Associations between coronary and carotid artery atherosclerosis in patients with inflammatory joint diseases.
ABSTRACT: Low association between cardiac symptoms and coronary artery disease (CAD) in patients with inflammatory joint diseases (IJD) demands for objective markers to improve cardiovascular risk stratification. Our main aim was to evaluate the prevalence and characteristics of CAD in patients with IJD with carotid artery plaques. Furthermore, we aimed to assess associations of carotid ultrasonographic findings and coronary plaques.Eighty-six patients (61% female) with IJD (55 with rheumatoid arthritis, 21 with ankylosing spondylitis and 10 with psoriatic arthritis) and carotid artery plaque were referred to coronary CT angiography (CCTA). CAD was evaluated using the modified 17-segment American Heart Association model. Calcium score, plaque composition, segment involvement score and segment stenosis score were assessed and correlated to the carotid artery plaques and cardiovascular disease risk factors in logistic and linear regression analyses. Risk prediction models were tested with various cut-off values for associating variables.Fifty-five patients (66%) had CAD assessed by CCTA and 36 (43%) of these had coronary plaques defined as either mixed or soft. Eleven patients (13%) had obstructive CAD. The best risk prediction model (area under the curve: 0.832, 95% CI 0.730 to 0.935) included the combination of variables with cut-off values: age ?55 years (OR: 12.18, 95% CI 2.80 to 53.05), the carotid-intima media thickness ?0.7 mm (OR: 4.08, 95% CI 1.20 to 13.89) and carotid plaque height ?1.5 mm (OR: 8.96, 95% CI 1.68 to 47.91), p<0.05.Presence of carotid plaque is alone not sufficient to identify patients at risk for CAD, and a combination of ultrasonographic measurements may be useful in risk stratification of patients with IJD.NCT01389388, Results.
Project description:This study aims at identifying gene expression patterns in the whole blood that could differentiate patients with severe coronary atherosclerosis from subjects without detectable coronary artery disease (CAD), and assess associations of gene expression patterns with plaque features at coronary CT angiography (CCTA). Patients undergoing CCTA for suspected CAD, with no cardiovascular history, were enrolled. Coronary stenosis was quantified and CCTA plaque features were assessed. The whole-blood transcriptome was analyzed by RNA-Sequencing. We detected highly significant differences in the circulating transcriptome between patients with high-degree coronary stenosis (> 70%) at CCTA and subjects with the absence of coronary plaques. Noteworthy, regression analysis revealed expression signatures associated with Leaman score, segment involved score, segment-stenosis score, and plaque volume with density <150 HU at CCTA. This pilot study shows that patients with significant coronary stenosis are characterized by whole blood transcriptome profiles that may discriminate them from patients without CAD. Furthermore, our results suggest that whole blood transcriptional profiles may predict plaque characteristics. Overall design: Whole blood poly(A)+ RNA profiles of 27 CAD and 25 noCAD patients were generated through RNA-Seq using Ion S5 system.
Project description:This study evaluates the association between high sensitivity troponin I (hsTnI) and T (hsTnT) and the morphology of coronary artery plaques detected by coronary computed tomography angiography (CCTA) in patients with suspected coronary artery disease (CAD).Patients undergoing CCTA were prospectively enrolled. CCTA was indicated by a low to intermediate pretest probability for CAD during routine clinical care. Within 24 hours of CCTA examination, peripheral blood samples were taken to measure hsTnI, hsTnT, and N-terminal probrain natriuretic peptide (NT-proBNP).A total of 99 patients were enrolled with 43% without CAD, 9% with noncalcified plaques, 28% with calcified plaques, and 19% with mixed type plaque lesions. Both hsTnI and hsTnT levels were able to discriminate significantly between the groups, especially in the presence of mixed coronary plaques (AUC range: 0.741-0.752; p = 0.0001). In multivariate logistic regression models, hsTnT, but not hsTnI, was still significantly associated with mixed coronary plaque morphology (odds ratio?=?8.968; 95% CI 1.999-40.241; p = 0.004).Both hsTnI and hsTnT are able to discriminate between different coronary artery plaques morphologies, whereas hsTnT was significantly associated with mixed coronary plaques in patients with suspected CAD. This trial is registered with NCT03074253.
