STUDY: Study finds condition is top trigger, worse than cholesterol
JOURNAL: New England Journal Of Medicine
AUTHORS: Dr. Paul Ridker
ABSTRACT: A landmark study offers the strongest evidence yet that simmering, painless inflammation deep within the body is the single most powerful trigger of heart attacks, worse even than high cholesterol.
COMMENTARY: The latest research is likely to encourage many doctors to make blood tests for inflammation part of standard physical exams for middle-aged people, especially those with other conditions that increase their risk of heart trouble.
The study, based on nearly 28,000 women, is by far the largest to look at inflammation’s role, and it shows that those with high levels are twice as likely as those with high cholesterol to die from heart attacks and strokes.
Over the past five years, research by Dr. Paul Ridker of Boston’s Brigham and Women’s Hospital has built the case for the “inflammation hypothesis.” With his latest study, many believe the evidence is overwhelming that inflammation is a central factor in cardiovascular disease, by far the world’s biggest killer.
“I don’t think it’s a hypothesis anymore. It’s proven,” said Dr. Eric Topol, chief of cardiology at the Cleveland Clinic.
Inflammation can be measured with a test that checks for C-reactive protein, or CRP, a chemical necessary for fighting injury and infection. The test typically costs between $25 and $50.
Diet and exercise can lower CRP dramatically. Cholesterol-lowering drugs called statins also reduce CRP, as do aspirin and some other medicines.
Doctors believe inflammation has many possible sources. Often, the fatty buildups that line the blood vessels become inflamed as white blood cells invade in a misguided defense attempt. Fat cells are also known to turn out these inflammatory proteins. Other possible triggers include high blood pressure, smoking and lingering low-level infections, such as chronic gum disease.
Inflammation is thought to weaken the fatty buildups, or plaques, making them more likely to burst. A piece of plaque can then lead to a clot that can choke off the blood flow and cause a heart attack.
For the first time, Ridker’s study establishes what level of CRP should be considered worrisome, so doctors can make sense of patients’ readings. However, experts are still divided over which patients to test and how to treat them if their CRP readings are high.
Some, such as Dr. Richard Milani of the Ochsner Clinic in New Orleans, recommend a CRP check for virtually anyone getting a cholesterol test. “If I have enough concern to check a patient’s cholesterol, it seems naive not to include an inexpensive test that would give me even more information,” he said.
Ridker said he believes a high CRP reading can help doctors persuade people with low cholesterol that they still need to diet and exercise.
“The CRP test can predict risk 15 to 25 years in the future,” Ridker said. “We have a long time to get our patients to change their lifestyles, and the change does not have to be huge — modest exercise, modest weight loss and stop smoking.”
Ridker’s latest study is based on an eight-year follow-up of 27,939 volunteers in the Women’s Health Study. About half of heart attacks and strokes occurred in those with seemingly safe levels of LDL, the bad cholesterol.
The lowest risk was in women whose CRP readings were below one-half milligram per liter of blood. It more than doubled when readings went over about three.
You've heard it before: Eat sensibly and get some exercise. But new findings on the dangers of inflammation offer still another reason to shape up.
Doctors say that both inactivity and obesity increase inflammatory proteins that can trigger heart attacks. People can substantially lower their levels of these proteins simply by improving their living habits. Even modest changes help, though studies show that vigorous exercise and a strict diet can cut inflammation levels in half in just three months.
Some research suggests that moderate alcohol consumption and fish oil are good for inflammation levels.
So too are giving up smoking and keeping blood pressure under control.
A variety of drugs and supplements may also do the trick. Ask your doctor to test you.
STUDY: People taking vitamin E supplements for at least 10 years were less likely to die from bladder cancer.
JOURNAL: Am J Epidemiol 2002;156:1002-1010
AUTHORS: Dr. Jacob
ABSTRACT: People who take vitamin E regularly are less likely than those in the general population to die of bladder cancer, researchers report, but it is not clear if the vitamin itself or some lifestyle factor is responsible for the reduced risk.
