No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Age- And sex-related features of atherosclerosis from coronary computed tomography angiography in patients prior to acute coronary syndrome: Results from the ICONIC study
Abstract
Aims:
Although there is increasing evidence supporting coronary atherosclerosis evaluation by coronary computed tomography angiography (CCTA), no data are available on age and sex differences for quantitative plaque features. The aim of this study was to investigate sex and age differences in both qualitative and quantitative atherosclerotic features from CCTA prior to acute coronary syndrome (ACS).
Methods and results:
Within the ICONIC study, in which 234 patients with subsequent ACS were propensity matched 1:1 with 234 non-event controls, our current subanalysis included only the ACS cases. Both qualitative and quantitative advance plaque analysis by CCTA were performed by a core laboratory. In 129 cases, culprit lesions identified by invasive coronary angiography at the time of ACS were co-registered to baseline CCTA precursor lesions. The study population was then divided into subgroups according to sex and age (<65 vs. ≥ 65 years old) for analysis. Older patients had higher total plaque volume than younger patients. Within specific subtypes of plaque volume, however, only calcified plaque volume was higher in older patients (135.9 ± 163.7 vs. 63.8 ± 94.2 mm3, P < 0.0001, respectively). Although no sex-related differences were recorded for calcified plaque volume, females had lower fibrous and fibrofatty plaque volume than males (Fibrofatty volume 29.6 ± 44.1 vs. 75.3 ± 98.6 mm3, P = 0.0001, respectively). No sex-related differences in the prevalence of qualitative high-risk plaque features were found, even after separate analyses considering age were performed.
Conclusion:
Our data underline the importance of age- and sex-related differences in coronary atherosclerosis presentation, which should be considered during CCTA-based atherosclerosis quantification.
... These results support the fundamental role of low-density/noncalcified plaque-volume quantification for accurate identification of vulnerable plaque that may be missed if only coronary calcium is assessed (Figure 4). Of note, as recently reported from the ICONIC study subanalysis, age and sex may influence plaque subcomponent quantification [36]; more precisely, the calcified plaque volume of a patient increases with age both in female and male subjects, while females have a lower noncalcified plaque volume on a per-patient level at all ages. On the contrary, no age-or sex-related differences were identified in the prevalence of qualitative high-risk plaque features and necrotic core volume. ...
... Assuming that CCTA cannot be performed in the entire population and that it is presently not recommended, it is of utmost importance to identify subgroups of patients that may potentially benefit from CCTA as screening tests targeting healthy people. Among others, asymptomatic diabetic patients may benefit from early CCTA, at least for the excellent prognosis if normal coronary arteries are found [33][34][35][36][37][38][39][40][41], even if data from the FACTOR-64 trial failed to demonstrate a prognostic benefit of CCTA [37]. Moreover, several biomarkers like pentraxin, hs-CRP, and hs-Tn-I have been suggested to be associated with high-risk atherosclerosis at CCTA and may help physicians to select healthy but higher-risk subjects [46]. ...
In the present article, an overview of advanced analysis of coronary atherosclerosis by coronary computed tomography angiography (CCTA) is provided, focusing on the potential application of this technique in a primary prevention setting. Coronary artery calcium score (CACS) has a well-demonstrated prognostic value even in a primary prevention setting; however, fibro-fatty, high-risk coronary plaque may be missed by this tool. On the contrary, even if not recommended for primary prevention in the general population, CCTA may enable early high-risk atherosclerosis detection, and specific subgroups of patients may benefit from its application. However, further studies are needed to determine the possible use of CCTA in a primary prevention setting.
... In coronary artery disease, initial studies have linked increased 18 F-NaF uptake with risk factors, culprit lesions more comprehensive disease phenotyping to provide optimal risk stratification [22]. In line with these discrepancies on coronary CT angiography, women show less obstructive coronary disease and fewer plaques with adverse morphological features when compared to men [23,24]. Fig. 1 Sex differences in coronary artery disease activity (Graphical Abstract). ...
Introduction
There are sex differences in the extent, severity, and outcomes of coronary artery disease. We aimed to assess the influence of sex on coronary atherosclerotic plaque activity measured using coronary ¹⁸F-sodium fluoride (¹⁸F-NaF) positron emission tomography (PET), and to determine whether ¹⁸F-NaF PET has prognostic value in both women and men.
Methods
In a post-hoc analysis of observational cohort studies of patients with coronary atherosclerosis who had undergone ¹⁸F-NaF PET CT angiography, we compared the coronary microcalcification activity (CMA) in women and men.
Results
Baseline ¹⁸F-NaF PET CT angiography was available in 999 participants (151 (15%) women) with 4282 patient-years of follow-up. Compared to men, women had lower coronary calcium scores (116 [interquartile range, 27–434] versus 205 [51–571] Agatston units; p = 0.002) and CMA values (0.0 [0.0-1.12] versus 0.53 [0.0-2.54], p = 0.01). Following matching for plaque burden by coronary calcium scores and clinical comorbidities, there was no sex-related difference in CMA values (0.0 [0.0-1.12] versus 0.0 [0.0-1.23], p = 0.21) and similar proportions of women and men had no ¹⁸F-NaF uptake (53.0% (n = 80) and 48.3% (n = 73); p = 0.42), or CMA values > 1.56 (21.8% (n = 33) and 21.8% (n = 33); p = 1.00). Over a median follow-up of 4.5 [4.0–6.0] years, myocardial infarction occurred in 6.6% of women (n = 10) and 7.8% of men (n = 66). Coronary microcalcification activity greater than 0 was associated with a similarly increased risk of myocardial infarction in both women (HR: 3.83; 95% CI:1.10-18.49; p = 0.04) and men (HR: 5.29; 95% CI:2.28–12.28; p < 0.001).
Conclusion
Although men present with more coronary atherosclerotic plaque than women, increased plaque activity is a strong predictor of future myocardial infarction regardless of sex.
... Beyond lumen stenosis severity, CCTA advanced atherosclerosis analysis has been shown to have a significant prognostic utility in a number of studies. Plaque subcomponent quantification may be influenced by age and sex, as was recently found in a subanalysis of the ICONIC research [71]. Specifically, the calcified plaque volume of a patient rises with age in both male and female subjects, while the noncalcified plaque volume is lower in females across all ages. ...
Cardiac computed tomography (CT) is an imaging modality that can visualize the anatomy of the heart and its surroundings. The technological advancement in cardiac CT gave better accuracy with lower radiation than earlier models. Its entire procedure took a relatively short time and minimal contact. Cardiac CT is an important imaging modality in clinical practice during emergencies and non-emergency settings and in planning comprehensive management of cardiac patients. Cardiac CT is useful in emergency settings, acting as a triple rule-out imaging modality. Cardiac CT in non-emergency settings can determine coronary artery calcium (CAC) score and detect left atrial appendage (LAA) thrombus before cardioversion. Furthermore, cardiac CT is now more commonly used as a modality in planning comprehensive management of cardiac patients’ especially coronary CT angiography (CCTA) in planning for cardiac intervention. This imaging modality becomes more relevant to use in clinical practice during the pandemic due to less contact with the patient needed during the procedure, and physicians may get used to cardiac CT. This article aims to explain the advantages of CCTA in emergency and non-emergency settings and discuss its limitation so that we can make the best use of it. This writing is a literature review. The literature search using PubMed and Google Scholar.
... Atherosclerotic cardiovascular disease (CVD) is the leading cause of death in both women and men globally [1]. Our understanding of sex differences in subclinical atherosclerosis and plaque composition and characteristics have greatly improved with the use of coronary computed tomography (CCTA) as it has emerged as an important tool to understand the role of non-obstructive atherosclerosis as well as diffuse, high risk plaque (HRP) as precursors of acute cardiac events in women [2][3][4]. CCTA can be used to identify HRP features which are associated with higher event rates [4]. High-risk coronary atherosclerosis features evaluated CCTA is suggested to have a prognostic role but the association of sex hormones and HRP in young to middle aged women with no clinical coronary artery disease is understudied. ...
Objective:
The association of sex-specific hormones with coronary computed tomography angiography(CCTA)-based plaque characteristics in women without cardiovascular disease is not well understood. We investigated the association of sex-specific hormones with coronary artery plaque characteristics in a contemporary multiracial cohort with no clinical coronary artery disease (CAD).
Methods:
In this cross-sectional analysis, we utilized data from 2,325 individuals with no clinical CAD from the Miami Heart (MiHeart) study. Multivariable logistic regression models were used to investigate the association of sex hormones: sex hormone binding globulin (SHBG), dehydroepiandrosterone (DHEA), free and total testosterone, estradiol, with plaque characteristics among women and men.
