HDL Types

[Guest guest]

Hi folks:

Both articles from the Cleveland Clinic:

" Good " Cholesterol not Always Beneficial, Study Shows

High density lipoprotein cholesterol—better known as HDL—is

characterized as the " good " cholesterol because of its ability to

protect arteries from accumulation of fatty deposits. But as new

research from the Cleveland Clinic has shown, good HDL has a " bad "

cousin. Reporting in the August 16 Journal of Clinical Investigation,

the researchers identified a " dysfunctional " HDL. That is, an HDL

type that in some individuals does not protect against

atherosclerosis.

" This study may help explain why not all persons with high HDL levels

are protected from getting heart disease, " said Stanley Hazen, M.D.,

Ph.D., head, Cleveland Clinic section of preventive cardiology and

rehabilitation.

The key to determining HDL's protective quality appears to be

inflammation. HDL becomes dysfunctional when myeloperoxidase (MPO),

an enzyme present in white blood cells, inhibits the HDL's ability to

remove cholesterol from building up in artery wall cells.

Previous Cleveland Clinic research led by Dr. Hazen found that in

patients seeking emergency care for chest pain, identifying elevated

MPO levels helped predict who was at increased risk for heart attack,

bypass surgery or death within the next six months. A new test is

being developed at the Clinic to measure MPO levels and determine

heart-disease risk.

The newer study showed for the first time a link among MPO, HDL and

HDL's role in removing cholesterol from arteries. The study also

describes the mechanism of how dysfunctional HDL is made.

Results of the study indicate that apolipoprotein A-I, or apoA-I, the

primary protein found in HDL, is targeted for damage by MPO; this in

turn disrupts HDL function. The new study suggests that MPO and apoA-

I interactions play a significant role in a person's overall risk for

cardiac disease.

A specific " chemical fingerprint, " or marker, for HDL damaged by MPO

was discovered in the blood of people with heart disease. Those with

a high level of the marker showed a 16-fold increase in heart-disease

risk. Thus, the study suggests this new test for dysfunctional HDL

could be a significantly better predictor of heart-disease risk

compared to tests that measure just cholesterol levels.

" Remarkably, up to 50 percent of the HDL recovered from

atherosclerotic plaque in some subjects does not promote cholesterol

removal, " Dr. Hazen said. " This study also helps explain why MPO is

predictive of atherosclerosis. "

What are the implications of this study for patients and clinicians?

Says Dr. Hazen: " This study reinforces the current guidelines' main

focus on LDL reduction as the primary lipid abnormality to treat. A

high HDL level does not provide a `free pass' for an individual with

an abnormal LDL. "

AND .................

Test Predicts Risk of Cardiac Trouble up to Six Months in Advance of

the Event

Cleveland Clinic researchers have identified a new blood test to

determine whether a person is in imminent danger of heart attack or

death. The test is especially valuable for identifying at-risk

patients not recognized by current diagnostic laboratory testing

methods.

The new test measures the level of myeloperoxidase (MPO) in the

bloodstream. MPO is an enzyme found in disease-fighting white blood

cells. The hope is that screening for MPO could in a few years time

become the primary means of predicting heart attack or the need for

surgical intervention in patients with coronary artery disease.

Previous Cleveland Clinic research has found that an elevated MPO

level in white blood cells can signal a person's risk for having

heart disease. This latest study goes a step further, determining

that a high MPO level in the blood also can identify people:

at increased risk for heart attack

in need of bypass surgery or angioplasty (a procedure used to restore

blood flow to an artery)

at increased risk for cardiac death within six months of presenting

to the emergency room with chest pain.

Complete study results appear in the October 23, 2003 issue of The

New England Journal of Medicine.

" We looked at more than 600 sequential patients who came to the

emergency room with chest pain, " said Stanley Hazen, M.D., Ph.D.,

head of the section of preventive cardiology at the Clinic. " We found

that adding MPO testing to current laboratory-based risk assessments

increased our ability to predict future cardiac risks over the next

30 days to six months from 50 percent to 95 percent of the time. "

Dr. Hazen, lead researcher for the study, said an elevated MPO level

in people with cardiovascular disease indicates arterial

inflammation. Previous studies have linked inflammation to increased

risk of cardiovascular events. His team sought to determine whether

MPO also was a predictor of vulnerable plaque. Such fatty deposits in

the arteries can become fragile and break, letting lose tiny debris

that can cut off blood flow to vital organs, such as the heart or

brain, and in turn cause heart attack or stroke.

Other measures of arterial inflammation, including C-reactive protein

(CRP) testing, also help doctors gauge the risk of cardiac events.

But in head-to-head comparisons in the emergency room setting, CRP

testing was much less effective than MPO in predicting an impending

heart attack.

The study included 604 patients who arrived at the emergency room

following the onset of chest pain. MPO levels were significantly

higher in those who were experiencing a heart attack. They also were

higher in patients who, within six months after presenting at the

emergency room, experienced a heart attack or stroke, required bypass

surgery or angioplasty, or died.

LDL losing its screening status?

For years, physicians have used cholesterol screening to help

identify patients who are at increased risk for heart attack or

stroke. " Bad " cholesterol—also known as low-density lipoprotein, or

LDL, cholesterol—is one of several ingredients of plaque, the trouble-

making concoction of biochemical garbage that accumulates on artery

walls and whose presence there is the reason people have heart

attacks and strokes.

Physicians know that when LDL cholesterol levels are high, trouble is

brewing in the arteries. Thus, cholesterol screening—particularly

measurement of LDL used in combination with other tests—is the basis

for identifying and preventing atherosclerosis from progressing to

the point at which it causes a major cardiovascular event. Thus, a

high LDL level is a " marker " for coronary artery disease and a risk

factor for cardiovascular events.

Although measurement of LDL is a useful tool, it has some key

limitations. Perhaps the most important limitation is that plenty of

people with low LDL levels still have heart attacks and strokes.

Moreover, LDL testing offers no hints about inflammation, a naturally

occurring but unnoticeable, and otherwise protective, process that in

the arteries can turn plaques into little time bombs by making

them " unstable. " When that occurs, tiny pieces of the plaque's

exterior can break away. Particles too large to pass through a narrow

coronary artery become lodged and stop blood flow. A reduction in

blood supply to heart tissue, in turn, results in heart attack.

The same scenario can occur in the carotid artery, which supplies

blood to the brain. An unstable plaque there can cause stroke (or

brain attack). Of course, inflammation as the catalyst for

cardiovascular events is still considered by some to be a theory and

not necessarily the biochemical truth.

It was less than a year ago, however, that a study touted the

screening power of CRP and suggested its potential for replacing LDL

testing. In an article published in the November 14, 2002, New

England Journal of Medicine, researchers from Harvard University

reported that high sensitivity c-reactive protein (hs-CRP) testing

proved more effective than LDL testing in identifying individuals at

high risk for cardiovascular events. The new study on MPO further

reduces LDL's role as the prime predictor of heart attack risk.

" MPO testing has remarkable promise as a unique window to the process

of arterial inflammation, " said J. Topol, M.D., chairman,

department of cardiovascular medicine at the Clinic. " It should make

a big difference in patient management in the future. "

Rodney.