dose information and heart sub-structures into feature extraction. The model whose inputs were CT, dose, and three sub-structures (LV, LAD, and RCA) reached 96% prediction accuracy on average and 0.94 area under the curve (AUC) on average in the cross-validation, and also achieved prediction accuracy of 83% and AUC of 0.83 in the independent test. On 10 correctly predicted cases out of 12 for the independent test, the activation maps implied that for cases of ACE toxicity, the higher intensity was more likely to be observed inside the LV. The proposed model characterized by modifications in model input with dose distributions and cardiac sub-structures, and serial processing of feature extraction and feature selection techniques can improve the predictive performance in ACE following breast RT.

Cardioprotective Effect of Low Level of LDL Cholesterol on Perioperative Myocardial Injury in Off-Pump Coronary Artery Bypass Grafting.

Background and Objectives: Coronary artery disease is still a major cause of death in developed countries. Low-density lipoprotein cholesterol (LDL-C) lowering with statin therapy is a key strategy in major acute coronary events’ prevention. The aim of the study was to establish if there is a cardioprotective effect of pre-operative LDL lowering therapy on perioperative myocaridal injury in patients undergoing off-pump coronary artery bypass grafting (CABG). Moreover, the impact of pre-operative LDL level on long term outcome was analysed. Materials and Methods: The retrospective single center analysis included 662 consecutive patients (431 (65%) males and 231 (35%) female, mean age of 65 ± 8) referred for cardiac surgery due to stable chronic coronary syndrome between 2012–2018. The follow up was 9 years. Results: A statistically significant difference was found in postoperative serum Troponin-I for LDL thresholds of 1.8 mmol/L (p = 0.009), 2.6 mmol/L (p = 0.03) and 3.0 mmol/L (p = 0.001). The results indicate that cardioprotective role of LDL is achieved within LDL concentration rate below 1.8 mmol/L (<70 mg/dL). Five patients died perioperatively, whereas 1-year and 9-year overall mortality rates were 4% (n = 28) and 18.6% (n = 123), respectively. Comparing the survival group with diseased, Mann-Whitney U test showed a statistically significant difference in HDL-C (p = 0.007), Troponin (p = 0.009), Castelli index (p = 0.001) and atherogenic index (p = 0.004). Preoperative levels of total cholesterol, LDL-C and HDL-C did not significantly differ between survivors and diseased. The 9-year mortality risk did not differ significantly between subgroups divided according to LDL-C thresholds of 1.4 mmol/L (55 mg/dL), 1.8 mmol/L (70 mg/dL), 2.6 mmol/L (100 mg/dL) and 3.0 mmol/L (116 mg/dL). Conclusions: Preoperative low level of LDL-C cholesterol (below 1.83 mmol/L, 70 mg/dL) has a cardioprotective effect on perioperative myocardial injury in off-pump coronary artery bypass grafting.

Vascular Calcification: The Evolving Relationship of Vascular Calcification to Major Acute Coronary Events.

Calcification in a coronary artery is accepted as definite evidence of coronary atherosclerosis. The extent and density of calcification, as combined in the Agatston score, is associated with the risk of a patient experiencing a major acute coronary event. Atherosclerosis occurs because damaged endothelial cells allow low-density lipoprotein cholesterol (LDLc) to leak into subintimal tissue. Proteoglycans in subendothelial collagen have a high affinity for LDLc, retaining the lipoprotein cholesterol complex. As the endothelial damage is repaired, the subintimal LDLc is trapped. Retained LDLc induces an inflammatory response in the overlying endothelium, causing the endothelium to express chemotactic peptides. Chemotactic peptides attract circulating monocytes, which follow the concentration gradient, enter the tissue, and become tissue macrophages to phagocytize and digest the irritating LDLc in the atheroma. In the process of digesting LDLc, enzymes in the macrophages oxidize the LDLc complex. Oxidized LDL is toxic to macrophages; when present in sufficient quantity, it may cause death of macrophages, contributing to inflammation in the atheroma. In a necrotic inflammatory lesion, the regulatory mechanisms that control tissue concentrations of calcium and phosphorus are lost, allowing the solubility product of calcium phosphate to be exceeded, resulting in the formation of microscopic calcium-phosphate crystals. With ongoing inflammation, additional calcium-phosphate crystals are formed, which may aggregate. When these aggregated calcium phosphate crystals exceed 1 mm, the lesions become visible on clinical CT as coronary calcifications. Serial gated CT scans of the heart have demonstrated that once formed, CT-visible calcifications do not decrease significantly in size but may increase.

