What's Hot Archive
March 30, 2001
Fitness predicts all-cause mortality risk
Cardiorespiratory fitness has proven to be a reliable indicator of risk of death from cardiovascular causes and to a smaller extent, from cancer, in several prospective studies, comparable to that of such risk factors as high cholesterol and smoking. A study of 1,294 Finnish men revealed that not only is cardiorespiratory fitness a reliable indicator of heart disease death, it as a good predictor of all cause mortality.
The study, published in the March 26 2001 issue of Annals of Internal Medicine, utilized middle-aged men who were participants in the Kuopio Ischemic Heart Disease Risk Factor Study in Finland. Men who had any heart or respiratory conditions were excluded. Participants were enrolled between 1984 and 1989. Researchers measured maximal oxygen uptake as a measure of cardiovascular fitness at the beginning of the study. This is a quantification of the amount of oxygen consumed during exercise, which provides an assessment of cardiac, circulatory and respiratory function. Exercise endurance was also measured.
During follow-up, which concluded at the end of 1997, there were eighty-two deaths from noncardiovascular causes and forty-two deaths from cardiovascular causes. After adjustment for other risk factors such as age and smoking status, low cardiorespiratory fitness as determined by low maximal oxygen uptake was associated with a 2.76-fold increase in overall mortality during the study period compared with those with a high maximal oxygen uptake. Short exercise duration was associated with a slightly lower risk, when the group with the lowest results was compared to that with the highest. Additional adjustment for other risk factors such as serum triglycerides, HDL, LDL, blood pressure, fibrinogen, diabetes, and insulin levels did not significantly change these associations. The risk of mortality during this time period associated with low maximal oxygen uptake and exercise duration were similar when noncardiovascular mortality was examined separately, and was higher when cardiovascular mortality alone was studied.
The study suggests thirty minutes a day of moderate physical activity to promote health and prevent chronic disease.
March 28, 2001
Drug helps prevent number one diabetic killer
Research published in the March 23 issue of the journal The Lancet revealed that the drug fenofibrate reduces the risk of progression of atherosclerosis in diabetics by up to 42 percent compared to untreated individuals. Atherosclerosis is the most common complication and the number one killer of type 2 diabetics.
The results were obtained from the Diabetes Atherosclerosis Intervention Study (DAIS) in collaboration with the World Health Organization to evaluate the benefits of correcting lipid abnormalities in type 2 diabetics. Four hundred-eighteen male and female participants from Scandinavia, France and Canada randomly received either fenofibrate or a placebo for a three year period. Patients received angiographic examinations at the beginning and at the conclusion of the study. In the group receiving the drug, total serum cholesterol, triglycerides, HDL and LDL all changed favorably after the three year period. Angiograms of the group receiving fenofibrate revealed less arterial narrowing, which the authors attribute to the correction of lipoprotein abnormalities, even in those subjects who had been believed not to need treatment.
Professor George Steiner, of Toronto General Hospital, Canada, Project Director stated, "DAIS has major implications for public health worldwide. There is an epidemic of diabetes. By the year 2010, there will be 239 million people with diabetes in the world. Approximately 80% of these people will have type 2 diabetes, a form which is generally seen in men and women above the age of 50 years. They have a 75-80% risk of dying of heart disease, a figure that is 2-4 times greater than that of the population without diabetes. For the first time, we now have a study entirely carried out in this patient population that shows that by effectively treating the lipid abnormalities which often occur in these patients, we can significantly reduce the risk of the primary cause of death and disability. There is a strong message from this study. Every person with type 2 diabetes should have their lipids measured when their diabetes is diagnosed and annually afterwards. Where their lipids are found to be abnormal, they should be treated with diet and optimum blood sugar control. If this is insufficient to normalise the lipids, a 'lipid lowering' drug should be added. Fenofibrate has been very effective in improving the reduced HDL and increased triglycerides that are typically seen in type 2 diabetes."
March 26, 2001
Vitamin E and oats prevent detrimental effects of high fat meals
In a study published in the February 2000 issue of the American Journal of Preventive Medicine, both vitamin E and oats were demonstrated to prevent one of the undesirable effects of consuming a high fat meal. Consuming high fat foods is known to cause constriction of the arteries, restricting blood flow.
