http://seattletimes.nwsource.com/html/nationworld/2001848873_heart02.html


New treatments may help clean out arteries

By Daniel Q. Haney
The Associated Press


Heart researchers may be closing in at last on a long-fantasized goal: treatments that flush out the nasty globs of gunk that clog the heart's plumbing.

The idea goes beyond merely preventing new coronary-artery disease. The intention is to clear away what's already there, to clean up the source of heart attacks before they happen.

Ideally, the human body already does that, and the new medicines are intended to enhance the natural artery cleansing. If testing goes as scientists hope, the strategy could prove to be as important for preventing heart disease as the cholesterol-lowering statin drugs introduced in the late 1980s.

"If it works, we are talking about the potential of reducing cardiac events by 50 or 60 percent or more," said Dr. Steven Nissen of the Cleveland Clinic. "We are talking about really controlling the disease."

Nissen is working with about a half-dozen of the drugs, and it is too soon to know which of them and others in the pipeline will make it into pharmacies. But when they arrive, they are likely to become part of a heart-protecting cocktail of medicines to increase good cholesterol, lower bad cholesterol and reduce bloodstream inflammation.

The new drugs boost high-density lipoproteins — HDL. This is the friendly half of cholesterol's yin and yang, often outgunned by its evil counterpart, LDL.

The interest in HDL is a big shift in attention for the field of heart-disease prevention. Since the arrival of statins, its main preoccupation has been reducing LDL, which carries in the cholesterol that clogs arteries.

The statins' benefits have been impressive, even though cardiovascular disease remains the world's biggest killer. They cut LDL in half, which helps stabilize the disease and reduce heart attacks and deaths by one-quarter to one-third.

"To an optimist, that's terrific," said Dr. Prediman Shah, cardiology chief at Cedars-Sinai Medical Center in Los Angeles. "But the glass is still two-thirds empty. To contain the continuing ravages of this disease, there has to be something else."


He and many others think that something is HDL. In its garbage-truck role, HDL scoops up cholesterol from arteries and carries it to the liver for disposal.

Doctors have suspected its importance since the 1970s. Studies that follow people through life show that the higher one's HDL, the lower the risk of heart attacks. Each single point of increase is matched by a 2 percent to 3 percent reduction in heart disease.

"Just like your LDL can't be too low, your HDL can't be too high," said Dr. Lori Mosca, head of preventive cardiology at Columbia University.

Until recently, the only pills that raised HDL even modestly were generic or over the counter. The best of them, niacin, is a vitamin. Without exclusive rights, drug companies have no incentive to prove such compounds work.

For many skeptics, though, the doubts began to fade last fall with the publication of a remarkable study. The story began in the early 1980s, when researchers discovered a man in the northern Italian village of Limone sul Garda who had very low HDL but no sign of cardiovascular disease. Blood tests revealed about 40 more villagers with the same peculiarity. All traced their origins to a common ancestor born in 1780.

It eventually was discovered those people carry a slightly unusual version of the main protein that makes up their HDL. Researchers called it ApoA-I Milano and wondered if it might be a supercharged version of HDL. In the first of many animal studies, Shah injected the protein into rabbits with clogged arteries. It quickly cleared them out.

Researchers still argue over whether ApoA-I Milano is a better artery cleaner than the normal version of HDL, but it hardly matters. The ordinary kind cannot be patented, so it never will be developed as a drug, but the mutant kind could be.

The biotech firm that owns the rights, Esperion Therapeutics, sponsored a pilot study in people. When the results were released in November, heart specialists simply were astonished. Artery clogging in people takes decades, so many assumed reversing it would be slow, too. But after only five weekly intravenous infusions, the volunteers' artery buildups had regressed about 4 percent. Nothing like that had ever been seen.

The study was small, involving just 47 patients. Years more testing will be needed to prove the treatment truly safe and effective.

Still, the results set off a frenzy among drug companies, all searching for a more practical pill version of the drug, said Nissen, who directed the study. However, the next HDL pill is likely to be an entirely different variety of medicine.

