Liver X Receptor Agonist 4β-Hydroxycholesterol as a Prognostic Factor in Coronary Artery Disease
Rahunen, Roosa; Tulppo, Mikko; Rinne, Valtteri; Lepojärvi, Samuli; Perkiömäki, Juha S; Huikuri, Heikki V; Ukkola, Olavi; Junttila, Juhani; Hukkanen, Janne (2024-02-23)
Wiley-Blackwell
23.02.2024
Rahunen, R., Tulppo, M., Rinne, V., Lepojärvi, S., Perkiömäki, J. S., Huikuri, H. V., Ukkola, O., Junttila, J., & Hukkanen, J. (2024). Liver x receptor agonist 4β‐hydroxycholesterol as a prognostic factor in coronary artery disease. Journal of the American Heart Association, 13(5), e031824. https://doi.org/10.1161/JAHA.123.031824
https://creativecommons.org/licenses/by/4.0/
© 2024 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
https://creativecommons.org/licenses/by/4.0/
© 2024 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
https://creativecommons.org/licenses/by/4.0/
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:oulu-202403122169
https://urn.fi/URN:NBN:fi:oulu-202403122169
Tiivistelmä
Abstract
Background:
Regardless of progress in treatment of coronary artery disease (CAD), there is still a significant residual risk of death in patients with CAD, highlighting the need for additional risk stratification markers. Our previous study provided evidence for a novel blood pressure–regulating mechanism involving 4β‐hydroxycholesterol (4βHC), an agonist for liver X receptors, as a hypotensive factor. The aim was to determine the role of 4βHC as a prognostic factor in CAD.
Methods and Results:
The ARTEMIS (Innovation to Reduce Cardiovascular Complications of Diabetes at the Intersection) cohort consists of 1946 patients with CAD. Men and women were analyzed separately in quartiles according to plasma 4βHC. Basic characteristics, medications, ECG, and echocardiography parameters as well as mortality rate were analyzed. At baseline, subjects with a beneficial cardiovascular profile, as assessed with traditional markers such as body mass index, exercise capacity, prevalence of diabetes, and use of antihypertensives, had the highest plasma 4βHC concentrations. However, in men, high plasma 4βHC was associated with all‐cause death, cardiac death, and especially sudden cardiac death (SCD) in a median follow‐up of 8.8 years. Univariate and comprehensively adjusted hazard ratios for SCD in the highest quartile were 3.76 (95% CI, 1.6–8.7; P=0.002) and 4.18 (95% CI, 1.5–11.4; P=0.005), respectively. In contrast, the association of cardiac death and SCD in women showed the lowest risk in the highest 4βHC quartile.
Conclusions:
High plasma 4βHC concentration was associated with death and especially SCD in men, while an inverse association was detected in women. Our results suggest 4βHC as a novel sex‐specific risk marker of cardiac death and especially SCD in chronic CAD.
Registration Information:
clinicaltrials.gov. Identifier NCT01426685.
Background:
Regardless of progress in treatment of coronary artery disease (CAD), there is still a significant residual risk of death in patients with CAD, highlighting the need for additional risk stratification markers. Our previous study provided evidence for a novel blood pressure–regulating mechanism involving 4β‐hydroxycholesterol (4βHC), an agonist for liver X receptors, as a hypotensive factor. The aim was to determine the role of 4βHC as a prognostic factor in CAD.
Methods and Results:
The ARTEMIS (Innovation to Reduce Cardiovascular Complications of Diabetes at the Intersection) cohort consists of 1946 patients with CAD. Men and women were analyzed separately in quartiles according to plasma 4βHC. Basic characteristics, medications, ECG, and echocardiography parameters as well as mortality rate were analyzed. At baseline, subjects with a beneficial cardiovascular profile, as assessed with traditional markers such as body mass index, exercise capacity, prevalence of diabetes, and use of antihypertensives, had the highest plasma 4βHC concentrations. However, in men, high plasma 4βHC was associated with all‐cause death, cardiac death, and especially sudden cardiac death (SCD) in a median follow‐up of 8.8 years. Univariate and comprehensively adjusted hazard ratios for SCD in the highest quartile were 3.76 (95% CI, 1.6–8.7; P=0.002) and 4.18 (95% CI, 1.5–11.4; P=0.005), respectively. In contrast, the association of cardiac death and SCD in women showed the lowest risk in the highest 4βHC quartile.
Conclusions:
High plasma 4βHC concentration was associated with death and especially SCD in men, while an inverse association was detected in women. Our results suggest 4βHC as a novel sex‐specific risk marker of cardiac death and especially SCD in chronic CAD.
Registration Information:
clinicaltrials.gov. Identifier NCT01426685.
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