Article

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: 15.34). 10/2010; 56(17):1397-406. DOI: 10.1016/j.jacc.2010.06.030
Source: PubMed

ABSTRACT 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.

Download full-text

Full-text

Available from: Hagen Kälsch, Jul 13, 2014
1 Follower
 · 
112 Views
  • Source
    [Show abstract] [Hide abstract]
    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 · 3.97 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Long-term exposures to particulate matter air pollution (PM2.5 and PM10) and high traffic load have been shown to be associated with markers of systemic inflammation. Epidemiological investigations have focused primarily on total PM, which represents a mixture of pollutants originating from different sources. We investigated associations between source-specific PM and high sensitive C-reactive protein (hs-CRP), an independent predictor of cardiovascular disease. We used data from the first (2000-2003) and second examination (2006-2008) of the Heinz Nixdorf Recall study, a prospective population-based German cohort of initially 4,814 participants (45 to 75 years). We estimated residential long-term exposure to local traffic- and industry-specific fine PM at participants' residences with a chemistry transport model. We used a linear mixed model with a random participant intercept to estimate associations of source-specific PM and natural log-transformed hs-CRP, controlling for age, sex, education, BMI, LDL/HDL, smoking variables, physical activity, season, humidity, and city (8,204 total observations). A 1-µg/m(3) increase in total PM2.5 was associated with a 4.53% increase in hs-CRP concentration (95% CI: 2.76, 6.33%). Hs-CRP was 17.89% (95% CI: 7.66, 29.09 6%) and 7.96% (95% CI: 3.45, 12.67%) higher in association with 1-µg/m(3) increases in traffic- and industry-specific PM2.5, respectively. Results for PM10 were similar. Long-term exposure to local traffic-specific PM (PM2.5, PM10) was more strongly associated with systemic inflammation than total PM. Associations of local industry-specific PM were slightly stronger, but not significantly different from, associations with total PM.
    Environmental Health Perspectives 04/2014; 122(7). DOI:10.1289/ehp.1307081 · 7.03 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: AimIrregular meal intakes have several harmful effects on health and yet it is largely unknown which factors are related to irregular meal intakes. In order to understand variations in regularity of meal intakes, associations between sociodemographics, health conditions, health behaviours, work characteristics and meal intakes were studied. Subject and methodsCross-sectional data of 2,395 men and 2,419 women (45–75years) participating in the Heinz Nixdorf Recall Study, a population-based prospective cohort study in Germany, were analysed. Information on the regularity of breakfast, lunch and supper intake was obtained from a self-reported questionnaire. Multivariate ordinal regression models were run to estimate associations between sociodemographics, health conditions, health behaviours, work characteristics and meal intakes. ResultsFindings confirm an association between age [odds ratio (OR) 0.95, 95% confidence interval (CI) 0.95–0.97], number of household members (OR 0.86, 95% CI 0.79–0.95), diabetes (OR 0.65, 95% CI 0.50–0.84), fruit and vegetable consumption (OR 0.63, 95% CI 0.54–0.73) and regular meal intakes. High body mass index (OR 1.03, 95% CI 1.01–1.06), being divorced, separated or widowed (OR 1.57, 95% CI 1.17–2.10), smoking (OR 1.79, 95% CI 1.51–2.11) and daily working hours (OR 1.06, 95% CI 1.03–1.08) were related to irregular meal intakes. ConclusionThese results indicate that indicators of social support such as number of household members or marital status, other health behaviours and work conditions influence the regularity of meal intakes rather than socioeconomic conditions per se. KeywordsMeal intake–Diet–Health behaviour–Sociodemographic characteristics–Diabetes–Work status
    Journal of Public Health 10/2011; 19(5):453-462. DOI:10.1007/s10389-011-0399-1 · 2.06 Impact Factor