Project description:BACKGROUND AND OBJECTIVES: Primary prevention of coronary artery disease (CAD) has become a public health issue, according to increasing awareness of the substantial risks posed by asymptomatic atherosclerosis. The aims of this study were to determine the prevalence and characteristics of subclinical CAD using coronary computed tomography angiography (CCTA), and to evaluate the role of this advanced technology in identifying subclinical CAD in asymptomatic Korean individuals, compared with conventional risk stratification. SUBJECTS AND METHODS: We enrolled 4,320 consecutive asymptomatic individuals (61% males, aged 50±9 years), who underwent 64-slice CCTA during a routine health check. RESULTS: Coronary artery plaques were present in 1,053 (24%) individuals. Significant stenosis (diameter stenosis ?50%) was identified in 139 (3%) subjects, and most of the significant lesions (87%) were located in the left anterior descending artery. CCTA revealed noncalcified plaques in 5% of subjects with a coronary calcium score of zero (n=801). Although 25% (n=10) of those with noncalcified plaque had significant stenosis, most of them (90%) were classified into low- or moderate-risk groups according to National Cholesterol Education Program risk stratification guidelines. In a young population (age ?55 years for males, ?65 years for females), 30% of subjects with significant stenosis were classified into a low-risk group and 60% had low (0 to 100) calcium scores. CONCLUSION: Subclinical CAD in asymptomatic individuals cannot be ignored for its considerable prevalence, CCTA may be helpful in identifying at-risk subclinical CAD in a noninvasive manner, especially in the young and traditionally low-risk population.
Project description:No prospective study of the relationship between intima-media thickness (IMT) progression and incident cardiovascular disease (CVD) has been performed.We studied 4724 participants (mean age: 59.7±11.9 years; without CVD at the baseline) who had carotid ultrasonographic measurement of IMT on both sides of the entire carotid artery area (ie, the entire scanned common carotid artery [CCA], carotid artery bulb, internal carotid artery, and external carotid artery areas for both sides) between April 1994 and August 2001. Carotid ultrasonographic follow-up was performed every 2 years between April 1994 and March 2005 in 2722 of these participants, newly revealing 193 CCA plaques (maximum IMT in the CCA >1.1 mm). We followed up for incident CVD until December 2013. Statistical analyses were performed using a Cox proportional hazards regression model, evaluated using C statistics, and net reclassification improvement. During the 59 909 person-years of follow-up, we observed 221 strokes and 154 coronary heart disease events. CCA plaque and maximum IMT in the whole carotid artery area >1.7 mm were risk factors for CVD. CCA plaque presented an increased risk of CVD based on C statistics and the reclassification improvement of the current risk prediction model. After adding the new incident CCA plaques, during the 23 702 person-years of follow-up, 69 strokes and 43 coronary heart disease events occurred. The adjusted hazard ratios for incident CCA plaque were 1.95 (95% confidence interval, 1.14-3.30) in CVD and 2.01 (95% confidence interval, 1.01-3.99) in stroke.Maximum IMT in the CCA contributed significantly but modestly to the predictive power of incident CVD used in calculating traditional risk factors. This study provides the first demonstration that new progression of incident CCA plaque is a CVD risk.
Project description:BACKGROUND:CXCL4 is a platelet chemokine released at micromolar concentrations upon platelet activation. CXCL4 has been shown to promote atherogenesis by various mechanisms. However, data on CXCL4 plasma levels in patients with coronary artery disease are largely inconclusive. Computed coronary artery angiography (CCTA) represents an excellent tool to quantify and characterize coronary atherosclerotic plaques. We hypothesized that increased CXCL4 plasma levels may be associated with features of plaque instability resulting in adverse cardiovascular events. Specifically, we sought to determine whether CXCL4 levels are correlated with specific features of coronary artery disease including (1) plaque volume, (2) calcium score, (3) degree of stenosis, or (4) vascular remodeling. METHODS AND RESULTS:CXCL4 plasma levels were measured by ELISA in 217 patients undergoing CCTA for suspected CAD (mean age 64.2 ± 9.4 years, 107 (49.3%) male). Mean CXCL4 plasma levels were 12.5 ± 4.6 ng/mL. There was no significant correlation between CXCL4 levels and any clinical or demographic parameters including cardiovascular risk factors. CXCL4 plasma levels did not differ between patient with or without coronary artery disease (CAD: 12.5 ± 4.5 ng/ml, no CAD: 12.5 ± 4.8 ng/ml). Neither univariate nor multivariate analysis showed an association between CXCL4 levels and plaque volume, total calcium score, degree of stenosis, or vascular remodeling. Subgroup analysis of patients with CAD as confirmed by CCTA did not show any association of CXCL4 levels with the extent of CAD. CONCLUSIONS:While CXCL4 may be present and active within the arterial wall, local increase of CXCL4 may not translate into systemically elevated CXCL4 levels. Further studies will have to test whether CXCL4 may still represent a suitable therapeutic target in human atherosclerosis.
