Why does LDL-C follow a different paradigm from other endocrine-metabolic diseases in cardiovascular prevention?

Area of Science:

• Endocrinology
• Cardiovascular Medicine
• Preventive Cardiology

Background:

• Traditional cardiovascular prevention emphasizes lowering low-density lipoprotein cholesterol (LDL-C) targets, especially in high-risk individuals.
• Emerging evidence highlights the significance of cumulative lifetime LDL-C exposure over isolated, late-life levels for cardiovascular risk.
• An endocrine perspective views LDL-C as a chronic metabolic exposure where duration and intensity impact pathogenicity.

Purpose of the Study:

• To integrate evidence on cumulative LDL-C exposure from epidemiological, genetic, and clinical studies.
• To contrast current lipid management with preventive strategies used for other endocrine-metabolic disorders.
• To advocate for incorporating cumulative LDL-C exposure into preventive decision-making, particularly for early intervention.

Main Methods:

• Review of longitudinal cohort studies.
• Analysis of familial hypercholesterolaemia data.
• Application of Mendelian randomisation analyses.
• Integration of evidence from endocrine-metabolic disorder management.

Main Results:

• Cardiovascular risk is significantly influenced by the total duration of LDL-C exposure throughout life.
• Current guidelines acknowledge LDL-C's causal role but may not fully operationalize early intervention based on lifetime risk.
• Limiting cumulative LDL-C exposure early offers potential long-term benefits, especially for younger individuals.

Conclusions:

• Cumulative LDL-C exposure is a critical factor in cardiovascular risk assessment and prevention.
• An endocrine framework suggests that reducing lifetime LDL-C burden is a valuable preventive strategy.
• This perspective complements existing guidelines by emphasizing early intervention to limit cumulative LDL-C exposure.