High-density lipoprotein

High-density lipoprotein (HDL) is one of the five major groups of

Increasing concentrations of HDL particles are associated with decreasing accumulation of atherosclerosis within the walls of arteries,^[4] reducing the risk of sudden plaque ruptures, cardiovascular disease, stroke and other vascular diseases.^[2] HDL particles are commonly referred to as "good cholesterol", because they transport fat molecules out of artery walls, reduce macrophage accumulation, and thus help prevent or even regress atherosclerosis.^[5] However, recent investigations have shown that very high concentrations of HDL particles can be associated with an increased mortality risk^[6] and an increased cardiovascular risk, especially in hypertensive patients.^[7]

Testing

Because of the high cost of directly measuring HDL and LDL (

The remainder of the serum cholesterol after subtracting the HDL is the non-HDL cholesterol. The concentration of these other components, which may cause atheroma, is known as the non-HDL-C. This is now preferred to LDL-C as a secondary marker as it has been shown to be a better predictor and it is more easily calculated.^[10]

Structure and function

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With a size ranging from 5 to 17 nm, HDL is the smallest of the

Several steps in the metabolism of HDL can participate in the transport of cholesterol from lipid-laden

Five subfractions of HDL have been identified. From largest (and most effective in cholesterol removal) to smallest (and least effective), the types are 2a, 2b, 3a, 3b, and 3c.[15]

Epidemiology

Men tend to have noticeably lower HDL concentrations, with smaller size and lower cholesterol content, than women. Men also have a greater incidence of atherosclerotic heart disease. Recent studies confirm the fact that HDL has a buffering role in balancing the effects of the hypercoagulable state in type 2 diabetics and decreases the high risk of cardiovascular complications in these patients. Also, the results obtained in this study revealed that there was a significant negative correlation between HDL and activated partial thromboplastin time (APTT).^{[citation needed]}

Epidemiological studies have shown that high concentrations of HDL (over 60 mg/dL) have protective value against

Data from the landmark Framingham Heart Study showed that, for a given level of LDL, the risk of heart disease increases 10-fold as the HDL varies from high to low. On the converse, however, for a fixed level of HDL, the risk increases 3-fold as LDL varies from low to high.^[16][17]

Even people with very low LDL levels under statins treatment are exposed to increased risk if their HDL levels are not high enough.^[18]

Estimating HDL via associated cholesterol

Clinical laboratories formerly measured HDL cholesterol by separating other lipoprotein fractions using either ultracentrifugation or chemical precipitation with divalent ions such as Mg²⁺, then coupling the products of a cholesterol oxidase reaction to an indicator reaction. The reference method still uses a combination of these techniques.^[19] Most laboratories now use automated homogeneous analytical methods in which lipoproteins containing apo B are blocked using antibodies to apo B, then a colorimetric enzyme reaction measures cholesterol in the non-blocked HDL particles.^[20] HPLC can also be used.^[21] Subfractions (HDL-2C, HDL-3C) can be measured,^[22] but clinical significance of these subfractions has not been determined.^[23] The measurement of apo-A reactive capacity can be used to measure HDL cholesterol but is thought to be less accurate.^{[citation needed]}

Recommended ranges

The

High LDL with low HDL level is an additional risk factor for cardiovascular disease.[27]

Measuring HDL concentration and sizes

As technology has reduced costs and clinical trials have continued to demonstrate the importance of HDL, methods for directly measuring HDL concentrations and size (which indicates function) at lower costs have become more widely available and increasingly regarded as important for assessing individual risk for progressive arterial disease and treatment methods.^{[citation needed]}

Electrophoresis measurements

Since the HDL particles have a net negative charge and vary by density & size, ultracentrifugation combined with electrophoresis have been utilized since before 1950 to enumerate the concentration of HDL particles and sort them by size with a specific volume of blood plasma. Larger HDL particles are carrying more cholesterol.