Rapid rule-out of suspected acute coronary syndrome in the Emergency Department by high-sensitivity cardiac troponin T levels at presentation.

The reliability of initial high-sensitivity cardiac troponin T (hs-cTnT) under limit-of-detection in ruling-out short- and long-term acute coronary events in subjects for suspected non-ST-segment elevation acute coronary syndrome (NSTE-ACS) is not definitely settled. In a retrospective chart review analysis, 1001 subjects with hs-cTnT ≤ 14ng/L out of 4053 subjects with hs-cTnT measured at Emergency Department (ED) presentation were recruited. The main outcome measure is fatal or non-fatal myocardial infarction (MI) within 30days; secondary outcomes are MI or major acute coronary events (MACE) as a combination of MI or re-hospitalization for unstable angina within 1year. In subjects with hs-cTnT < 5ng/L [32.6% of cases, mean age 63years (interquartile range 23)], no cases (0%, NPV 100%) had MI within 30days, 2 cases (0.6%, NPV 99.4%) MI at 1-year, and 11 cases (3.4%, NPV 96.6%) MACE at 1-year. Patients with hs-cTnT < 5ng/L would have benefited from a shortened decision (9.30h and 53% overnight ED stay saved). Hs-cTnT < 5ng/L is confirmed as safe for patients and comfortable for physicians in ruling out MI or MACE both at short and long term, suggesting that a sizable number of patients can be rapidly discharged without unnecessary diagnostic tests and ED observation.

Multimodality Intracoronary Imaging With Near-Infrared Spectroscopy and Intravascular Ultrasound in Asymptomatic Individuals With High Calcium Scores.

This study sought to determine the frequency of large lipid-rich plaques (LRP) in the coronary arteries of individuals with high coronary artery calcium scores (CACS) and to determine whether the CACS correlates with coronary lipid burden. Combined near-infrared spectroscopy and intravascular ultrasound was performed in 57 vessels in 20 asymptomatic individuals (90% on statins) with no prior history of coronary artery disease who had a screening CACS ≥300 Agatston units. Among 268 10-mm coronary segments, near-infrared spectroscopy images were analyzed for LRP, defined as a bright yellow block on the near-infrared spectroscopy block chemogram. Lipid burden was assessed as the lipid core burden index (LCBI), and large LRP were defined as a maximum LCBI in 4 mm ≥400. Vessel plaque volume was measured by quantitative intravascular ultrasound. Vessel-level CACS significantly correlated with plaque volume by intravascular ultrasound (r=0.69; P<0.0001) but not with LCBI by near-infrared spectroscopy (r=0.24; P=0.07). Despite a high CACS, no LRP was detected in 8 (40.0%) subjects. Large LRP having a maximum LCBI in 4 mm ≥400 were infrequent, found in only 5 (25.0%) of 20 subjects and in only 5 (1.9%) of 268 10-mm coronary segments analyzed. Among individuals with a CACS ≥300 Agatston units mostly on statins, CACS correlated with total plaque volume but not LCBI. This observation may have implications on coronary risk among individuals with a high CACS considering that it is coronary LRP, rather than calcification, that underlies the majority of acute coronary events.

Uncertain association between depression and stroke risk in a Chinese mega-study

ABSTRACT FROM: Sun J, Ma H, Yu C, et al . Association of major depressive episodes with stroke risk in a prospective study of 0.5 million Chinese adults. Stroke 2016;47:2203–8....

Assessment of vulnerable and unstable carotid atherosclerotic plaques on endarterectomy specimens.

