Sex differences in lipidomic and bile acid plasma profiles in patients with and without coronary artery disease

TY - JOUR

T1 - Sex differences in lipidomic and bile acid plasma profiles in patients with and without coronary artery disease

AU - Bay, Benjamin

AU - Fuh, Marceline M

AU - Rohde, Julia

AU - Worthmann, Anna

AU - Goßling, Alina

AU - Arnold, Natalie

AU - Koester, Lukas

AU - Lorenz, Thiess

AU - Blaum, Christopher

AU - Kirchhof, Paulus

AU - Blankenberg, Stefan

AU - Seiffert, Moritz

AU - Brunner, Fabian J

AU - Waldeyer, Christoph

AU - Heeren, Joerg

N1 - © 2024. The Author(s).

PY - 2024/6/26

Y1 - 2024/6/26

N2 - BACKGROUND: Lipids, including phospholipids and bile acids, exert various signaling effects and are thought to contribute to the development of coronary artery disease (CAD). Here, we aimed to compare lipidomic and bile acid profiles in the blood of patients with and without CAD stratified by sex.METHODS: From 2015 to 2022, 3,012 patients who underwent coronary angiography were recruited in the INTERCATH cohort. From the overall cohort, subgroups were defined using patient characteristics such as CAD vs. no CAD, 1st vs. 3rd tertile of LDL-c, and female vs. male sex. Hereafter, a matching algorithm based on age, BMI, hypertension status, diabetes mellitus status, smoking status, the Mediterranean diet score, and the intake of statins, triglycerides, HDL-c and hs-CRP in a 1:1 ratio was implemented. Lipidomic analyses of stored blood samples using the Lipidyzer platform (SCIEX) and bile acid analysis using liquid chromatography with tandem mass spectrometry (LC‒MS/MS) were carried out.RESULTS: A total of 177 matched individuals were analyzed; the median ages were 73.5 years (25th and 75th percentile: 64.1, 78.2) and 71.9 years (65.7, 77.2) for females and males with CAD, respectively, and 67.6 years (58.3, 75.3) and 69.2 years (59.8, 76.8) for females and males without CAD, respectively. Further baseline characteristics, including cardiovascular risk factors, were balanced between the groups. Women with CAD had decreased levels of phosphatidylcholine and diacylglycerol, while no differences in bile acid profiles were detected in comparison to those of female patients without CAD. In contrast, in male patients with CAD, decreased concentrations of the secondary bile acid species glycolithocholic and lithocholic acid, as well as altered levels of specific lipids, were detected compared to those in males without CAD. Notably, male patients with low LDL-c and CAD had significantly greater concentrations of various phospholipid species, particularly plasmalogens, compared to those in high LDL-c subgroup.CONCLUSIONS: We present hypothesis-generating data on sex-specific lipidomic patterns and bile acid profiles in CAD patients. The data suggest that altered lipid and bile acid composition might contribute to CAD development and/or progression, helping to understand the different disease trajectories of CAD in women and men.REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT04936438 , Unique identifier: NCT04936438.

AB - BACKGROUND: Lipids, including phospholipids and bile acids, exert various signaling effects and are thought to contribute to the development of coronary artery disease (CAD). Here, we aimed to compare lipidomic and bile acid profiles in the blood of patients with and without CAD stratified by sex.METHODS: From 2015 to 2022, 3,012 patients who underwent coronary angiography were recruited in the INTERCATH cohort. From the overall cohort, subgroups were defined using patient characteristics such as CAD vs. no CAD, 1st vs. 3rd tertile of LDL-c, and female vs. male sex. Hereafter, a matching algorithm based on age, BMI, hypertension status, diabetes mellitus status, smoking status, the Mediterranean diet score, and the intake of statins, triglycerides, HDL-c and hs-CRP in a 1:1 ratio was implemented. Lipidomic analyses of stored blood samples using the Lipidyzer platform (SCIEX) and bile acid analysis using liquid chromatography with tandem mass spectrometry (LC‒MS/MS) were carried out.RESULTS: A total of 177 matched individuals were analyzed; the median ages were 73.5 years (25th and 75th percentile: 64.1, 78.2) and 71.9 years (65.7, 77.2) for females and males with CAD, respectively, and 67.6 years (58.3, 75.3) and 69.2 years (59.8, 76.8) for females and males without CAD, respectively. Further baseline characteristics, including cardiovascular risk factors, were balanced between the groups. Women with CAD had decreased levels of phosphatidylcholine and diacylglycerol, while no differences in bile acid profiles were detected in comparison to those of female patients without CAD. In contrast, in male patients with CAD, decreased concentrations of the secondary bile acid species glycolithocholic and lithocholic acid, as well as altered levels of specific lipids, were detected compared to those in males without CAD. Notably, male patients with low LDL-c and CAD had significantly greater concentrations of various phospholipid species, particularly plasmalogens, compared to those in high LDL-c subgroup.CONCLUSIONS: We present hypothesis-generating data on sex-specific lipidomic patterns and bile acid profiles in CAD patients. The data suggest that altered lipid and bile acid composition might contribute to CAD development and/or progression, helping to understand the different disease trajectories of CAD in women and men.REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT04936438 , Unique identifier: NCT04936438.

KW - Aged

KW - Female

KW - Humans

KW - Male

KW - Middle Aged

KW - Bile Acids and Salts/blood

KW - Cholesterol, HDL/blood

KW - Cholesterol, LDL/blood

KW - Coronary Artery Disease/blood

KW - Lipidomics

KW - Sex Characteristics

KW - Sex Factors

KW - Tandem Mass Spectrometry

KW - Triglycerides/blood

KW - Cohort Studies

U2 - 10.1186/s12944-024-02184-z

DO - 10.1186/s12944-024-02184-z

M3 - SCORING: Journal article

C2 - 38926753

VL - 23

SP - 197

JO - LIPIDS HEALTH DIS

JF - LIPIDS HEALTH DIS

SN - 1476-511X

IS - 1

ER -