---
title: "Lipid Biomarkers: Total to HDL Cholesterol Ratio"
description: Cholesterol | Cardiovascular | Functional Blood Chemistry Analysis  | Total to HDL Cholesterol Ratio Blood Test
---

[The Optimal DX Research Blog ](https://www.optimaldx.com/research-blog)

# [Lipid Biomarkers: Total to HDL Cholesterol Ratio](https://www.optimaldx.com/research-blog/lipid-biomarkers)

 Written by [ODX Research](https://www.optimaldx.com/research-blog/author/odx-research) | Dec 27, 2022 4:30:00 PM

### Optimal Takeaways

Assessing the ratio of total cholesterol to HDL-cholesterol provides information about cholesterol metabolism and processing in the body. An increasing ratio indicates a relative decrease in HDL, the lipoprotein that scavenges and clears excess cholesterol. An elevated ratio is associated with an increased risk of atherosclerosis, carotid plaque, and non-alcoholic fatty liver disease. A lower ratio is considered desirable.

**Standard Range:** 0.00 - 5.00 Ratio

**The ODX Range:** 0.00 - 3.00 Ratio

**Low** total cholesterol:HDL-C ratio suggests a decreased risk of cardiovascular disease.

**High** total cholesterol:HDL-C ratio is associated with an increased risk of cardiovascular disease, atherosclerosis, arterial stiffness, and major adverse cardiac events (Acevedo 2012, Wen 2019, Kappelle 2011), as well as NAFLD (Ren 2019).

### Overview

The ratio of total cholesterol to HDL-cholesterol (TC:HDL), also known as the atherogenic or Castelli Index, is considered a better predictive indicator of CVD than isolated biomarkers such as LDL-C. A ratio of 3:1 is desirable in general, with targets for secondary prevention in women and men below 3 and 3.5, respectively (Pagana 2022, Millan 2009).

In a cross-sectional study of 1,624 adults 25-64, TC:HDL was the most significant predictor of increased intima-media thickness, an indicator of subclinical carotid atherosclerosis. Non-HDL and HDL-C were also significant indicators, while LDL-C was not. Researchers noted that a TC:HDL above 5.1 increased the risk of carotid plaque 1.5-2-fold (Acevedo 2012).

A TC:HDL ratio of 4 or above was also associated with arterial stiffness, another indicator of atherosclerosis. In a large population study of 16,733 healthy individuals, a TC:HDL ratio of 4 or above was associated with arterial stiffness, even if LDL-C was below 70 mg/dL (1.8 mmol/L) (Wen 2019).

The association of elevated TC:HDL with early signs of atherosclerosis also translates into adverse cardiovascular events. A prospective study assessed the value of TC:HDL in predicting MACEs in 6,948 individuals free of CVD at baseline. Results indicate that TC:HDL was significantly higher in those who experienced MACEs, with a mean of 5.78. Those suffering from MACEs also had significantly higher baseline TC, LDL-C, non-HDL-C, triglycerides, and hs-CRP and were more likely to be older and male, smoke, and have diabetes, obesity, and hypertension (Kappelle 2011).

A large prospective study of 73,302 individuals at high risk for CVD but without a diagnosis of CVD found that all-cause mortality and hospitalization for stroke and coronary heart disease were lowest with a TC:HDL of 2.96, higher with a median ratio of 4.42 and highest with a ratio of 5.58 (Orozco-Beltran 2017). A 17-year follow-up of 6,537 women found the lowest incidence of ischemic heart disease in those with a mean TC:HDL of 2.4, while the highest incidence occurred in those with a TC:HDL of 5.6 (Calling 2021).

The prospective Atherosclerosis Risk in Communities (ARIC) study of 14,403 subjects confirmed the value of using the TC:HDL ratio for identifying cardiovascular event risk in those without atherosclerotic cardiovascular disease at baseline. A TC:HDL at or above a cut-off of 4.2 significantly increased risk, especially when LDL-C or non-HDL-C were below median values of 135 mg/dL (3.48 mmol/L) and 158 mg/dL (4.09 mmol/L), respectively (Quispe 2020).

The TC:HDL ratio may also be predictive of NAFLD. The Jinchang cohort study of 31,121 subjects found that the incidence of NAFLD increased significantly as the TC:HDL ratio increased. Researchers conclude that TC:HDL was a better predictor of NAFLD than TC or HDL-C alone and better than the Apo B/ApoA1 ratio. They also point out that the risk factors for low HDL-C—obesity, diabetes, and lack of exercise—are also risk factors for NAFLD (Ren 2019).

### References

Acevedo, Mónica et al. [Total/HDL cholesterol ratio and non HDL cholesterol as predictors for increased intima media thickness]. Revista medica de Chile vol. 140,8 (2012): 969-76. doi:10.4067/S0034-98872012000800001

Calling, Susanna et al. “Total cholesterol/HDL-C ratio versus non-HDL-C as predictors for ischemic heart disease: a 17-year follow-up study of women in southern Sweden.” BMC cardiovascular disorders vol. 21,1 163. 5 Apr. 2021, doi:10.1186/s12872-021-01971-1

Kappelle, P J W H et al. “Apolipoprotein B/A-I and total cholesterol/high-density lipoprotein cholesterol ratios both predict cardiovascular events in the general population independently of nonlipid risk factors, albuminuria and C-reactive protein.” Journal of internal medicine vol. 269,2 (2011): 232-42. doi:10.1111/j.1365-2796.2010.02323.x

Millan, Jesus et al. “Lipoprotein ratios: Physiological significance and clinical usefulness in cardiovascular prevention.” Vascular health and risk management vol. 5 (2009): 757-65.

Orozco-Beltran, Domingo et al. “Lipid profile, cardiovascular disease and mortality in a Mediterranean high-risk population: The ESCARVAL-RISK study.” PloS one vol. 12,10 e0186196. 18 Oct. 2017, doi:10.1371/journal.pone.0186196

Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 15th ed., Mosby, 2021.

Quispe, Renato et al. “Total cholesterol/HDL-cholesterol ratio discordance with LDL-cholesterol and non-HDL-cholesterol and incidence of atherosclerotic cardiovascular disease in primary prevention: The ARIC study.” European journal of preventive cardiology vol. 27,15 (2020): 1597-1605. doi:10.1177/2047487319862401

Ren, Xiao Yu et al. “Total cholesterol to high-density lipoprotein cholesterol ratio is a significant predictor of nonalcoholic fatty liver: Jinchang cohort study.” Lipids in health and disease vol. 18,1 47. 11 Feb. 2019, doi:10.1186/s12944-019-0984-9

Wen, Jia et al. “Associations of non-high-density lipoprotein cholesterol, triglycerides and the total cholesterol/HDL-c ratio with arterial stiffness independent of low-density lipoprotein cholesterol in a Chinese population.” Hypertension research : official journal of the Japanese Society of Hypertension vol. 42,8 (2019): 1223-1230. doi:10.1038/s41440-019-0251-5

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