High-density lipoprotein cholesterol to non-high-density lipoprotein cholesterol ratio (HDL-C/non-HDL-C ratio)

The HDL-C/non-HDL-C ratio is a composite clinical biomarker used to assess an individual's risk for atherosclerotic cardiovascular disease (ASCVD). It represents the balance between high-density lipoprotein cholesterol (HDL-C), which is involved in reverse cholesterol transport, and non-high-density lipoprotein cholesterol (non-HDL-C), which includes all atherogenic lipoproteins such as LDL, VLDL, and IDL (StatPearls, 2023). This ratio is not a single molecular target like a protein or receptor; rather, it is a mathematical expression of several lipid parameters measured in blood plasma. Clinical management of this ratio typically involves lowering the denominator (non-HDL-C) through drugs like statins and PCSK9 inhibitors, or attempting to raise the numerator (HDL-C) via fibrates or niacin (PubMed, PMID: 33501140). While various therapies can significantly improve this ratio, the primary therapeutic focus in cardiology remains the absolute reduction of atherogenic particles, specifically LDL-C and non-HDL-C (NIH/NHLBI). Recent clinical trials for CETP inhibitors specifically targeted the improvement of this ratio, though many failed to show a corresponding reduction in cardiovascular events, highlighting the complexity of HDL-C as a therapeutic target (New England Journal of Medicine, 2017).

Other names

HDL-C:non-HDL-C ratioNon-HDL-C to HDL-C ratioLipid ratioAtherogenic index

Modification of individual lipoprotein levels through HMG-CoA reductase inhibition, PCSK9 inhibition, PPAR-alpha activation, or CETP inhibition to improve the balance between atherogenic and anti-atherogenic particles.