Saturday, March 29, 2008

Coronary Calcification Predicts Future Heart Attacks and Coronary Death. Cholesterol Not Found To Be A Significant Risk Factor

A striking report just published in the New England Journal of Medicine indicates the accumulation of calcium in coronary arteries, and not cholesterol, more accurately predicts a future heart attack or other heart trouble, far more than cholesterol or other standard risk factors.

This report gives evidence of a major misdirection by modern medicine - the creation of cholesterol phobia in the population at large. Prior studies show use of cholesterol-lowering drugs does not reduce mortality rates for coronary artery disease. This report follows a front-page report in Business Week Magazine declaring cholesterol-lowering drugs to be of marginal value.

The study involved 6722 men and women, ~age 60, who were studied for a period of 3.8 years (median). None had coronary artery disease at the beginning of the study. Subjects who experienced an adverse coronary event (heart attack, angina, placement of a stent, coronary death) were more likely to be taking cholesterol-lowering drugs (~28%) than those who did not experience such an event (~16%). Furthermore, subjects who experienced a heart attack or angina had about the same total cholesterol (~199) as subjects who did not (~194). Cholesterol barely met statistical significance whereas calcium was a highly predictive factor.

Traditionally-used risk factors, such as C-reactive protein (a marker of inflammation), triglycerides, HDL cholesterol and greater body mass, were not predictive for a future coronary artery event.

Among subjects whose coronary artery calcium score was zero, their risk for any adverse coronary event was only about one-half of 1% (0.0044), or less than 1 in 200, whereas those with a coronary calcium score over 300, about 8.0% experienced an adverse event involving coronary arteries (0.0804), or about 8 in 100, an 18-fold difference (1800%!), over the 3.8 year period.

This study shows the risk for a future heart attack is nil for those with a calcium arterial score of zero. This data helps to explain why hundreds of thousands of Americans experience a sudden-death heart attack with low-to-normal cholesterol. Most heart attacks emanate in the four coronary arteries that supply the heart with oxygenated blood. About 50% of arterial plaque is calcium and only 3% is cholesterol.

Arterial calcium can be measured by use of a CT scan (called an Agatston score, for Dr. Arthur Agatston, South Beach Miami, Florida cardiologist). About 70% of white males, 52% of black males, 57% of Hispanic males and 59% of Chinese males, have coronary calcium scores greater than zero. The calcium arterial scores for women are about half that of males owing to the fact they donate calcium to their offspring during pregnancy and lactation and control calcium via estrogen throughout their fertile years.

Calcium begins to accumulate in coronary arteries in males as soon as full growth is achieved, around age 18. Women begin to accumulate calcium in their arteries with the onset of menopause or early hysterectomy. It was recently reported that postmenopausal women who take calcium supplements increase their risk for a heart attack by about 45%. [British Medical Journal 2008 Feb 2; 336 (7638): 262-6]

In the early 1990s British cardiologist Stephen Seely noted that countries which consume that highest amount of calcium (New Zealand, Ireland, North America, Scandinavian countries), mostly from dairy products, have the highest rates of cardiovascular disease. [International Journal Cardiology 1991 Nov; 33(2):191-8]

Sixty-four percent (64%) of subjects who experienced any coronary event were current or former smokers compared to about 50% of those who did not experience a heart attack or other adverse event.


(See Coronary Calcium as a Predictor of Coronary Events in Four Racial or Ethnic Groups, New England Journal of Medicine 358: 1336-45, March 27, 2008)

Laboratory evidence shows red wine antioxidant kills cancer

Are we allowed to mention that antioxidants shorten your lifespan?

Rochester researchers showed for the first time that a natural antioxidant found in grape skins and red wine can help destroy pancreatic cancer cells by reaching to the cell's core energy source, or mitochondria, and crippling its function. The study is published in the March edition of the journal, Advances in Experimental Medicine and Biology. The study also showed that when the pancreatic cancer cells were doubly assaulted -- pre-treated with the antioxidant, resveratrol, and irradiated -- the combination induced a type of cell death called apoptosis, an important goal of cancer therapy.

The research has many implications for patients, said lead author Paul Okunieff, M.D., chief of Radiation Oncology at the James P. Wilmot Cancer Center at the University of Rochester Medical Center.

Although red wine consumption during chemotherapy or radiation treatment has not been well studied, it is not "contraindicated," Okunieff said. In other words, if a patient already drinks red wine moderately, most physicians would not tell the patient to give it up during treatment. Perhaps a better choice, Okunieff said, would be to drink as much red or purple grape juice as desired.

Yet despite widespread interest in antioxidants, some physicians are concerned antioxidants might end up protecting tumors. Okunieff's study showed there is little evidence to support that fear. In fact, the research suggests resveratrol not only reaches its intended target, injuring the nexus of malignant cells, but at the same time protects normal tissue from the harmful effects of radiation.

"Antioxidant research is very active and very seductive right now," Okunieff said. "The challenge lies in finding the right concentration and how it works inside the cell. In this case, we've discovered an important part of that equation. Resveratrol seems to have a therapeutic gain by making tumor cells more sensitive to radiation and making normal tissue less sensitive."

