Coronary Risk Stratification, Discrimination, and Reclassification Improvement Based on Quantification of Subclinical Coronary Atherosclerosis The Heinz Nixdorf Recall Study

Department of Cardiology, West-German Heart Center Essen, University Duisburg-Essen, Essen, Germany.
Journal of the American College of Cardiology (Impact Factor: 16.5). 10/2010; 56(17):1397-406. DOI: 10.1016/j.jacc.2010.06.030
Source: PubMed


The purpose of this study was to determine net reclassification improvement (NRI) and improved risk prediction based on coronary artery calcification (CAC) scoring in comparison with traditional risk factors.
CAC as a sign of subclinical coronary atherosclerosis can noninvasively be detected by CT and has been suggested to predict coronary events.
In 4,129 subjects from the HNR (Heinz Nixdorf Recall) study (age 45 to 75 years, 53% female) without overt coronary artery disease at baseline, traditional risk factors and CAC scores were measured. Their risk was categorized into low, intermediate, and high according to the Framingham Risk Score (FRS) and National Cholesterol Education Panel Adult Treatment Panel (ATP) III guidelines, and the reclassification rate based on CAC results was calculated.
After 5 years of follow-up, 93 coronary deaths and nonfatal myocardial infarctions occurred (cumulative risk 2.3%; 95% confidence interval: 1.8% to 2.8%). Reclassifying intermediate (defined as 10% to 20% and 6% to 20%) risk subjects with CAC <100 to the low-risk category and with CAC ≥400 to the high-risk category yielded an NRI of 21.7% (p = 0.0002) and 30.6% (p < 0.0001) for the FRS, respectively. Integrated discrimination improvement using FRS variables and CAC was 1.52% (p < 0.0001). Adding CAC scores to the FRS and National Cholesterol Education Panel ATP III categories improved the area under the curve from 0.681 to 0.749 (p < 0.003) and from 0.653 to 0.755 (p = 0.0001), respectively.
CAC scoring results in a high reclassification rate in the intermediate-risk cohort, demonstrating the benefit of imaging of subclinical coronary atherosclerosis. Our study supports its application, especially in carefully selected individuals with intermediate risk.