Results:
Of the 1,155 women, 34.2% had any plaque and 3.4% had any high-risk plaque features (HRP) while among men (n = 1170), 63.1% had any plaque and 10.4% had HRP. Among women, estradiol and SHBG were associated with lower odds of any plaque after adjusting for age and race-ethnicity (estradiol OR per SD increase: 0.87, 95%CI: 0.76-0.98; SHBG OR per SD increase: 0.82, 95%CI: 0.72-0.93) but the significance did not persist after adjustment of cardiovascular risk factors. High free testosterone was associated with higher odds of HRP (aOR:3.48, 95%CI:1.07-11.26) but null associations for the other sex hormones with HRP, in the context of limited sample size. Among men, there were no significant associations between sex-specific hormones and plaque or HRP.
Conclusion:
Among young to middle-aged women with no clinical CAD, increasing estradiol and SHBG were associated with lower odds of any plaque and higher free testosterone was associated with HRP. Larger cohorts may be needed to validate this.
... In ICONIC, both HRP features and quantitative assessment of fibrofatty and necrotic core plaque volume were more often associated with incident ACS while total plaque volume was similar between ACS and controls, independent of coronary stenosis [24]. Additionally, women had lower fibrous and fibrofatty plaque volumes compared to men, without sex-based differences in calcified plaque volumes [56]. Furthermore, in the ICONIC cohort, lesion location and vessel geometry were independently associated with the risk of ACS [57] Nadjiri et al. demonstrated in 1168 consecutive patients with suspected CAD that LAP, NRS, and total plaque volume were all predictive of MACE. ...
Purpose of Review
Imaging of adverse coronary plaque features by coronary computed tomography angiography (CCTA) has advanced greatly and at a fast pace. We aim to describe the evolution, present and future in plaque analysis, and its value in comparison to plaque burden.
Recent Findings
Recently, it has been demonstrated that in addition to plaque burden, quantitative and qualitative assessment of coronary plaque by CCTA can improve the prediction of future major adverse cardiovascular events in diverse coronary artery disease scenarios. The detection of high-risk non-obstructive coronary plaque can lead to higher use of preventive medical therapies such as statins and aspirin, help identify culprit plaque, and differentiate between myocardial infarction types. Even more, over traditional plaque burden, plaque analysis including pericoronary inflammation can potentially be useful tools for tracking disease progression and response to medical therapy.
Summary
The identification of the higher risk phenotypes with plaque burden, plaque characteristics, or ideally both can allow the allocation of targeted therapies and potentially monitor response. Further observational data are now required to investigate these key issues in diverse populations, followed by rigorous randomized controlled trials.
... In addition, the Kaplan-Meier analysis provides a quality visualization of the significantly higher incidence of MACE in both men and women who have low-attenuation plaques and greater than median EAT volumes. A sub-study of the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial [5] and the ICONIC study (Incident COronary EveNts Identified by Computed Tomography) [24] used quantitative plaque analysis to show a strong association between plaque composition and high-risk plaque features with adverse cardiovascular events in men and women. However, they did not assess the impact of EAT which is a novel biomarker for MACE prediction. ...
Background: To investigate gender differences in epicardial adipose tissue (EAT) and plaque composition by coronary CT angiography (CCTA) and the association with cardiovascular outcome. Methods: Data of 352 patients (64.2 ± 10.3 years, 38% female) with suspected coronary artery disease (CAD) who underwent CCTA were retrospectively analyzed. EAT volume and plaque composition from CCTA were compared between men and women. Major adverse cardiovascular events (MACE) were recorded from follow-up. Results: Men were more likely to have obstructive CAD, higher Agatston scores, and a larger total and non-calcified plaque burden. In addition, men displayed more adverse plaque characteristics and EAT volume compared to women (all p < 0.05). After a median follow-up of 5.1 years, MACE occurred in 8 women (6%) and 22 men (10%). In multivariable analysis, Agatston calcium score (HR 1.0008, p = 0.014), EAT volume (HR 1.067, p = 0.049), and low-attenuation plaque (HR 3.82, p = 0.036) were independent predictors for MACE in men, whereas only low-attenuation plaque (HR 2.42, p = 0.041) showed predictive value for events in women. Conclusion: Women demonstrated less overall plaque burden, fewer adverse plaque characteristics, and a smaller EAT volume compared to men. However, low-attenuation plaque is a predictor for MACE in both genders. Thus, a differentiated plaque analysis is warranted to understand gender differences of atherosclerosis to guide medical therapy and prevention strategies.
... In addition to coronary lumen stenosis quantification, CCTA also enables the identification of coronary atherosclerosis itself and advanced plaque characterization has been correlated with cardiovascular prognosis. 55 Conte et al. 56 studied sex and age differences in both qualitative and quantitative atherosclerotic features from CCTA prior to acute coronary syndrome (ACS). Nevertheless, gaps in evidences remain and clinical situation are still requiring the best from the echocardiographic analysis. ...
The European Heart Journal-Cardiovascular Imaging was introduced in 2012 and has during these 10 years become one of the leading multimodality cardiovascular imaging journals. The journal is currently ranked as Number 19 among all cardiovascular journals. It has an impressive impact factor of 9.130 and our journal is well established as one of the top cardiovascular journals. The most important studies published in our Journal in 2021 will be highlighted in two reports. Part I of the review will focus on studies about myocardial function and risk prediction, myocardial ischaemia, and emerging techniques in cardiovascular imaging, while Part II will focus on valvular heart disease, heart failure, cardiomyopathies, and congenital heart disease.
... In the CCTA literature, an age-based study was recently conducted by Conte et al who evaluated a subgroup of patients from the ICONIC (Incident Coronary Syndromes Identified by Computed Tomography) trial to determine whether APCs of culprit lesions varied by age and showed that older patients had greater total PV, specifically calcified plaque, as well as greater segment involvement and segment severity scores than younger patients. 26 However, again, the study cohort was comprised of ACS patients and the lesion level analysis pertained specifically to culprit lesions, limiting the ability to generalise findings. Additionally, Kim et al initiated a substudy of the PARADIGM (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging) trial, a cohort with suspected or known CAD, and showed that the rate of plaque progression, specifically densely calcified plaque, increased with age. ...
Objective
The study evaluates the relationship of coronary stenosis, atherosclerotic plaque characteristics (APCs) and age using artificial intelligence enabled quantitative coronary computed tomographic angiography (AI-QCT).
Methods
This is a post-hoc analysis of data from 303 subjects enrolled in the CREDENCE (Computed TomogRaphic Evaluation of Atherosclerotic Determinants of Myocardial IsChEmia) trial who were referred for invasive coronary angiography and subsequently underwent coronary computed tomographic angiography (CCTA). In this study, a blinded core laboratory analysing quantitative coronary angiography images classified lesions as obstructive (≥50%) or non-obstructive (<50%) while AI software quantified APCs including plaque volume (PV), low-density non-calcified plaque (LD-NCP), non-calcified plaque (NCP), calcified plaque (CP), lesion length on a per-patient and per-lesion basis based on CCTA imaging. Plaque measurements were normalised for vessel volume and reported as % percent atheroma volume (%PAV) for all relevant plaque components. Data were subsequently stratified by age <65 and ≥65 years.
Results
The cohort was 64.4±10.2 years and 29% women. Overall, patients >65 had more PV and CP than patients <65. On a lesion level, patients >65 had more CP than younger patients in both obstructive (29.2 mm ³ vs 48.2 mm ³ ; p<0.04) and non-obstructive lesions (22.1 mm ³ vs 49.4 mm ³ ; p<0.004) while younger patients had more %PAV (LD-NCP) (1.5% vs 0.7%; p<0.038). Younger patients had more PV, LD-NCP, NCP and lesion lengths in obstructive compared with non-obstructive lesions. There were no differences observed between lesion types in older patients.
Conclusion
AI-QCT identifies a unique APC signature that differs by age and degree of stenosis and provides a foundation for AI-guided age-based approaches to atherosclerosis identification, prevention and treatment.
... A previous CCTA study demonstrated less calcified plaques and more noncalcified plaques in women than in men [5]. Moreover, it has been noted that women have less coronary plaque burden on a per-patient level than men (with lower fibrous/ fibrofatty plaque volume and total plaque volume) [6]. In addition, women show significantly slower progression of coronary atherosclerosis on serial CCTA scans [7]. ...
... Other potential causes include myocardial infarction caused by coronary spasm [45], microembolization [46], and a misdiagnosis of ACS in patients with a variety of different clinical entities, such as myocarditis and Takatsubo cardiopathy, [47], among others. CMRI may be used to rule out potential causes, and is a useful tool for the management of ACS presenting with normal coronary angiography, as it aids diagnosis and adaptation of treatment in a large proportion of cases [48][49][50]. The prognosis of patients with ACS and normal coronary arteries was considered to be excellent, based off of several small studies showing a low recurrence rate of ACS and a high 10-year survival rate [16]. ...
Background: Acute myocardial infarction is a relatively rare phenomenon in the young population. The incidence has nevertheless increased from years past, likely due to the presence of multiple risk factors from an increasingly younger age. Regardless of whether they have atherosclerotic coronary artery disease or normal coronary angiogram, young patients with risk factors for coronary artery disease (CAD), chest pain, and positive troponin, are initially treated in a similar fashion. Our goal was to shed light on whether risk factors between these two groups differ to help guide physicians in clinically determining whether or not an atherosclerotic cardiovascular event has occurred, as well as to potentially identify young patients at risk of acute coronary syndrome (ACS) despite normal coronary arteries.