The drugs, being developed by several companies, work by blocking a protein that allows HDL to give away its cholesterol. HDL ordinarily hauls much of its load back to the liver, but it also hands off some of it to LDL, which in turn may cart it back to the artery walls. Shutting down this transfer can make HDL levels go up substantially.

The version furthest along is Pfizer's torcetrapib, which Nissen is testing in a two-year study on 886 volunteers.

Among other approaches:

• An experimental vaccine against the cholesterol-transferring protein raises HDL about 8 percent, but only in those not already on statins. Una Ryan, president of Avant Immunotherapeutics, said the twice yearly shots could be targeted at the estimated 21 million Americans with low HDL but normal LDL.

• Several companies are testing new versions of drugs called peroxisome proliferator-activated receptors, which also help direct cholesterol flow in the arteries. They raise HDL about 25 percent, lower triglycerides and improve the body's use of insulin. The medicines may prove especially useful for those at risk of diabetes.

• Shah hopes within the next year or two to try gene therapy to prompt the body to manufacture more HDL. His strategy: Insert large quantities of the gene that makes ApoA-I Milano, the HDL protein found in the Italian village, into volunteers' bone marrow. "The idea is to have a permanent supply from one single treatment," Shah said.


Copyright © 2004 The Seattle Times Company

__________________
...Tracy

'00 ML320 "Casper"
'92 400E "Stella"

thought this was good


http://www.designinglogic.com/upload/www.aor.ca/proddetail.asp?prod_id=282&exec_sum=summ

__________________
89 300E
79 240D
72 Westy
63 Bug sunroof
85 Jeep CJ7
86 Chevy 6.2l diesel PU

"The object of life is not to be on the side of the majority, but to escape finding oneself in the ranks of the insane."
Marcus Aurelius

http://seattletimes.nwsource.com/html/nationworld/2001874832_cholesterol090.html

Low-cholesterol drug found key to heart health

By The Washington Post and Los Angeles Times


Heart-disease patients are much less likely to have a heart attack or stroke or to die if they take high doses of a commonly used cholesterol-lowering drug, according to a new study that many experts are calling a landmark.

The results, released yesterday, provide the first direct answer to one of the most important questions being debated today about cardiovascular disease: Will more aggressive use of the popular anti-cholesterol drugs called statins help more people avoid or survive the nation's No. 1 killer?

The study is likely to prompt doctors to give much higher doses of the drugs to hundreds of thousands of patients who already have severe heart problems.

In addition, it will probably encourage physicians to start giving the medications to millions of people who are not yet on them and to boost dosages for some of those already taking them to push their cholesterol even lower, experts said.

"It's a really, really important study," said Frank Sacks, a professor of cardiovascular-disease prevention at the Harvard School of Public Health, who was not involved in the research. "It's a breakthrough. It shows for the first time that lowering to very low levels is better."

The results represent a "sea change" in the treatment of heart disease, wrote Eric Topol, chairman of the department of cardiovascular medicine at the Cleveland Clinic in Ohio, in an editorial that will accompany the study in the April 8 issue of The New England Journal of Medicine.

The study was released early on the Web to coincide with a presentation of the eagerly awaited data at an American College of Cardiology meeting in New Orleans.

"This is a sea change, and I don't use that term lightly," Topol repeated in a telephone interview. "This is big. This will mean a major change in the daily practice of medicine."

About 64 million Americans have cardiovascular disease and about 1.4 million die from it each year.

An estimated 11 million Americans take statin drugs, which have been proven to safely reduce the risk that people will develop cardiovascular disease, suffer chest pain, have heart attacks or strokes, or die from any of those causes.

But even under existing guidelines, more than three times that number, about 36 million people, should be taking the drugs. Worldwide, only about 25 million people take the drugs, even though more than 200 million meet existing criteria for getting them.

Evidence has been accumulating in recent years that driving cholesterol even lower than the current recommendations may produce additional benefits.

But researchers have been hesitant to begin prescribing higher dosages of the costly drugs until they had clear evidence it would keep people healthier and reduce their risk of dying. In rare cases, the drugs can cause liver problems.

The new study, led by Dr. Christopher Cannon, a cardiologist at the Brigham and Women's Hospital in Boston, involved 4,162 patients at 349 sites in eight countries who had been taken to the emergency room because of severe chest pain or a heart attack.