The types of lesion instability responsible for the majority of acute coronary events frequently include plaque disruption and plaque erosion with superimposed thrombosis. The term 'vulnerable plaque is used to describe atherosclerotic (ATS) plaques that are particularly prone to rupture and susceptible to thrombus formation, such as the thin-cap fibroatheroma (TCFA). The aim of the present study was to assess the morphological and histological differences between plaques that are unstable and those that are vulnerable to instability. Carotid artery endarterectomy specimens were obtained from 26 patients with carotid artery stenosis, consisting of 20 men and 6 women (age range, 35-80 years). Histological and morphometric methods were used to visualize and characterize the ATS plaques. Among the 26 carotid ATS plaques, 23% were stable, 23% were unstable and 54% were vulnerable. With regard to morphometric characteristics, the following mean values were obtained for the TCFA and unstable plaques, respectively: Fibrous cap thickness, 21.91 and 11.66 µM; proportion of necrotic core area in the total plaque area, 25.90 and 22.03%; and the proportion of inflammatory area in the total plaque area, 8.41 and 3.04%. No plaque calcification was observed in any of them. Since ATS coronary artery disease is considerably widespread and fatal, it is crucial to further study ATS lesions to obtain an improved understanding of the nature of vulnerable and unstable plaques. The methods used to detect plaque size, necrotic core area and fibrous cap thickness are considered to be particularly useful for identifying vulnerable and unstable plaques.

Abstract 12063: High-risk Plaque Co-localizes With Low Endothelial Shear Stress and Expansive Remodeling in Human Coronary Arteries: A 3D Optical Coherence Tomography Study

Background: High risk plaque accounts for the majority of acute coronary events. Low endothelial shear stress (ESS) is a key factor of the natural history of atherosclerosis. The role of ESS in high risk plaque formation is not well studied in man. Hypothesis: To explore the association of low ESS with high risk plaque and to identify the ESS milieu and vascular remodeling response in high risk vs. non high risk plaque. Methods: 35 coronary arteries from 30 patients were 3D reconstructed with fusion of coronary angiography and optical coherence tomography (Fig A-D) . ESS was calculated in the 3D reconstructed arteries using computational fluid dynamics (Fig E) and classified into low, moderate and high in 3 mm long segments. In each segment: i) fibroatheromas were classified into high risk and non high risk based on fibrous cap thickness and lipid pool size ii) vascular remodeling was classified into constrictive, compensatory and expansive. Results: Fibroatheromas in low ESS segments had significantly thinner fibrous cap compared to high ESS segments (89±84 vs.138±83 μm, p&lt;0.05). Lipid pool size was comparable across all ESS categories. The majority of low ESS segments co-localized with high risk plaques (29 vs. 9%, p&lt;0.05), whereas the majority of high ESS co-localized with non high risk plaques (24 vs. 9%, p&lt;0.05, Fig F ). Compensatory and expansive remodeling was the predominant remodeling response in low ESS segments containing high risk plaques. In non-stenotic fibroatheromas (expansive or compensatory remodeling) low ESS was predominantly associated with high risk plaques (29 vs. 3%, p&lt;0.05) whereas high ESS was associated with non high risk plaques (Fig F) . Conclusions: Novel combined anatomic and functional imaging with 3D OCT showed that low ESS and non-constrictive remodeling are associated with high risk plaque in man. Further studies are needed to assess the role of ESS and vascular remodeling in high risk plaque rupture and precipitation of clinical outcomes.

Patient selection for elective revascularization to reduce myocardial infarction and mortality: new lessons from randomized trials, coronary physiology, and statistics.

As stated in American College of Cardiology/American Heart Association Guidelines, randomized trials have not demonstrated that elective percutaneous coronary intervention (PCI) reduces myocardial infarction (MI) or mortality over medical treatment. Even the Fractional Flow Reserve Guided PCI Versus Medical Therapy in Stable Coronary Disease (FAME 2) trial showed no statistically significant benefit of PCI over the deferred group by traditional intention-to-treat, nonbenchmark analysis starting at randomization that includes procedure-related events. Benchmark analysis in FAME 2 beginning 1 week after PCI removed procedure-related events that counterbalanced subsequent reduced MI and mortality compared with the deferred group. Meta-analysis of the literature on risk of events related to fractional flow reserve (FFR), including FFR Versus Angiography in Multivessel Evaluation (FAME), and other physiological measures of severity reveal an underappreciated, powerful interdependence among physiological severity of stenosis, diffuse coronary artery disease (CAD), event rates, sample size, and statistical certainty of differences. This analytic review synthesizes an evidenced-based, quantitative hypothesis and potential solution to this issue based on hard data from the literature by coauthors of diverse cardiovascular disciplines in trial design, biostatistics, invasive procedures, coronary physiology, fluid dynamics, coronary pathology, and quantitative imaging. Our synthesis elucidates a dual hypothesis for failure of elective PCI in stable CAD to reduce MI or mortality and novel trial design for selecting patients for whom PCI will likely reduce these events. First, a large burden of global diffuse CAD carries a high risk of coronary events unmitigated by PCI of a focal stenosis. Second, focal stenosis severity in previous randomized revascularization trials has been too modest without objectively quantified sufficient severity to observe benefit of PCI. In previous trials, mixture of diffuse coronary disease and intermediate stenosis may not incur high enough risk for potential benefit by PCI for sample size of reported trials. Greater quantitative severity with …