Methods: A retrospective cross sectional study was undertaken over an 8 year period at Tawam Hospital. 576 patients aged 50 or under who underwent coronary angiography were selected for the study. Medical records were analyzed for the patient's demographics and CAD risk factor profile, including the following variables: family history of CAD, smoking status, Body Mass Index category, lipid profile, and diagnosis of hyperlipidemia, diabetes, or hypertension. Details of the coronary angiogram were also reviewed.
Results: Statistically significant outcomes included a higher prevalence of diabetes, hyperlipidemia, and smoking history in patients with CAD compared to the patients with normal coronary angiogram. Diabetes was one of the strongest risk factors in CAD patients, with an odds ratio of 1.98 (p= 0.011), followed by hyperlipidemia at 1.85 (p= 0.021). Smoking history had an odds ratio of 2.93 (p <0.001).
Conclusion: Risk factors were present in both groups, but significantly more in the CAD group. No particular risk factor stood out for the development of ACS in those with normal coronary arteries, other than mean BMI being slightly higher in this group. Based on our analysis, no single variable can accurately predict the risk for ACS in normal coronaries. To our knowledge, few studies have been done in the young population with angiographically normal coronary arteries to determine possible risk factors for development of ACS. Further research needs to be done to determine whether the risk factors that were common amongst both groups are coincidental, or a cause of ACS in those with normal coronary arteries.
... In the ICONIC sub-study of the CONFIRM trial, increased cross-sectional plaque burden, fibrofatty plaque volume, and necrotic core volume were all associated with increased risk of subsequent acute coronary syndrome in 234 patients with acute coronary syndrome compared to matched control pairs [33]. Interestingly, they found that there were no sex-based differences in calcified plaque volume, but women had lower fibrous and fibrofatty plaque volume compared to men [47]. Nadjiri et al. found that in 1168 patients undergoing CCTA for suspected coronary artery disease the volume of non-calcified plaque and low-attenuation plaque was higher in patients that experienced MACE during 5 years of follow-up [48]. ...
Background The capabilities of coronary computed tomography angiography (CCTA) have advanced significantly in the past decade. Its capacity to detect stenotic coronary arteries safely and consistently has led to a marked decline in invasive diagnostic angiography. However, CCTA can do much more than identify coronary artery stenoses.
Method This review discusses applications of CCTA beyond coronary stenosis assessment, focusing in particular on the visual and quantitative analysis of atherosclerotic plaque.
Results Established signs of visually assessed high-risk plaque on CT include positive remodeling, low-attenuation plaque, spotty calcification, and the napkin-ring sign, which correlate with the histological thin-cap fibroatheroma. Recently, quantification of plaque subtypes has further improved the assessment of coronary plaque on CT. Quantitatively assessed low-attenuation plaque, which correlates with the necrotic core of the thin-cap fibroatheroma, has demonstrated superiority over stenosis severity and coronary calcium score in predicting subsequent myocardial infarction. Current research aims to use radiomic and machine learning methods to further improve our understanding of high-risk atherosclerotic plaque subtypes identified on CCTA.
Conclusion Despite rapid technological advances in the field of coronary computed tomography angiography, there remains a significant lag in routine clinical practice where use is often limited to lumenography. We summarize some of the most promising techniques that significantly improve the diagnostic and prognostic potential of CCTA.
Key Points:
Citation Format
... 8 Current study adds to the understanding of the pathophysiology of ACS by uncovering differences in pre-event coronary plaque morphology based on age and sex, which may hold potential for improved patient mangement. 9 The study may be praised for a robust design, including relatively large group of patients with coronary CTA examination preceding ACS. According to Conte et al. women with future ACS have smaller arteries, with slightly less vulnerable plaque content than men, but with equal proportion of the qualitative highrisk coronary plaques. ...
Background
In coronary artery disease (CAD), plaque progression and plaque composition are associated with cardiovascular risk. Whether compositional plaque progression in non-obstructive CAD differs between women and men is less studied.
Methods
We included 31 patients (42% women) with chronic non-obstructive CAD from the Norwegian Registry of Invasive Cardiology, undergoing serial coronary computed tomography angiography (CCTA) on clinical indication (median inter-scan interval 1.8 [1.5–2.2] years). We performed quantitative and qualitative plaque analysis of all coronary artery segments.
Results
Women were older compared to men (65 ± 8 years vs. 55 ± 12 years, p = 0.019), while there was no difference in the prevalence of hypertension, diabetes, smoking or statin treatment between groups. At baseline, women had a higher total plaque burden, more calcified plaques, and less fibro-fatty and necrotic core plaques compared to men (all p < 0.05). During follow-up, men showed faster progression of fibro-fatty plaques (4.0 ± 5.4 % per year vs. −0.6 ± 3.1 % per year, p = 0.019) and a greater reduction of fibrous plaques (-7.3 ± 6.1 % per year vs. 2.1 ± 7.2 % per year, p = 0.003) compared to women even after age adjustment. At follow-up, total plaque burden remained higher in women compared to men (24.9 ± 3.3 % vs. 21.1 ± 2.6 %, p = 0.001), while men had an increase in fibro-fatty (21.2 ± 9.3 % vs. 28.6 ± 9.8 %, p = 0.004) and necrotic core plaques (5.6 ± 3.6 % vs. 10.8 ± 7.2 %, p = 0.006), and a decrease in fibrous plaques (69.0 ± 11.9 % vs. 54.7 ± 13.7 %, p < 0.001). Women’s plaque composition remained unaltered.
Conclusion
In non-obstructive CAD, serial CCTA demonstrated a higher total plaque burden and a stable plaque composition in women, while men had a faster progression of unstable low-attenuating fibro-fatty plaques.
Clinical trial registration: ClinicalTrials.gov: Identifier NCT04009421.
Background:
Coronary artery calcium (CAC) scoring is a proven predictor for future adverse cardiovascular events (CVE) in asymptomatic individuals. Data is emerging regarding the usefulness of non-calcified plaque (NCP) assessment on cardiac computed tomography (CCT) angiography in symptomatic patients with a zero CAC score for further risk assessment.
Methods:
A retrospective review from January 2019 to January 2022 of 696 symptomatic patients with no known CAD and a zero CAC score identified 181 patients with NCP and 515 patients without NCP by a visual assessment on CCT angiography. The primary endpoint was to identify predictors for NCP presence and adverse CVEs (death, myocardial infarction, or cerebrovascular accident) within two years.
Results:
Based on logistic regression, age (OR 1.039, 95% CI [1.020-1.058], p < 0.001), diabetes mellitus (OR 2.192, 95% CI [1.307-3.676], p < 0.003), tobacco use (OR 1.748, 95% CI [1.157-2.643], p < 0.008), low-density lipoprotein cholesterol level (OR 1.009, 95% CI [1.003-1.015], p < 0.002), and hypertension (OR 1.613, 95% CI [1.024-2.540], p < 0.039) were found to be predictors of NCP presence. NCP patients had a higher pretest probability for CAD using the Morise risk score (p < 0.001∗), with NCP detection increasing as pretest probability increased from low to high (OR 55.79, 95% CI [24.26-128.26], p < 0.001∗). 457 patients (66%) reached a full two-year period after CCT angiography completion, with NCP patients noted to have shorter follow-up times and higher rates of elective coronary angiography, intervention, and CVEs. The presence of NCP (aOR 2.178, 95% CI [1.025-4.627], p < 0.043) was identified as an independent predictor for future adverse CVEs when adjusted for diabetes mellitus, age, and hypertension.
Conclusion:
NCP was identified at high rates (26%) in our symptomatic Appalachian population with no known CAD and a zero CAC score. NCP was identified as an independent predictor of future adverse CVEs within two years.
We aimed to examine the correlation of T-cell immunoglobulin and ITIM domain (TIGIT)-expressing CD3 + CD56 + cells (TNKS) with coronary artery disease (CAD), atherosclerotic lesion progression, and inflammatory environment. A total of 199 subjects, including 98 patients with acute coronary syndrome (ACS), 52 patients with chronic coronary syndrome (CCS), and 49 control subjects, were recruited in the study. The TIGIT-expressing TNKS were quantified by flow cytometric analysis; the severity of coronary artery lesions was evaluated by the Gensini score. Whole blood cells were stimulated with interleukin-2 (IL-2), interleukin-7 (IL-7), and interleukin-15 (IL-15) in presence or absence of STAT, PI3K, and P38 MAPK inhibitors, respectively. The TIGIT-expressing TNKS was significantly increased in patients with CAD, ACS, and CCS compared to the control group (P < 0.05). The TIGIT-expressing TNKS were independent predictors of CAD, ACS and CCS (P < 0.05). The TIGIT-expressing TNKS were positively associated with Gensini score (P < 0.05). The TIGIT-expressing TNKS was positively correlated with age, and being male (P < 0.05). The inflammatory microenviroment with increased IL-2, IL-7, and IL-15 contributed to upregulation of TIGIT expression in TNKS. PI3K and P38 MAPK inhibitors could inhibit the upregulation of TIGIT expression in TNKS induced by IL-2, IL-7, and IL-15. The TIGIT-expressing TNKS may be involved in common pathogenesis of ACS and CCS, and atherosclerotic lesion progression. Meanwhile, the increased TIGIT-expressing TNKS might be associated with a proatherogenic microenvironment or inflammatory microenvironment. PI3K and P38 MAPK signaling pathways were involved in the regulation of TIGIT expression.
