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

Kyriakos E Kypreos1,2,3, Anca Violeta Gafencu2, Ourania Andreopoulou1

  • 1Pharmacology Laboratory, Department of Medicine, University of Patras, 26500 Rio Achaias, Greece.

Pharmaceuticals (Basel, Switzerland)
|July 28, 2026
PubMed

Insights

Cardiovascular disease risk persists despite lipid lowering. New research explores factors beyond LDL cholesterol, including lipoproteins and inflammation, for better prevention and treatment.

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.

Keywords:
Lipoprotein(a)apolipoprotein Batherosclerosisdyslipidemiashigh-density lipoproteinsinflammationmental healthresidual cardiovascular riskrisk factors

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