Current Atherosclerosis Reports

, Volume 14, Issue 1, pp 1–10 | Cite as

Residual Cardiovascular Risk Despite Optimal LDL Cholesterol Reduction with Statins: The Evidence, Etiology, and Therapeutic Challenges

  • Uchechukwu K. Sampson
  • Sergio Fazio
  • MacRae F. LintonEmail author
Statin Drugs (M Clearfield, Section Editor)


This review captures the existence, cause, and treatment challenges of residual cardiovascular risk (CVR) after aggressive low-density lipoprotein cholesterol (LDL-C) reduction. Scientific evidence implicates low high-density lipoprotein cholesterol (HDL-C) and high triglycerides (TG) in the CVR observed after LDL-C lowering. However, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) lipid trial with fenofibrate, the Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) study with torcetrapib, and the recently terminated Atherothrombosis Intervention in Metabolic Syndrome with Low HDL Cholesterol/High Triglyceride and Impact on Global Health Outcomes (AIM-HIGH) study with niacin, do not clearly attribute risk reduction value to HDL-C/TG modulation. The optimum approach to long-term lipid-modifying therapies for CVR reduction remains uncertain. Consequently, absolute risk modulation via lifestyle changes remains the centerpiece of a strategy addressing the physiologic drivers of CVR associated with HDL-C/TG, especially in the context of diabetes/metabolic syndrome.


Statins LDL cholesterol CV risk reduction Residual CV risk 



Funding support for Dr. Sampson was provided in part by the Harold Amos Medical Faculty Development Award of the Robert Wood Johnson Foundation and the Vanderbilt Clinical and Translational Scholars Award. Drs. Fazio and Linton were partially supported by NIH grants HL65709, HL086988, and HL105375.


U.K. Sampson: none. S. Fazio is a scientific advisory board member of Merck, Sharp, and Dohme; is a consultant for Merck, Takeda, Kowa, and Pfizer; has received grants (paid to his institution) from the National Institutes of Health, Merck, and Pfizer; and has had travel expenses covered by Merck. M.F. Linton is a consultant for Merck and Kowa and has received grants from ISIS, Genzyme, and Merck.


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Uchechukwu K. Sampson
    • 1
    • 2
    • 3
  • Sergio Fazio
    • 1
    • 2
  • MacRae F. Linton
    • 1
    • 4
    Email author
  1. 1.Department of MedicineVanderbilt University Medical CenterNashvilleUSA
  2. 2.Department of PathologyVanderbilt University Medical CenterNashvilleUSA
  3. 3.Department of Radiology and Radiological SciencesVanderbilt University Medical CenterNashvilleUSA
  4. 4.Department of PharmacologyVanderbilt University Medical CenterNashvilleUSA

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