Comparison of Everolimus- and Biolimus-Eluting Coronary Stents With Everolimus-Eluting Bioresorbable Vascular Scaffolds

BackgroundThe first CE-approved bioresorbable vascular scaffold (BVS) is effective at treating simple lesions and stable coronary artery disease, but it has yet to be assessed versus the best-in-class drug-eluting stents (DES). ObjectivesThis study sought to compare the performance of a BVS with that of everolimus-eluting stents (EES) and biolimus-eluting stents (BES) in all-comer patients. MethodsThe EVERBIO II (Comparison of Everolimus- and Biolimus-Eluting Stents With Everolimus-Eluting Bioresorbable Vascular Scaffold Stents II) trial was a single-center, assessor-blinded study of 240 patients randomly assigned in a 1:1:1 ratio to EES, BES, or BVS. The only exclusion criterion was a reference vessel diameter >4.0 mm, which precluded treatment with BVS. The primary endpoint was angiographic late lumen loss (LLL) at 9 months. Secondary endpoints included patient-oriented major acute coronary events (MACE) (death, myocardial infarction [MI], and any revascularization), device-oriented MACE (cardiac death, MI, and target lesion revascularization), and stent thrombosis at the 9-month clinical follow-up. ResultsFollow-up angiography was performed in 216 patients (90.7%) at 9 months. In-stent LLL was similar between patients treated with BVS (0.28 ± 0.39 mm) and those treated with EES/BES (0.25 ± 0.36 mm; p = 0.30). Clinical outcomes were similar at 9 months: the patient-oriented MACE rate was 27% in BVS and 26% in the EES/BES group (p = 0.83) and the device-oriented MACE rate was 12% in BVS and 9% in the EES/BES group (p = 0.6). ConclusionsNew-generation metallic DES (EES/BES) were not superior to BVS in terms of angiographic LLL and clinical outcomes. (Comparison of Everolimus- and Biolimus-Eluting Stents With Everolimus-Eluting Bioresorbable Vascular Scaffold Stents [EVERBIO II]; NCT01711931)

The Regression of Atherosclerosis: The Power of Multimodality Imaging

Coronary artery disease remains a leading cause of death in the Western world. It is well known that the reduction of cholesterol levels by statin therapy is associated with significant decreases in plaque burden. However, a critical question has been the ability of statin therapy to lead to lipid egress from plaque and subsequent plaque stabilization. This is crucial since lipid-rich coronary plaques are at increased risk for rupture and thrombus leading to events. We recently addressed this issue by conducting the YELLOW (reduction in yellow plaque by aggressive lipid-lowering therapy) trial. We reported that short-term intensive statin therapy reduces lipid content as assessed by near infrared spectroscopy (NIRS) in obstructive lesions. Histopathological studies suggest that the majority of acute coronary events are related to occlusive thrombus formation after disruption of a thin-cap fibroatheroma (TCFA) overlying a large necrotic lipid core. Optical coherence tomography (OCT) is an imaging modality with powerful resolution to allow for plaque characterization including the identification of TCFA. Yet, it still remains unknown as to the efficacy of high dose statin therapy for enhancing anatomic features of plaque stabilization. The YELLOW II Trial was therefore designed with the goal of combining the utilization of OCT and NIRS in the coronary arteries to extend our initial findings as well as link them to changes in plaque morphology with alterations in lipoprotein biology, HDL function and macrophage behaviour.

