Effects of renin-angiotensin-aldosterone-system inhibitors on coronary atherosclerotic plaques: The PARADIGM registry

Curtis Williams; Donghee Han; Hidenobu Takagi; Christopher B. Fordyce; Stephanie Sellers; Philipp Blanke; Fay Y. Lin; Leslee J. Shaw; Sang Eun Lee; Daniele Andreini; Mouaz H. Al-Mallah; Matthew J. Budoff; Filippo Cademartiri; Kavitha Chinnaiyan; Jung Hyun Choi; Edoardo Conte; Hugo Marques; Pedro de Araújo Gonçalves; Ilan Gottlieb; Martin Hadamitzky; Erica Maffei; Gianluca Pontone; Sanghoon Shin; Yong Jin Kim; Byoung Kwon Lee; Eun Ju Chun; Ji Min Sung; Renu Virmani; Habib Samady; Peter H. Stone; Daniel S. Berman; Jagat Narula; Jeroen J. Bax; Jonathon A. Leipsic; Hyuk Jae Chang

doi:10.1016/j.atherosclerosis.2023.117301

Effects of renin-angiotensin-aldosterone-system inhibitors on coronary atherosclerotic plaques: The PARADIGM registry

Curtis Williams, Donghee Han, Hidenobu Takagi, Christopher B. Fordyce, Stephanie Sellers, Philipp Blanke, Fay Y. Lin, Leslee J. Shaw, Sang Eun Lee, Daniele Andreini, Mouaz H. Al-Mallah, Matthew J. Budoff, Filippo Cademartiri, Kavitha Chinnaiyan, Jung Hyun Choi, Edoardo Conte, Hugo Marques, Pedro de Araújo Gonçalves, Ilan Gottlieb, Martin HadamitzkyErica Maffei, Gianluca Pontone, Sanghoon Shin, Yong Jin Kim, Byoung Kwon Lee, Eun Ju Chun, Ji Min Sung, Renu Virmani, Habib Samady, Peter H. Stone, Daniel S. Berman, Jagat Narula, Jeroen J. Bax, Jonathon A. Leipsic, Hyuk Jae Chang

Research output: Contribution to journal › Article › peer-review

Abstract

Background and aims: Inhibition of Renin-Angiotensin-Aldosterone-System (RAAS) has been hypothesized to improve endothelial function and reduce plaque inflammation, however, their impact on the progression of coronary atherosclerosis is unclear. We aim to study the effects of RAAS inhibitor on plaque progression and composition assessed by serial coronary CT angiography (CCTA). Methods: We performed a prospective, multinational study consisting of a registry of patients without history of CAD, who underwent serial CCTAs. Patients using RAAS inhibitors were propensity matched to RAAS inhibitor naïve patients based on clinical and CCTA characteristics at baseline. Atherosclerotic plaques in CCTAs were quantitatively analyzed for percent atheroma volume (PAV) according to plaque composition. Interactions between RAAS inhibitor use and baseline PAV on plaque progression were assessed in the unmatched cohort using a multivariate linear regression model. Results: Of 1248 patients from the registry, 299 RAAS inhibitor taking patients were matched to 299 RAAS inhibitor naïve patients. Over a mean interval of 3.9 years, there was no significant difference in annual progression of total PAV between RAAS inhibitor naïve vs taking patients (0.75 vs 0.79%/year, p = 0.66). With interaction testing in the unmatched cohort, however, RAAS inhibitor use was significantly associated with lower non-calcified plaque progression (Beta coefficient −0.100, adjusted p = 0.038) with higher levels of baseline PAV. Conclusions: The use of RAAS inhibitors over a period of nearly 4 years did not significantly impact on total atherosclerotic plaque progression or various plaque components. However, interaction testing to assess the differential effect of RAAS inhibition based on baseline PAV suggested a significant decrease in progression of non-calcified plaque in patients with a higher burden of baseline atherosclerosis, which should be considered hypothesis generating.

Original language	English (US)
Article number	117301
Journal	Atherosclerosis
Volume	383
DOIs	https://doi.org/10.1016/j.atherosclerosis.2023.117301
State	Published - Oct 2023

Keywords

ACE inhibitor
Coronary CT angiography
Plaque morphology
Plaque progression
RAAS inhibitor
Stable coronary artery disease

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1016/j.atherosclerosis.2023.117301

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Williams, C., Han, D., Takagi, H., Fordyce, C. B., Sellers, S., Blanke, P., Lin, F. Y., Shaw, L. J., Lee, S. E., Andreini, D., Al-Mallah, M. H., Budoff, M. J., Cademartiri, F., Chinnaiyan, K., Choi, J. H., Conte, E., Marques, H., de Araújo Gonçalves, P., Gottlieb, I., ... Chang, H. J. (2023). Effects of renin-angiotensin-aldosterone-system inhibitors on coronary atherosclerotic plaques: The PARADIGM registry. Atherosclerosis, 383, Article 117301. https://doi.org/10.1016/j.atherosclerosis.2023.117301