Project description:Brachial-artery pulse wave velocity (baPWV) is a simple and reliable tool for measurement of arterial stiffness. Our previous studies suggested that baPWV is associated with the presence and severity of coronary artery disease (CAD) and the risk of cardiovascular events. In the present data article, we provided supplementary data supporting the independent prognostic value of arterial stiffness, assessed by baPWV, in patients with suspected CAD (Hwang et al., 2017) . The data was obtained from 523 patients undergoing coronary CT angiography (CCTA), and baPWV was measured at the time of CCTA. Patients with vulnerable coronary plaque or obstructive CAD on CCTA had higher age, more cardiovascular risk factors, and higher baPWV values. Given the significant association between high baPWV and the presence of vulnerable plaque or obstructive CAD as shown in this data article, the prognostic value of baPWV was further assessed in subgroups divided according to the CCTA findings (vulnerable plaque or obstructive CAD). In each subgroup by CCTA findings, multivariable Cox proportional hazard model analysis showed that high baPWV was an independent risk factor for cardiovascular events even after adjusting for clinical risk factors.
Project description:To evaluate the predictive value of carotid atherosclerotic disease (CAD) and intima-media thickness (IMT) on incident cardiovascular disease and mortality in hemodialysis patients.Multicenter, observational, prospective study including 110 patients, followed-up to 6 years. Carotid doppler ultrasonographic findings were classified in 4 degrees of severity: 1) IMT <0.9 mm, 2) IMT >0.9 mm, 3) carotid plaque with stenosis <50% and 4) plaque with stenosis >50%. The associations between IMT and CAD and cardiovascular events, total and cardiovascular mortality were assessed.83% of the patients had atherosclerotic plaques (CAD degrees 3-4). During follow-up, 29.1% of patients experienced cardiovascular events, and 28.2% died, 38.7% of cardiovascular origin. The presence of plaques was associated with cardiovascular events (p = 0.03) while calcified plaques were associated with both cardiovascular events (p = 0.01), cardiovascular mortality (p = 0.03) and non-significantly with overall mortality (p = 0.08) in the survival analysis. Carotid IMT was not associated with outcomes. Cardiovascular events correlated with CAD severity (HR 2.27, 95% CI 1.13-4.54), age (HR 1.04, 1.01-1.06), previous cardiovascular disease (HR 1.75, 1.05-4.42), dyslipidemia (HR 2.25, 1.11-4.53), lipoprotein (a) (HR 1.01, 1.00-1.02), troponin I (HR 3.89, 1.07-14.18), fibrinogen levels (HR 1.38, 0.98-1.94) and antiplatelet therapy (HR 2.14, 1.04-4.4). In an age-adjusted multivariate model, cardiovascular events were independently associated with previous coronary artery disease (HR 3.29, 1.52-7.15) and lipoprotein (a) (HR 1.01, 1.00-1.02).The presence of carotid plaques and, especially, calcified plaques, are predictors of new cardiovascular events and cardiovascular mortality in hemodialysis patients, while IMT was not. The prognostic value of calcified plaques should be confirmed in future studies.
