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Density and morphology of coronary artery calcium for the prediction of cardiovascular events: insights from the Framingham Heart Study

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Abstract

Objectives

To investigate the association between directly measured density and morphology of coronary artery calcium (CAC) with cardiovascular disease (CVD) events, using computed tomography (CT).

Methods

Framingham Heart Study (FHS) participants with CAC in noncontrast cardiac CT (2002–2005) were included and followed until 2016. Participants with known CVD or uninterpretable CT scans were excluded. We assessed and correlated (Spearman) CAC density, CAC volume, and the number of calcified segments. Moreover, we counted morphology features including shape (cylindrical, spherical, semi-tubular, and spotty), location (bifurcation, facing pericardium, or facing myocardium), and boundary regularity. In multivariate Cox regression analyses, we associated all CAC characteristics with CVD events (CVD-death, myocardial infarction, stroke).

Results

Among 1330 included participants (57.8 ± 11.7 years; 63% male), 73 (5.5%) experienced CVD events in a median follow-up of 9.1 (7.8–10.1) years. CAC density correlated strongly with CAC volume (Spearman’s ρ = 0.75; p < 0.001) and lower number of calcified segments (ρ = − 0.86; p < 0.001; controlled for CAC volume). In the survival analysis, CAC density was associated with CVD events independent of Framingham risk score (HR (per SD) = 2.09; 95%CI, 1.30–3.34; p = 0.002) but not after adjustment for CAC volume (p = 0.648). The extent of spherically shaped and pericardially sided calcifications was associated with fewer CVD events accounting for the number of calcified segments (HR (per count) = 0.55; 95%CI, 0.31–0.98; p = 0.042 and HR = 0.66; 95%CI, 0.45–0.98; p = 0.039, respectively).

Conclusions

Directly measured CAC density does not predict CVD events due to the strong correlation with CAC volume. The spherical shape and pericardial-sided location of CAC are associated with fewer CVD events and may represent morphological features related to stable coronary plaques.

Key Points

• Coronary calcium density may not be independently associated with cardiovascular events.

• Coronary calcium density correlates strongly with calcium volume.

• Spherical shape and pericardial-sided location of CAC are associated with fewer CVD events.

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Abbreviations

AS:

Agatston score

AUC:

Area under the curve

BMI:

Body mass index

CAC:

Coronary artery calcium

CT:

Computed tomography

CVD:

Cardiovascular disease

FHS:

Framingham Heart Study

FRS:

Framingham risk score

HU:

Hounsfield units

ICC:

Intra-class correlation coefficient

IVUS:

Intravascular ultrasound

LAD:

Left anterior descending

LCx:

Left circumflex artery

MESA:

Multi-Ethnic Study of Atherosclerosis

RCA:

Right coronary artery

VIF:

Variance inflation factor

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Acknowledgments

This study used in part data and resources from the Framingham Heart Study of the National Heart, Lung, and Blood Institute of the National Institutes of Health and Boston University School of Medicine. Dr. Borek Foldyna, Dr. Udo Hoffmann, and Dr. Christopher J. O’Donnell have had full access to all the study data and take responsibility for the data integrity and the analysis accuracy.

Our project was presented at the SCCT 2018 in Dallas, TX, USA, and received the Siemens Outstanding Academic Research (SOAR) award.

Funding

The authors state that this work has not received any funding.

Author information

Authors and Affiliations

  1. Cardiac MR PET CT Program, Massachusetts General Hospital, Harvard Medical School, 165 Cambridge Street, Suite 400, Boston, MA, 02114, USA

    Borek Foldyna, Parastou Eslami, Jan-Erik Scholtz, Michael T. Lu, Maros Ferencik & Udo Hoffmann

  2. Radiology and Nuclear Medicine, CARIM, Maastricht University Medical Centre, Maastricht, Netherlands

    Borek Foldyna & Hugo J. W. L. Aerts

  3. Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Frankfurt, Germany

    Jan-Erik Scholtz

  4. Department of Mathematics, Boston University, Boston, MA, USA

    Kristin Baltrusaitis, Joseph M. Massaro & Ralph B. D’Agostino Sr

  5. Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, USA

    Maros Ferencik

  6. Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Hugo J. W. L. Aerts

  7. The Framingham Heart Study of the National Heart, Lung, and Blood Institute, Framingham, MA, USA

    Christopher J. O’Donnell

  8. Cardiology Section, VA Boston Healthcare System, West Roxbury, MA, USA

    Christopher J. O’Donnell

Authors
  1. Borek Foldyna
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  2. Parastou Eslami
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  4. Kristin Baltrusaitis
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  6. Joseph M. Massaro
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  7. Ralph B. D’Agostino Sr
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  8. Maros Ferencik
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  9. Hugo J. W. L. Aerts
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  10. Christopher J. O’Donnell
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  11. Udo Hoffmann
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Corresponding author

Correspondence to Borek Foldyna.

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Conflict of interest

Dr. Foldyna received unrelated funding from the German Research Foundation (DFG), project 290004377 (FO993/1) and support from the National Institutes of Health 5K24HL113128-07. Dr. Hoffmann received unrelated Research Grants (U01HL092040, U01HL092022, Heart Flow Inc., MedImmune; KOWA Inc.). Dr. Ferencik reports receiving an unrelated grant from the American Heart Association. This work was further supported by the NIH Heart, Lung, and Blood Institute’s Framingham Heart Study (contract nos. N01- HC-25195, HL076784, AG028321, HL070100, HL060040, HL080124, HL071039, HL077447, HL107385). The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

Study subjects or cohorts overlap

Some study subjects or cohorts have been previously reported in the scope of prior Framingham Heart Study investigations.

This study used in part data and resources from the Framingham Heart Study of the National Heart, Lung, and Blood Institute of the National Institutes of Health and Boston University School of Medicine. Dr. Borek Foldyna, Dr. Udo Hoffmann, and Dr. Christopher J. O’Donnell have had full access to all the study data and take responsibility for the data integrity and the analysis accuracy.

Methodology

• retrospective

• observational

• performed at one institution (study center)

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Foldyna, B., Eslami, P., Scholtz, JE. et al. Density and morphology of coronary artery calcium for the prediction of cardiovascular events: insights from the Framingham Heart Study. Eur Radiol 29, 6140–6148 (2019). https://doi.org/10.1007/s00330-019-06223-7

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  • DOI: https://doi.org/10.1007/s00330-019-06223-7

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