What Is Good Cholesterol?

Introduction

Cholesterol is a fat-like substance present in all body cells. Cholesterol is also found in dietary sources such as meat and dairy products. The body needs cholesterol to make steroid hormones, bile acids, and vitamin D. However, a high blood cholesterol level raises the risk of many diseases. HDL (high-density lipoproteins) and LDL (low-density lipoproteins) are two types of lipoproteins (a combination of lipids and proteins for easy movement in the bloodstream).

HDL is termed the "good" cholesterol as it carries cholesterol from other body parts to the liver for breakdown and removal (reverse cholesterol transport, RCT). Moreover, high HDL cholesterol (HDL-C) levels are connected to a lower heart disease risk. Similarly, LDL is called the "bad" cholesterol due to its tendency to build up in the blood vessel walls (atherosclerosis).

What Are the Diseases Associated With Low Levels of Good Cholesterol?

Various disorders are linked to defective HDL metabolism.

1. Genetic Diseases: Genetic mutations present with marked or complete HDL deficiency and characteristic syndromes.

• Apo A-I Deficiency: The APO A-I gene is involved in the production of a protein called apolipoprotein A-I (apo A-I, a component of HDL). APO A1 gene mutations cause familial HDL deficiency, an inherited condition with low blood HDL levels and a risk for cardiovascular disease (CVD) at an early age (before 50).

• Familial Lecithin Cholesterol Acyltransferase Deficiency: Familial lecithin cholesterol acyltransferase (LCAT, an enzyme that increases HDL-C) deficiency is an inherited disease that presents with corneal opacity (loss of corneal transparency), dyslipidemia (abnormal blood lipid levels), and proteinuria (excretion of proteins in the urine). It comprises end-stage renal disease (ESRD, a condition in which kidneys stop functioning and a patient requires dialysis or a kidney transplant) that occurs around the fourth decade of life.

• Tangier Disease: Tangier disease occurs due to severe deficiency or absence of HDL-C and the accumulation of cholesterol within an organ. The disease appears in the first decade of life as tonsillar enlargement and clouding of the cornea. Furthermore, neuropathy (nerve pathology) and CVD are the most devastating outcomes of Tangier's disease.

2. Metabolic Syndrome and Diabetes: Metabolic syndrome comprises several disorders, including obesity, high blood pressure, high blood triglycerides (TG, a form of lipids), low HDL- C, and insulin resistance. Compared to genetic abnormalities in HDL metabolism, low HDL-C occurs more frequently in patients with metabolic syndrome or diabetes mellitus (DM).

3. Cardiovascular Disease: Coronary artery disease (CAD) is one of the frequent global causes of death. Dyslipidemia in CAD denotes elevated low-density lipoprotein cholesterol (LDL-C) and decreased HDL-C. It is a well-known risk factor for the development and progression of atherosclerosis in CAD.

4. Inflammatory Diseases: Low HDL-C levels are linked to many systemic inflammatory disorders. Moreover, reduced levels of HDL-C are also a sign of autoimmune diseases, including rheumatoid arthritis (RA, a joint disease), systemic lupus erythematosus (SLE), and inflammatory bowel disease (IBD).

5. Neoplasia: In cases of extremely low HDL-C, a diagnosis of neoplasia (cancer) or sepsis (widespread infection in the body) can be given.

What Are the Beneficial Functions of Good Cholesterol?

1. Anti-atherosclerotic Effects: RCT and cholesterol clearance from the body explains HDL's association with the protection of the blood vessels. Evidence is also available from animal experiments for the anti-atherosclerotic effects of HDL.

2. Anti-oxidant Effects: HDL is associated with several anti-oxidant enzymes in the body. In healthy individuals, HDL inhibits the oxidation of LDL-C. Further, HDL itself gets oxidized and is cleared rapidly from circulation.

3. Anti-inflammatory Effects: Adhesion and migration of immune cells and inflammatory mediators into the vessel wall are essential for atherosclerosis. Animal models show HDL-C to inhibit these molecules. Further, it supports endothelial (endothelium is the blood vessel lining) repair mechanisms. Hence, all these findings make HDL-C a vital part of the immune system.

4. Anti-thrombotic Effects: HDL-C has anti-thrombotic (clot-inhibiting) and fibrinolytic (clot-dissolving) properties. It does so by inhibiting platelet activation and aggregation. On the other hand, it also enhances the activity of anti-clotting factors (proteins C and S).

How to Increase Good Cholesterol Levels in the Body?

The positive effects of HDL-C are an attractive target for chronic or acute vascular (blood vessel) disease management. Approaches to increase HDL-C include lifestyle changes and medications.

1. Lifestyle Changes: HDL-C can be increased through various lifestyle changes. The most crucial are physical activity and dietary changes. Studies suggest that lifestyle changes that increase HDL-C reduce the risk of CVD. Physical activity leads to an increase in HDL-C and also augments HDL function. At the same time, the metabolism of other lipoproteins improves. Smoking and secondhand smoke exposure can also lower HDL-C levels. Further, excessive alcohol consumption may also decrease HDL-C. Hence, it is wise to avoid cigarette smoking and alcohol.

2. Medications:

• Statins: Statins (e.g., Atorvastatin, Rosuvastatin, Simvastatin) cause an HDL-C and apo A-I increase and lower LDL-C. Such changes contribute to the cardiovascular benefits of these drugs.

• Fibrates: Fibrates (Fibric acids) are indicated to treat hypercholesterolemia (increased blood cholesterol). They reduce LDL-C, total cholesterol, and TGs, and increase HDL-C.

• Niacin: Niacin (nicotinic acid, vitamin B3) is the oldest and most effective substance in raising HDL-C levels. Many clinical trials are evaluating its benefit on CVD alone or in combination with other drugs.

Drugs containing testosterone and other steroids can decrease HDL-C. Hence, avoiding them may help increase HDL-C. Doctors usually do not prescribe medicines only to raise HDL-C levels; however, if a patient has a low HDL-C and high LDL-C, appropriate medication is given.

What Is the Clinical Significance of Good Cholesterol?

HDL plays a central role in RCT. Studies have found an inverse relationship between HDL-C concentration and CVD. Also, studies show the protective effects of a genetically high HDL-C concentration. Low HDL-C is a clinical indicator of disturbed metabolism of TGs (in DM) or chronic inflammation. Hence, one must keep a few points in mind.

1. HDL-C cannot determine the prognosis of CVD. It is because the ratio of HDL-C to LDL-C may be misleading if HDL-C is high. It is also true if underlying diseases such as DM or chronic kidney disease (CKD) exist.

2. Increasing HDL-C through physical activity and smoking cessation is associated with protective effects in the blood vessels.

3. At present, HDL-C is not a target for pharmacological treatment. It is because the primary goal is currently the reduction of LDL-C.

Conclusion

HDL is a molecule that varies in size and composition. Various studies reveal its potentially beneficial functions. One must note that low HDL-C indicates that the affected individual should be examined for an underlying disease. However, the importance of HDL-C levels and HDL particles is questioned, as raising the HDL-C does not meet expectations in treatment. Still, HDL-C should be a viable therapeutic option for those at high cardiovascular risk.