Causes of high-density lipoprotein elevation and lowering

A decrease in HDL-C concentration below 0.9 mmol/L is associated with an increased risk of developing atherosclerosis. Epidemiological studies have shown an inverse relationship between HDL-C concentrations and the prevalence of coronary heart disease. Determination of HDL-C helps to identify the risk of developing coronary heart disease. A decrease in HDL-C concentration by every 5 mg/dL, or 0.13 mmol/L below the average leads to an increase in the risk of developing coronary heart disease by 25%.

An increased concentration of HDL-C is regarded as an antiatherogenic factor.

An elevated HDL level is considered to be greater than 80 mg/dL (>2.1 mmol/L).

Elevated HDL levels reduce cardiovascular risk; however, high HDL levels caused by some primary genetic abnormalities may not protect against cardiovascular disease because of associated lipid metabolism and metabolic disturbances.

Primary causes are single or multiple genetic mutations that result in overproduction or decreased excretion of HDL. Secondary causes of high HDL include chronic alcoholism leading to liver cirrhosis, primary biliary cirrhosis, hyperthyroidism, and the use of certain medications (eg, glucocorticoids, insulin, phenytoin). In case of unexpected clinical findings of high HDL levels in patients not taking lipid-lowering drugs, a diagnostic evaluation of secondary causes of this condition should be performed immediately, with mandatory measurement of AST, ALT, and TSH; a negative result indicates possible primary causes of dyslipidemia.

Cholesterol ester transfer protein (CETP) deficiency is a rare autosomal recessive inherited disorder caused by a mutation in the CETP gene. CETP facilitates the transfer of cholesteryl esters from HDL to other lipoproteins, and thus CETP deficiency results in low LDL cholesterol and delayed HDL clearance. Patients do not have any clinical symptoms or signs of disease, but have HDL levels > 150 mg/dL. No reduction in cardiovascular risk is observed. No treatment is required.

Familial hyperalpha-apoproteinemia is an autosomal dominant inherited condition caused by various unknown and known genetic mutations, including those that result in overproduction of apolipoprotein A-1 and apolipoprotein C type III. The disorder is usually discovered incidentally when plasma HDL levels are > 80 mg/dL. Patients have no other clinical symptoms or signs. No treatment is required.

Currently, the concentration of HDL-C in the blood serum below 0.91 mmol/L is considered an indicator of a high risk of coronary heart disease, while the level above 1.56 mmol/L plays a protective role. Simultaneous assessment of the concentration of total cholesterol and HDL-C in the blood serum is important for determining the treatment tactics. If the patient's HDL-C concentration is low (less than 0.91 mmol/L) and total cholesterol is normal, the most effective measures for preventing coronary heart disease include physical exercise, smoking cessation, and weight loss. If the concentration of total cholesterol increases and the content of HDL-C decreases (less than 0.91 mmol/L), medical intervention programs should be aimed at reducing the level of total cholesterol using special diets or, if necessary, drug therapy.

Having determined the HDL-C content in the blood, it is possible to calculate the cholesterol atherogenic coefficient (C atherogenic _coefficient ): C atherogenic _coefficient = (Total C-HDL-C) / HDL-C. C _atherogenic coefficient actually reflects the ratio of the atherogenic LP content in the blood to the antiatherogenic ones. This coefficient is no more than 1 in newborns, reaches 2.5 in healthy men aged 20-30, and 2.2 in healthy women of the same age. In men aged 40-60 without clinical manifestations of atherosclerosis, C _{atherogenic coefficient} ranges from 3 to 3.5. In people with coronary heart disease, it is greater than 4, often reaching 5-6. It is noteworthy that C _{atherogenic coefficient} is relatively low in long-livers: in people over 90 years old, it does not exceed 3. C atherogenic _coefficient more accurately reflects the favorable and unfavorable combination of LP in terms of the risk of developing coronary heart disease and atherosclerosis.

When analyzing the results of the study, it should be taken into account that an increase or decrease in HDL-C levels is possible with a number of diseases or conditions.

Diseases and conditions that may alter HDL-C levels in the blood

Increased values	Reduced values
Primary biliary cirrhosis of the liver	Diabetes mellitus
Chronic hepatitis	Kidney and liver diseases
Alcoholism	GLP type IV
Other chronic intoxications	Acute bacterial and viral infections

However, using only HDL-C values to assess the risk of developing atherosclerosis may provide potentially incorrect diagnostic information, so its values should be assessed in comparison with the concentration of total cholesterol and LDL-C.