How Do I Increase HDL Cholesterol?

High density liptein cholesterol (HDL-C) is mainly synthesized in the liver. It is an anti-atherosclerotic lipoprotein that transports cholesterol from extrahepatic tissues to the liver for metabolism and is excreted by the bile ^{[ 1]} The plasma level is negatively related to the risk of cardiovascular disease ^[1] .

High-density lipoprotein can take cholesterol from cell membranes, catalyze lecithin cholesterol acyltransferase into cholesterol esters, and then transfer the carried cholesterol esters to very low density lipoproteins and low density lipoproteins. High-density lipoprotein has a relatively fixed cholesterol content, which contains about 20% to 30% of the total cholesterol in the human body. ^[2]

Chinese name: High density lipoprotein cholesterol
Foreign name: High-density lipoprotein cholesterol
Short name: HDL-C

Diameter: 8 to 13 nm
Density: 1.063 to 1.21 g / ml
Shape: Discoid

High density lipoprotein cholesterol disease relationship

Plasma high-density lipoprotein cholesterol (HDL-C) levels are inversely related to the occurrence of coronary heart disease. It mainly promotes anti-atherosclerosis by promoting reverse cholesterol transport (RCT), antioxidant, and anti-inflammatory mechanisms. . ^[3]

High-density lipoprotein cholesterol standard range

Epidemiological and clinical studies have shown that HDL-C is negatively correlated with the incidence of diseases such as coronary heart disease and atherosclerosis. According to the judging standards proposed by China's "Recommendations for the Prevention and Treatment of Dyslipidemia (2015 Edition)" ^[4] :

Adult male HDL-C is higher at 1.16 to 1.42 mmol / L (45 to 55 mg / dl), and higher at 1.29 to 1.55 mmol / L (50 to 60 mg / dl). Normal HDL-C accounts for about 25% to 30% of cholesterol.

HDL-C ideal range:> 1.04 mmol / L (> 40 mg / dL)

Elevation: 1.55 mmol / L (60 mg / dL)

Reduction: <0.91 mmol / L (<35 mg / dL)

The level of medical decision proposed by NCEP ATP is:

<1.03 mmol / L (40 mg / dL) is to reduce the risk of coronary heart disease; 1.55 mmol / L (60 mg / dL) to reduce the risk of coronary heart disease.

ATP increased HDL-C from the original <35 mg / dL (0.9 mmol / L) to <40 mg / dL (1.03 mmol / L) in order to allow more people to receive preventive treatment (men will change from the original 15 % Increased to about 40%, and women from the original 5% to 15% were classified as high-risk groups). ^[4]

Clinical significance of high density lipoprotein cholesterol

The main clinical value of high-density lipoprotein cholesterol elevation is to be able to transfer foam cells from atherosclerotic plaques to the liver to be excreted from the body. It can be seen in primary hyper HDL, and it is found that there are many longevity in this family. Patients receiving estrogen, insulin, or certain drugs (such as niacin, vitamin E, heparin, etc.) can also increase ^[5] .

High-density lipoprotein cholesterol reduction is commonly found in cerebrovascular disease, coronary heart disease, hypertriglyceridemia, and liver damage such as acute and chronic hepatitis, liver cirrhosis, liver cancer, diabetes, smoking, and lack of exercise. The reduction can be used as the risk of coronary heart disease Indicator ^[5] .

Elevated high-density lipoprotein cholesterol

Physiological increase: exercise (such as athletes generally have higher HDL-C), alcohol consumption, women taking contraceptives, some cholesterol-lowering drugs (such as Nuoheng), etc. ^[6] .
Pathologically elevated: chronic liver disease, chronic toxic disease, hereditary hyper HDLemia ^[6] .

Decreased HDL cholesterol

Physiological decline: People with less exercise, after stress response ^[6] .
Pathologically reduced patients with coronary heart disease, hypertriglyceridemia, cirrhosis, diabetes, chronic renal insufficiency, and malnutrition ^[6] .