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Available from: Hagen Kälsch, Jul 13, 2014
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    • "In particular, adding CAC score (!400 Agatston units, AU) to traditional coronary heart disease (CHD) scoring systems improved prediction of coronary death and nonfatal AMI in asymptomatic subjects at intermediate risk (i.e. Framingham risk score of 10e20% and Adult Treatment Panel score of 6e20%), with reclassification to the high-risk category [9]. As a consequence, the American College of Cardiology Foundation/American Heart Association guidelines recommend to include measurement of CAC by multidetector or electron beam computer tomography (CT) in CVD risk assessment in these individuals [10]. "
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    ABSTRACT: Vascular calcification is an unfavorable event in the natural history of atherosclerosis that predicts cardiovascular morbidity and mortality. However, increasing evidence suggests that different calcification patterns are associated with different or even opposite histopathological and clinical features, reflecting the dual relationship between inflammation and calcification. In fact, initial calcium deposition in response to pro-inflammatory stimuli results in the formation of spotty or granular calcification ("microcalcification"), which induces further inflammation. This vicious cycle favors plaque rupture, unless an adaptive response prevails, with blunting of inflammation and survival of vascular smooth muscle cells (VSMCs). VSMCs promote fibrosis and also undergo osteogenic transdifferentiation, with formation of homogeneous or sheet-like calcification ("macrocalcification"), that stabilizes the plaque by serving as a barrier towards inflammation. Unfortunately, little is known about the molecular mechanisms regulating this adaptive response. The advanced glycation/lipoxidation endproducts (AGEs/ALEs) have been shown to promote vascular calcification and atherosclerosis. Recent evidence suggests that two AGE/ALE receptors, RAGE and galectin-3, modulate in divergent ways, not only inflammation, but also vascular osteogenesis, by favoring "microcalcification" and "macrocalcification", respectively. Galectin-3 seems essential for VSMC transdifferentiation into osteoblast-like cells via direct modulation of the WNT-β-catenin signaling, thus driving formation of "macrocalcification", whereas RAGE favors deposition of "microcalcification" by promoting and perpetuating inflammation and by counteracting the osteoblastogenic effect of galectin-3. Further studies are required to understand the molecular mechanisms regulating transition from "microcalcification" to "macrocalcification", thus allowing to design therapeutic strategies which favor this adaptive process, in order to limit the adverse effects of established atherosclerotic calcification. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    Atherosclerosis 12/2014; 238(2):220-230. DOI:10.1016/j.atherosclerosis.2014.12.011 · 3.99 Impact Factor
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    • "Recently, cardiovascular risk estimation tools have begun to include measures of subclinical atherosclerosis and newer markers of risk to improve risk discrimination and classification [7e9]. In the Multi-Ethnic Study of Atherosclerosis (MESA) [7], the Rotterdam Study [8], and the Heinz Nixdorf Recall (HNR) study [9], the strongest measures of risk were coronary artery calcium (CAC) score and brain natriuretic peptide (BNP), two " novel " markers excluded from the Framingham Risk Score and the UKPDS. It therefore seems reasonable to explore whether some newer markers of risk could better discriminate risk among patients with T2DM. "
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    ABSTRACT: Objective: It is unclear to what extent subclinical cardiovascular disease (CVD) such as coronary artery calcium (CAC), carotid intima-media thickness (CIMT), and brachial flow-mediated dilation (FMD) are mediators of the known associations between traditional cardiovascular risk factors and incident CVD events. We assessed the portion of the effects of risk factors on incident CVD events that are mediated through CAC, CIMT, and FMD. Approach and results: Six thousand three hundred fifty-five of 6814 Multi-Ethnic Study of Atherosclerosis participants were included. Nonlinear implementation of structural equation modeling (STATA mediation package) was used to assess whether CAC, CIMT, or FMD are mediators of the association between traditional risk factors and incident CVD event. Mean age was 62 years, with 47% men, 12% diabetics, and 13% current smokers. After a mean follow-up of 7.5 years, there were 539 CVD adjudicated events. CAC showed the highest mediation while FMD showed the least. Age had the highest percent of total effect mediated via CAC for CVD outcomes, whereas current cigarette smoking had the least percent of total effect mediated via CAC (percent [95% confidence interval]: 80.2 [58.8-126.7] versus 10.6 [6.1-38.5], respectively). Body mass index showed the highest percent of total effect mediated via CIMT (17.7 [11.6-38.9]); only a negligible amount of the association between traditional risk factors and CVD was mediated via FMD. Conclusions: Many of the risk factors for incident CVD (other than age, sex, and body mass index) showed a modest level of mediation via CAC, CIMT, and FMD, suggesting that current subclinical CVD markers may not be optimal intermediaries for gauging upstream risk factor modification.
    Arteriosclerosis Thrombosis and Vascular Biology 05/2014; 34(8). DOI:10.1161/ATVBAHA.114.303753 · 6.00 Impact Factor
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    • "Therefore, the CVD risk stratification algorithms have recently gained increasing attention [4, 5]. In addition, it can be noticed that the majority of serious cardiovascular events occur in subjects or cases at low or intermediate risk [6, 7]. However, the population-based risk algorithms suffer from poor individual predictive ability. "
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    ABSTRACT: A novel method for characterizing and visualizing the progression of waves along the walls of the carotid artery is presented. The new approach is noninvasive and able to simultaneously capture the spatial and the temporal propagation of wavy patterns along the walls of the carotid artery in a completely automated manner. Spatiotemporal and spatiospectral 2D maps describing these patterns (in both the spatial and the frequency domains, resp.) were generated and analyzed by visual inspection as well as automatic feature extraction and classification. Three categories of cases were considered: pathological elderly, healthy elderly, and healthy young cases. Automatic differentiation, between cases of these three categories, was achieved with a sensitivity of 97.1% and a specificity of 74.5%. Two features were proposed and computed to measure the homogeneity of the spatiospectral 2D map which presents the spectral characteristics of the carotid artery wall's wavy motion pattern which are related to the physical, mechanical (e.g., elasticity), and physiological properties and conditions along the artery. These results are promising and confirm the potential of the proposed method in providing useful information which can help in revealing the physiological condition of the cardiovascular system.
    International Journal of Biomedical Imaging 05/2014; 2014:876267. DOI:10.1155/2014/876267
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