TCT-380 Integrated intravascular ultrasound (IVUS) optical coherence tomography (OCT) system for identifying thin-cap fibroatheroma

It has been found that the majority of acute coronary events are caused by the rupture of a thin-cap fibroatheroma (TCFA), characterized by a large lipid or necrotic core with a relatively thin fibrous cap. Identifying vulnerable plaques and optimizing the therapy accordingly holds great promise for

Unstable angina pectoris prior to ST elevation myocardial infarction in patients treated with primary percutaneous coronary intervention has no influence on prognosis

Pre-infarction unstable angina pectoris (UAP) can be considered ischemic preconditioning. The aim of this study was to compare short and long term outcomes in patients with or without pre-infarction UAP and ST elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). 593 patients with STEMI (388 without and 205 with UAP) were evaluated. Levels of biomarkers (troponin I, BNP, NT-ProBNP, neopterin, endoglin and pentraxin-3) at hospital admission and 24 h after STEMI onset were assessed. Echocardiography was undertaken on the fourth day after MI and after 12 months. The median follow-up was 37 months. We found no significant differences in sex, age or risk factors for atherosclerosis between the UAP and non-UAP group. As the median time from the onset of chest pain to admission was significantly longer in the UAP group (228 min vs 258 min; P=0.009), we used a propensity score to obtain comparable matched groups for use in further analyses. The levels of NT-proBNP were significantly higher on admission and after 24 hours in the UAP group. Left ventricular functions according to invasive and echocardiographic parameters were entirely comparable at hospitalization and after 12 months. No differences were found in severity index of acute heart failure during hospitalization. The incidence of major acute coronary events during follow-up was comparable for the groups. In patients with STEMI treated with primary PCI, pre-infarction UAP has no beneficial clinical effect during hospitalization or during long-term follow-up.

Histopathologic Characteristics of Atherosclerotic Coronary Disease and Implications of the Findings for the Invasive and Noninvasive Detection of Vulnerable Plaques

The goal of this study was to identify histomorphologic characteristics of atherosclerotic plaques and to determine the amenability of some of these components to be used as markers for invasive and noninvasive imaging. Rupture of the atherosclerotic plaques is responsible for the majority of acute coronary events, and the culprit lesions demonstrate distinct histopathologic features. It has been tacitly believed that plaque rupture (PR) is associated with angiographically minimally occlusive lesions. We obtained 295 coronary atherosclerotic plaques, including stable (fibroatheroma [FA]; n = 105), vulnerable (thin-cap fibroatheroma [TCFA]; n = 88), and disrupted plaques (plaque rupture [PR]; n = 102) from the hearts of 181 men and 32 women who had died suddenly. The hierarchical importance of fibrous cap thickness, percent luminal stenosis, macrophage area, necrotic core area, and calcified plaque area was evaluated by using recursive partitioning analysis. Because clinical assessment of fibrous cap thickness is not possible by noninvasive imaging, it was excluded from the second set of partitioning analysis. Thickness of the fibrous cap emerged as the best discriminator of plaque type; the cap thickness measured <55 μm in ruptured plaques, and all FA were associated with >84-μm cap thickness. Although the majority of TCFA were found in the 54- to 84-μm thickness group, those with <54-μm thickness were more likely to show <74% luminal stenosis (area under the curve: FA, 1.0; TCFA, 0.89; PR, 0.90). After exclusion of cap thickness, analysis of the plaque characteristics revealed macrophage infiltration and necrotic core to be the 2 best discriminators of plaque types (area under the curve: FA, 0.82; TCFA, 0.58; PR, 0.72). More than 75% cross-section area stenosis was seen in 70% of PR and 40% of TCFA; only 5% PR and 10% TCFA were <50% narrowed. This postmortem study defines histomorphologic characteristics of vulnerable plaques, which may help develop imaging strategies for identification of such plaques in patients at a high risk of sustaining acute coronary events.

