Sex Differences in Lipid Metabolism: Implications for Systemic Lupus Erythematosus and Cardiovascular Disease Risk

Area of Science:

• Cardiovascular Science
• Immunology
• Endocrinology

Background:

• Healthy women exhibit lower cardiovascular disease (CVD) risk than age-matched men, attributed to favorable lipid profiles (lower LDL/VLDL, higher HDL).
• Systemic lupus erythematosus (SLE), prevalent in women, paradoxically increases CVD and atherosclerosis risk.
• Dyslipidemia in women with SLE (elevated LDL, reduced HDL) negates the typical sex-specific CVD protection.

Purpose of the Study:

• To explore the paradox of increased CVD risk in women with SLE despite general female cardioprotection.
• To review sex differences in lipid metabolism and CVD risk in healthy individuals and those on hormone therapy.
• To examine how autoimmune inflammation compromises these sex-specific lipid differences and increases CVD risk.

Main Methods:

• Literature review of sex differences in lipid metabolism and CVD risk.
• Analysis of lipid profiles in healthy populations, transgender individuals on hormone therapy, and patients with SLE.
• Examination of the impact of autoimmune inflammation on lipid metabolism and atherosclerosis.

Main Results:

• Healthy women generally have atheroprotective lipid profiles compared to men.
• Women with SLE often display dyslipidemia (elevated LDL, reduced HDL), increasing their atherosclerosis and CVD risk.
• Cross-sex hormone therapy can alter lipid profiles, potentially influencing CVD risk.

Conclusions:

• The sex-specific CVD protection observed in healthy women is diminished or reversed in the context of SLE.
• Understanding altered lipid metabolism in autoimmunity is crucial for identifying therapeutic targets to reduce CVD risk.
• Mechanistic insights into sex differences in lipid metabolism and CVD risk in autoimmunity are needed.