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Cited by 49Cardiac Imaging and DiagnosticsMedical Imaging and Pathology StudiesCardiovascular Health and Disease Prevention

Sex Differences in Coronary Artery and Thoracic Aorta Calcification and Their Association With Cardiovascular Mortality in Heavy Smokers

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Lessmann, Nikolas, de Jong, Pim A., Celeng, Csilla, Takx, Richard A.P., Viergever, Max A., van Ginneken, Bram, Išgum, Ivana·2019·JACC: Cardiovascular Imaging
DOI 10.1016/j.jcmg.2018.10.026
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Abstract

Objectives The aim of this study was to investigate sex differences in the prevalence, extent, and association of coronary artery calcium (CAC) and thoracic aorta calcium (TAC) scores with cardiovascular mortality in a population eligible for lung screening. Background CAC and TAC scores derived from chest computed tomography (CT) might be useful biomarkers for individualized cardiovascular disease prevention and could be especially relevant in high-risk populations such as heavy smokers. Therefore, it is important to know the prevalence of arterial calcifications in male and female heavy smokers, and if there are differences in the predictive value calcifications carry. Methods We performed a nested case-control study with 5,718 participants of the CT arm of the NLST (National Lung Screening Trial). Prevalence and extent of CAC and TAC were resampled to the full cohort to provide unbiased estimates of the typical calcium burden of male and female heavy smokers. Weighted Cox proportional hazards regression was used to assess differences in the association of CAC and TAC scores with all-cause and cardiovascular mortality. Results CAC was substantially more common and more severe in men (prevalence: 81% vs. 60%; median volume: 104 mm³ vs. 12 mm³). Women had CAC comparable to that of men who were 10 years younger. TAC was equally common in men and women, with a tendency to be more pronounced in women (prevalence: 92% vs. 93%; median volume: 388 mm³ vs. 404 mm³). Both types of calcification were associated with increased cardiovascular and all-cause mortality. TAC scores improved the prediction of coronary heart disease mortality over CAC in men, but not in women. In both sexes, TAC, but not CAC, was associated with cardiovascular mortality other than coronary heart disease. Conclusions CAC develops later in women, whereas TAC develops equally in both sexes. CAC is strongly associated with coronary heart disease, whereas TAC is especially associated with extracardiac vascular mortality in either sex.

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  • Other studies that investigated deep learning algorithms for automated coronary calcium quantification used smaller cohorts or proprietary technologies.

    “Although other studies have investigated deep learning algorithms for automated coronary calcium quantification34–42, they used smaller cohorts or proprietary technologies.”

    From Deep convolutional neural networks to predict cardiovascular risk from computed tomography (2021) · cites this paper as [35]

    The Image Analysis section says the study used automatic, in-house software with a deep-learning approach to score coronary calcification. The Statistical Analysis section reports 5,718 analyzed scans, but the paper does not establish that this cohort was smaller than the citing study’s or that the software was proprietary. (LLM, conf=0.84)

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Research works printed but not linked: 39

