High-density lipoprotein cholesterol to total cholesterol ratio (HDL-C/TC ratio)

The HDL-C/total cholesterol ratio is a clinical biomarker and metabolic index used to evaluate an individual's risk for atherosclerotic cardiovascular disease (ASCVD). This ratio represents the balance between cardioprotective high-density lipoprotein cholesterol (HDL-C), which facilitates reverse cholesterol transport, and the total cholesterol (TC) pool, which includes pro-atherogenic fractions like low-density lipoprotein (LDL-C) and very-low-density lipoprotein (VLDL-C). While not a physical drug target such as a protein or enzyme, it serves as a powerful diagnostic and prognostic tool; a higher ratio (indicating more HDL relative to total cholesterol) is generally associated with decreased cardiovascular risk. Pharmacological agents do not target the ratio itself but rather the underlying pathways of lipid metabolism. For instance, statins lower total cholesterol by inhibiting HMG-CoA reductase, while fibrates and CETP inhibitors specifically aim to elevate HDL-C or reduce triglycerides. Consequently, the HDL-C/TC ratio is widely utilized in clinical trials and practice to monitor the efficacy of lipid-modifying therapies and to stratify patients based on their metabolic health.

Other names

Castelli Risk Index ITotal cholesterol to HDL cholesterol ratioTC/HDL-C ratioCholesterol ratioAtherogenic index

Pharmacological agents do not target the ratio directly; instead, they modulate individual lipid components. HMG-CoA reductase inhibitors (statins) decrease total cholesterol by inhibiting hepatic synthesis, while fibrates activate PPAR-alpha to increase HDL-C and decrease triglycerides. PCSK9 inhibitors increase LDL receptor density to lower the total cholesterol pool, thereby improving the HDL-C/TC ratio.