Progressive deterioration of left ventricular function in a patient with a normal coronary angiogram

Cardiac ischemia with a normal coronary angiogram can be caused by coronary microvascular dysfunction. A favorable prognosis, with excellent long-term clinical outcome, without major acute coronary events, has been consistently reported in these patients. We report a patient with a normal coronary angiogram and 3 episodes of myocardial infarctions, where the formation of a ventricular aneurysm and progressive deterioration of left ventricular function was documented, and hypoperfusion of the myocardium was confirmed by cardiovascular magnetic resonance imaging. This case suggests that myocardial ischemia caused by coronary microvascular dysfunction could have a poor prognosis. Whether this case represents a special clinical condition which is between the cardiac syndrome X and coronary artery disease remains to be investigated.

Effects of Increasing High-Density Lipoprotein Cholesterol and Decreasing Low-Density Lipoprotein Cholesterol on the Incidence of First Acute Coronary Events (from the Air Force/Texas Coronary Atherosclerosis Prevention Study)

Reducing low-density lipoprotein (LDL) cholesterol with statins reduces cardiovascular risk, but the associations between increases in high-density lipoprotein (HDL) cholesterol and cardiovascular risk at different LDL levels have been less well characterized. To evaluate the associations between the 1-year changes in HDL cholesterol and LDL cholesterol with lovastatin and subsequent acute major coronary events (AMCEs), we studied 2,928 patients in the lovastatin arm who were followed for 5.2 years in a post-hoc analysis of the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS). The percentage of HDL cholesterol increase and apolipoproteins at year 1 and the incidence of AMCEs thereafter were assessed stratified by the LDL cholesterol levels. With lovastatin, LDL cholesterol was reduced by 25% on average to 115 mg/dl at year 1, and HDL cholesterol increased 6.0%. Patients with both an increase in HDL cholesterol of > or =7.5% and LDL cholesterol of <115 mg/dl at year 1 had the lowest event rate (3.53/1,000 person-years; p = 0.028). Similar results were found for an increase in HDL cholesterol of > or =7.5% and a decrease in LDL cholesterol of >25%, as well as for apolipoproteins A-I and B. The 1-year percent increase in HDL cholesterol appeared to be associated with a reduction in AMCEs in subsequent follow-up (p = 0.07 with the percentage of HDL cholesterol increase analyzed continuously). Patients with an HDL cholesterol increase of > or =7.5% had an AMCE rate of 5.18 compared with 7.66/1,000 person-years in patients with a lower HDL cholesterol increase (p = 0.08). In conclusion, lovastatin therapy was associated with a greater risk reduction of AMCEs when LDL cholesterol was substantially reduced and the HDL cholesterol increased by > or =7.5%.

Progressing From Risk Factors to Omics

Many factors contribute to the development of clinical atherosclerotic disease in adults. Observational studies conducted from the late 1940s onward have helped us to identify cigarette smoking, cholesterol levels, diabetes, blood pressure, and other factors as important determinants of cardiovascular disease (CVD) outcomes.1,2 The effects are multiplicative. For example, smoking, hypertension, and diabetes each double the risk of a heart attack, and having all 3 factors can lead to a risk that was ≈8 times that of an adult of similar age and sex who did not have any of the factors.3 A major focus in the earlier population and clinical studies was identification of persons at increased risk before the clinical atherosclerotic event. Less attention has been directed toward other types of events, such as occurrence of a myocardial infarction in persons presenting with chest pain, recurrent CVD events, and long-term vascular disease complications such as cardiac failure. The determinants of these vascular events are likely to include some of the classical risk factors, but new factors will no doubt be important as well. Improvements in outpatient and inpatient care, diagnosis, and biomarker discovery have reshaped the landscape. It is possible to visualize subclinical CVD with modern atherosclerotic imaging techniques such as carotid intima-media thickness and arterial calcification assessments. Clinical chemists and geneticists identify new biomarkers that promise to help refine assessments of CVD risk, but it is not clear how such tests should be used for research or for clinical care. This article addresses several of the questions posed above and takes the perspective of research and care for clinical atherosclerotic disease, emphasizing the progress we have made from traditional risk factor assessment to the present time that includes newer assessment methods such as genomics, metabolomics, and predictive medicine. ### Traditional Risk Factors for Cardiovascular Disease The traditional risk factors include cholesterol, blood …