Before they left the hospital, their doctors starting giving them either the standard dose of 40 milligrams a day of Pravachol, a statin made by Bristol-Myers Squibb, or 80 milligrams a day of Pfizer's top seller, Lipitor, which is usually prescribed at about 10 or 20 milligrams.

The team looked at both total cholesterol levels and levels of low-density lipoprotein or LDL, the so-called bad cholesterol. Current guidelines recommend that LDL levels be reduced below 100 milligrams per deciliter.

The team found that the 40-milligram dose of Pravachol reduced the LDL levels about a quarter, to an average of 95. The higher dose of Lipitor reduced it by half, to an average of 62.

Over an average of 2-˝ years, the patients receiving Lipitor were 16 percent less likely to suffer chest pain, to require angioplasty or a bypass or to have another heart attack or stroke. Overall, their chances of dying were reduced by 28 percent. Women benefited from the drugs more than men.

Those benefits were observed within the first 30 days of the study and were sustained over the entire study period, Cannon said.

Each year, about 1.7 million Americans are hospitalized because of a serious heart problem. The findings indicate that doctors should immediately consider putting all of them on high-dose statins, which should help reduce the toll from heart disease, Cannon and others said.

"I hope this change will prevent many heart attacks and strokes, cardiac procedures, and deaths," Cannon said. "This is a turning point for the field."

Although the study only showed a benefit for Lipitor, the findings likely apply to all statins at high doses, he said.

Three other large trials are under way to examine the question more broadly.

But the findings are likely to influence all treatment of heart disease even before those studies produce results, experts said.

"What this tells us is that treating cholesterol is very important, not just for high-risk patients but for everyone," Cannon said.

Other experts agreed.

"I think the practical implications are that there's going to be spillover in terms of aggressive therapy across the board," said Dr. Daniel Rader, a cardiologist at the University of Pennsylvania.

Widespread use of the drugs could have a major impact on health-care costs, which are already climbing dramatically. A year's regimen of the drugs can cost as much as $1,400.

Cannon's study was funded by Bristol-Myers Squibb, which manufactures Pravachol.

Sidebar:

Key points of cholesterol study:


Finding:


Some heart-attack victims already are given drugs called statins to lower low-density lipoprotein or LDL, the so-called "bad" cholesterol. The new study found benefits to lowering LDL cholesterol to levels substantially below current guidelines and suggests using much higher doses.

Another study in November found the more intensive treatment resulted in less artery clogging, but the new report is considered even more convincing because it weighed the risk of death and other complications of heart patients.

Researchers:


Team led by Dr. Christopher Cannon of Brigham and Women's Hospital in Boston performed the most recent study. Presented at the American College of Cardiology and appearing in next month's issue of the New England Journal of Medicine. It is posted on the Web at content.nejm.org/.

Impact


: Because levels of LDL dropped to an average of just 62 (milligrams per deciliter) in this study, present federal guidelines aimed at getting LDL below 100 will most likely be lowered. An editorial accompanying the study said 36 million Americans should take statins, although only a third do now.

The drugs


: Both studies compared 40 milligrams daily of Pravachol to 80 milligrams of Lipitor, the highest-approved doses. Pravachol is an older statin made by Bristol-Myers Squibb, which financed the recent study, while the newer and more potent Lipitor is made by Pfizer, which financed the earlier study in November. Statins — a family of drugs that also includes Zocor, Crestor and Lescol — block cholesterol synthesis and reduce the rate of heart attacks and strokes. They also reduce inflammation, protect against dilation of heart ventricles, and decreasing overactivity of the sympathetic nervous system, all of which increase the likelihood of a heart attack.

Who's affected:


Nearly 1 million Americans die of cardiovascular disease each year. About 1.7 million are hospitalized after a heart attack. According to the American Heart Association, 42 percent of heart-attack victims die within the first year.

Cautions:


The most significant adverse reaction was an increased level of certain liver enzymes, an indicator of potential liver damage. In addition, widespread use of the drugs could have a major impact on health-care costs. Statins are the biggest selling category of prescription drugs at $12.5 billion in the United States each year. The dose of Pravachol used in the study costs about $900 a year, while Lipitor costs $1,400.