High density lipoprotein cholesterol influencing factors

With severe malnutrition, HDL-C will also decrease with a marked decrease in plasma cholesterol, and obesity will have a lower HDL-C ^[7] ;
Disease states such as diabetes, hepatitis and cirrhosis can be accompanied by low HDL-C ^[7] ;
Patients with hypertriglyceridemia are often accompanied by low HDL-C ^[7] ;
HDL-C reduction is also seen in acute infections, diabetes, chronic renal failure, nephrotic syndrome, etc. ^[7] ;
Low to moderate drinking and physical activity can cause HDL-C to increase, and smoking can cause HL-C to decrease ^[7] ;
Injecting estrogen insulin, taking contraceptives, niacin, insulin, heparin, vitamin e and other drugs can also cause HDL-C to rise. In this case, just take a proper rest, stop taking or reduce the dose to return to normal ^[7] ;
HDL-C content is too high (such as more than 2.6 mmo / L), which is a pathological condition and is often defined as hyper HDL-Cemia, which can be divided into two categories: primary hyperHDLC The cause may be cholesterol ester transfer protein (CETP) deficiency, decreased liver lipase (HL) activity, or other unknown causes; secondary etiology of hyperHDL-C may be dyskinesia, excessive drinking, chronic toxic disease, chronic Time of aerobic metabolism, primary biliary cirrhosis, drug-induced hyperlipidemia, and other unknown causes. In short, the decrease in cholesterol ester transporter and liver lipase activity is the main cause of hyperHDL-C bloodemia ^[7] .

High density lipoprotein cholesterol protection

High-density lipoprotein cholesterol- mediated cholesterol reverse transport

HDL can transport cholesterol from surrounding tissues (including atherosclerotic plaques) to the liver for recycling or excretion in the form of bile acid. This process is called reverse cholesterol transport. HDL mediates the reverse transport of cholesterol, on the one hand, it clears cholesterol in the arterial wall and inhibits the growth of new plaques; on the other hand, it reduces cholesterol while increasing the stability of plaques, inhibiting plaque rupture, and reducing cardiovascular events. Hazard ^[8] .

High-density lipoprotein cholesterol antioxidant effect

LDL-C plays an important role in the initiation of atherosclerosis, while HDL can delay this process. At present, it is believed that natural LDL-C does not have a strong atherosclerotic effect. When it forms oxidized LDL-C, it will cause the occurrence and development of atherosclerosis. HDL granules contain a variety of antioxidant enzymes, the most studied of which are lecithin cholesterol acyltransferase, glutathione selenium peroxidase, platelet activating factor-acetylhydrolase (PAF-AH), and oxygenase (PON). They inhibit the oxidative modification of LDL through different chemical reactions, destroy the corresponding enzymes or enzyme activities and their oxidized phosphates during the oxidative modification of LDL, reduce the level of LDL lipid peroxides and directly damage the structure of LDL, and reduce oxidation. The formation of modified LDL and its damage to vascular endothelial cells, while also resisting HDL oxidation, protecting the structure and function of HDL, and finally reaching its antioxidant effect ^[8] .

High-density lipoprotein cholesterol promotes fibrinolysis

Endothelial cells can release tissue plasminogen activator (t-PA) and tissue plasminogen activator inhibitor-1 (tPAI-1) to control plasmin, To regulate the fibrinolytic process. Ren et al. Found that LDL and glycated LDL can reduce the production of t-PA and increase the production of tPAI-1, but HDL can eliminate this effect and restore endothelial cells to normal t-PA and tPAI-1. Release. Plasma tPAI-1 levels also have a negative correlation with HDL-C / TC ratio, further explaining that HDL can promote fibrinolysis by reducing tPAI-1 ^[8] .