Globally, coronary artery disease (CAD) is the primary cause of death in both younger and older individuals. However, the differences in cardiovascular risk between younger and older patients based on geographical regions were lacking. Hence, this review discusses the unique cardiovascular profiles between younger and older patients with CAD in the Asian and Western populations.
Despite the prevalent use of ‘premature CAD’, no definite age cut-off for this condition exists. Asian patients seem to develop premature CAD earlier and CAD is conventionally considered a ‘men’s disease’.
Risk factors of CAD varied between both younger and older patients regardless of geographical regions. Based on the limited evidence, no differences were observed between the Asian and Western populations in terms of disease severity, plaque characterization as well as clinical presentation and electrocardiographic changes. Overall, targeting specific risk factors for early CAD interventions should be performed to allow better disease prevention and prognosis.
Myocardial work derived from pressure-strain analysis resembles a novel non-invasive method for myocardial function evaluation. Left ventricular hypertrophy (LVH) is commonly detected in Fabry disease (FD), cardiac amyloidosis (CA) and hypertension (HTN). The study aimed to demonstrate the characteristics of myocardial work in patients with LVH suffering from FD, CA, and HTN. Echocardiography were performed in patients with LVH suffering from FD (n = 13), light chain associated cardiac amyloidosis (AL-CA) (n = 29) and HTN (n = 72), 25 healthy controls were also included in the current study. Conventional and myocardial work parameters were assessed and compared among FD, AL-CA, HTN and controls. Patients with FD and AL-CA were included in the group of infiltrative cardiomyopathy. Logistic regression analysis was used to identify independent predictors for discriminating infiltrative cardiomyopathy from hypertension. Compared with controls, HTN patients had preserved global work index (GWI) and global constructive work (GCW) and reduced global longitudinal strain (GLS) and global work efficiency (GWE) (p < 0.05), but patients with FD and AL-CA had reduced GLS, GWI, GCW and GWE and increased global wasted work (GWW) (p < 0.05). GWI and GCW could discriminate infiltrative cardiomyopathy from HTN independently with high accuracy (GWI cut-off value 1626 mmHg%, sensitivity 0.87, specificity 0.82, area under the curve 0.90; GCW cut-off value 2021 mmHg%, sensitivity 0.84, specificity 0.88, area under the curve 0.91). GWI and GCW were reduced in FD and AL-CA patients, but not in patients with HTN. Myocardial work had an addictive value in differentiating infiltrative cardiomyopathy from hypertension.
Cardiovascular diseases (CVDs), particularly ischemic heart disease (IHD) and stroke, present epidemiologically in a different way among sexes. The reasons of these sex-based differences should be delved into sex-specific cardiovascular (CV) risk factors and different mechanisms of atherosclerotic progression. Imaging techniques of both carotid and coronary atherosclerotic plaques represent a tool to demonstrate sex-related features which might be used to further and better assess CV risk of male and female population. The aim of this review is to evaluate current knowledge on sex-specific qualitative and quantitative plaque features of coronary and carotid atherosclerosis. We also discuss the clinical implication of a sex-based plaque phenotype, evaluated with non-invasive imaging techniques, such as CT-angiography and MRI-angiography, to stratify CV risk.
Purpose of review:
Multicenter studies showed that the characterization of coronary atherosclerosis by coronary computed tomography (CT) angiography (CCTA) provides independent and incremental prognostic value above and beyond traditional measures of coronary artery disease (CAD) and is able to identify patients at risk of future event. Aim of the present review is to expound the major imaging plaque features associated with increased risk of coronary event and to review the data supporting the usefulness of CCTA as tool for plaque assessment and for monitoring the changes in atherosclerotic burden.
Recent findings:
The evaluation of coronary atherosclerosis, including the measurement of imaging risk scores (e.g. CT-adapted Leaman score) was demonstrated as independent long-term predictor of acute coronary events. In particular, qualitative (remodelling index, low-attenuation plaque, napkin-ring sign, small spotty calcifications) and quantitative (plaque burden, total-, noncalcific- and fibrofatty plaque volume) plaque features were associated with increased risk. CCTA was also demonstrated to accurately quantify plaque volume vs. intravascular ultrasound and findings from PARADIGM and EVAPORATE studies supported the use of CCTA as noninvasive tool to follow the effect of medication on plaque progression/regression. Finally, interesting relationship between plaque features, coronary physiology and biomarkers have been described.
Summary:
Latest guidelines on the management of patients with stable CAD recommended CCTA in Class I of evidence, particularly when 'information on atherosclerosis are desired', underlining the usefulness of CCTA to characterize and quantify the atherosclerotic burden.
An important advantage of computed tomography coronary angiography (CCTA) is its ability to visualize the presence and severity of atherosclerotic plaque, rather than just assessing coronary artery stenoses. Until recently, assessment of plaque subtypes on CCTA relied on visual assessment of the extent of calcified/non-calcified plaque, or visually identifying high-risk plaque characteristics. Recent software developments facilitate the quantitative assessment of plaque volume or burden on CCTA, and the identification of subtypes of plaque based on their attenuation density. These techniques have shown promise in single and multicenter studies, demonstrating that the amount and type of plaque are associated with subsequent cardiac events. However, there are a number of limitations to the application of these techniques, including the limitations imposed by the spatial resolution of current CT scanners, challenges from variations between reconstruction algorithms, and the additional time to perform these assessments. At present, these are a valuable research technique, but not yet part of routine clinical practice. Future advances that improve CT resolution, standardize acquisition techniques and reconstruction algorithms and automate image analysis will improve the clinical utility of these techniques. This review will discuss the technical aspects of quantitative plaque analysis and present pro and con arguments for the routine use of quantitative plaque analysis on CCTA.
Objectives
This study was designed to investigate whether coronary computed tomography angiography assessments of coronary plaque might explain differences in the prognosis of men and women presenting with chest pain.
Background
Important sex differences exist in coronary artery disease. Women presenting with chest pain have different risk factors, symptoms, prevalence of coronary artery disease and prognosis compared to men.
Methods
Within a multicenter randomized controlled trial, we explored sex differences in stenosis, adverse plaque characteristics (positive remodeling, low-attenuation plaque, spotty calcification, or napkin ring sign) and quantitative assessment of total, calcified, noncalcified and low-attenuation plaque burden.
Results
Of the 1,769 participants who underwent coronary computed tomography angiography, 772 (43%) were female. Women were more likely to have normal coronary arteries and less likely to have adverse plaque characteristics (p < 0.001 for all). They had lower total, calcified, noncalcified, and low-attenuation plaque burdens (p < 0.001 for all) and were less likely to have a low-attenuation plaque burden >4% (41% vs. 59%; p < 0.001). Over a median follow-up of 4.7 years, myocardial infarction (MI) occurred in 11 women (1.4%) and 30 men (3%). In those who had MI, women had similar total, noncalcified, and low-attenuation plaque burdens as men, but men had higher calcified plaque burden. Low-attenuation plaque burden predicted MI (hazard ratio: 1.60; 95% confidence interval: 1.10 to 2.34; p = 0.015), independent of calcium score, obstructive disease, cardiovascular risk score, and sex.
Conclusions
Women presenting with stable chest pain have less atherosclerotic plaque of all subtypes compared to men and a lower risk of subsequent MI. However, quantitative low-attenuation plaque is as strong a predictor of subsequent MI in women as in men. (Scottish Computed Tomography of the HEART Trial [SCOT-HEART]; NCT01149590).
Background
Sex differences in the calculation of coronary heart disease risk have been analysed extensively. However, data on coronary plaque morphology diverge. We analysed plaque characteristics in patients with suspected coronary artery disease (CAD) and defined prognostic factors using coronary computed tomography angiography (CCTA).
Methods
A total of 6,050 consecutive patients underwent CCTA and were enrolled in the registry. Patients with known CAD were excluded. The patients were propensity score matched (1:1 male:female) for age and known coronary risk factors. Coronary arteries were evaluated for stenosis, plaque types (non-calcified, mixed and calcified) and high-risk plaque features (napkin-ring sign, low-attenuation plaque, spotty calcifications, positive remodelling). Clinical follow-up was performed.
