Total Cholesterol / HDL Ratio - Kresser Institute Membership Site

Marker Name: Total Cholesterol/HDL Ratio

REFERENCE RANGES FOR TOTAL CHOLESTEROL/HDL RATIO:

Laboratory reference range: 0–5

Functional reference range: 0–3

DESCRIPTION:

The total cholesterol/HDL ratio is the mathematical ratio of total cholesterol to HDL cholesterol in the blood. It is also known as the atherogenic or Castelli index.¹ HDL is an acronym for high-density lipoprotein, and, as listed in this ratio, it specifically refers to HDL cholesterol (HDL-C). The total cholesterol/HDL ratio more accurately predicts coronary heart disease risk than LDL cholesterol alone.^2-5

HDL is one of the five major lipoproteins in plasma and one of the cholesterol types that combine to provide a total cholesterol measurement. Cholesterol provides structural integrity to cell membranes throughout the body and is a precursor to various steroid molecules.^6,7 HDL carries fatty acids from fat-containing cells to the liver for eventual excretion in the feces—the so-called reverse cholesterol transport pathway.^8-10 Importantly, HDL also removes cholesterol from lipid-filled macrophages in atherosclerotic plaques.¹¹

Nascent HDL particles are synthesized de novo by the liver and small intestine.¹² They draw free cholesterol molecules from atherosclerotic plaques and fat-containing cells to form a mature HDL particle.⁸ At the end of the particle’s lifespan, the liver catabolizes senescent HDL particles and HDL remnants.^11,13

Other components of total cholesterol are generated via the exogenous or endogenous pathways.⁸ In the exogenous pathway, dietary cholesterol and fatty acids are absorbed from the gastrointestinal tract.⁹ Triglycerides and cholesterol combine to form chylomicrons, which enter the circulation and travel throughout the body. Remnants of these chylomicrons form HDL. In the endogenous pathway, VLDL is created in the liver from triglycerides and cholesterol esters and is eventually incorporated into LDL.⁹

The total cholesterol-to-HDL cholesterol ratio is higher than normal if total cholesterol is proportionally higher than HDL cholesterol. This could be due to an excess of total cholesterol, the relative lack of HDL cholesterol, or both. As such, abnormal elevations in the total cholesterol-to-HDL cholesterol ratio are caused by the same conditions that increase total cholesterol and/or decrease HDL cholesterol. Increased total cholesterol may be due to endocrine disturbances, such as diabetes or hypothyroidism, diseases of the kidney or liver, the effect of various stressors, such as cigarette smoking, or the effect of various drugs.¹⁴ On the other hand, obesity and lifestyle issues such as smoking and physical inactivity are associated with abnormally low HDL-C levels. Acute infection, inflammation, and certain chronic diseases can lower HDL cholesterol levels, thus raising the total-to-HDL cholesterol ratio.¹⁵

Relative reductions in total cholesterol and elevations in HDL cholesterol are generally considered healthy.¹⁶

Total cholesterol and HDL cholesterol are measured in a standard serum lipid profile.¹⁷

PATHOLOGICAL/CONVENTIONAL RANGE INDICATIONS: High in:^14,18-22

Primary disorders of cholesterol metabolism
- Familial hypercholesterolemia
- Familial combined hypercholesterolemia
- Familial hyperapobetalipoproteinemia
- Polygenic hypercholesterolemia
- Familial primary hypoalphalipoproteinemia
- Non-familial hypoalphalipoproteinemia
- Familial hypoalphalipoproteinemia with hypertriglyceridemia
Obesity
Sedentary lifestyle
Cigarette smoking
Excessive alcohol consumption
Diabetes mellitus
Hypothyroidism
Nephrotic syndrome
Renal failure
Obstructive liver disease
Hepatitis
Acute intermittent porphyria
Anorexia nervosa
Systemic lupus erythematosus
Von Gierke disease
Elevated cholesteryl ester transfer protein activity
Lipoprotein lipase deficiency
Elevated hepatic triglyceride lipase activity
Drugs
- Adrenal steroids
- Beta-blockers
- Benzodiazepines
- Isotretinoin
- Thiazides
- Anticonvulsants
- Protease inhibitors
- Anabolic steroids
- Oral estrogens

Low in:

Not clinically relevant

FUNCTIONAL RANGE INDICATIONS:

High in:

Early stages of conventional indications above

Low in:

Impaired liver function
Not clinically significant

References: