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Fasting ketonuria is inversely associated with coronary artery calcification in non-diabetic individuals

Fasting ketonuria is inversely associated with coronary artery calcification in non-diabetic individuals
Fasting ketonuria is inversely associated with coronary artery calcification in non-diabetic individuals

Background and aims

Increased levels of ketone bodies, an alternative fuel when glucose availability is low, may exert beneficial effects on cardiovascular disease (CVD) risk factors. Whether increased ketone bodies are associated with coronary artery calcium (CAC), a recognized and strong cardiovascular risk factor, remains unknown. We investigated the association of fasting ketonuria with CAC and its progression.

Methods

Cross-sectional and longitudinal studies were conducted in adults without diabetes or CVD. Subjects underwent routine health examinations including cardiac computed tomography estimations of CAC scores. Logistic regression models were performed to compute the odds ratios (ORs), 95% confidence intervals (CIs), for prevalent CAC scores >0 according to fasting ketonuria categories (0, 1, and ≥2). Linear mixed models with random intercepts and random slopes were used to estimate CAC progression.

Results

Of 144,346 subjects, 12.3% had CAC scores >0 at baseline. Overall, higher fasting ketonuria was associated with decreased prevalence of coronary calcification than no ketonuria. Multivariable-adjusted ORs (95% CIs) for prevalent CAC by comparing ketonuria categories 1 and ≥2 with no ketonuria, were 0.94 (0.84–1.06) and 0.82 (0.71–0.95), respectively. The associations did not differ according to clinically relevant subgroups. Ketonuria was associated with lower CAC progression over time; the multivariable adjusted ratio of progression rates comparing ketonuria ≥2 versus no ketonuria was 0.976 (0.965–0.995).

Conclusions

We found an inverse association between fasting ketonuria and subclinical coronary atherosclerosis, in both prevalence and progression. The potentially protective role of increased ketone body formation in CVD requires further investigation.

 

Atherosclerosis, Coronary artery calcium, Coronary artery disease, Ketone bodies, Ketosis
0021-9150
1 - 7
Cho, In Young
675a50d7-5b74-4afc-8b09-eed036ac0b7b
Chang, Yoosoo
cb926bfb-b138-4b67-9345-30868bfdb9b0
Sung, Eunju
b216088e-cd42-4b3d-bd6f-1bf6b3078870
Kim, Yejin
6c3ae3de-e235-437c-a18e-1330d2a1c2ac
Kang, Jae-Heon
8a0c9031-2405-4d88-9b24-722efe5493b8
Shin, Hocheol
805b1fc9-ad00-477b-839e-f3dc7273f727
Wild, Sarah H.
fccd6b84-96a8-41b0-ac9a-50d894515d37
Byrne, Christopher
1370b997-cead-4229-83a7-53301ed2a43c
Ryu, Seungho
b17b879c-174c-4bb0-83d1-6116d4649347
Cho, In Young
675a50d7-5b74-4afc-8b09-eed036ac0b7b
Chang, Yoosoo
cb926bfb-b138-4b67-9345-30868bfdb9b0
Sung, Eunju
b216088e-cd42-4b3d-bd6f-1bf6b3078870
Kim, Yejin
6c3ae3de-e235-437c-a18e-1330d2a1c2ac
Kang, Jae-Heon
8a0c9031-2405-4d88-9b24-722efe5493b8
Shin, Hocheol
805b1fc9-ad00-477b-839e-f3dc7273f727
Wild, Sarah H.
fccd6b84-96a8-41b0-ac9a-50d894515d37
Byrne, Christopher
1370b997-cead-4229-83a7-53301ed2a43c
Ryu, Seungho
b17b879c-174c-4bb0-83d1-6116d4649347

Cho, In Young, Chang, Yoosoo, Sung, Eunju, Kim, Yejin, Kang, Jae-Heon, Shin, Hocheol, Wild, Sarah H., Byrne, Christopher and Ryu, Seungho (2022) Fasting ketonuria is inversely associated with coronary artery calcification in non-diabetic individuals. Atherosclerosis, 348, 1 - 7. (doi:10.1016/j.atherosclerosis.2022.03.018).

Record type: Article

Abstract

Background and aims

Increased levels of ketone bodies, an alternative fuel when glucose availability is low, may exert beneficial effects on cardiovascular disease (CVD) risk factors. Whether increased ketone bodies are associated with coronary artery calcium (CAC), a recognized and strong cardiovascular risk factor, remains unknown. We investigated the association of fasting ketonuria with CAC and its progression.

Methods

Cross-sectional and longitudinal studies were conducted in adults without diabetes or CVD. Subjects underwent routine health examinations including cardiac computed tomography estimations of CAC scores. Logistic regression models were performed to compute the odds ratios (ORs), 95% confidence intervals (CIs), for prevalent CAC scores >0 according to fasting ketonuria categories (0, 1, and ≥2). Linear mixed models with random intercepts and random slopes were used to estimate CAC progression.

Results

Of 144,346 subjects, 12.3% had CAC scores >0 at baseline. Overall, higher fasting ketonuria was associated with decreased prevalence of coronary calcification than no ketonuria. Multivariable-adjusted ORs (95% CIs) for prevalent CAC by comparing ketonuria categories 1 and ≥2 with no ketonuria, were 0.94 (0.84–1.06) and 0.82 (0.71–0.95), respectively. The associations did not differ according to clinically relevant subgroups. Ketonuria was associated with lower CAC progression over time; the multivariable adjusted ratio of progression rates comparing ketonuria ≥2 versus no ketonuria was 0.976 (0.965–0.995).

Conclusions

We found an inverse association between fasting ketonuria and subclinical coronary atherosclerosis, in both prevalence and progression. The potentially protective role of increased ketone body formation in CVD requires further investigation.

 

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More information

Accepted/In Press date: 15 March 2022
e-pub ahead of print date: 30 March 2022
Published date: May 2022
Additional Information: Funding Information: This work was supported by the SKKU Excellence in Research Award Research Fund, Sungkyunkwan University , 2020. CDB is supported in part by the Southampton NIHR Biomedical Research Centre (IS-BRC-20004), UK .
Keywords: Atherosclerosis, Coronary artery calcium, Coronary artery disease, Ketone bodies, Ketosis

Identifiers

Local EPrints ID: 456046
URI: http://eprints.soton.ac.uk/id/eprint/456046
ISSN: 0021-9150
PURE UUID: 30a71e61-c4dd-43e0-b38d-9180ae6bb728
ORCID for Christopher Byrne: ORCID iD orcid.org/0000-0001-6322-7753

Catalogue record

Date deposited: 12 Apr 2022 17:12
Last modified: 24 Jul 2022 01:36

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Contributors

Author: In Young Cho
Author: Yoosoo Chang
Author: Eunju Sung
Author: Yejin Kim
Author: Jae-Heon Kang
Author: Hocheol Shin
Author: Sarah H. Wild
Author: Seungho Ryu

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