  1. Lerner DJ, Kannel WB. Patterns of coronary heart disease morbidity and mortality in the sexes: a 26-year follow-up of the Framingham popula- tion. Am Heart J 1986;111:383-90.
  2. Detrano R, Guerci AD, Carr JJ, et al. Coronary calcium as a predictor of coronary events in four racial or ethnic groups. N Engl J Med 2008;358: 1336-45.
  3. Mets OM, de Jong PA, Prokop M. Computed tomographic screening for lung cancer: an op- portunity to evaluate other diseases. JAMA 2012; 308:1433-4.
  4. Chiles C, Duan F, Gladish GW, et al. Association of coronary artery calcification and mortality in the National Lung Screening Trial: a comparison of three scoring methods. Radiology 2015;276:82-90.
  5. Jacobs PC, Gondrie MJA, van der Graaf Y, et al. Coronary artery calcium can predict all-cause mortality and cardiovascular events on low-dose CT screening for lung cancer. Am J Roentgenol 2012;198:505-11.
  6. Mets OM, Vliegenthart R, Gondrie MJ, et al. Lung cancer screening CT-based prediction of cardiovascular events. J Am Coll Cardiol Img 2013; 6:899-907.
  7. Nasir K, Roguin A, Sarwar A, Rumberger JA, Blumenthal RS. Gender differences in coronary arteries and thoracic aorta calcification. Arte- rioscler Thromb Vasc Biol 2007;27:1220-2.
  8. Jacobs PC, Prokop M, van der Graaf Y, et al. Comparing coronary artery calcium and thoracic aorta calcium for prediction of all-cause mortality and cardiovascular events on low-dose non- gated computed tomography in a high-risk population of heavy smokers. Atherosclerosis 2010;209:455-62.
  9. Hermann DM, Lehmann N, Gronewold J, et al. Thoracic aortic calcification is associated with incident stroke in the general population in addi- tion to established risk factors. Eur Heart J Car- diovasc Imaging 2015;16:684-90.
  10. National Lung Screening Trial Research Team, Aberle DR, Adams AM, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011;365:395-409.
  11. National Lung Screening Trial Research Team. The National Lung Screening Trial: overview and study design. Radiology 2011;258:243-53.
  12. Aberle DR, Adams AM, Berg CD, et al. Baseline characteristics of participants in the randomized National Lung Screening Trial. J Natl Cancer Inst 2010;102:1771-9.
  13. Lessmann N, van Ginneken B, Zreik M, et al. Automatic calcium scoring in low-dose chest CT using deep neural networks with dilated convo- lutions. IEEE Trans Med Imaging 2018;37:615-25.
  14. Hecht HS. Coronary artery calcium scanning. J Am Coll Cardiol Img 2015;8:579-96.
  15. Ohnesorge B, Flohr T, Fischbach R, et al. Reproducibility of coronary calcium quantification in repeat examinations with retrospectively ECG-gated multisection spiral CT. Eur Radiol 2002;12:1532-40.
  16. Rao JNK, Scott AJ. On simple adjustments to chi-square tests with sample survey data. Ann Stat 1987;15:385-97.
  17. Lumley T, Scott AJ. Two-sample rank tests under complex sampling. Biometrika 2013;100:831-42.
  18. Therneau TM, Grambsch PM. Modeling Sur- vival Data: Extending the Cox Model. New York: Springer; 2000.
  19. Donders ART, van der Heijden GJMG, Stijnen T, Moons KGM. Review: a gentle intro- duction to imputation of missing values. J Clin Epidemiol 2006;59:1087-91.
  20. Hoff JA, Chomka EV, Krainik AJ, Daviglus M, Rich S, Kondos GT. Age and gender distributions of coronary artery calcium detected by electron beam tomography in 35,246 adults. Am J Cardiol 2001;87:1335-9.
  21. Nasir K, Raggi P, Rumberger JA, et al. Coronary artery calcium volume scores on electron beam tomography in 12,936 asymptomatic adults. Am J Cardiol 2004;93:1146-9.
  22. McClelland RL, Chung H, Detrano R, Post W, Kronmal RA. Distribution of coronary artery cal- cium by race, gender, and age: results from the Multi-Ethnic Study of Atherosclerosis (MESA). Circulation 2006;113:30-7.
  23. Hoffmann U, Massaro JM, Fox CS, Manders E, O'Donnell CJ. Defining normal distributions of coronary artery calcium in women and men (from the Framingham Heart Study). Am J Cardiol 2008; 102:1136-41.
  24. Jairam PM, de Jong PA, Mali WP, et al. Age and sex based reference values for incidental coronary artery and thoracic aorta calcifications on routine clinical chest CT: a powerful tool to appreciate available imaging findings. Atherosclerosis 2014; 235:546-53.
  25. Ohmoto-Sekine Y, Yanagibori R, Amakawa K, et al. Prevalence and distribution of coronary calcium in asymptomatic Japanese subjects in lung cancer screening computed tomography. J Cardiol 2016;67:449-54.
  26. Takasu J, Katz R, Nasir K, et al. Relationships of thoracic aortic wall calcification to cardiovas- cular risk factors: the Multi-Ethnic Study of Atherosclerosis (MESA). Am Heart J 2008;155: 765-71.
  27. Wong ND, Sciammarella M, Arad Y, et al. Relation of thoracic aortic and aortic valve calcium to coronary artery calcium and risk assessment. Am J Cardiol 2003;92:951-5.
  28. Kälsch H, Lehmann N, Möhlenkamp S, et al. Prevalence of thoracic aortic calcification and its relationship to cardiovascular risk factors and coronary calcification in an unselected population- based cohort: the Heinz Nixdorf Recall Study. Int J Cardiovasc Imaging 2012;29:207-16.
  29. Kardys I, Vliegenthart R, Oudkerk M, Hofman A, Witteman JC. The female advantage in cardiovascular disease: do vascular beds contribute equally? Am J Epidemiol 2007;166: 403-12.
  30. Nakanishi R, Li D, Blaha MJ, et al. All-cause mortality by age and gender based on coronary artery calcium scores. Eur Heart J Cardiovasc Im- aging 2016;17:1305-14.
  31. Bellasi A, Lacey C, Taylor AJ, et al. Comparison of prognostic usefulness of coronary artery calcium in men versus women (results from a meta-and pooled analysis estimating all-cause mortality and coronary heart disease death or myocardial infarction). Am J Cardiol 2007;100: 409-14.
  32. Raggi P, Shaw LJ, Berman DS, Callister TQ. Gender-based differences in the prognostic value of coronary calcification. J Womens Health 2004; 13:273-83.
  33. LaMonte MJ, FitzGerald SJ, Church TS, et al. Coronary artery calcium score and coronary heart disease events in a large cohort of asymptomatic men and women. Am J Epidemiol 2005;162:421-9.
  34. McEvoy JW, Blaha MJ, Rivera JJ, et al. Mortality rates in smokers and nonsmokers in the presence or absence of coronary artery calcification. J Am Coll Cardiol Img 2012;5: 1037-45.
  35. Budoff MJ, Nasir K, Katz R, et al. Thoracic aortic calcification and coronary heart disease events: the Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis 2011;215:196-202.
  36. Budoff MJ, Nasir K, Kinney GL, et al. Coronary artery and thoracic calcium on noncontrast thoracic CT scans: comparison of ungated and gated examinations in patients from the COPD Gene cohort. J Cardiovasc Comput Tomogr 2011;5: 113-8.
  37. Hecht HS, Cronin P, Blaha MJ, et al. 2016 SCCT/STR guidelines for coronary artery calcium scoring of noncontrast noncardiac chest CT scans: A report of the Society of Cardiovascular Computed Tomography and Society of Thoracic Radiology. J Cardiovasc Comput Tomogr 2017;11: 74-84.
  38. Bernheim A, Auffermann WF, Stillman AE. The dubious value of coronary calcium scoring on lung cancer screening CT. J Am Coll Radiol 2017;14: 343-4.
  39. Ridker PM, Everett BM, Thuren T, et al. Anti- inflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med 2017;377: 1119-31.