Results
A total of 1,050 patients (525 female, 525 male) in matched cohorts were selected for analysis. CCTA showed significantly higher calcium scores for males (mean 180.5 vs 67.8 AU, p < 0.0001) and a higher rate of CAD (66.0% vs 34.1%, p < 0.0001). In a total of 16,800 segments, males had significantly more plaques (861 vs 752, p < 0.0001) with a significantly larger proportion of calcified plaques, while females had more mixed and non-calcified plaques (33.5% vs 24.4%, p = 0.006 and 24.1% vs 13.6%, p = 0.22, respectively). After a mean follow-up of 5.6 years, major adverse cardiac event (MACE) rate was 5.3% in male and 1.9% in female patients (p < 0.05). The relative odds ratio for high-risk plaque features to predict MACE was higher in females.
Conclusion
Based on a higher relative risk for women with high-risk plaque features, the findings of our study support the increased importance of a differentiated qualitative plaque analysis to improve the risk stratification for both sexes.
Each year, the American Heart Association (AHA), in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together in a single document the most upto-date statistics related to heart disease, stroke, and the factors in the AHA's Life's Simple 7 (Figure1), which include core health behaviors (smoking, physical activity [PA], diet, and weight) and health factors (cholesterol, blood pressure [BP], and glucose control) that contribute to cardiovascular health. The Statistical Update represents a critical resource for the lay public, policy makers, media professionals, clinicians, healthcare administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions. Cardiovascular disease (CVD) and stroke produce immense health and economic burdens in the United States and globally. The Update also presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure (HF), valvular disease, venous disease, and peripheral arterial disease) and the associated outcomes (including quality of care, procedures, and economic costs). Since 2006, the annual versions of the Statistical Update have been cited >20000 times in the literature. In 2015 alone, the various Statistical Updates were cited '4000 times.
Aims:
Recent studies suggested that even non-obstructive coronary artery disease (CAD) increases major cardiovascular adverse events (MACE) rate. Aim of this study was to evaluate whether coronary computed tomography angiography (CCTA) may detect specific plaque characteristics that may affect prognosis in patients with non-obstructive CAD.
Methods:
We enrolled 245 patients who underwent CCTA between April 2004 and April 2007 for suspected CAD and were found to have non-obstructive CAD. Positive remodelling index (PRI), low-attenuation plaque (LAP), plaque burden (PB), spotty calcification (SC), and napkin-ring sign (NRS) have been evaluated for each coronary plaque detected. Acute coronary syndrome, all-cause/cardiac death, and very late elective revascularization (vl-ER) were the endpoints of the study.
Results:
A total of 28 events were recorded (2 STEMI, 4 NSTEMI, 6 UA, 2 cardiac deaths, 4 non-cardiac death, and 10 vl-ERs) at long-term follow-up (98 ± 20 months). When adjusted for significant clinical variables PRI > 1.4 (HR 3.31 CI 95% 1.11-9.91, P = 0.0392), LAP (HR 8.45 CI 95% 2.22-32.21, P = 0.0019), PB > 0.7 (HR 5.25 CI 95% 1.45-19.03, P = 0.0120), and NRS (HR 12.52 CI 95% 1.51-103.90, P = 0.0198) were still significantly associated with higher rate of hard cardiac events at follow-up. The Kaplan-Meyer curves confirmed lower cumulative hard cardiac events-free survival in patients presenting at least one coronary plaque with two or more high-risk characteristics when compared with patients with no lesion with more than one high-risk plaque characteristics (log-rank P < 0.0001).
Conclusions:
High-risk plaque characteristics at CCTA (PRI > 1.4, PB > 0.7, LAP, and NRS) seem to be promising for risk stratification of patients with non-obstructive CAD.
Objectives:
The purpose of this study was to examine sex-specific associations, if any, between per-vessel coronary artery disease (CAD) extent and the risk of major adverse cardiovascular events (MACE) over a 5-year study duration.
Background:
The presence and extent of CAD diagnosed by coronary computed tomography angiography (CTA) is associated with increased short-term mortality and MACE. Nevertheless, some uncertainty remains regarding the influence of sex on these findings.
Methods:
5,632 patients (mean age 60.2 ± 11.8 years, 36.5% women) from the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry were followed for 5 years. Obstructive CAD was defined as ≥50% luminal stenosis in a coronary vessel. Using Cox proportional hazards models, we calculated the hazard ratio (HR) for incident MACE among women and men, defined as death or myocardial infarction.
Results:
Obstructive CAD was more prevalent in men (42% vs. 26%; p < 0.001), whereas women were more likely to have normal coronary arteries (43% vs. 27%; p < 0.001). There were a total of 798 incident MACE events. After adjustment, there was a strong association between increased MACE risk and nonobstructive CAD (HR: 2.16 for women, 2.56 for men; p < 0.001 for both), obstructive 1-vessel CAD (HR: 3.69 and 2.66; p < 0.001), 2-vessel CAD (HR: 3.92 and 3.55; p < 0.001), and 3-vessel/left main CAD (HR: 5.94 and 4.44; p < 0.001). Further exploratory analyses of atherosclerotic burden did not identify sex-specific patterns predictive of MACE.
Conclusions:
In a large prospective coronary CTA cohort followed long-term, we did not observe an interaction of sex for the association between MACE risk and increased per-vessel extent of obstructive CAD. These findings highlight the persistent prognostic significance of anatomic CAD subsets as detected by coronary CTA for the risk of MACE in both women and men.
Atherosclerotic cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally. Considerable research has been done over the last several decades to understand the pathophysiology of atherosclerosis. It is widely believed that estrogen is responsible for the protection of women from CVD in the premenopausal age group. However, hormone replacement therapy has failed to decrease CVD events in clinical studies which points to the complexity of the relationship between vascular biology and estrogen hormones. Interestingly, preponderance of vascular and connective tissue disorders in women also points to an inherent role of hormones and tissue factors in maintenance of vascular endothelial function. The differential effect of GPER, lipoprotein A, TLRs, leucocyte-platelet aggregate markers in men and women also suggests inherent gender-related differences in the pathophysiology of atherosclerosis. A better understanding of the pathophysiology is likely to open ways to improve evidence-based treatment of CVD in women.
The cardiovascular science community has pursued the quest to identify vulnerable atherosclerotic plaque in patients for decades, hoping to prevent acute coronary events. However, despite major advancements in imaging technology that allow visualization of rupture-prone plaques, clinical studies have not demonstrated improved risk prediction compared with traditional approaches. Considering the complex relationship between plaque rupture and acute coronary event risk suggested by pathology studies and confirmed by clinical investigations, these results are not surprising. This review summarizes the evidence supporting a multifaceted hypothesis of the natural history of atherosclerotic plaque rupture. Managing patients at risk of acute coronary events mandates a greater focus on the atherosclerotic disease burden rather than on features of individual plaques.
The European Society of Cardiology (ESC) has recently published new guidelines on the diagnosis and management of chronic coronary syndromes (CCS). The 2019 guideline identified six common clinical scenarios of CCS defined by the different evolutionary phases of coronary artery disease (CAD), excluding the situations in which an acute coronary event, often with coronary thrombus formation, dominates the clinical presentation. This review aims at providing a summary of novel or revised concepts in the guidelines together with the recent data underlying the major changes on the use of cardiac imaging in patients with suspected or known CCS.
Based on data from contemporary cohorts of patients referred for diagnostic testing, the pre-test probabilities of CAD based on age, sex and symptoms have been adjusted substantially downward as compared with 2013 ESC guidelines. Further, the impact of various risk factors and modifiers on the pre-test probability was highlighted and a new concept of ‘Clinical likelihood of CAD’ was introduced. Recommendations regarding diagnostic tests to establish or rule-out obstructive CAD have been updated with recent data on their diagnostic performance in different patient groups and impact on patient outcome. As the initial strategy to diagnose CAD in symptomatic patients, non-invasive functional imaging for myocardial ischaemia, coronary computed tomography angiography or invasive coronary angiography combined with functional evaluation may be used, unless obstructive CAD can be excluded by clinical assessment alone. When available, imaging tests instead of the exercise electrocardiogram are recommended when following the non-invasive diagnostic strategy.
Objectives:
This study sought to assess whether coronary atherosclerosis analysis by coronary computed tomography angiography (CTA) may improve prognostic stratification among patients with diffuse coronary artery disease (CAD) BACKGROUND: Coronary CTA has recently emerged as a promising noninvasive tool for advanced analysis of coronary atherosclerosis.
Methods:
The multicenter CAPIRE (Coronary Atherosclerosis in outlier subjects: Protective and novel Individual Risk factors Evaluation) study is part of the GISSI Outlier Project. A prospective cohort of subjects who underwent coronary CTA for suspected CAD was enrolled. Based on risk factor (RF) burden, patients were defined as having a low clinical risk (0 to 1 RF with the exclusion of patients with diabetes mellitus as single RF) or at high clinical risk (3 or more RFs). Patients with 2 RFs were not enrolled in the study. Coronary CTA advanced plaque assessment was performed. Outcome measures were 3 combined endpoints: acute coronary syndrome (ACS), cardiac death + ACS, and cardiac death + ACS + late revascularization.
