Cholesterol: How low should you go?

Study finds level below standard better for heart attack recovery

Monday, March 8, 2004 Posted: 10:45 AM EST (1545 GMT)

http://www.cnn.com/2004/HEALTH/cond...g.ap/index.html

NEW ORLEANS, Louisiana (AP) -- Lowering heart attack victims' cholesterol to levels dramatically below current standards appears to be an important strategy for saving lives and preventing new heart problems, a major new study shows.

Drugs called statins are already standard medicine for people recovering from heart attacks. But the study suggests newer, more potent varieties work best for these high-risk patients.

"The message for these people going home from the hospital is they should be on a high-intensity regimen," said Dr. Christopher Cannon of Boston's Brigham and Women's Hospital. "For everyone else, treating cholesterol and getting it down is very important."

The much-anticipated study helps answer one of the most discussed questions in cardiology: How low should cholesterol go? For those getting over recent heart attacks, at least, the answer appears to be very low indeed.

Those who did best in this study saw their levels of LDL, the bad cholesterol, plunge in half to an average of just 62. The goal in current federal guidelines is to get LDL below 100.

The study was to be presented Monday in New Orleans at the annual scientific meeting of the American College of Cardiology. It also will be published in Thursday's issue of the New England Journal of Medicine.

The latest work reinforces the conclusion of another head-to-head comparison of statin drugs released last November. In that study, doctors found the more intensive treatment resulted in less artery clogging. The new report is considered even more persuasive because it looks for differences in the risk of death and other clearly measurable misfortunes of heart patients.

Both studies compared 40 milligrams daily of Pravachol to 80 milligrams of Lipitor, the highest approved doses of both drugs when the research started. Pravachol is an older statin made by Bristol-Myers Squibb, while the newer and more potent Lipitor is made by Pfizer. Last fall's study was financed by Pfizer, and this one was paid for by Bristol-Myers Squibb. Lipitor came out on top in both comparisons.

Getting aggressive

In Cannon's study, 4,162 patients with new heart attacks or severe chest pain were randomly assigned to the two drugs. After two years of follow up, 26 percent getting the weaker Pravachol had died or experienced a variety of other ill events, including new heart attacks, bypass surgery, rehospitalization for chest pain or strokes. The same happened in 22 percent on Lipitor.

LDL levels of those taking Pravachol fell to 95, which is considered successful treatment under the government guidelines drawn up several years ago.

Dr. Thomas Pearson, head of preventive medicine at of the University of Rochester, helped write those guidelines. "The goal of less than 100 was an approximation using some very early data," he said. "It was the best guess at that moment. It may need some improvement. Now we are getting the science, and that's really exciting."

In a journal editorial, Dr. Eric Topol of the Cleveland Clinic called the latest finding "a major surprise," in part because the superiority of the stronger statin became obvious within a month of the start of treatment.

Topol said 36 million Americans should be on statins, although only a third that many actually are. Nevertheless, statins are the biggest selling category of prescription drugs at $12.5 billion in the United States each year.

Other studies in the works should help settle whether people with less serious heart disease benefit from the more aggressive cholesterol lowering possible with the newer statins. The more powerful drugs carry a slightly higher risk of side effects and are more expensive. Topol noted that the dose of Pravachol used in the study costs about $900 a year, while Lipitor costs $1,400.

Dr. Andrew Bodnar, head of medical affairs at Bristol-Myers Squibb, said until more studies are done, "doctors should reserve judgment about the general coronary disease population." He noted abnormal liver enzymes were more common in patients on Lipitor in the latest study and said Pravachol "has an unsurpassed safety record."

May we refer them to www.thincs.org or www.ravnskov.nu ?

Topol said 36 million Americans should be on statins, although only a third that many actually are

Somebody stop the insanity - 12 million people are on expensive medicines with extremely serious side effects that can actually harm cardiac health by breaking down and weakening heart muscle tissue and that really havent been shown in an unbiased way to do any good at all.

http://www.mercola.com/2003/jul/26/...terol_drugs.htm

"Somebody stop the insanity"

HA! I'm waiting for someone to recomend theyput in our water, just like flouride!!!!!

Never mind that the statin drugs CAUSE heart attacks.....

No they don't Quindal....didn't you read the article?????

DOH! I forgot!
I guess I'm just one of those black sheep that won't follow any health warning the gov't gives us! I'll probably die from that really unhealthy thing called ketosis that diabetics get from eating nothing but blocks of lard fried in butter! Because that's all us LCers eat, right??

I asked Anthony Colpo what he thought of this study... here's his reply:

"These patients were evidently folks with advanced CHD, and I don't have a whole lot of trouble believing that a higher dose of statins increased survival.

I do, however, think that the inference that the extra benefit was derived from greater reductions in cholesterol to be ludicrous. Via the same pathway that statins inhibit cholesterol production in the liver, they also inhibit production of an enzyme that reduces Nitric Oxide levels in arteries. NO is extermely important for arteries - it has anti-inflammatory, vasodilating, and antioxidant actions. Because statin trials have shown repeatedly that their mortality-lowering effects occur independent of the degree of cholesterol-lowering, I don't think it is a huge leap of faith to assume that is their anti-inflammatory, vasodilating, and antioxidant effects that provide the benefits.