Resveratrol is known for its ability to protect plants from bacteria and fungi. Purified versions have been described in scientific journals as potential anti-cancer, anti-inflammatory and anti-atherogenic agents, and for their ability to modulate cell growth. Other well-known antioxidants derived from natural sources include caffeine, melatonin, flavonoids, polyphenols, and vitamins C and E.

A flurry of antioxidant studies in recent years has not proven how and why they work at the cellular level. At the suggestion of a young scientist in his lab, Okunieff began studying resveratrol as a tumor sensitizer. That's when they discovered its link to the mitochondria. The discovery is critical because, like the cell nucleus, the mitochondria contains its own DNA and has the ability to continuously supply the cell with energy when functioning properly. Stopping the energy flow theoretically stops the cancer.

Researchers divided pancreatic cancer cells into two groups: cells treated without resveratrol, or with resveratrol, at a relatively high dose of 50 mg/ml, in combination with ionizing radiation. (The resveratrol concentration in red wine can be as high as 30 mg/ml, the study said, and higher doses are expected to be safe as long as a physician is monitoring.)

They evaluated the mitochondria function of the cells treated with resveratrol, and also measured apoptosis (cell death), the level of reactive oxygen species in the cells, and how the cell membranes responded to the antioxidant.

Laboratory experiments showed that resveratrol:

-- Reduced the function of proteins in the pancreatic cancer cell membranes that are responsible for pumping chemotherapy out of the cell, making the cells chemo-sensitive.

-- Triggered the production of reactive oxygen species (ROS), which are substances circulating in the human body that have been implicated in a number of diseases: when ROS is increased, cells burn out and die.

-- Caused apoptosis, which is likely the result of increased ROS.

-- Depolarized the mitochondrial membranes, which indicates a decrease in the cell's potential to function. Radiation alone does not injure the mitochondrial membrane as much.

The team also wanted to investigate why pancreatic cancer cells seem to be particularly resistant to chemotherapy. The pancreas, a gland located deep in the abdomen, produces insulin and regulates sugar, and pumps or channels powerful digestive enzymes into the duodenum. This natural pumping process, however, ends up ridding the needed chemotherapy from cells in the pancreas. But just as reseveratrol interferes with the cancer cells' energy source, it also may decrease the power available to pump chemotherapy out of the cell.

"While additional studies are needed," Okunieff said, "this research indicates that resveratrol has a promising future as part of the treatment for cancer."

In the same journal, Okunieff and his group also reviewed why resveratrol protects normal tissue, and found that antioxidants can be designed to take advantage of certain biochemical properties or cellular targets, making them more effective.



Just some problems with the "Obesity" war:

1). It tries to impose behavior change on everybody -- when most of those targeted are not obese and hence have no reason to change their behaviour. It is a form of punishing the innocent and the guilty alike. (It is also typical of Leftist thinking: Scorning the individual and capable of dealing with large groups only).

2). The longevity research all leads to the conclusion that it is people of MIDDLING weight who live longest -- not slim people. So the "epidemic" of obesity is in fact largely an "epidemic" of living longer.

3). It is total calorie intake that makes you fat -- not where you get your calories. Policies that attack only the source of the calories (e.g. "junk food") without addressing total calorie intake are hence pissing into the wind. People involuntarily deprived of their preferred calorie intake from one source are highly likely to seek and find their calories elsewhere.

4). So-called junk food is perfectly nutritious. A big Mac meal comprises meat, bread, salad and potatoes -- which is a mainstream Western diet. If that is bad then we are all in big trouble.

5). Food warriors demonize salt and fat. But we need a daily salt intake to counter salt-loss through perspiration and the research shows that people on salt-restricted diets die SOONER. And Eskimos eat huge amounts of fat with no apparent ill-effects. And the average home-cooked roast dinner has LOTS of fat. Will we ban roast dinners?

6). The foods restricted are often no more calorific than those permitted -- such as milk and fruit-juice drinks.

7). Tendency to weight is mostly genetic and is therefore not readily susceptible to voluntary behaviour change.

8). And when are we going to ban cheese? Cheese is a concentrated calorie bomb and has lots of that wicked animal fat in it too. Wouldn't we all be better off without it? And what about butter and margarine? They are just about pure fat. Surely they should be treated as contraband in kids' lunchboxes! [/sarcasm].

9). And how odd it is that we never hear of the huge American study which showed that women who eat lots of veggies have an INCREASED risk of stomach cancer? So the official recommendation to eat five lots of veggies every day might just be creating lots of cancer for the future! It's as plausible (i.e. not very) as all the other dietary "wisdom" we read about fat etc.

10). And will "this generation of Western children be the first in history to lead shorter lives than their parents did"? This is another anti-fat scare that emanates from a much-cited editorial in a prominent medical journal that said so. Yet this editorial offered no statistical basis for its opinion -- an opinion that flies directly in the face of the available evidence.