Antithrombotic effect of high density lipoprotein cholesterol

HDL's antithrombotic effect mainly regulates endothelial-derived vasodilation factor nitric oxide (NO), prostacyclin I2 (PGI2), thromboxane A2 (TXA2), platelet activating factor (PAF), vonWillebrand factor (vWF) As well as protein C and protein S. The main role of NO is to activate the guanylate cyclase system in smooth muscle cells to cause vascular smooth muscle relaxation. At the same time, NO can also inhibit platelet aggregation and leukocyte adhesion to the endothelium. LDL and other lipids that cause atherosclerosis impair the synthesis of NO in endothelial cells, and HDL can restore this synthesis of NO, which indirectly inhibits the aggregation of platelets, thus acting as an antithrombosis. Like NO, PGI2 can also inhibit platelet aggregation, PGI2 can also increase the synthesis of NO in endothelial cells, and in turn NO can increase the activity of PGI2 to relax smooth muscle. HDL can promote the synthesis of PGI2 by endothelial cells, and through the apolipoprotein AI (apoA-I), it can prolong the half-life of PGI2 in the blood and enhance its anti-platelet aggregation effect, thereby playing an important role in preventing thrombosis in the coronary arteries. ^[8] .

High-density lipoprotein cholesterol intervention strategy

High-density lipoprotein cholesterol changes lifestyle

The National Cholesterol Education Program emphasizes that lifestyle changes should be taken for anyone whose blood lipid levels exceed target values. Lifestyle changes can help increase HDL-C. For example, smoking cessation can increase HDL-C by 20%; moderate drinking can significantly increase HDL-C and reduce the risk of coronary heart disease, but there is no consistent standard for what is meant by moderate drinking . Obese and overweight people should increase exercise and control diet. For every 3 kg of weight loss, HDL-C can increase by 0.025 mmol / L. Exercise and weight reduction are simple and effective for improving insulin resistance and increasing HDL-C ^[8] .

High density lipoprotein cholesterol medication

Existing lipid-lowering drugs have the effect of increasing HDL-C, but at the same time can reduce non-HDL-C (including LDL-C and very low-density lipoprotein cholesterol) and TG. Drugs ^[8] .

The currently used lipid-lowering drugs are:

(1) Niacin

Nicotinic acid drugs are believed to significantly increase HDL-C levels, while significantly reducing blood lipids and lipoproteins caused by arteriosclerosis such as plasma TG and lipoproteins, and promoting the conversion of small and dense LDL to large and sparse LDL particles. The longest, economical and effective drug to treat low levels of HDL-C ^[8] .

(2) statins

Statins are hydroxyglutaryl coenzyme A reductase inhibitors, which increase HDL-C by about 6% to 14% by stimulating apoA-I expression and mildly inhibiting cholesterol ester transfer protein (CETP) ^[8] .

(3) Bates

Fibrates stimulate HDL-C biosynthesis by 6% -20% by stimulating liver apoA-I expression and lipoprotein lipase activity ^[8] .

(4) Cholesteryl ester transporter inhibitor

torcetrapib is a potent cholesterol ester transfer protein (CETP) inhibitor that increases HDL-C levels by inhibiting CETP. In addition, torcetrapib significantly changed the distribution of cholesterol between HDL and LDL subgroups, increasing the average particle size of HDL and LDL in each group ^[8] .

High density lipoprotein cholesterol biotherapy

Biotherapy is a method that uses proteins, DNA, antibodies, or other substances that are extracted or synthesized from living tissues to obtain a therapeutic effect. The development of molecular biology technology has made it possible for recombinant proteins to be used as drugs for parenteral applications.

The more advanced in vivo test is apolipoprotein composed of apoA-I Milano and a phospholipid complex. Infusion of these apolipoproteins into animal models and humans has proven to reduce the incidence of atherosclerosis. Generating neutralizing antibodies against cholesterol ester transporters through autoimmunity is also in clinical trials. Gene therapies aimed at reducing LDL-C and increasing HDL-C have been initially established.

Therefore, simply increasing HDL-C levels is not the best goal for developing new treatments for HDL-C. Some new treatments are aimed at further enhancing the reverse transport effect of HDL on cholesterol. Direct apoA-I therapy and research on the regulation of ABCA1 and ABCG1 gene expression are important manifestations of this new concept ^[8] .