So in high-risk patients, this may be a warranted strategy. What I am betting however, is that these findings will be used to promote higher dosages among the rest of the statin-using population for "preventive" purposes.

If so, then I think we will see a sharp rise in cancer, liver disorders, and heart failure in the not-too-distant future. In fact, a statin-induced jump in heart failure may well be underway. Statins reduce levels of coenzyme Q10 in the body, a substance required by every cell in the body for energy production - including those of the heart. Since the early nineties - when statin drugs first appeared on pharmacy shelves - there has been a marked upturn in the trajectory of deaths from congestive heart failure in the US.

There's an article by Overdose author Jay S. Cohen (a great book by the way) at www.mercola.com that discusses the pitfalls of upping statin doses:

http://www.mercola.com/2001/aug/25/baycol.htm"


Val

"So in high-risk patients, this may be a warranted strategy. What I am betting however, is that these findings will be used to promote higher dosages among the rest of the statin-using population for "preventive" purposes. "

Well, I've alread seen articles that are quoting docs that say statins should be increased and blood levels should be brought down as low as possible.

I agree with Colpo tho. It's great for people post MI. But those of us "at risk" shouldn't take it unless there is no other option.

Gee, it sounds like they think heart disease is caused by high cholesterol.



I wonder if there was a control group, and if their mortality/complication rate was better or worse than 22-26%.

Kristine, if Colpo is correct in suspecting that the reason for the good results is not due to lowering cholesterol, but by lowering the enzyme that reduces nitric oxide, then a control would have been to
lower the enzyme, or increase nitric oxide, which I believe can be done simply and cheaply, then compare outcomes.

Val

Well, I just found this:
...............................................................

Regulation of Endothelial Nitric Oxide Synthase Production by Inhibition of HMG-CoA Reductase


Laufs, U (Brigham and Women's Hospital, Boston, USA)
Endres, M (Massachusetts General Hospital, Boston, USA)
Moskowitz, MA (Massachusetts General Hospital, Boston, USA)
Liao, JK (Brigham and Women's Hospital, Boston, USA)

-------------------------------------------------------------------
Abstract
Endothelial-derived nitric oxide (NO) is an important mediator of vascular function. Clinical studies indicate that HMG-CoA reductase inhibitors (statins) improve endothelial function. Treatment of human endothelial cells with statins increased the expression of endothelial NO synthase (eNOS) protein and mRNA expression. Statins increased eNOS mRNA half-life but did not change eNOS gene transcription. Inhibition of mevalonate synthesis by statins not only blocks the formation of cholesterol but also of isoprenoids. The upregulation of eNOS expression by statins was mediated via the inhibition of geranylgeraniol, but not farnesiol. Immunoblot analyses, [35S]-GTPgS-binding assays and transfection studies revealed that statins upregulate eNOS expression by blocking the geranylgeranylation of the GTPase Rho which is necessary for its membrane-associated activity. Studies with mice showed, that statin treatment upregulates eNOS expression and function independent of serum cholesterol levels. Prophylactic treatment with statins augmented cerebral blood flow and reduced cerebral infarcts in normocholesterolemic mice. These effects of statins were completely absent in eNOS-deficient mice indicating that enhanced eNOS activity by statins is the predominant mechanism by which these agents protect against cerebral injury. Our results suggest that statins provide a novel prophylactic treatment strategy for increasing blood flow and reducing brain injury during cerebral ischemia.
...............................................................

Note this sentence: "Studies with mice showed, that statin treatment upregulates eNOS expression and function independent of serum cholesterol levels. "

Val

Kristine, others,

Thinking this through more, it is not going to be possible for a study to have a 'control' group in patients at cardiac risk. It would not get through the ethics committee. I think it would have to be via animal models and I have no idea how it could be tested in humans who have had heart attacks, as current best practice is to prescribe statins.

Val

Also a thought here. . .

The specific enzyme that statins inhibit -- HMGCoa reductase -- is also NATURALLY inhibited in the body by the hormone glucagon, which is insulin's counter-hormone, so to speak.

Insulin STIMULATES the HMGCoa reductase enzyme, glucagon INHIBITS it.

Eating low-carb, with ample protein, and not overeating will favor glucagon, and lower insulin. (Also, skipping a meal now and then tends to drive up glucagon.)

I wonder if glucagon has the same effect on the Nitric Oxide in endothelial tissue. I would think it might. Hmmm.

And. . . a perspective on the study from Malcolm Kendrick, MD, who is not a fan of statins, nor of the cholesterol=heart disease.

http://www.redflagsweekly.com/kendrick/2004_mar10.html




Basically, he says the actual (not RELATIVE) reduction in death was tiny. About 1 percent difference between the two drugs. The study was designed for marketing purposes: "our drug is better than theirs".

He also makes the point that the degree of LDL lowering has never been linked to improvement in survival. Statins may help somewhat, but it ain't because of cholesterol lowering.