Williams, C, Han, D, Takagi, H, Fordyce, CB, Sellers, S, Blanke, P, Lin, FY, Shaw, LJ, Lee, SE, Andreini, D, Al-Mallah, MH, Budoff, MJ, Cademartiri, F, Chinnaiyan, K, Choi, JH, Conte, E, Marques, H, de Araújo Gonçalves, P, Gottlieb, I, Hadamitzky, M, Maffei, E, Pontone, G, Shin, S, Kim, YJ, Lee, BK, Chun, EJ, Sung, JM, Virmani, R, Samady, H, Stone, PH, Berman, DS, Narula, J, Bax, JJ, Leipsic, JA & Chang, HJ 2023, 'Effects of renin-angiotensin-aldosterone-system inhibitors on coronary atherosclerotic plaques: The PARADIGM registry', Atherosclerosis, vol. 383, 117301. https://doi.org/10.1016/j.atherosclerosis.2023.117301

@article{e2e636200b784bdcb1ff31371c14d168,

title = "Effects of renin-angiotensin-aldosterone-system inhibitors on coronary atherosclerotic plaques: The PARADIGM registry",

abstract = "Background and aims: Inhibition of Renin-Angiotensin-Aldosterone-System (RAAS) has been hypothesized to improve endothelial function and reduce plaque inflammation, however, their impact on the progression of coronary atherosclerosis is unclear. We aim to study the effects of RAAS inhibitor on plaque progression and composition assessed by serial coronary CT angiography (CCTA). Methods: We performed a prospective, multinational study consisting of a registry of patients without history of CAD, who underwent serial CCTAs. Patients using RAAS inhibitors were propensity matched to RAAS inhibitor na{\"i}ve patients based on clinical and CCTA characteristics at baseline. Atherosclerotic plaques in CCTAs were quantitatively analyzed for percent atheroma volume (PAV) according to plaque composition. Interactions between RAAS inhibitor use and baseline PAV on plaque progression were assessed in the unmatched cohort using a multivariate linear regression model. Results: Of 1248 patients from the registry, 299 RAAS inhibitor taking patients were matched to 299 RAAS inhibitor na{\"i}ve patients. Over a mean interval of 3.9 years, there was no significant difference in annual progression of total PAV between RAAS inhibitor na{\"i}ve vs taking patients (0.75 vs 0.79%/year, p = 0.66). With interaction testing in the unmatched cohort, however, RAAS inhibitor use was significantly associated with lower non-calcified plaque progression (Beta coefficient −0.100, adjusted p = 0.038) with higher levels of baseline PAV. Conclusions: The use of RAAS inhibitors over a period of nearly 4 years did not significantly impact on total atherosclerotic plaque progression or various plaque components. However, interaction testing to assess the differential effect of RAAS inhibition based on baseline PAV suggested a significant decrease in progression of non-calcified plaque in patients with a higher burden of baseline atherosclerosis, which should be considered hypothesis generating.",

keywords = "ACE inhibitor, Coronary CT angiography, Plaque morphology, Plaque progression, RAAS inhibitor, Stable coronary artery disease",

author = "Curtis Williams and Donghee Han and Hidenobu Takagi and Fordyce, {Christopher B.} and Stephanie Sellers and Philipp Blanke and Lin, {Fay Y.} and Shaw, {Leslee J.} and Lee, {Sang Eun} and Daniele Andreini and Al-Mallah, {Mouaz H.} and Budoff, {Matthew J.} and Filippo Cademartiri and Kavitha Chinnaiyan and Choi, {Jung Hyun} and Edoardo Conte and Hugo Marques and {de Ara{\'u}jo Gon{\c c}alves}, Pedro and Ilan Gottlieb and Martin Hadamitzky and Erica Maffei and Gianluca Pontone and Sanghoon Shin and Kim, {Yong Jin} and Lee, {Byoung Kwon} and Chun, {Eun Ju} and Sung, {Ji Min} and Renu Virmani and Habib Samady and Stone, {Peter H.} and Berman, {Daniel S.} and Jagat Narula and Bax, {Jeroen J.} and Leipsic, {Jonathon A.} and Chang, {Hyuk Jae}",

note = "Publisher Copyright: {\textcopyright} 2023",

year = "2023",

month = oct,

doi = "10.1016/j.atherosclerosis.2023.117301",

language = "English (US)",

volume = "383",

journal = "Atherosclerosis",

issn = "0021-9150",

publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - Effects of renin-angiotensin-aldosterone-system inhibitors on coronary atherosclerotic plaques

T2 - The PARADIGM registry

AU - Williams, Curtis

AU - Han, Donghee

AU - Takagi, Hidenobu

AU - Fordyce, Christopher B.

AU - Sellers, Stephanie

AU - Blanke, Philipp

AU - Lin, Fay Y.

AU - Shaw, Leslee J.

AU - Lee, Sang Eun

AU - Andreini, Daniele

AU - Al-Mallah, Mouaz H.

AU - Budoff, Matthew J.