Results:
Among the 544 patients enrolled in the CAPIRE study, in 522 patients, a mean follow-up of 37 ± 10 months was obtained (16 patients were excluded due to 1 < segment involvement score <5 at core lab coronary CTA analysis and 6 patients were lost at follow-up). Higher atherosclerotic burden was found in patients with higher clinical risk, but prevalence of elevated noncalcified plaque volume did not significantly differ between low- versus high-risk patients. Quantitative plaque parameters by coronary CTA were associated with composite endpoints at multivariable analysis when corrected for univariate predictors. Elevated noncalcified plaque volume, expressed as dichotomic variable, was associated with all combined endpoints. Even if the low absolute number of events represents a limitation to the present study, patients with low noncalcified plaque volume had similar risk of cardiac events independently from the presence of multivessel disease, while patients with high noncalcified plaque volume had higher rates of cardiac events.
Conclusions:
The CAPIRE study confirmed the prognostic value of atherosclerosis assessment by coronary CTA, demonstrating high noncalcified plaque volume as the most ACS-predictive parameter in patients with extensive CAD. (GISSE Outliers CAPIRE [CAPIRE]; NCT02157662).
Aims:
The emerging role of coronary computed tomography angiography (CCTA) as a non-invasive tool for atherosclerosis evaluation is supported by data reporting a good correlation between CCTA and intravascular ultrasound (IVUS) for plaque volume quantification. Aim of the present study was to evaluate whether a last generation CT-scanner may improve coronary plaque volume assessment using IVUS as standard-of-reference.
Methods and results:
From a registry of 1915 consecutive, all-comers, patients who underwent a clinically indicated IVUS evaluation we enrolled 59 patients who underwent CCTA with a 64-slice CT (Group 1) and 59 patients who underwent CCTA with whole-heart coverage CT scanner (Group 2). Patients who underwent CCTA with unfavourable heart rhythm were not excluded from the analysis. Image quality (4-point Likert scale) focused on plaque analysis was evaluated. Plaque volume quantification by CCTA was compared to IVUS. No difference in clinical characteristics was found between Group 1 and Group 2. Plaque volume quantification by CCTA was considered not feasible in 11 plaques of Group 1 and in 4 plaques of Group 2 (P = 0.09). Higher correlation for plaque volume quantification by CCTA vs. IVUS was demonstrated in Group 2 when compared with Group 1 (r = 0.9888 vs. 0.9499; P < 0.0001). The Bland-Altman analysis showed plaque volume overestimation by CCTA of 11.9 mm3 in Group 1 and 4 mm2 in Group 2 (P < 0.001). Effective radiation dose of CCTA was significantly lower in Group 2 vs. Group 1 (2.7 ± 0.9 vs. 8.1 ± 3.6 mSv, respectively; P < 0.001).
Conclusions:
CCTA using a new scanner generation showed to be an accurate non-invasive tool to assess and quantify coronary plaque volume.
Background:
The association of atherosclerotic features with first acute coronary syndromes (ACS) has not accounted for plaque burden.
Objectives:
The purpose of this study was to identify atherosclerotic features associated with precursors of ACS.
Methods:
We performed a nested case-control study within a cohort of 25,251 patients undergoing coronary computed tomographic angiography (CTA) with follow-up over 3.4 ± 2.1 years. Patients with ACS and nonevent patients with no prior coronary artery disease (CAD) were propensity matched 1:1 for risk factors and coronary CTA-evaluated obstructive (≥50%) CAD. Separate core laboratories performed blinded adjudication of ACS and culprit lesions and quantification of baseline coronary CTA for percent diameter stenosis (%DS), percent cross-sectional plaque burden (PB), plaque volumes (PVs) by composition (calcified, fibrous, fibrofatty, and necrotic core), and presence of high-risk plaques (HRPs).
Results:
We identified 234 ACS and control pairs (age 62 years, 63% male). More than 65% of patients with ACS had nonobstructive CAD at baseline, and 52% had HRP. The %DS, cross-sectional PB, fibrofatty and necrotic core volume, and HRP increased the adjusted hazard ratio (HR) of ACS (1.010 per %DS, 95% confidence interval [CI]: 1.005 to 1.015; 1.008 per percent cross-sectional PB, 95% CI: 1.003 to 1.013; 1.002 per mm3 fibrofatty plaque, 95% CI: 1.000 to 1.003; 1.593 per mm3 necrotic core, 95% CI: 1.219 to 2.082; all p < 0.05). Of the 129 culprit lesion precursors identified by coronary CTA, three-fourths exhibited <50% stenosis and 31.0% exhibited HRP.
Conclusions:
Although ACS increases with %DS, most precursors of ACS cases and culprit lesions are nonobstructive. Plaque evaluation, including HRP, PB, and plaque composition, identifies high-risk patients above and beyond stenosis severity and aggregate plaque burden.
Aims:
Although coronary artery calcium (CAC) has been established as a robust tool for predicting total mortality during intermediate follow-up, less is known about the long-term predictive value of CAC.
Methods and results:
This study included 13 092 asymptomatic patients without known cardiovascular disease who underwent a clinically indicated CAC scan. CAC was categorized as an Agatson score of 0, 1-99, 100-399, and ≥400. We used multivariable Cox proportional hazards to calculate adjusted hazard ratios (HRs) for mortality stratified by age (younger, intermediate, or older) and gender. The mean age of participants was 58 ± 11 years and 67% were men. During a median follow-up of 11.0 ± 3.2 years, there were 522 deaths (4.0%). Compared with CAC = 0, increasing CAC was associated with higher mortality rate: 1-99 [HR: 1.5, 95% confidence interval (95% CI): 1.1-2.1]; 100-399 (HR: 1.8, 95% CI: 1.3-2.5); ≥400 (HR: 2.6, 95% CI: 1.9-3.6). Relative risk according to CAC category did not differ between genders. The strongest associations between CAC and mortality were observed for young and intermediate age participants. Nonetheless, the mortality rate of the older patients with CAC = 0 was far lower than that of the general US population. CAC was more predictive of long-term (15 years) than intermediate-term (5 years) mortality for men [receiver operator characteristics (ROC): 0.723 vs. 0.702] and women (ROC: 0.69 vs. 0.65).
Conclusion:
CAC is strongly associated with the long-term risk of mortality in young- and middle-aged men and women. In older patients, the long-term risk stratification of CAC is lower, due principally to increased mortality rate in patients with low calcium scores; however, even in the older patients, those with absent or low CAC are at a significantly lower risk of mortality compared with the general population.
Recognition of ischemic heart disease (IHD) is often delayed or deferred in women. Thus, many at risk for adverse outcomes are not provided specific diagnostic, preventive, and/or treatment strategies. This lack of recognition is related to sex-specific IHD pathophysiology that differs from traditional models using data from men with flow-limiting coronary artery disease (CAD) obstructions. Symptomatic women are less likely to have obstructive CAD than men with similar symptoms, and tend to have coronary microvascular dysfunction, plaque erosion, and thrombus formation. Emerging data document that more extensive, nonobstructive CAD involvement, hypertension, and diabetes are associated with major adverse events similar to those with obstructive CAD. A central emerging paradigm is the concept of nonobstructive CAD as a cause of IHD and related adverse outcomes among women. This position paper summarizes currently available knowledge and gaps in that knowledge, and recommends management options that could be useful until additional evidence emerges.
Coronary computed tomography angiography (CTA)-verified positive remodeling and low attenuation plaques are considered morphological characteristics of high-risk plaque (HRP) and predict short-term risk of acute coronary syndrome (ACS).
This study evaluated whether plaque characteristics by CTA predict mid-term likelihood of ACS.
The presence of HRP and significant stenosis (SS) of ≥70% were evaluated in 3,158 patients undergoing CTA. Serial CTA was performed in 449 patients, and plaque progression (PP) was evaluated. Outcomes (fatal and nonfatal ACS) were recorded during follow-up (mean 3.9 ± 2.4 years).
ACS occurred in 88 (2.8%) patients: 48 (16.3%) of 294 HRP(+) and 40 (1.4%) of 2,864 HRP(-) patients. ACS was also significantly more frequent in SS(+) (36 of 659; 5.5%) than SS(-) patients (52 of 2,499; 2.1%). HRP(+)/SS(+) (19%) and HRP(+)/SS(-) (15%) had higher rates of ACS compared with no-plaque patients (0.6%). Although ACS incidence was relatively low in HRP(-) patients, the cumulative number of patients with ACS developing from HRP(-) lesions (n = 43) was similar to ACS patients with HRP(+) lesions (n = 45). In patients with serial CTA, PP also was an independent predictor of ACS, with HRP (27%; p < 0.0001) and without HRP (10%) compared with HRP(-)/PP(-) patients (0.3%).
CTA-verified HRP was an independent predictor of ACS. However, the cumulative number of ACS patients with HRP(-) was similar to patients with HRP(+). Additionally, plaque progression detected by serial CTA was an independent predictor of ACS.
Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
To evaluate the diagnostic performance of automated coronary atherosclerotic plaque quantification (QCT) by different users (expert/non-expert/automatic).