NMR measurements

Concentration and sizes of lipoprotein particles can be estimated using nuclear magnetic resonance fingerprinting.^[28]

Optimal total and large HDL concentrations

The HDL particle concentrations are typically categorized by event rate percentiles based on the people participating and being tracked in the MESA^[29] trial, a medical research study sponsored by the United States National Heart, Lung, and Blood Institute.

The lowest incidence of atherosclerotic events over time occurs within those with both the highest concentrations of total HDL particles (the top quarter, >75%) and the highest concentrations of large HDL particles. Multiple additional measures, including LDL particle concentrations, small LDL particle concentrations, VLDL concentrations, estimations of insulin resistance and standard cholesterol lipid measurements (for comparison of the plasma data with the estimation methods discussed above) are routinely provided in clinical testing.

Increasing HDL levels

While higher HDL levels are correlated with lower risk of cardiovascular diseases, no medication used to increase HDL has been proven to improve health.^[2][30] As of 2017, numerous lifestyle changes and drugs to increase HDL levels were under study.^[2]

HDL lipoprotein particles that bear

Certain changes in diet and exercise may have a positive impact on raising HDL levels:[32]

• Decreased intake of
  simple carbohydrates.^{[33][34][35][36]}
• Aerobic exercise^[37]
• Weight loss^[38]
• Avocado consumption^[39]
• Magnesium supplements raise HDL-C.^[40]
• Addition of soluble fiber to diet^[41]
• Consumption of
  omega-3 fatty acids such as fish oil^[42] or flax oil^[43]
• Increased intake of unsaturated fats^[44]
• Removal of trans fatty acids from the diet^[45]

Most

HDL levels can be increased by smoking cessation,^[38] or mild to moderate alcohol intake.^{[47][48][49][50][51][52]}

Cannabis in unadjusted analyses, past and current cannabis use was not associated with higher HDL-C levels.^[53] A study performed in 4635 patients demonstrated no effect on the HDL-C levels (P=0.78) [the mean (standard error) HDL-C values in control subjects (never used), past users and current users were 53.4 (0.4), 53.9 (0.6) and 53.9 (0.7) mg/dL, respectively].^[53]

Exogenous

Pharmacologic (1- to 3-gram/day) niacin doses increase HDL levels by 10–30%,[59] making it the most powerful agent to increase HDL-cholesterol.^[60][61] A randomized clinical trial demonstrated that treatment with niacin can significantly reduce atherosclerosis progression and cardiovascular events.^[62] Niacin products sold as "no-flush", i.e. not having side-effects such as "niacin flush", do not, however, contain free nicotinic acid and are therefore ineffective at raising HDL, while products sold as "sustained-release" may contain free nicotinic acid, but "some brands are hepatotoxic"; therefore the recommended form of niacin for raising HDL is the cheapest, immediate-release preparation.^[63] Both fibrates and niacin increase artery toxic homocysteine, an effect that can be counteracted by also consuming a multivitamin with relatively high amounts of the B-vitamins, but multiple European trials of the most popular B-vitamin cocktails, trial showing 30% average reduction in homocysteine, while not showing problems have also not shown any benefit in reducing cardiovascular event rates. A 2011 extended-release niacin (Niaspan) study was halted early because patients adding niacin to their statin treatment showed no increase in heart health, but did experience an increase in the risk of stroke.^[64]

In contrast, while the use of statins is effective against high levels of LDL cholesterol, most have little or no effect in raising HDL cholesterol.^[60] Rosuvastatin and pitavastatin, however, have been demonstrated to significantly raise HDL levels.^[65]

The PPAR modulator GW501516 has shown a positive effect on HDL-C^[67] and an antiatherogenic where LDL is an issue.^[68] However, research on the drug has been discontinued after it was discovered to cause rapid cancer development in several organs in rats.^[69][70]

See also

• Asymmetric dimethylarginine
• Cardiovascular disease
• Cholesteryl ester storage disease
• Endothelium
• Lipid profile
• Lysosomal acid lipase deficiency

References