The LDL - HDL Ratio

The LDL:HDL Ratio

Dr. Dicken Weatherby & Beth Ellen DiLuglio, MS, RDN, LDN

Calculation of the LDL-cholesterol to HDL-cholesterol ratio provides a better assessment of cardiovascular risk than measuring either biomarker alone.

  • As useful as total cholesterol to HDL ratio for assessing cardiovascular risk[i]
  • May be a better assessment of cardiovascular risk when triglyceride levels are also taken into account.
    • Note that calculation of LDL is considered inaccurate if triglyceride levels exceed 300 mg/dL
    • Blood draw should be after 9-12 hour fast
  • A decrease in LDL or an increase in HDL will favorably affect the ratio and help reduce cardiovascular risk.
  • However, LDL:HDL ratio does not take into account particle size, oxidation, or inflammation, therefore additional testing will help further assess cardiovascular risk

Increased ratio reflects

  • Imbalance in cholesterol delivery (LDL) and cholesterol scavenging (HDL)
  • A relative increase in LDL-cholesterol that can cause atherosclerotic plaque and blood vessel damage when it becomes oxidized
  • A relative decrease in HDL (that collects cholesterol and carries it away from tissues and blood vessels
  • Increased risk of cardiovascular disease and even sudden death.

In general,

  • Cardiovascular risk is high when LDL is above 190 mg/dL (4.9 mmol/L) and HDL is below 40 mg/dL (1.05 mmol/L), yielding a ratio of LDL:HDL of 4.75.
  • Cardiovascular risk is considered low when LDL is below 100 mg/dL (2.6 mmol/L) and HDL is above 50 mg/dL (1.3 mmol/L), yielding a ratio of LDL:HDL of 2.

These levels and ratios can provide general guidelines. However, cardiovascular risk can be further defined using additional information such as free radical load, oxidized LDL, inflammatory markers, macrophages, and foam cells.[ii]

Hao et al 2014[iii]: Atherosclerosis schematics: the presence of ox-LDL in the intima causes monocytes to migrate from the lumen into the intima. Monocytes differentiate into macrophages which endocytose ox-LDL and become foam cells. SMCs are attracted from the media into intima by chemotaxis and haptotaxis. Cytokines released by macrophages, foam cells and SMCs activate T cells. T cells enhance activation of macrophages. HDL helps prevent atherosclerosis.

A retrospective study following 1,784 individuals undergoing coronary angiography (CAG) divided subjects into those with a LDL:HDL cholesterol ratio of less than 2.33 (mean of 1.79) and those with a ratio of 2.33 or greater (mean of 3.11).

  • Preliminary results published in 2020 found that those with a higher LDL:HDL ratio had a significantly higher incidence of total major adverse cardiac events (MACE) and rehospitalization for unstable angina or heart failure in the ~4-year follow-up period.[iv]

A 23-year prospective cohort study of 2,626 middle-aged men found that an elevated LDL:HDL ratio was independently associated with increased risk of sudden cardiac death (SCD), a phenomenon that accounts for half of all cardiovascular deaths.

  • The association was evident even though there was no association with LDL or HDL individually.
  • Those in the highest quintile for LDL:HDL (greater than 4.22) also had greater incidence of diabetes, prior MIs, higher BMI, and smoked cigarettes more, but consumed less alcohol than those in the lowest quintile (less than or equal to 2.3).
  • The men who died of SCD also had significantly higher hs-CRP levels (3.38 versus 2.36 mmol/L).[v]

Cardiometabolic health should always be assessed as a whole and evaluation of glucose tolerance is prudent when assessing cardiovascular risk. In one cross-sectional study of 2,680 participants, the mean LDL:HDL cholesterol ratio of individuals with normal glucose tolerance was 2.13 while the ratio was 2.56 for those with impaired glucose regulation and 2.6 for those diagnosed with type 2 diabetes.[vi]

There may be some risk with a lower LDL:HDL in some disorders as a lower ratio (1.52 or less) was observed in those suffering hemorrhagic transformation (HT) following an acute ischemic stroke than in those who did not experience HT.[vii]

Clinical Implications High Clinical Implications Low

Cardiovascular disease risk increase

Familial hypercholesterolemia [viii]

Sudden cardiac death

Reduced risk of cardiovascular disease

Reduced risk of sudden cardiac death

Hemorrhagic transformation

References

[i] Millán, Jesús et al. “Lipoprotein ratios: Physiological significance and clinical usefulness in cardiovascular prevention.” Vascular health and risk management vol. 5 (2009): 757-65. [R]

[ii] Hao, Wenrui, and Avner Friedman. “The LDL-HDL profile determines the risk of atherosclerosis: a mathematical model.” PloS one vol. 9,3 e90497. 12 Mar. 2014, doi:10.1371/journal.pone.0090497 [R]

[iii] Hao, Wenrui, and Avner Friedman. “The LDL-HDL profile determines the risk of atherosclerosis: a mathematical model.” PloS one vol. 9,3 e90497. 12 Mar. 2014, doi:10.1371/journal.pone.0090497 [R] 

[iv] Zhao, Y., et al. "The LDL-C/HDL-C ratio and 4-year risk of coronary artery disease: a retrospective study." (2020). [R]

[v] Kunutsor, Setor K et al. “Is High Serum LDL/HDL Cholesterol Ratio an Emerging Risk Factor for Sudden Cardiac Death? Findings from the KIHD Study.” Journal of atherosclerosis and thrombosis vol. 24,6 (2017): 600-608. doi:10.5551/jat.37184 [R]   

[vi] Guo, Wen et al. “Diagnostic values and appropriate cutoff points of lipid ratios in patients with abnormal glucose tolerance status: a cross-sectional study.” Lipids in health and disease vol. 18,1 130. 1 Jun. 2019, doi:10.1186/s12944-019-1070-z [R]

[vii] Wang, Yanan et al. “Reduction in the Ratio of Low-density Lipoprotein Cholesterol to Highdensity Lipoprotein Cholesterol is Associated with Increased Risks of Hemorrhagic Transformation in Patients with Acute Ischemic Stroke.” Current neurovascular research vol. 16,3 (2019): 266-272. doi:10.2174/1567202616666190619151914 [R}  

[viii] Panagiotakos, Demosthenes B et al. “Importance of LDL/HDL cholesterol ratio as a predictor for coronary heart disease events in patients with heterozygous familial hypercholesterolaemia: a 15-year follow-up (1987-2002).” Current medical research and opinion vol. 19,2 (2003): 89-94. [R]  

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