Researchers at Yale University recruited twenty-five men and twenty-five women to participate in a randomized, crossover study. The participants were nonsmokers, free of known vascular disease, but were chosen from different age groups most likely to be at risk for subclinical atherosclerosis for each sex. All of the women in the study were postmenopausal. Subjects were asked to consume a high-fat meal on three occasions one week apart. Each meal was randomly followed by 800 iu vitamin E, oatmeal containing beta-glucan or a wheat cereal. Prior to consuming the high-fat meal, and following the meal, the participants received brachial artery reactivity studies by ultrasound to measure arterial endothelial function. While consumption of wheat cereal was found to do nothing to halt the decline in endothelial function following a high-fat meal, both the ingestion of oats and vitamin E were associated with no change in brachial artery flow. The authors conclude that the consumption of oats or vitamin E, but not wheat prevent the endothelial dysfunction induced by acute fat ingestion in healthy adults, and stress the importance of nutrient distribution and meal composition in cardiovascular health.
March 23, 2001
Another cancer associated with hormone replacement therapy
The use of hormone replacement therapy (HRT) by women during and following menopause has recently been found to be linked with an elevated risk of breast and endometrial cancer, as well as failing to protect against cardiovascular disease. A large study published in the March 21 2001 issue of the Journal of the American Medical Association shows that hormone replacement appears to increase the risk of ovarian cancer as well. Ovarian cancer is usually detected in its late stages making it difficult to treat.
The study utilized data from the American Cancer Society's Cancer Prevention Study II, which followed up participants for mortality from 1982 to 1996. Of the 676,526 people enrolled in this study who completed questionnaires in 1982, there were 211,581 postmenopausal cancer-free women who did not report a hysterectomy. During the fourteen year follow-up period, 944 members of this group succumbed to death from ovarian cancer.
Twenty-two percent of the women reported noncontraceptive hormone replacement use on their questionnaires. The highest risk of ovarian cancer was found in women who had used hormone replacement therapy for ten or more years. This risk was present up to twenty-nine years after hormone replacement was discontinued. Those who were using hormone replacement the most recently experienced a higher risk than those who had previously used it. Women who had used HRT for less than ten years had a small, but insignificant increased risk. The lowest risk of ovarian cancer was found in women who had never been on HRT, who experienced an annual age-adjusted death rate from ovarian cancer of 26.4 per 100,000 women, compared to that of 64.4 for those who were on HRT at the beginning of the study and who had used it for ten or more years.
The authors postulate two mechanisms of action: decreased gonadotropins due to elevated serum estradiol and estrone levels, or a direct effect of estrogen on ovarian cells. They state that if their results are confirmed, clinicians will need to add ovarian cancer to the list of longterm estrogen use risks.
March 16, 2001
Reconsideration suggested for heparin as antimetastatic agent
The March 13 2001 issue of the journal, Proceedings of the National Academy of Sciences published an article featuring a recommendation that the use of the drug heparin be reconsidered as a preventive against cancer metastasis. Heparin is a well known anticoagulant drug which is used in the treatment of blood clots and heart attack, and is also used prophylactically in some cases to prevent clotting during and after surgery. Studies in mice with cancer have shown that heparin administration leads to decreased metastasis and prolonged survival, but heparin's antimetastatic mechanism remained unelucidated. Tumor spread in mice occurs through the formation of tumor cell complexes with white blood cells and platelets, which are blood cells necessary for clotting, but heparin's effects in preventing metastasis are not primarily due to its anticlotting ability. It was found that heparin inhibits P-selectin-mediated interactions of platelets with a substance called mucin on the cancer cell surface. The study's researchers noted that while a single dose of heparin only prevented this interaction for a few hours, it was found to prevent longterm metastasis when the mice were examined six weeks later. Similar results were seen in another experiment in which heparinized mice examined twelve weeks following tumor injection, demonstrating that metastasis was prevented, not just delayed.
When comparing recombinant human P-selectin and mouse P-selectin, human P-selectin was found to be even more sensitive to heparin than mouse P-selectin.
The authors speculated that other mechanisms are involved in the tumor-cell platelet complex formation that leads to tumor metastasis. Not all tumor cells have P-selectin binding sites, and there may be other methods of metastasis. However, because of the success shown by heparin in these and other studies, they suggest early treatment with heparin prior to tumor surgery to prevent metastasis.
March 14, 2001
Trans fatty acid consumption increases coronary heart disease risk
A prospective study of 667 men aged 64 to 84 who were initially free of coronary heart disease revealed that the amount of trans fatty acids consumed was associated with risk of the disease. Trans fatty acids are fats which have been artificially hydrogenated to increase their shelf life, and are contained in most margarines and in vegetable shortening. Adding hydrogen creates a solid compound less subject to rancidity than liquid oils, but concerns have been voiced that hydrogenated fats not found in nature may have adverse effects on the humans that consume them. The study, published in the March 10, 2001 issue of The Lancet, examined data from the Zutphen Elderly Study, which followed a group of older men in the Netherlands. Dietary surveys and medical examinations were conducted at the study's onset and after five and ten years. The trans fatty acid consumption for each participant was calculated with the aid of time-specific Dutch food tables. Both fatal and nonfatal heart attacks were tracked over a decade, and cause of deaths, when they occurred, were verified. Nonfatal heart attacks were confirmed by examination of hospital records.
