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Sleep apnea and carotid atherosclerosis in the Multi-Ethnic Study of Atherosclerosis (MESA): leveraging state-of-the-art vascular imaging

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Abstract

Purpose

To further characterize the relationship between obstructive sleep apnea (OSA) and carotid atherosclerosis, we examined the structural and metabolic features of carotid plaque using hybrid 18-F-fluorodeoxyglucose (FDG) Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods

We studied 46 individuals from the MESA-PET and MESA-Sleep ancillary studies. OSA was defined as an apnea hypopnea index [AHI] ≥ 15 events per hour (4% desaturation). PET/MRI was used to measure carotid plaque inflammation (using target-to-background-ratios [TBR]) and carotid wall thickness (CWT). Linear regression was used to assess the associations between OSA, CWT and TBR.

Results

The mean age was 67.9 years (SD 8.53) and the mean BMI was 28.9 kg/m2 (SD 4.47). There was a trend toward a higher mean CWT in the OSA (n = 11) vs. non-OSA group (n = 35), 1.51 vs. 1.41 (p = 0.098). TBR did not differ by OSA groups, and there was no significant association between OSA and carotid plaque inflammation (TBR) in adjusted analyses. Although there was a significant interaction between OSA and obesity, there were no statistically significant associations between OSA and vascular inflammation in stratified analysis by obesity.

Conclusion

Despite a trend toward a higher carotid wall thickness in OSA vs. non-OSA participants, we did not find an independent association between OSA and carotid plaque inflammation using PET/MRI in MESA. Our findings suggest that simultaneous assessments of structural and metabolic features of atherosclerosis may fill current knowledge gaps pertaining to the influence of OSA on atherosclerosis prevalence and progression.

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Data availability

The data analyzed in this study is subject to the following licenses/restrictions: MESA data can be accessed after submitting a manuscript proposal to MESA Publications & Presentations Committee and obtaining its approval to conduct the research work. Requests to access these datasets should be directed to Karen Hansen, hansenk3@u.washington.edu.

Abbreviations

AASM:

American Academy of Sleep Medicine

ADA:

American Diabetes Association

AHI:

Apnea–hypopnea index

BMI:

Body mass index

CAD:

Coronary artery disease

CHD:

Coronary heart disease

CIMT:

Carotid intima media thickness

CMR:

Cardiac magnetic resonance

CWT:

Carotid wall thickness

CPAP:

Continuous positive airway pressure

CVD:

Cardiovascular disease

ECG:

Electrocardiogram

EMG:

Electromyography

HDL:

High density lipoprotein

LDL:

Low density lipoprotein

LGE:

Late-gadolinium enhancement

LV:

Left ventricular

MESA:

Multi-Ethnic Study of Atherosclerosis

MI:

Myocardial infarction

OSA:

Obstructive sleep apnea

PET/MRI:

Positron emission tomography/magnetic resonance imaging

PSG:

Polysomnography

PWV:

Pulse wave velocity

REM:

Rapid eye movement

SA:

Sleep apnea

SCD:

Sudden cardiac death

SDB:

Sleep disordered breathing

SUV:

Standardized uptake value

TBR:

Target-to-background ratio

TST:

Total sleep time

TWPAS:

Typical week physical activity survey

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Acknowledgements

The authors thank the investigators, staff, and participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. Imaging studies were performed at the Biomedical Engineering and Imaging Institute (BMEII) at Mount Sinai, NY. Participants for the MESA-PET Ancillary Study were recruited at Columbia University, NY by Dr. Steven Shea (R01HL127637—MESA Exam 6). Manuscript preparation was conducted at the Icahn School of Medicine at Mount Sinai, NY (Dr. Neomi Shah—R01HL143221).

Funding

This research was supported by contracts with University of Washington Coordinating Center (HHSN268201500003I, N01-HC-95159), UCLA Field Center (N01-HC-95160), Columbia University Field Center ( N01-HC-95161), Johns Hopkins University Field Center (N01-HC-95162), University of Minnesota Field Center (N01-HC-95163), Northwestern University Field Center (N01-HC-95164), Wake Forest University Field Center (N01-HC-95165),Central Laboratory (N01-HC-95166), Ultrasound Reading Center (N01-HC-95167), MRI Reading Center (N01-HC-95168) and CT Reading Center (N01-HC-95169) from the National Heart, Lung, and Blood Institute, and by grants UL1-TR-000040 (Columbia CTSA), UL1-TR-001079 (Johns Hopkins ICTR), and UL1-TR-001420 (Wake Forest University CTSA) from NCATS. The MESA Sleep study was support by NHLBI grant R01HL56984. The MESA-PET study was supported by NHLBI grant R01HL127637. Dr. Susan Redline was partially supported by R35 HL135818. Dr. Neomi A Shah has funding from the National Institute of Health/National Heart, Lung, and Blood Institute (1R03HL140273-01, 1R01HL143221-01).

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Author notes

  1. Steven Shea and Susan Redline are joint senior authorship.

Authors and Affiliations

  1. Division of Pulmonary, Critical Care and Sleep Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Neomi Shah & Vaishnavi Kundel

  2. Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital, Boston, MA, USA

    Michelle Reid & Susan Redline

  3. Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Venkatesh Mani & Zahi A. Fayad

  4. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA

    Robert C. Kaplan

  5. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Robert C. Kaplan

  6. Departments of Medicine, Epidemiology and Biostatistics, San Francisco Veterans Affairs Health Care System and University of California San Francisco, San Francisco, CA, USA

    Jorge R. Kizer

  7. Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, and Department of Epidemiology, Mailman School of Public Health, New York, NY, USA

    Steven Shea

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Contributions

All authors contributed meaningfully to this work. All authors have seen and approved this manuscript for publication.

Corresponding author

Correspondence to Neomi Shah.

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Conflict of interest

Ms. Michelle Reid declares that she has no conflict of interest. Dr. Venkatesh Mani declares that he has no conflict of interest. Dr. Vaishnavi Kundel declares that she has no conflict of interest. Dr. Robert Kaplan declares that he has no conflict of interest. Dr. Zahi Fayad declares that he has no conflict of interest. Dr. Steven Shea declares that he has no conflict of interest. Dr. Neomi Shah reports receiving funding and consulting funds from Itamar and Respicardia, unrelated to this project and stock ownership in Abbott Laboratories. Dr. Susan Redline reports receiving grants and consulting funds from Jazz Pharmaceuticals and consulting fees from Eisai Pharmaceuticals, unrelated to this project. Dr. Jorge Kizer reports stock ownership in Abbott, Bristol-Myers Squibb, Johnson & Johnson, Medtronic, Merck and Pfizer.

Research involving human participants and/or animals

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The MESA protocol was approved by the Institutional Review Board from each participating institution [Wake Forest University (IRB00008492), Columbia University (IRB00002973), Johns Hopkins University (IRB00001656), University of Minnesota (IRB00000438), Northwestern University (IRB00005003), University of California Los Angeles (IRB00000172), and University of Washington (IRB00005647)]. Additionally, Institutional Review Board approval was obtained by the Columbia University institutional review board (IRB AAAQ1318) for the MESA PET ancillary study.

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Informed consent was obtained from all individual participants included in the study.

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Shah, N., Reid, M., Mani, V. et al. Sleep apnea and carotid atherosclerosis in the Multi-Ethnic Study of Atherosclerosis (MESA): leveraging state-of-the-art vascular imaging. Int J Cardiovasc Imaging 39, 621–630 (2023). https://doi.org/10.1007/s10554-022-02743-4

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