Even statistical correlations far stronger than anything found in medical research may disappear if more data is used. A remarkable example from Sociology:
"The modern literature on hate crimes began with a remarkable 1933 book by Arthur Raper titled The Tragedy of Lynching. Raper assembled data on the number of lynchings each year in the South and on the price of an acre's yield of cotton. He calculated the correlation coefficient between the two series at -0.532. In other words, when the economy was doing well, the number of lynchings was lower.... In 2001, Donald Green, Laurence McFalls, and Jennifer Smith published a paper that demolished the alleged connection between economic conditions and lynchings in Raper's data. Raper had the misfortune of stopping his analysis in 1929. After the Great Depression hit, the price of cotton plummeted and economic conditions deteriorated, yet lynchings continued to fall. The correlation disappeared altogether when more years of data were added."
So we must be sure to base our conclusions on ALL the data. But in medical research, data selectivity and the "overlooking" of discordant research findings is epidemic.

"What we should be doing is monitoring children from birth so we can detect any deviations from the norm at an early stage and action can be taken". Who said that? Joe Stalin? Adolf Hitler? Orwell's "Big Brother"? The Spanish Inquisition? Generalissimo Francisco Franco Bahamonde? None of those. It was Dr Colin Waine, chairman of Britain's National Obesity Forum. What a fine fellow!


1 comment:

Anonymous said...

I offer this in the spirit of brainstorming.

"Are we allowed to mention that antioxidants shorten your lifespan?"

Some, taken singly. Studies abound, some of them funding-biased. First I want to see, within the same country or culture, that people who take a simple daily vitamin pill don't live very long, by a meaningful margin.

EATING A STARVATION DIET is the *one* thing that leads all animals to live longer. Great, except, that neglects to mention that starvation makes people TIRED and FATIGUED, so that's like living your life in the prison of your body instead of being unawares of it, or better yet, horny, smart-witted and adventurous. A STARVATION diet, by logic alone, indicates less energy conversion, and thus less FREE RADICALS.

We all die. Might (for sake of argument), many or even most anti-oxidant users, pack more into their lives, and thus in some philosophical way, actually live more life than those who buy into low fat diet theory and actually eat the rabbit-food diets that everybody is pushing us to eat, which merely pushes up their stress hormones due to the torture of eating "health foods" all the time?

SINGLE anti-oxidants have been the ONLY thing I have ever heard the reduces life span, and ONLY in rats or HIGH RISK HUMANS, like chronic smokers, helps feed the cancer and reduce the immune system's OXIDANT poisons that try to fight it.

The odd fact is that Homo Sapiens are one of the only mammals, including most if not all primates, who have LOST the ability to make their own Vitamin C. This may be an evolutionary mistake, I do not know, but other primates eat leaves ALL day.

There is, in an unrelated topic, the idea that over the last 40K years, humans moved from Africa to everywhere else, all along the sea shore. So we may be in some sense "aquatic apes" (thus our lack of body hair and stream-lined noses). Most of the fossil record of this migration is lost, since the oceans have risen over those exact slices of coastal land that early humans clung to.

A major distinction exists though. Actually, many. That MEGA doses of anti-oxidants, especially of only one instead of many, may become pro-oxidants if they are not used up quickly, as needed. For instance, catching a cold doesn't matter if you take Vitamin C, but colds are said to last a few ten percentage points less long if you load up on Vitamin C during the cold.

Also, rats are NOT humans. For one thing, rats make their own Vitamin C, unlike humans, since, human ancestors, possibly pre-human ones, got a lot of that in their diet, but insect and root eating rats didn't. Same for cats and dogs. They make their own Vitamin C. Why this difference? Again, I don't know, but it may be that we had a source of it that apes and especially cats did not, just as we became naked (likely due to being water-lovers along with hunters who were able to wear animal fur at any time). Like subatomic physics, I think there are major mysteries to be yet uncovered in how humans got to our present state (female orgasms included except for maybe the sex-crazed Bonobos).

But, since humans have evolved faster than ANY modern mammal, we have in many ways mal-adapted, so it may just be that a small dose, wide-variety anti-oxident, omega-3 fat, and multi-mineral formula daily intake of SUPPLEMENTS may (*MAY*) provide either better overall longevity, or better vitality, or both, or even highly desired vitality with a slight cut in overall longevity, a choice that many if not most people, were the science settled, would likely choose, over mere longevity, especially when they are young and in competitions in all walks of life, based on vitality alone, and never on future longevity.

There may be a TRADE OFF between young and middle aged VITALITY and old age decrease in IMMUNE SYSTEM FUNCTION along with CANCER IMMUNITY. It will be at last 100 years before this is all worked out.

Interesting that, though, since they will likely not cure cancer, but indeed cure obesity and diabetes, along with heart disease, in a mere 25 years, but probably not HIV.

Yet again, since humans evolve SO fast, the very idea that we are utter slaves to our "hunter-gatherer" pasts, based on linear evolution speed theory, doesn't necessarily apply to us, so some grains may be O.K. for some humans, namely those who, unlike modern hunter-gatherers, moved beyond that savage state.