Trans fatty acid consumption fell during the ten year period, which is a recent dietary trend in the Netherlands due to concerns regarding their potential harm. After adjustment for other cardiovascular risk factors, a high intake of trans fatty acids at the study's baseline was found to be strongly correlated with the risk of coronary heart disease.
The authors comment that the decrease in trans fatty acid consumption in the Netherlands to 2 - 4% of their total dietary intake could have contributed to 23% fewer coronary fatalities.
March 12, 2001
Food fortification with folic acid not enough
Homocysteine, a non-protein forming amino acid, has been linked to an increase in cardiovascular disease and other conditions. The B vitamins folic acid, pyridoxine and vitamin B12 as well as other nutrients have been demonstrated help lower homocysteine levels. Supplementation with 1 mg or more folic acid per day has proven to be maximal in lowering homocysteine levels. A study published in the March 12, 2001 issue of Archives of Internal Medicine, attempted to determine the homocysteine-lowering ability of the amounts of folic acid typically received in the American diet, which contains some foods fortified with the vitamin. One hundred fifty-one participants with ischemic heart disease were randomized to receive daily doses of 0.2, 0.4, 0.6, 0.8 and 1.0 mg folic acid. The participants' fasting serum homocysteine levels were taken at the beginning of the study, after three months of supplementation and three months after the end of the supplementation period.
With each increased dose of folic acid, median serum homocysteine levels decreased. A folic acid dose of 0.8 mg (800 mcg) per day achieved the maximum reduction of homocysteine, which was 23%, similar to that achieved with doses of 1.0 mg folic acid. Those with the highest homocysteine levels experienced the greatest reductions in their serum levels when supplementing with folic acid.
The researchers concluded that 0.8 mg per day folic acid is necessary to acheive the greatest possible reduction in serum homocysteine levels across the range of homocysteine levels in the population, and that current fortification levels in the United States will achieve only a small part of the homocysteine reduction that is possible.
March 9, 2001
Calorie restriction does not effect bone mineral metabolism or hormones in female primates
Calorie, or energy restriction is a remarkable method of delaying aging and death through a reduction in caloric intake which has shown success across species in extending maximum lifespan and preventing many diseases associated with aging. In exploring energy restriction's effects in male rhesus monkeys, it had previously been found to delay sexual and skeletal maturity and lower bone mass, despite the numerous benefits it confers. Similar effects have been seen in rats. In a study published in the March 2001 issue of the Journal of Nutrition, researchers from the National Institute of Aging attempted to determine if energy restriction has similar effects on female rhesus monkeys. Female rhesus monkeys undergo menopause and changes in reproductive hormones similar to that of human females.
Forty female rhesus monkeys ranging in age from one to twenty-one were fed either a standard diet or a diet consisting of 30% less calories than the control diet for six years prior to data collection. The restricted diet was formulated to exceed the National Research Council's standards for vitamin and mineral status by 30-40% to compensate for the loss of vitamins created by lower food intake. No monkeys were postmenopausal at the time of the collection of the data.
While body fat was lowered in the monkeys receiving the restricted diet, lean body mass was not. Although bone mineral density tended to be lower with age in the restricted group, bone mass controlled for age and weight measured at several sites was not effected by energy restriction, and correlated with lean body mass, a correlation that has been observed in human females. Concentrations of the reproductive hormones estradiol, follicle-stimulating hormone (FSH), progesterone and luteinizing hormone were not affected by calorie restriction, nor was menstrual cycling, although estradiol and FSH declined with age and menstrual cycling began to become less frequent in older animals. Parathyroid hormone and vitamin D levels were also unaffected. The researchers speculated that females may have a different response to calorie restriction than males. Ongoing longitudinal studies at the NIA will further elucidate this area.
March 7, 2001
Study confirms B vitamin supplements association with lower homocysteine
A study of participants in the Framingham Offspring Study, consisting of children of participants in the original Framingham Heart Study, confirmed the association between fasting plasma homocysteine and the intake of B vitamins of dietary and supplementary source. Homocysteine is a non-protein forming sulfur amino acid which has been found to be a risk factor for cardiovascular and other diseases when blood levels are elevated. The study examined data from 1,960 men and women between the ages of twenty-eight and eighty-two from the years 1991 to1994, before the implementation of folic acid fortification in the United States.