On the Web:




http://content.nejm.org/


Sources: The Associated Press, Los Angeles Times, New England Journal of Medicine Web site.

__________________
...Tracy

'00 ML320 "Casper"
'92 400E "Stella"

http://www.nytimes.com/2004/03/21/health/21HEAR.html?hp

Studies Question Effectiveness of Artery-Opening Operations

By GINA KOLATA

Published: March 21, 2004


A new and emerging understanding of how heart attacks occur indicates that increasingly popular aggressive treatments may be doing little or nothing to prevent them.
The artery-opening methods, like bypass surgery and stents, the widely used wire cages that hold plaque against an artery wall, can alleviate crushing chest pain. Stents can also rescue someone in the midst of a heart attack by destroying an obstruction and holding the closed artery open.

But the new model of heart disease shows that the vast majority of heart attacks do not originate with obstructions that narrow arteries.

Instead, recent and continuing studies show that a more powerful way to prevent heart attacks in patients at high risk is to adhere rigorously to what can seem like boring old advice — giving up smoking, for example, and taking drugs to get blood pressure under control, drive cholesterol levels down and prevent blood clotting.

Researchers estimate that just one of those tactics, lowering cholesterol to what guidelines suggest, can reduce the risk of heart attack by a third but is followed by only 20 percent of heart patients.

"It's amazing and it's completely backwards in terms of prioritization," said Dr. David Brown, an interventional cardiologist at Beth Israel Medical Center in New York. Heart experts say they understand why the disconnect occurred: they, too, at first found it hard to believe what research was telling them. For years, they were wedded to the wrong model of heart disease.
"There has been a culture in cardiology that the narrowings were the problem and that if you fix them the patient does better," said Dr. David Waters, a cardiologist at the University of California at San Francisco.

The old idea was this: Coronary disease is akin to sludge building up in a pipe. Plaque accumulates slowly, over decades, and once it is there it is pretty much there for good. Every year, the narrowing grows more severe until one day no blood can get through and the patient has a heart attack. Bypass surgery or angioplasty — opening arteries by pushing plaque back with a tiny balloon and then, often, holding it there with a stent — can open up a narrowed artery before it closes completely. And so, it was assumed, heart attacks could be averted.

But, researchers say, most heart attacks do not occur because an artery is narrowed by plaque. Instead, they say, heart attacks occur when an area of plaque bursts, a clot forms over the area and blood flow is abruptly blocked. In 75 to 80 percent of cases, the plaque that erupts was not obstructing an artery and would not be stented or bypassed. The dangerous plaque is soft and fragile, produces no symptoms and would not be seen as an obstruction to blood flow.

That is why, heart experts say, so many heart attacks are unexpected — a person will be out jogging one day, feeling fine, and struck with a heart attack the next. If a narrowed artery were the culprit, exercise would have caused severe chest pain.
Heart patients may have hundreds of vulnerable plaques, so preventing heart attacks means going after all their arteries, not one narrowed section, by attacking the disease itself. That is what happens when patients take drugs to aggressively lower their cholesterol levels, to get their blood pressure under control and to prevent blood clots.

Yet, researchers say, old notions persist.
"There is just this embedded belief that fixing an artery is a good thing," said Dr. Eric Topol, an interventional cardiologist at the Cleveland Clinic in Ohio.

In particular, Dr. Topol said, more and more people with no symptoms are now getting stents. According to an analysis by Merrill Lynch, based on sales figures, there will be more than a million stent operations this year, nearly double the number performed five years ago.

Some doctors still adhere to the old model. Others say that they know it no longer holds but that they sometimes end up opening blocked arteries anyway, even when patients have no symptoms.
Dr. David Hillis, an interventional cardiologist at the University of Texas Southwestern Medical Center in Dallas, explained: "If you're an invasive cardiologist and Joe Smith, the local internist, is sending you patients, and if you tell them they don't need the procedure, pretty soon Joe Smith doesn't send patients anymore. Sometimes you can talk yourself into doing it even though in your heart of hearts you don't think it's right."

