High density lipoprotein overview
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High-density lipoproteins form a class of lipoproteins, varying somewhat in their size (8–11 nm in diameter), that carry cholesterol from the body's tissues to the liver. About thirty percent of blood cholesterol is carried by HDL.
It is hypothesized that HDL can remove cholesterol from atheroma within arteries and transport it back to the liver for excretion or re-utilization— which is the main reason why HDL-bound cholesterol is sometimes called "good cholesterol", or HDL-C. A high level of HDL-C seems to protect against cardiovascular diseases, and low HDL cholesterol levels (less than 40 mg/dL for males and less than 50 mg/dL for females) increase the risk for heart disease. When measuring cholesterol, any contained in HDL particles is considered as protection to the body's cardiovascular health, in contrast to "bad" LDL cholesterol.
Most clinical trials on prevention of coronary artery disease focus on lowering the levels of LDL cholesterol in the blood using statins and other lipid lowering drugs. These have shown improved clinical outcomes and reduction in mortality.
However, a causal relationship between low HDL cholesterol levels and development of significant coronary artery disease has not been established. There is a lack of evidence for proving that raising HDL levels can reduce cardiovascular events in those with coronary artery disease. Statins are used in the treatment of patients with low HDL levels to reduce the levels of "bad" LDL cholesterol in the blood.
High density lipoprotein (HDL) is considered "good cholesterol" as its levels are inversely proportional to CAD. It is regarded as a positive cardiac risk factor if the levels are below 35 mg/dL or total cholesterol to HDL ratio in > 5.0 (in men) or total cholesterol to HDL ratio in > 4.5 (in women). When the levels are above 60 mg/dL it is considered a negative cardiac risk factor.
Epidemiology and Demographics
Epidemiological studies have shown that high concentrations of HDL (over 60 mg/dL) have protective value against cardiovascular diseases such as ischemic stroke and myocardial infarction. Low concentrations of HDL (below 40 mg/dL for men, below 50 mg/dL for women) are a positive risk factor for these atherosclerotic diseases.
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. Conversely, for a fixed level of HDL, the risk increases 3-fold as LDL varies from low to high.
Low HDL and Cardiovascular Risk
The plasma levels of HDL are inversely proportional to the development of coronary artery disease (CAD) making HDL a negative cardiac risk factor. Low serum HDL-cholesterol can be an isolated abnormality or can be associated with hypercholesterolemia. Patients with premature coronary artery disease, defined as CAD in men less than 55 to 60 years of age and women less than 65 years of age, have a primary reduction in HDL-cholesterol. Studies have shown that low HDL risk is independent of the risk attributed to elevated LDL-cholesterol (low density lipoprotein) in the serum. Findings from large scale prospective studies indicate that for every 1 mg/dL rise in serum HDL levels the risk of CAD reduces by 2% to 3% in men and women respectively.
Even though a causal relationship has not been established between low HDL-C levels in the serum and the incidence of coronary artery disease, low HDL-C is considered a significant risk factor for CAD. Numerous clinical trials, like VA-HIT, AIM-HIGH, 4S etc., were conducted to study the effects of various novel lipid lowering agents on the levels of HDL-C and the corresponding changes in cardiovascular morbidity and mortality.
Statins and fibrate appear to be effective in patients with low HDL levels compared to those in normal HDL levels in terms of risk reduction. Fibrates are more effective when low HDL levels coincide with low levels of LDL levels. Before a combination of statins and fibrates are considered, dietary modifications and lifestyle changes can be effective tools to raise HDL levels. However, a combination therapy of statins with fibrates can result in myopathy as a potential adverse effect.
Future or Investigational Therapies
There are promising future therapies that include CETP inhibitors, which are currently in the experimental phase. A combination therapy with statins and ACE inhibitors is also a safe option in patients with HDL levels who also share features with dysmetabolic syndrome. However, the preventive effects of these two drugs tend to be cumulative.
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