One hundred fifty coronary artery segments from 142 patients who underwent coronary computed tomography angiography (CCTA) and intravascular ultrasound (IVUS) were analyzed. Minimal lumen area (MLA), maximal lumen area stenosis percentage (%AS), mean plaque burden percentage (%PB), and plaque volume were measured semi-automatically by expert, non-expert, and fully automatic QCT analyses, and then compared to IVUS.
Between IVUS and expert QCT analysis, the correlation coefficients (r) for the MLA, %AS, %PB, and plaque volume were excellent: 0.89 (p < 0.001), 0.84 (p < 0.001), 0.91 (p < 0.001), and 0.94 (p < 0.001), respectively. There were no significant differences in the mean parameters (all p values >0.05) except %AS (p = 0.01). The automatic QCT analysis showed comparable performance to non-expert QCT analysis, showing correlation coefficients (r) of the MLA (0.80 vs. 0.82), %AS (0.82 vs. 0.80), %PB (0.84 vs. 0.73), and plaque volume (0.84 vs. 0.79) when they were compared to IVUS, respectively.
Fully automatic QCT analysis showed clinical utility compared with IVUS, as well as a compelling performance when compared with semiautomatic analyses.
• Coronary CTA enables the assessment of coronary atherosclerotic plaque. • High-risk plaque characteristics and overall plaque burden can predict future cardiac events. • Coronary atherosclerotic plaque quantification is currently unfeasible in practice. • Quantitative computed tomography coronary plaque analysis software (QCT) enables feasible plaque quantification. • Fully automatic QCT analysis shows excellent performance.
Prior studies examining coronary atherosclerosis in the young have been limited by retrospective analyses in small cohorts. We examined the relationship between cardiovascular risk factors (RFs) and prevalence and severity of coronary atherosclerosis in a large, prospective, multinational registry of consecutive young individuals undergoing coronary computerized tomographic angiography (CCTA).
Of 27 125 patients undergoing CCTA, 1635 young (<45 years) individuals without known coronary artery disease (CAD) or coronary anomalies were identified. Coronary plaque was assessed for any CAD, obstructive CAD (≥50% stenosis), and presence of calcified plaque (CP) and non-calcified plaque (NCP). Among 1635 subjects (70% men, age 38 ± 6 years), any CAD, obstructive CAD, CP, and NCP were observed in 19, 4, 5, and 8%, respectively. Compared with women, men demonstrated higher rates of any CAD (21 vs. 12%, P < 0.001), CP (6 vs. 3%, P = 0.01), and NCP (9 vs. 5%, P = 0.008), although no difference was observed for rates of obstructive CAD (5 vs. 4%, P = 0.46). Any CAD, obstructive CAD, and NCP were higher for young individuals with diabetes, hypertension, dyslipidaemia, current smoking, or family history of CAD; while only diabetes and dyslipidaemia were associated with CP. Increasing cardiovascular RFs was associated with a greater prevalence and extent and severity of CAD, with individuals with 0, 1, 2, ≥3 RFs manifesting a dose-response increase in any CAD (P < 0.001, for trend), obstructive CAD (P < 0.001, for trend), NCP (P < 0.001, for trend), and CP (P < 0.001, for trend). In multivariable analysis adjusting for sex and cardiovascular RFs, male sex was the strongest predictor for any CAD (odds ratio [OR] = 1.95, 95% confidence interval [CI] = 1.43-2.66, P < 0.001), CP (OR = 1.46, 95% CI = 1.08-1.98, P = 0.01), and NCP (OR = 1.33, 95% CI = 1.06-1.67, P = 0.01); family history of CAD was the strongest predictor for obstructive CAD (OR = 2.71, 95% CI = 1.65-4.45, P < 0.001).
Any and obstructive CAD is present in 1 in 5 and 1 in 20 young individuals, respectively, with family history associated with the greatest risk of obstructive CAD.
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.
Plaque constitution on computed tomography coronary angiography (CTA) is associated with prognosis. At present only visual assessment of plaque constitution is possible. An accurate automatic, quantitative approach for CTA plaque constitution assessment would improve reproducibility and allows higher accuracy. The present study assessed the feasibility of a fully automatic and quantitative analysis of atherosclerosis on CTA. Clinically derived CTA and intravascular ultrasound virtual histology (IVUS VH) datasets were used to investigate the correlation between quantitatively automatically derived CTA parameters and IVUS VH. A total of 57 patients underwent CTA prior to IVUS VH. First, quantitative CTA quantitative computed tomography (QCT) was performed. Per lesion stenosis parameters and plaque volumes were assessed. Using predefined HU thresholds, CTA plaque volume was differentiated in 4 different plaque types necrotic core (NC), dense calcium (DC), fibrotic (FI) and fibro-fatty tissue (FF). At the identical level of the coronary, the same parameters were derived from IVUS VH. Bland–Altman analyses were performed to assess the agreement between QCT and IVUS VH. Assessment of plaque volume using QCT in 108 lesions showed excellent correlation with IVUS VH (r = 0.928, p < 0.001) (Fig. 1). The correlation of both FF and FI volume on IVUS VH and QCT was good (r = 0.714, p < 0.001 and r = 0.695, p < 0.001 respectively) with corresponding bias and 95 % limits of agreement of 24 mm3 (−42; 90) and 7.7 mm3 (−54; 70). Furthermore, NC and DC were well-correlated in both modalities (r = 0.523, p < 0.001) and (r = 0.736, p < 0.001). Automatic, quantitative CTA tissue characterization is feasible using a dedicated software tool.
Fig. 1
Schematic illustration of the characterization of coronary plaque on CTA: cross-correlation with IVUS VH. First, the 3-dimensional centerline was generated from the CTA data set using an automatic tree extraction algorithm (Panel I). Using a unique registration a complete pullback series of IVUS images was mapped on the CTA volume using true anatomical markers (Panel II). Fully automatic lumen and vessel wall contour detection was performed for both imaging modalities (Panel III). Finally, fusion-based quantification of atherosclerotic lesions was based on the lumen and vessel wall contours as well as the corresponding reference lines (estimate of normal tapering of the coronary artery), as shown in panel IV. At the level of the minimal lumen area (MLA) (yellow lines), stenosis parameters, could be calculated for both imaging techniques. Additionally, plaque volumes and plaque types were derived for the whole coronary artery lesion, ranging from the proximal to distal lesion marker (blue markers). Fibrotic tissue was labeled in dark green, Fibro-fatty tissue in light green, dense calcium in white and necrotic core was labeled in red
Objective:
Determine plaque subtype and volume difference in male and female patients with obstructive and non-obstructive CAD using 320-row MDCTA.
Materials and methods:
128 patients with suspected CAD underwent MDCTA. All studies were divided into two groups based on disease severity. 0-70% stenosis (non-obstructive CAD) & >70% (obstructive). All were compared for plaque quantity and subtypes by gender. Main arteries, RCA, LM, LAD and LCX were analyzed using Vitrea 5.2 software to quantify fatty, fibrous and calcified plaque. Thresholds for coronary plaque quantification (volume in mm(3)) were preset at 35 ± 12 HU for fatty, 90 ± 24 HU for fibrous and >130 HU for calcified/mixed plaque and analyzed using STATA software.
Results:
Total plaque burden in 118 patients [65M: 53F] was significantly higher in all arteries in males compared to females with non-obstructive disease. Total plaque volume for males vs. females was: RCA: 10.10 ± 5.02 mm(3) vs. 6.89 ± 2.75 mm(3), respectively, p = 0.001; LAD: 7.21 ± 3.38 mm(3) vs. 5.89 ± 1.93 mm(3), respectively, p = 0.04; LCX: 9.13 ± 3.27 mm(3) vs. 7.16 ± 1.73 mm(3), respectively, p = 0.002; LM 15.13 ± 4.51 mm(3) vs. 11.85 ± 4.03 mm(3), respectively, p = 0.001. In sub-analyses, males had significantly more fibrous and fatty plaque in LM, LAD & LCX than females. However in the RCA, only fibrous plaque was significantly greater in males. Calcified plaque volume was not significantly different in both genders. Only 8% of patients had obstructive CAD (>70% stenosis); there was no significant difference in plaque volume or subtypes.
Conclusion:
In patients with non-obstructive CAD, males were found to have significantly higher total coronary plaque volume with predominance of fibrous and fatty subtypes compared to females of the same age and BMI. There was no significant difference in plaque subtype or volume in patients with obstructive disease.
The aim of this study was to assess the long-term prognostic role of multidetector computed tomography coronary angiography (CTA) in patients with suspected coronary artery disease (CAD).
Use of CTA is increasing in patients with suspected CAD. Although there is a large body of data supporting the prognostic role of CTA for major adverse cardiac events in the intermediate term, its long-term prognostic role in patients with suspected CAD is not well studied.
Between February 2005 and March 2008, 1,304 consecutive patients were prospectively studied with CTA for detecting the presence and assessing extent of CAD (disease extension and coronary plaque scores). Patients were classified according to the presence of normal coronaries and nonobstructive (<50%) and obstructive (>50%) coronary lesions. The composite rates of hard cardiac events (cardiac deaths and nonfatal myocardial infarctions) and all cardiac events (including late revascularization) were the endpoints of the study.
