Lipid Biomarkers: LDL to HDL Cholesterol Ratio

Optimal Takeaways

Assessing the ratio of LDL-C to HDL-C provides information about the delivery of cholesterol (LDL) and the scavenging and processing of cholesterol (HDL). An increased ratio is associated with risk of atherosclerosis, MACE, ischemic stroke, NAFLD, and diabetes in those with hypertension. A decreased ratio is considered desirable unless LDL cholesterol falls to unhealthy levels.

Standard Range:

Male 0.00 - 4.90 Ratio

Female 0.00 - 4.12 Ratio

The ODX Range:

Male 0.00 - 2.28 Ratio

Female 0.00 - 2.4 Ratio            

Low LDL:HDL ratio suggests a decreased risk of cardiometabolic disease, though it may reflect a decrease in LDL to unhealthy levels.

High LDL:HDL ratio is associated with cardiovascular risk, diabetes (Hong 2020), increased carotid intima-media thickness (Qin 2021), and NAFLD (Zou 2021).

Overview

The ratio of LDL-C to HDL-C (LDL:HDL) reflects the balance between cholesterol delivery (LDL) and reverse cholesterol transport (HDL). The ratio is considered a valuable biomarker for identifying cardiovascular risk (Fernandez 2008).

A cohort study of 13,612 Chinese adults found that an LDL:HDL ratio above 2.78 was significantly associated with increased carotid intima-media thickness, an indicator of increased atherosclerotic plaque (Qin 2021). Higher LDL:HDL ratio of 2.7 or above versus below 2.7 was also associated with increased incidence of MACE following percutaneous coronary intervention and stent placement in subjects placed on statin therapy. Age and diabetes were also independent predictors of MACE. No significant difference was observed in CVD death or MI (Zhong 2019).

The LDL:HDL ratio is also useful as a significant and independent marker for identifying risk of diabetes in those with hypertension. A cross-sectional hospital-based study found that hypertensives diagnosed with diabetes had a significantly increased LDL:HDL with the highest risk at a ratio above 2.5 and lowest risk below 1.9, with risk increasing as triglycerides increased. Those diagnosed with diabetes also had significantly higher non-HDL-C, TC:HDL-C, triglycerides, TG:HDL-C, BMI, and waist circumference, and significantly lower HDL-C (Hong 2019).

Although research suggests that risk of ischemic stroke increases by 31% with a two-fold increase in LDL:HDL ratio, a higher ratio may be protective for subjects on statins in the early months following occurrence. One hospital-based follow-up study found that a higher LDL:HDL ratio was associated with reduced rates of death, recurrence, and disability in the first 3 months following an initial ischemic stroke. Participants with a ratio of 2.23-2.88 had the lowest rate of complications at three months. The same group had the lowest risk of death at 12 months, compared to an LDL:HDL ratio below 2.23 or above 3.56 (Liu 2020). Further research should assess the impact of statins on short- and long-term prognosis with ischemic stroke.

A 5-year follow-up study of 9,767 non-obese Chinese adults found that elevated LDL:HDL was significantly associated with new-onset NAFLD despite normal levels of LDL-C and HDL-C, though the association decreased with age. Adjusted values suggest that risk of NAFLD increases by 66% for each 1 unit increase in LDL:HDL. Researchers suggest an LDL:HDL cut-off of 1.66 for predicting NAFLD (Zou 2021).

References

Fernandez, Maria Luz, and Densie Webb. “The LDL to HDL cholesterol ratio as a valuable tool to evaluate coronary heart disease risk.” Journal of the American College of Nutrition vol. 27,1 (2008): 1-5. doi:10.1080/07315724.2008.10719668

Hong, Mengyang et al. “Contribution and interaction of the low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and triglyceride to diabetes in hypertensive patients: A cross-sectional study.” Journal of diabetes investigation vol. 10,1 (2019): 131-138. doi:10.1111/jdi.12856

Liu, Li et al. “Association of LDL-C/HDL-C Ratio With Stroke Outcomes Within 1 Year After Onset: A Hospital-Based Follow-Up Study.” Frontiers in neurology vol. 11 408. 15 May. 2020, doi:10.3389/fneur.2020.00408

Qin, Pei et al. “Low-Density Lipoprotein Cholesterol/High-Density Lipoprotein Cholesterol Ratio and Carotid Intima-Media Thickness: A Cohort Study in China.” Lipids vol. 56,1 (2021): 59-68. doi:10.1002/lipd.12274

Zhong, Zhixiong et al. “Assessment of the LDL-C/HDL-C ratio as a predictor of one year clinical outcomes in patients with acute coronary syndromes after percutaneous coronary intervention and drug-eluting stent implantation.” Lipids in health and disease vol. 18,1 40. 2 Feb. 2019, doi:10.1186/s12944-019-0979-6

Zou, Yang et al. “LDL/HDL cholesterol ratio is associated with new-onset NAFLD in Chinese non-obese people with normal lipids: a 5-year longitudinal cohort study.” Lipids in health and disease vol. 20,1 28. 25 Mar. 2021, doi:10.1186/s12944-021-01457-1