Project description:BACKGROUND:Risk stratification is crucial to improve tailored therapy in patients with suspected coronary artery disease (CAD). This study investigated the ability of targeted proteomics to predict presence of high-risk plaque or absence of coronary atherosclerosis in patients with suspected CAD, defined by coronary computed tomography angiography (CCTA). METHODS:Patients with suspected CAD (n?=?203) underwent CCTA. Plasma levels of 358 proteins were used to generate machine learning models for the presence of CCTA-defined high-risk plaques or complete absence of coronary atherosclerosis. Performance was tested against a clinical model containing generally available clinical characteristics and conventional biomarkers. FINDINGS:A total of 196 patients with analyzable protein levels (n?=?332) was included for analysis. A subset of 35 proteins was identified predicting the presence of high-risk plaques. The developed machine learning model had fair diagnostic performance with an area under the curve (AUC) of 0·79?±?0·01, outperforming prediction with generally available clinical characteristics (AUC?=?0·65?±?0·04, p?<?0·05). Conversely, a different subset of 34 proteins was predictive for the absence of CAD (AUC?=?0·85?±?0·05), again outperforming prediction with generally available characteristics (AUC?=?0·70?±?0·04, p?<?0·05). INTERPRETATION:Using machine learning models, trained on targeted proteomics, we defined two complementary protein signatures: one for identification of patients with high-risk plaques and one for identification of patients with absence of CAD. Both biomarker subsets were superior to generally available clinical characteristics and conventional biomarkers in predicting presence of high-risk plaque or absence of coronary atherosclerosis. These promising findings warrant external validation of the value of targeted proteomics to identify cardiovascular risk in outcome studies. FUND: This study was supported by an unrestricted research grant from HeartFlow Inc. and partly supported by a European Research Area Network on Cardiovascular Diseases (ERA-CVD) grant (ERA CVD JTC2017, OPERATION). Funders had no influence on trial design, data evaluation, and interpretation.
Project description:Prior studies identified the incremental value of non-invasive imaging by CT-angiogram (CTA) to detect high-risk coronary atherosclerotic plaques. Due to their superficial locations, larger calibers and motion-free imaging, the carotid arteries provide the best anatomic access for the non-invasive characterization of atherosclerotic plaques. We aim to assess the ability of predicting obstructive coronary artery disease (CAD) or acute myocardial infarction (MI) based on high-risk carotid plaque features identified by CTA. We retrospectively examined carotid CTAs of 492 patients that presented with acute stroke to characterize the atherosclerotic plaques of the carotid arteries and examined development of acute MI and obstructive CAD within 12-months. Carotid lesions were defined in terms of calcifications (large or speckled), presence of low-attenuation plaques, positive remodeling, and presence of napkin ring sign. Adjusted relative risks were calculated for each plaque features. Patients with speckled (<3 mm) calcifications and/or larger calcifications on CTA had a higher risk of developing an MI and/or obstructive CAD within 1 year compared to patients without (adjusted RR of 7.51, 95%CI 1.26-73.42, P?=?0.001). Patients with low-attenuation plaques on CTA had a higher risk of developing an MI and/or obstructive CAD within 1 year than patients without (adjusted RR of 2.73, 95%CI 1.19-8.50, P?=?0.021). Presence of carotid calcifications and low-attenuation plaques also portended higher sensitivity (100 and 79.17%, respectively) for the development of acute MI. Presence of carotid calcifications and low-attenuation plaques can predict the risk of developing acute MI and/or obstructive CAD within 12-months. Given their high sensitivity, their absence can reliably exclude 12-month events.
Project description:Coronary stenosis severity is both a powerful and a still debated predictor of prognosis in coronary artery disease. Coronary computed tomographic angiography (CCTA) has emerged as a noninvasive technique that enables anatomic visualization of coronary artery disease (CAD). CCTA with newer applications, plaque characterization and physiologic/functional evaluation, allows a comprehensive diagnostic and prognostic assessment of otherwise low-intermediate subjects for primary prevention. CCTA measures the overall plaque burden, differentiates plaque subtypes, and identifies high-risk plaque with good reproducibility. Research in this field may also advance towards an era of personalized risk prediction and individualized medical therapy. It has been demonstrated that statins may delay plaque progression and change some plaque features. The potential effects on plaque modifications induced by other medical therapies have also been investigated. Although it is not currently possible to recommend routinely serial scans to monitor the therapeutic efficacy of medical interventions, the plaque modulation, as a part of risk modification, appears a feasible strategy. In this review we summarize the current evidence regarding vulnerable plaque and effects of lipid lowering therapy on morphological features of CAD. We also discuss the potential ability of CCTA to characterize coronary atherosclerosis, stratify prognosis of asymptomatic subjects, and guide medical therapy.