Unmet Cardiovascular Risk Beyond LDL-C: A Perspective on Managing Residual Cardiovascular Risk

Area of Science:

• Cardiology
• Atherosclerosis Research
• Lipid Metabolism

Background:

• Cardiovascular disease (CVD) remains a leading cause of death globally.
• Intensive low-density lipoprotein cholesterol (LDL-C) lowering reduces events but residual risk persists.
• Atherosclerosis is increasingly viewed as multifactorial, involving various lipoproteins and inflammation.

Purpose of the Study:

• To review emerging risk factors contributing to residual cardiovascular risk.
• To highlight novel therapeutic strategies beyond LDL-C reduction.
• To advocate for a multifactorial approach to atherosclerosis management.

Main Methods:

• Literature review of current research on atherosclerosis and cardiovascular risk factors.
• Synthesis of evidence on emerging risk factors including lipoproteins and psychological influences.
• Analysis of novel therapeutic strategies beyond LDL-C lowering.

Main Results:

• Residual cardiovascular risk is associated with factors beyond LDL-C, such as triglyceride-rich lipoproteins (TRLs), apolipoprotein B (APOB), dysfunctional high-density lipoproteins (HDLs), and lipoprotein(a) [Lp(a)].
• Endothelial dysfunction, chronic vascular inflammation, and psychological factors like stress also contribute to CVD risk.
• Novel therapeutic strategies are emerging that target these additional risk factors.

Conclusions:

• A shift from an LDL-C-centric view to a multiple risk factor approach is necessary for effective atherosclerosis prevention and treatment.
• Addressing TRLs, Lp(a), inflammation, and psychological factors is crucial for reducing residual cardiovascular risk.
• Future research and clinical practice should integrate these broader aspects for comprehensive cardiovascular care.