COMMENTARY: Researchers tracked nearly 1 million US adults for 16 years and interviewed them about their diet. Those who reported taking vitamin E supplements for at least 10 years were less likely to die from bladder cancer, compared with adults who reported shorter durations of use.
In contrast, there was no association between regular vitamin C use and bladder cancer mortality, report researchers in the December issue of the American Journal of Epidemiology.
The current findings support those of two previous studies that showed an inverse relationship between bladder cancer risk and vitamin E intake.
Exactly how vitamin E may protect against bladder cancer is unclear. It might result from its antioxidant effect in neutralizing DNA-damaging free radicals. Alternatively, vitamin E may boost the immune system or prevent the formation of carcinogenic nitrosamines.
However, if vitamin E's antioxidant properties are responsible for the protective effect, it is not clear why vitamin C use confers no protection against the malignancy.
Dr. Jacob emphasized that further studies are needed to verify the current results and to possibly shed light on vitamin E's mechanism of action.
STUDY: Popular arthritis drug may not protect stomach from ulcers
JOURNAL: New England Journal of Medicine
AUTHORS: Dr. John H. Klippel
ABSTRACT: The blockbuster arthritis drug Celebrex doesn’t protect the stomach from dangerous bleeding ulcers as well as thought, a study suggests.
COMMENTARY: CELEBREX AND two similar new anti-inflammatory drugs are heavily advertised as being safer for arthritis patients based on earlier research that found they caused fewer ulcers and other gastrointestinal complications than older anti-inflammatory medicines.
Together, the three new drugs have annual sales exceeding $6 billion.
But their safety has been called into question recently. The new study, which focused on arthritis patients at high risk of recurrent ulcers, escalates the controversy involving Celebrex, showing nearly 10 percent each year would develop another bleeding ulcer.
The study found the same thing for an older anti-inflammatory drug combined with ulcer medicine Prilosec, which doctors often give arthritis patients to protect their stomachs. In addition, neither treatment protected as many patients from dangerous kidney complications as past studies showed, the researchers said.
The Hong Kong researchers and some other experts said the results, while showing the treatments work the same, indicate more study is needed on preventing bleeding stomach ulcers in vulnerable older people who for years ease joint pain with nonsteroidal anti-inflammatory drugs, or NSAIDs.
“I think patients and doctors need to be aware ... there is a risk of gastrointestinal bleeding and there is a risk of renal toxicity,” so high-risk patients should be monitored closely by their doctor, said Dr. John H. Klippel, medical director of the Arthritis Foundation.
These drugs, which also include Vioxx and Bextra, do not block action of the cox-1 enzyme, which protects the lining of the stomach. Older NSAIDs such as diclofenac block both cox enzymes, and so can cause stomach irritation and exacerbate ulcers.
Complications from taking older anti-inflammatory drugs hospitalize about 107,000 Americans, and ulcer complications kill an estimated 16,500 each year.
Of the study patients receiving Celebrex, about 5 percent had recurrent bleeding during the six months of research, compared with about 6.5 percent for those getting diclofenac and Prilosec.
However, that equates to annual rates of about 9 percent and 11 percent, respectively, Dr. David Y. Graham of the Veterans Affairs Medical Center in Houston wrote in an accompanying editorial. “The results were unexpected: Neither regimen provided a good or even acceptable level of protection from recurrent bleeding,” Graham wrote.
Both treatments did a good job in reducing pain and enabling patients to perform daily activities over the six-month experiment.
But about 25 percent of those in the Celebrex group and 31 percent in the diclofenac/Prilosec group suffered kidney complications, including high blood pressure and swollen ankles; about 6 percent in each group suffered life-threatening kidney failure.