Dr. Topol said a patient typically goes to a cardiologist with a vague complaint like indigestion or shortness of breath, or because a scan of the heart indicated calcium deposits — a sign of atherosclerosis, or buildup of plaque. The cardiologist puts the patient in the cardiac catheterization room, examining the arteries with an angiogram. Since most people who are middle-aged and older have atherosclerosis, the angiogram will more often than not show a narrowing. Inevitably, the patient gets a stent.

"It's this train where you can't get off at any station along the way," Dr. Topol said. "Once you get on the train, you're getting the stents. Once you get in the cath lab, it's pretty likely that something will get done."
One reason for the enthusiastic opening of blocked arteries is that it feels like the right thing to do, Dr. Hillis said. "I think it is ingrained in the American psyche that the worth of medical care is directly related to how aggressive it is," he said. "Americans want a full-court press."

Dr. Hillis said he tried to explain the evidence to patients, to little avail. "You end up reaching a level of frustration," he said. "I think they have talked to someone along the line who convinced them that this procedure will save their life. They are told if you don't have it done you are, quote, a walking time bomb."
Researchers are also finding that plaque, and heart attack risk, can change very quickly — within a month, according to a recent study — by something as simple as intense cholesterol lowering.
"The results are now snowballing," said Dr. Peter Libby of Harvard Medical School. "The disease is more mutable than we had thought."

The changing picture of what works to prevent heart attacks, and why, emerged only after years of research that was initially met with disbelief.

Early attempts to show that opening a narrowed artery saves lives or prevents heart attacks were unsuccessful. The only exception was bypass surgery, which was found to extend the lives of some patients with severe illness but not to prevent heart attacks. It is unclear why those patients lived longer; some think the treatment prevented their heart rhythms from going awry, while others say that the detour created by a bypass might be giving blood an alternate route when a clot formed somewhere else in the artery.

Some early studies indicated what was really happening, but were widely dismissed. As long ago as 1986, Dr. Greg Brown of the University of Washington at Seattle published a paper showing that heart attacks occurred in areas of coronary arteries where there was too little plaque to be stented or bypassed. Many cardiologists derided him.

Around the same time, Dr. Steven Nissen of the Cleveland Clinic started looking directly at patients' coronary arteries with a miniature ultrasound camera that he threaded into blood vessels. He found that the arteries were riddled with plaque, but almost none of it was obstructing blood vessels. Soon he began proposing that the problem was not the plaque that produced narrowings but the hundreds of other areas that were ready to burst. Cardiologists were skeptical.

In 1999, Dr. Waters of the University of California got a similar reaction to his study of patients who had been referred for angioplasty, although they did not have severe symptoms like chest pain. The patients were randomly assigned to angioplasty followed by a doctor's usual care, or to aggressive cholesterol-lowering drugs but no angioplasty. The patients whose cholesterol was aggressively lowered had fewer heart attacks and fewer hospitalizations for sudden onset of chest pain.
The study "caused an uproar," Dr. Waters said. "We were saying that atherosclerosis is a systemic disease. It occurs throughout all the coronary arteries. If you fix one segment, a year later it will be another segment that pops and gives you a heart attack, so systemic therapy, with statins or antiplatelet drugs, has the potential to do a lot more." But, he added, "there is a tradition in cardiology that doesn't want to hear that."

Even more disquieting, Dr. Topol said, is that stenting can actually cause minor heart attacks in about 4 percent of patients. That can add up to a lot of people suffering heart damage from a procedure meant to prevent it.

"It has not been a welcome thought," Dr. Topol said.
Stent makers say they do not mislead doctors or patients. Their new stents, coated with drugs to prevent scar tissue from growing back in the immediate area, are increasingly popular among cardiologists, and sales are exploding. But there is not yet any evidence that they change the course of heart disease.
"It's really not about preventing heart attacks per se," said Paul LaViolette, a senior vice president at Boston Scientific, a stent manufacturer. "The obvious purpose of the procedure is palliation and symptom relief. It's a quality-of-life gain."

__________________
...Tracy

'00 ML320 "Casper"
'92 400E "Stella"

I hope that this doesn't become another one of those coral calcium type nonsense fads. I'll keep an open mind until I find out something to the contrary. I won't give on eating a low fat diet and exercise on a regular basis though.