Examination of the study participants included testing for levels of fasting plasma homocysteine, folate (a determination of folic acid status), vitamin B12, and pyridoxal-5'-phosphate, which is the active circulating form of pyridoxine, or vitamin B6. Dietary intake questionnaires assessed the amounts of nutrients consumed from food and supplements.
Homocysteine levels were higher in men than in women and higher in individuals over 65 years of age than in those 45 years old or younger. In the group having the lowest folate concentrations, homocysteine levels were 49% higher than those who in the group with the highest folate concentrations. A similar, but less dramatic association was seen with vitamin B12. Supplementation with B vitamins was associated with 18% lower homocysteine levels than that of nonsupplement users. Smoking, the use of antihypertensives (but not hypertension), and alcohol and caffeine consumption were all associated with an increase in homocysteine.
The study, published in March's American Journal of Clinical Nutrition, reiterates the advisability of B vitamin supplementation rather than reliance on dietary nutrition as optimal in preventing the dangerous elevation of homocysteine levels.
March 5, 2001
Enzyme identified as cause of Alzheimer's plaques
A National Institute of Aging funded study conducted at Johns Hopkins University School of Medicine discovered the enzyme responsible for developing the characteristic plaques of Alzheimer's disease (AD). It had recently been confirmed that plaques containing beta amyloid that form in the brains of individuals with Alzheimer's disease are responsible for the symptoms experienced by these patients (see What's Hot, January 3, 2001).
The study, published in the the March 2001 issue of the journal Nature Neuroscience, sought to determine which of two enzymes involved in the the generation of Alzheimer's disease, called beta secretase 1 and beta secretase 2, is responsible for plaque formation. Prior research had shown that one of the beta secretases, beta secretase 1 (BACE1) was possibly the initiator in the process of cleaving amyloid precursor protein in the brain, causing beta amyloid fragments to form. The researchers confirmed BACE1's role in cultures of embryonic neurons from mice bred to lack BACE1 in which secretion of beta amyloid peptides was eliminated. BACE2 was found to play a much smaller role in amyloid protein precursor cleavage.
Creighton H. Phelps, Ph.D., director of the NIA's Alzheimer's Disease Centers Program commented, "This study marks another important step in our understanding of the etiology of AD, of how abnormal proteins are processed in the brain as the disease develops. Further research is needed to determine the relationship between the deposition of amyloid and changes in brain function. But with information such as this, we are one step closer to defining targets for treatment that might prevent the deposition of toxic beta amyloid in the brain."
The mice bred to lack BACE1 appeared to be no different from controls within a six month period of time, but the researchers wish to follow them for a longer period to observe the longterm effect of BACE1 inhibition, which could become an important therapy in Alzheimer's disease.
March 2, 2001
Lymphangiogenesis discoveries may lead to methods of combatting metastasis
Angiogenesis, the formation of new blood vessels, has received much well deserved attention recently in regard to its role in the growth and metastasis of malignant tumors. In addition to forming new blood vessels, cancerous tissue also forms a large amount of new lymph vessels, a process called lymphangiogenesis, whose mechanisms have not been fully understood. The lymphatic system is a network of vessels that carries lymphatic fluid, consisting in part of water and proteins, from the tissues to the bloodstream. Migration to the lymph nodes via the lymph vessels is a common mechanism of tumor metastasis, and the primary method of metastasis in breast cancer. The February issue of the journal Nature Medicine, published several reports on this subject which provide information that will aid in understanding the phenomenon.
Lymphangiogenesis as well as angiogenesis involve receptors known as vascular endothelial growth factors receptors (VEGFR). When one type of vascular endothelial growth factor receptor known as VEGFR-3 is stimulated, new lymph vessels are formed, whereas stimulation of VEGFR-2 grows new blood vessels. In one study researchers showed that VEGF-D, a molecule that attaches to VEGFR-3, triggered the growth of both new blood and lymph vessels within mouse tumors, enabling cancer cells to spread to the lymph nodes. The researchers were able to block this effect with a VEGF-D antibody. In another study, the molecule VEGF-C, which is overexpressed in human breast cancer cells and which also attaches to VEGFR-3, was found to stimulate lymph vessel growth in mice who received transplanted human breast tumors, resulting in increased metastasis to the lymph nodes.
The third study showed that the expression of the soluble form of VEGFR-3 in mice is not susceptible to stimulation by VEGF-C or VEGF-D. These findings clarify the roles of vascular endothelial growth factors and receptors and may lead to a means to aid in blocking metastasis of cancer, which is responsible for the deadliness of the disease.
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