Klippel said that shows doctors must monitor high-risk patients on these anti-inflammatory drugs for increased pain and bloody stools indicating an ulcer flareup. They also should watch for swelling in the extremities and elevated blood pressure — signs the kidneys can’t excrete enough fluid.
“Physicians should avoid prescribing these drugs to patients with known kidney diseases, poorly controlled hypertension and heart failure."
We have many alternatives to these drugs. Let's make sure that we educate patients as to the best choices for them.
STUDY: Extra weight in middle age a risk factor for earlier death
JOURNAL: Annals of Internal Medicine
AUTHORS: Dr. Serge Jabbour
ABSTRACT: People who are overweight at 40 are likely to die at least three years sooner than those who are slim, meaning that in terms of life expectancy, being fat during middle age is just as bad as smoking.
COMMENTARY: Nonsmokers who were classified as overweight, but not obese, lost an average of three years off their lives. Obese people died even sooner. Obese female nonsmokers lost an average 7.1 years, while men lost 5.8 years.
Scientists have long known that overweight people have shorter life expectancies, but few large-scale studies have been able to pinpoint how many years they lose.
“This study is saying that if you are overweight by your mid-30s to mid-40s, even if you lose some weight later on, you still carry a higher risk of dying,” said Dr. Serge Jabbour, director of the weight-loss clinic at Thomas Jefferson University Hospital in Philadelphia. “The message is that you have to work early on your weight. If you wait a long time, the damage may have been done.”
For smokers, the results were even worse. Obese female smokers died 7.2 years sooner than normal-weight smokers, and 13.3 years sooner than normal-weight nonsmoking women. Obese male smokers lived 6.7 years less than trim smokers, and 13.7 years less than normal-weight nonsmokers.
The results were culled from vital statistics collected from 3,457 volunteers in Framingham, Mass., from 1948 to 1990. The data were analyzed by researchers at Erasmus Medical Center and the University of Gronigen in the Netherlands.
Obesity is defined as having a body-mass index of 30 or above. The index is a measure of weight relative to height. Healthy weight is a BMI of less than 25.
JOURNAL: J Natl Cancer Inst 2003;95:132-141.
AUTHORS: Dr. Joanne F. Dorgan
ABSTRACT: Adolescent girls who follow a low-fat diet have reduced sex hormone levels that may decrease their risk of breast cancer in adulthood.
COMMENTARY: However, whether these findings translate into a lower risk of breast cancer later in life is not clear, according to the report published in the January 15th issue of the Journal of the National Cancer Institute.
Reduced levels of estrogens and progesterones might slow down the rate of cell division, thereby decreasing the likelihood of carcinogenic mutations, lead author Dr. Joanne F. Dorgan, from the Fox Chase Cancer Center in Philadelphia, said in a statement.
Elevated body fat is another risk factor for premenopausal breast cancer, although it is not clear how excess fat may contribute to the risk.
To investigate the relationship between fat intake during puberty and blood levels of hormones associated with breast cancer, the research team studied 286 girls between 8 and 10 years of age. The girls were already enrolled in a study to evaluate the ability of a diet to lower levels of LDL cholesterol.
About half of the patients attended individual and group nutrition counseling sessions on how to follow a low fat diet, in which 28% of calories came from fat and 8% came from saturated fat. The other half received written material on nutrition from the American Heart Association, but did not take part in nutrition counseling.
After 5 years, the girls in the counseling group had lower levels of several estrogens that have been linked to breast cancer. For instance, estradiol levels were about 30% lower and estrone levels were about 20% lower, the study found. Levels of progesterone were also lower, the findings indicate.
Finally, girls in the counseling group reported eating fewer calories, less fat and saturated fat, and more fiber, compared with girls in the other group.
"These results suggest that the modest reductions in total fat, saturated fat, and perhaps energy intake during adolescence may alter the function of the hypothalamic-pituitary-ovarian axis, which regulates ovarian hormone production," the researchers note. Whether these differences ultimately influence breast cancer risk is currently unknown.