__________________
DJ


84 300D Turbodiesel 190K with 4 speed manual sold in 03/2012

Synthetic is better.

http://story.news.yahoo.com/news?tmpl=story&cid=97&ncid=97&e=3&u=/hsn/20040520/hl_hsn/peelawayhighcholesterol

Peel Away High Cholesterol

THURSDAY, May 20 (HealthDayNews) -- Compounds found in orange and tangerine peels may lower cholesterol more effectively than some prescription drugs and do so without causing side effects.



That's what new animal research by American and Canadian scientists suggests.


These compounds, called polymethoxylated flavones (PMFs), are similar to other plant pigments found in citrus fruits that may protect against heart disease, cancer and inflammation. It's believed this study is the first to show that PMFs may lower cholesterol.


Researchers gave food containing 1 percent PMFs to hamsters with high cholesterol. The hamsters' levels of LDL (bad) cholesterol was lowered by 32 percent to 40 percent.


"Our study has shown that PMFs have the most potent cholesterol-lowering effect of any other citrus fruit flavonoid," lead investigator Elzbieta Kurowska, vice president of research at KGK Synergize in Canada, said in a prepared statement.


"We believe that PMFs have the potential to rival and even beat the cholesterol-lowering effect of some prescription drugs, without the risk of side effects," she said.


The study appears in the May 12 issue of the Journal of Agricultural and Food Chemistry.

__________________
...Tracy

'00 ML320 "Casper"
'92 400E "Stella"

Great! Now I have to eat the whole orange

__________________
past MB rides:
'68 220D
'68 220D(another one)
'67 230
'84 SD
Current rides:
'06 Lexus RX330
'93 Ford F-250
'96 Corvette
'99 Polaris 700 RMK sled
2011 Polaris Assault
'86 Yamaha TT350(good 'ol thumper)

.....Or take a couple of pills......

http://store.yahoo.com/iherb/sytrinol.html

__________________
...Tracy

'00 ML320 "Casper"
'92 400E "Stella"

I offer this as a worning to those concerned with high cholesterol. Since MB has been staedyling lowering the quality of there cars to improve the bottom line, you will defintly see your cholesterol go way up when they start using Chrysler parts in their cars. When this happens, I'll probaly switch to BMW. MB had better be careful 'cause a lot of US customers think Chrysler repersents junk and is always reffered to the "third" auto maker in the US. Go figure.

Pardon me if I've miss-understood you, because I think I have. So.....if you weren’t trying to say something without saying that you wereen’t trying to say something what would you be saying?

__________________
...Tracy

'00 ML320 "Casper"
'92 400E "Stella"

LeBenz: Call me old fashion, but I hope that MB never decides to save money by using Chrysler parts in their cars. MB's are unique and should remain that way. With close to 200K mile on my '97 c, I have never had to seek a dealer for repairs. The car runs like it is new while I;ve done tires, batt, oil/filter and small simple things to keep it in top shape. I doubt if many Chrysler owners would ever have the nerve to drive their car that many miles because they know that a Chrysler usuallly falls apart well before then. Chryslers are, well Chrysler, while Mercedes are a good thing that may be going "south".

Well all right then, that clears it right up!

May God bless and keep you always
May your wishes all come true
May you always do for others
And let others do for you
May you build a ladder to the stars
And climb on every rung
May you stay forever young
Forever young, forever young
May you stay forever young.

May you grow up to be righteous
May you grow up to be true
May you always know the truth
And see the lights surrounding you
May you always be courageous
Stand upright and be strong
May you stay forever young
Forever young, forever young
May you stay forever young.

May your hands always be busy
May your feet always be swift
May you have a strong foundation
When the winds of changes shift
May your heart always be joyful
And may your song always be sung
May you stay forever young
Forever young, forever young
May you stay forever young

-Bob Dylan

__________________
...Tracy

'00 ML320 "Casper"
'92 400E "Stella"

i think the good doctor is saying stop running after shadows.

heart disease, car wrecks, OBL, we are all going to die someday.
enjoy our fine mb cars

don