AU - Cademartiri, Filippo

AU - Chinnaiyan, Kavitha

AU - Choi, Jung Hyun

AU - Conte, Edoardo

AU - Marques, Hugo

AU - de Araújo Gonçalves, Pedro

AU - Gottlieb, Ilan

AU - Hadamitzky, Martin

AU - Maffei, Erica

AU - Pontone, Gianluca

AU - Shin, Sanghoon

AU - Kim, Yong Jin

AU - Lee, Byoung Kwon

AU - Chun, Eun Ju

AU - Sung, Ji Min

AU - Virmani, Renu

AU - Samady, Habib

AU - Stone, Peter H.

AU - Berman, Daniel S.

AU - Narula, Jagat

AU - Bax, Jeroen J.

AU - Leipsic, Jonathon A.

AU - Chang, Hyuk Jae

PY - 2023/10

Y1 - 2023/10

N2 - Background and aims: Inhibition of Renin-Angiotensin-Aldosterone-System (RAAS) has been hypothesized to improve endothelial function and reduce plaque inflammation, however, their impact on the progression of coronary atherosclerosis is unclear. We aim to study the effects of RAAS inhibitor on plaque progression and composition assessed by serial coronary CT angiography (CCTA). Methods: We performed a prospective, multinational study consisting of a registry of patients without history of CAD, who underwent serial CCTAs. Patients using RAAS inhibitors were propensity matched to RAAS inhibitor naïve patients based on clinical and CCTA characteristics at baseline. Atherosclerotic plaques in CCTAs were quantitatively analyzed for percent atheroma volume (PAV) according to plaque composition. Interactions between RAAS inhibitor use and baseline PAV on plaque progression were assessed in the unmatched cohort using a multivariate linear regression model. Results: Of 1248 patients from the registry, 299 RAAS inhibitor taking patients were matched to 299 RAAS inhibitor naïve patients. Over a mean interval of 3.9 years, there was no significant difference in annual progression of total PAV between RAAS inhibitor naïve vs taking patients (0.75 vs 0.79%/year, p = 0.66). With interaction testing in the unmatched cohort, however, RAAS inhibitor use was significantly associated with lower non-calcified plaque progression (Beta coefficient −0.100, adjusted p = 0.038) with higher levels of baseline PAV. Conclusions: The use of RAAS inhibitors over a period of nearly 4 years did not significantly impact on total atherosclerotic plaque progression or various plaque components. However, interaction testing to assess the differential effect of RAAS inhibition based on baseline PAV suggested a significant decrease in progression of non-calcified plaque in patients with a higher burden of baseline atherosclerosis, which should be considered hypothesis generating.

AB - Background and aims: Inhibition of Renin-Angiotensin-Aldosterone-System (RAAS) has been hypothesized to improve endothelial function and reduce plaque inflammation, however, their impact on the progression of coronary atherosclerosis is unclear. We aim to study the effects of RAAS inhibitor on plaque progression and composition assessed by serial coronary CT angiography (CCTA). Methods: We performed a prospective, multinational study consisting of a registry of patients without history of CAD, who underwent serial CCTAs. Patients using RAAS inhibitors were propensity matched to RAAS inhibitor naïve patients based on clinical and CCTA characteristics at baseline. Atherosclerotic plaques in CCTAs were quantitatively analyzed for percent atheroma volume (PAV) according to plaque composition. Interactions between RAAS inhibitor use and baseline PAV on plaque progression were assessed in the unmatched cohort using a multivariate linear regression model. Results: Of 1248 patients from the registry, 299 RAAS inhibitor taking patients were matched to 299 RAAS inhibitor naïve patients. Over a mean interval of 3.9 years, there was no significant difference in annual progression of total PAV between RAAS inhibitor naïve vs taking patients (0.75 vs 0.79%/year, p = 0.66). With interaction testing in the unmatched cohort, however, RAAS inhibitor use was significantly associated with lower non-calcified plaque progression (Beta coefficient −0.100, adjusted p = 0.038) with higher levels of baseline PAV. Conclusions: The use of RAAS inhibitors over a period of nearly 4 years did not significantly impact on total atherosclerotic plaque progression or various plaque components. However, interaction testing to assess the differential effect of RAAS inhibition based on baseline PAV suggested a significant decrease in progression of non-calcified plaque in patients with a higher burden of baseline atherosclerosis, which should be considered hypothesis generating.

KW - ACE inhibitor

KW - Coronary CT angiography

KW - Plaque morphology

KW - Plaque progression

KW - RAAS inhibitor

KW - Stable coronary artery disease

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UR - http://www.scopus.com/inward/citedby.url?scp=85172273191&partnerID=8YFLogxK

U2 - 10.1016/j.atherosclerosis.2023.117301

DO - 10.1016/j.atherosclerosis.2023.117301

M3 - Article

C2 - 37769454

AN - SCOPUS:85172273191

SN - 0021-9150

VL - 383

JO - Atherosclerosis

JF - Atherosclerosis

M1 - 117301

ER -

Effects of renin-angiotensin-aldosterone-system inhibitors on coronary atherosclerotic plaques: The PARADIGM registry

Abstract

Keywords

ASJC Scopus subject areas

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