The vulnerable and unstable atherosclerotic plaque

The lesion responsible for the overwhelming majority of acute coronary events is plaque disruption or erosion with superimposed thrombosis. The term "vulnerable plaque" has been used to describe those atherosclerotic plaques that are particularly susceptible to disruption. Vulnerable plaques are generally characterized as those having a thin inflamed fibrous cap over a very large lipid core. However, only a small percentage of such plaques rupture, and plaques with different characteristics may also rupture and thrombose. Most autopsy, intravascular ultrasound, and recent computed tomography angiographic studies of coronary arteries reveal large plaques at sites of rupture. While angiographic data are said to show less severe narrowing at sites of plaque rupture, actual review of data indicates that, even angiographically, more than 50% of plaques have greater than 75% cross-sectional area stenosis at sites of plaque rupture. If plaque rupture is more common at the shoulder region of a plaque, one could envision that this would be at a peripheral site of the plaque where the plaque may not be as large or occlusive. New knowledge about vulnerable plaques is emerging through the evolution of novel techniques used to study plaques in vivo. These methods combine sophisticated imaging techniques, often in conjunction with molecular biomarkers, that provide new insights into plaque biology. Since atherosclerotic coronary artery disease is such a widespread and fatal disease, it is important that we continue to strive for a greater understanding of the nature of the vulnerable plaque. Only then can rational interventions for this disorder be developed and implemented.

Safety and efficacy of drug‐eluting balloons in percutaneous treatment of bifurcation lesions the DEBIUT (drug‐eluting balloon in bifurcaton utrecht) registry

To evaluate outcomes after percutaneous coronary intervention (PCI) with a drug-eluting balloon catheter (paclitaxel-coated) in patients with coronary artery bifurcation lesions. The current practice of provisional stenting of the main branch (MB) is reasonable; however, long-term results of side-branch (SB) treatment are suboptimal. The use of drug-eluting stents has not improved these results, regardless of the implantation technique, and could potentially lead to a significant increase in (late) thrombotic events. To evaluate short-term safety and efficacy of a drug-eluting balloon (DEB) in patients with bifurcation lesions followed by provisional stenting of the main branch, we set up the DEBIUT Registry. This registry enrolled 20 eligible patients with coronary artery bifurcation lesions. Patients received a PCI with a paclitaxel-coated balloon catheter, followed by provisional stenting of the MB with a bare-metal stent. Acute angiographic and clinical follow-up were performed after 1 and 4 months. The procedure was successful in all patients. The use of sequential predilatation with DEB was safe and well tolerated. No acute or subacute closure of side branches occurred after treating with DEB. All patients were treated according to the provisional stenting technique; no stents were placed in the SB. At 4-month follow-up no major acute coronary events and no subacute vessel closure were reported. The use of a drug-eluting balloon in patients with bifurcation lesions was effective and safe up to 4 months following PCI in patients with coronary artery bifurcation lesions.

Quantification of Roughness of Calcific Deposits in Computed Tomography Scans of Human Coronary Arteries

The incidence of coronary artery disease has been shown to be greater in patients with calcific deposits than in those without. It has been suggested that the pattern of distribution of coronary calcific deposits within coronary arteries is of greater predictive value for acute coronary events than the overall quantity. Whether roughness of calcific deposits is a predictor of acute coronary events is not known. We derived and tested an algorithm, Voxel-Based Bosselation (VBB), for noninvasive quantification of roughness of calcific deposits in human coronary arteries imaged by computed tomography (CT). VBB was tested on 213 coronary calcific deposits from electron beam CT scans of 27 patients. This algorithm evaluates the 3-dimensional connectedness of surface voxels of each deposit: smooth masses have low VBB and rough masses high VBB. The algorithm was calibrated with artificially generated phantoms as well as background noise mimicking calcific deposits and surrounding heart tissue. The VBB algorithm is applicable to calcific deposits of all scales and gradations. The VBB values of the deposits in this study did not correlate with deposit size further supporting its validity as a measurement of roughness. The VBB index corresponded directly with visual reconstruction using Phong-shaded algorithms. The VBB index, derived here, is a noninvasive method of quantifying the roughness of calcific deposits in CT scan data which can now be used in future clinical studies to determine possible correlations with increased plaque vulnerability and major acute coronary events.