Seventy patients were excluded because their CTA data were uninterpretable. Of the remaining 1,234 patients, clinical follow-up (mean 52 ± 22 months) was obtained for 1,196 (97%). A total of 475 events were recorded, with 136 hard events (18 cardiac deaths and 118 nonfatal myocardial infarctions) and 123 late revascularizations. A total of 216 patients with early elective revascularizations were excluded from the survival analysis. Significant independent predictors of events in multivariate analysis were multivessel disease and left main CAD. Cumulative event-free survival was 100% for hard and all events in patients with normal coronary arteries, 88% for hard events and 72% for all events in patients with nonobstructive CAD, and 54% for hard events and 31% for all events in patients with obstructive CAD. Multivessel CAD was associated with a higher rate of hard cardiac events.
CTA provides prognostic information in patients with suspected CAD and unknown cardiac disease, showing excellent long-term prognosis when there is no evidence of atherosclerosis and allowing risk stratification when CAD is present.
In a computed tomographic (CT) angiography study, we identified the characteristics of atherosclerotic lesions that were associated with subsequent development of acute coronary syndrome (ACS).
The CT characteristics of culprit lesions in ACS include positive vessel remodeling (PR) and low-attenuation plaques (LAP). These 2 features have been observed in the lesions that have already resulted in ACS, but their prospective relation to ACS has not been previously described.
In 1,059 patients who underwent CT angiography, atherosclerotic lesions were analyzed for the presence of 2 features: PR and LAP. The remodeling index, and plaque and LAP areas and volumes were calculated. The plaque characteristics of lesions resulting in ACS during the follow-up of 27 +/- 10 months were evaluated.
Of the 45 patients showing plaques with both PR and LAP (2-feature positive plaques), ACS developed in 10 (22.2%), compared with 1 (3.7%) of the 27 patients with plaques displaying either feature (1-feature positive plaques). In only 4 (0.5%) of the 820 patients with neither PR nor LAP (2-feature negative plaques) did ACS develop. None of the 167 patients with normal angiograms had acute coronary events (p < 0.001). ACS was independently predicted by PR and/or LAP (hazard ratio: 22.8, 95% confidence interval: 6.9 to 75.2, p < 0.001). Among 2- or 1-feature positive segments, those resulting in ACS demonstrated significantly larger remodeling index (126.7 +/- 3.9% vs. 113.4 +/- 1.6%, p = 0.003), plaque volume (134.9 +/- 14.1 mm(3) vs. 57.8 +/- 5.7 mm(3), p < 0.001), LAP volume (20.4 +/- 3.4 mm(3) vs. 1.1 +/- 1.4 mm(3), p < 0.001), and percent LAP/total plaque area (21.4 +/- 3.7 mm(2) vs. 7.7 +/- 1.5 mm(2), p = 0.001) compared with segments not resulting in ACS.
The patients demonstrating positively remodeled coronary segments with low-attenuation plaques on CT angiography were at a higher risk of ACS developing over time when compared with patients having lesions without these characteristics.
Screening for early-stage asymptomatic cancers (eg, cancers of breast and colon) to prevent late-stage malignancies has been widely accepted. However, although atherosclerotic cardiovascular disease (eg, heart attack and stroke) accounts for more death and disability than all cancers combined, there are no national screening guidelines for asymptomatic (subclinical) atherosclerosis, and there is no government- or healthcare-sponsored reimbursement for atherosclerosis screening. Part I and Part II of this consensus statement elaborated on new discoveries in the field of atherosclerosis that led to the concept of the "vulnerable patient." These landmark discoveries, along with new diagnostic and therapeutic options, have set the stage for the next step: translation of this knowledge into a new practice of preventive cardiology. The identification and treatment of the vulnerable patient are the focuses of this consensus statement. In this report, the Screening for Heart Attack Prevention and Education (SHAPE) Task Force presents a new practice guideline for cardiovascular screening in the asymptomatic at-risk population. In summary, the SHAPE Guideline calls for noninvasive screening of all asymptomatic men 45-75 years of age and asymptomatic women 55-75 years of age (except those defined as very low risk) to detect and treat those with subclinical atherosclerosis. A variety of screening tests are available, and the cost-effectiveness of their use in a comprehensive strategy must be validated. Some of these screening tests, such as measurement of coronary artery calcification by computed tomography scanning and carotid artery intima-media thickness and plaque by ultrasonography, have been available longer than others and are capable of providing direct evidence for the presence and extent of atherosclerosis. Both of these imaging methods provide prognostic information of proven value regarding the future risk of heart attack and stroke. Careful and responsible implementation of these tests as part of a comprehensive risk assessment and reduction approach is warranted and outlined by this report. Other tests for the detection of atherosclerosis and abnormal arterial structure and function, such as magnetic resonance imaging of the great arteries, studies of small and large artery stiffness, and assessment of systemic endothelial dysfunction, are emerging and must be further validated. The screening results (severity of subclinical arterial disease) combined with risk factor assessment are used for risk stratification to identify the vulnerable patient and initiate appropriate therapy. The higher the risk, the more vulnerable an individual is to a near-term adverse event. Because <10% of the population who test positive for atherosclerosis will experience a near-term event, additional risk stratification based on reliable markers of disease activity is needed and is expected to further focus the search for the vulnerable patient in the future. All individuals with asymptomatic atherosclerosis should be counseled and treated to prevent progression to overt clinical disease. The aggressiveness of the treatment should be proportional to the level of risk. Individuals with no evidence of subclinical disease may be reassured of the low risk of a future near-term event, yet encouraged to adhere to a healthy lifestyle and maintain appropriate risk factor levels. Early heart attack care education is urged for all individuals with a positive test for atherosclerosis. The SHAPE Task Force reinforces existing guidelines for the screening and treatment of risk factors in younger populations. Cardiovascular healthcare professionals and policymakers are urged to adopt the SHAPE proposal and its attendant cost-effectiveness as a new strategy to contain the epidemic of atherosclerotic cardiovascular disease and the rising cost of therapies associated with this epidemic.
Coronary plaque rupture is a phenomenon underlying most acute coronary events. Although gender is an important determinant of the incidence and clinical course of coronary atherosclerosis, its relation to plaque rupture is unknown. Therefore, we assessed gender differences in native artery plaque rupture characteristics and their related clinical presentations. There were 468 intravascular ultrasound (IVUS) preintervention images of ruptured plaques retrospectively identified. There were 328 men (81.6%) with 387 plaque ruptures and 74 women (18.4%) with 81 plaque ruptures. Patient demographics, angiographic characteristics, and qualitative and quantitative IVUS analyses of ruptured plaques were assessed. On average women were older than men (67.6 +/- 11.8 vs 62.6 +/- 11.4 years, p = 0.001) and more often presented with an acute coronary syndrome (89.2% vs 72.9%, p = 0.003). Older women had smaller vessel areas at the rupture site (p = 0.001), minimum lumen site (p = 0.002), and reference segments (p = 0.002) and smaller lumen areas at the rupture site (p = 0.026) and reference segments (p = 0.03). Ruptured plaques in older women were more often associated with IVUS-evident thrombus (48.1% vs 34.6%, p = 0.022). Independent predictors of acute clinical presentation were female gender (p = 0.006), smoking (p = 0.013), and presence of thrombus (p = 0.049). Independent predictors of the presence of thrombus were female gender (p = 0.025), smaller lumen area (p = 0.023) and larger plaque area (p = 0.008) at the rupture site, longer plaque ruptures (p = 0.016), and smoking (p = 0.045). In conclusion, coronary plaque ruptures are more often associated with thrombus and acute presentations in women than in men.
generation computed tomography scanners
generation computed tomography scanners. Eur Heart J Cardiovasc Imaging 2020;
21:191-201.
Emergence of nonobstructive coronary artery disease: a woman's problem and need for change in definition on angiography
- C J Pepine
- K C Ferdinand
- L J Shaw
- K A Light-Mcgroary
- R U Shah
- M Gulati
Pepine CJ, Ferdinand KC, Shaw LJ, Light-McGroary KA, Shah RU, Gulati M et al..
Emergence of nonobstructive coronary artery disease: a woman's problem and
need for change in definition on angiography. J Am Coll Cardiol 2015;66:1918-33.
The myth of the "vulnerable plaque": transitioning from a focus on individual lesions to atherosclerotic disease burden for coronary artery disease risk assessment
- A Arbab-Zadeh
- V Fuster
Arbab-Zadeh A, Fuster V. The myth of the "vulnerable plaque": transitioning from a focus on individual lesions to atherosclerotic disease burden
for coronary artery disease risk assessment. J Am Coll Cardiol 2015;65:
846-85.
Emergence of nonobstructive coronary artery disease: a woman's problem and need for change in definition on angiography
- CJ Pepine
- KC Ferdinand
- LJ Shaw
- KA Light-McGroary
- RU Shah
- M Gulati