Cited by

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Authors
Lessmann, N., de Jong, P. A., Celeng, C., Takx, R. A. P., Viergever, M. A., van Ginneken, B., & Išgum, I.
Affiliations
  • University Medical Center Utrecht (NL)
  • Utrecht University (NL)
Corresponding author
Lessmann, Nikolas
ORCID
Venue
JACC: Cardiovascular Imaging
Publisher
Elsevier BV
Published
2019-09
Volume
12
Issue
9
Pages
1808-1817
ISSN
  • 1876-7591 (ISSN-L)
  • 1936-878X
DOI
10.1016/j.jcmg.2018.10.026
OpenAlex
W2909651166
Cited by
49
References
1
Citations by year
2026: 6 · 2025: 7 · 2024: 12 · 2023: 9 · 2022: 3 · 2021: 6 · 2020: 5 · 2019: 1
FWCI
2.48
Type
journal article
Language
en
Open access
Licence
Locations
  • JACC. Cardiovascular imaging (publishedVersion)
  • PubMed (publishedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
  • Pure Amsterdam UMC (submittedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
  • Radboud Repository (Radboud University) (submittedVersion, other-oa)
  • Utrecht University Repository (Utrecht University) (submittedVersion)
Funders
National Cancer Institute
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Cardiac Imaging and Diagnostics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Medical Imaging and Pathology Studies
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
Keywords
coronary artery calcification, sex differences, heavy smokers, cardiovascular mortality, all-cause mortality, coronary heart disease mortality, lung cancer screening, National Lung Screening Trial, arterial calcification, cardiovascular risk prediction
MeSH terms
Computed Tomography Angiography, Smokers, Age Factors, Aged, Aorta, Thoracic, Aortic Diseases, Aortography, Cause of Death, Coronary Artery Disease, Female, Humans, Male, Middle Aged, Retrospective Studies, Risk Factors, Sex Factors, Smoking, Prevalence, Coronary Angiography, Sex Distribution, Risk Assessment, Vascular Calcification

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