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Questioning LDL Targets

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“Clinical guidelines have progressively lowered the recommended LDL-C target for high-risk CVD patients to below 70 mg/dL, but scientific support for this target is arguably questionable.” 

A review published recently in the Journal of Clinical Medicine adds to research questioning the relationship between LDL-cholesterol (LDL-C) and cardiovascular disease (CVD). Previous blogs and Research Forums have highlighted numerous studies identifying people with very high LDL-C, yet coronary artery calcium scores of zero, indicating low risk for cardiovascular events. Starting from the premise that LDL-C is a poor predictor of CVD risk, the authors of the new review argue that the preponderance of evidence does not support targeting LDL-C to below 70 mg/dL either for cardiovascular health or overall health. 

The authors cite numerous studies that fail to show a linear relationship between LDL-C and CVD risk, “challenging the promotion of aggressive LDL-C reduction”—particularly for primary prevention. They also emphasize that studies have shown an association between high LDL-C and better health and increased longevity among the elderly, likely owing to superior immune function, resistance to infection, and a reduction in cancer-related mortality that has been found in individuals with the highest LDL-C. 

A 2022 meta-analysis found that the benefits of statin drug therapy for reducing the incidence of stroke or heart attack, and reducing all-cause mortality, are highly inflated owing to the use of relative risk reduction rather than absolute risk reduction. This new review suggests that the small benefit statins impart may not be a consequence of lowering LDL-C, but rather, from their antithrombotic effects and other pleiotropic effects.  

 

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