Fish Oils May Slow Genetic Aging

By Kristina Fiore, Staff Writer, MedPage Today
Published: January 19, 2010
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner   
Earn CME/CE credit
for reading medical news

For heart disease patients, omega-3 fatty acids may protect against morbidity and mortality by slowing biological aging, researchers say.

Patients who had the highest omega-3 fatty acid blood levels also had telomeres that shortened at a significantly slower rate than patients with lower intake, Ramin Farzaneh-Far, MD, of the University of California San Francisco, and colleagues reported in the Jan. 20 JAMA.

Patients in the lowest quartile of omega-3 fatty acid blood levels had the fastest rate of telomere shortening over five years: 0.13 telomere-to-single-copy gene ratio (95% CI 0.09 to 0.17).

Those who had the highest omega-3 fatty acid blood levels had the slowest rate of telomere shortening: 0.05 telomere-to-single copy ratio (95% CI 0.02 to 0.08, P<0.001).
Action Points 
Explain that patients who had the highest intake of omega-3 fatty acids had the slowest decrease in telomere length. On the other hand, patients with the lowest levels of omega-3s in their blood had the fastest rate of telomere shortening.
Telomeres are the protective caps at the end of chromosomes that reveal how biological stress ages a person.
"Patients with the highest levels of omega-3 fish oils were found to display the slowest decrease in telomere length, whereas those with the lowest levels of omega-3 fish oils in the blood had the fastest rate of telomere shortening," Farzaneh-Far said. "This suggests that these patients were aging faster than those with higher fish oil levels."

They said omega-3s may protect against oxidative stress, or increase the activity of the telomerase enzyme, which would decrease telomere shortening by creating more accurate telomere copies.

But some cardiologists were quick to point out that the results are preliminary and need to be replicated before physicians can use them in practice.

Since the study was observational and couldn't prove cause-and-effect, "we don't really know whether ingestion of omega-3 fatty acids resulted in this 'benefit,'" Steven E. Nissen, MD, of the Cleveland Clinic, noted in an e-mail. "It remains entirely possible that individuals who consume more fish also have other favorable healthy habits."

Nissen also pointed out that the study was not randomized to compare fish oil directly with a placebo treatment, and cautioned that "the relationship between telomere shortening and cardiovascular health is not well established."

Studies have shown that omega-3s appear to be effective for patients with coronary artery disease. Yet the underlying mechanisms are not well understood. Some researchers think it may have something to do with anti-inflammatory, triglyceride-lowering, antihypertensive, antiplatelet, or antiarrhythimic effects.

Research has shown that the length of telomeres -- chromosome caps that have long been compared to the plastic ends of shoelaces -- may be a marker of biological age. Biological age is independent of chronological age, and takes into account genetic and environmental stressors that may wreak havoc on cells.

Since there's been increasing evidence that omega-3s exert direct effects on aging and age-related diseases, the researchers decided to investigate them as a potential mechanism for protective effects in heart patients.

So they conducted a prospective cohort study of 608 patients in California with stable coronary artery disease. Patients were recruited from the Heart and Soul Study between September 2000 and December 2002.

They were followed for five years, and the researchers assessed telomere length of their leukocytes at baseline and again at the end of follow-up.

"By measuring telomere length at two different times," Farzaneh-Far said, "we were able to see the speed at which the telomers are shortening and that gives us some indication of how rapidly the biological aging process is taking place in these patients."

The researchers found that baseline omega-3 fatty acid levels were positively correlated with changes in telomere length over five years (P=0.001).

The relationships remained after controlling for potential confounders including demographics, blood pressure, serum lipids, and inflammatory biomarkers.

The researchers noted that each standard-deviation increase in fatty acid levels was associated with a 32% reduction in the odds of telomere shortening (95% CI 0.47 to 0.98).

So how do omega-3s stop telomeres from getting smaller?

They may protect against oxidative stress, which is a major driver of telomere shortening and aging. Or, fatty acids may increase the activity of the enzyme telomerase, which can result in more accurate copying and hence, longer telomeres, the researchers suggested.

The researchers agreed that the study was limited by its observational nature, which leaves no room for definitive conclusions about causality. Also, they only measured telomere length in leukocytes, which means the findings may not translate to other cell types, including myocardial or endothelial cells.

Researchers who were not involved in the study noted that omega-3s have been shown to have effects on other factors that contribute to heart disease risk.

"Omega-3 fatty acids have a potent positive impact on lipids that circulate in the blood stream and damage the heart," said Cam Patterson, MD, of the University of North Carolina Chapel Hill McAllister Heart Institute. "The effects of omega-3 fatty acids on lipids are still the best advertisement for their use to prevent heart disease."

Merle Myerson, MD, of Columbia University, agreed. "[The researchers] don't mention that omega-3 fatty acids lower triglycerides and non-HDL cholesterol, and stabilize cell membranes -- all of which may reduce risk for coronary artery disease and sudden cardiac death."

Myerson said the findings need to be replicated in future studies.

While their study may not have implications for intake of omega-3s among the general population, the researchers said it upholds recommendations for patients with heart disease.

"The results of our study underscore the recommendations of the American Heart Association, that patients with known coronary artery disease should be getting at least one gram a day of omega-3 fish oil," Farzaneh-Far said.

Gastric Bypass Extends Life for Most Patients

By John Gever, Senior Editor, MedPage Today Published: January 18, 2010 Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner Earn CME/CE credit for reading medical news

For most patients in most categories, bariatric surgery increases life expectancy, according to a new mathematical model. Only when short-term mortality following bariatric surgery is expected to be high or the likelihood of success is low will the procedure fail to improve life expectancy, researchers reported in the January Archives of Surgery. Computer modeling predicted that a hypothetical "base case" patient -- a 42-year-old woman with a body mass index of 45 -- would gain 2.95 years of additional survival following bariatric surgery, according to Daniel P. Schauer, MD, of the University of Cincinnati, and colleagues. Surgery failed to be beneficial in the model only when 30-day mortality reached 9.5% or the likelihood that surgery would not add life-years was 2% or less, they found. Baseline 30-day mortality in the model was 0.2%, and the baseline efficacy of surgery in extending life expectancy was 53%. "While not all patients are guaranteed a good outcome, our model indicates that gastric bypass increases life expectancy for most patient subgroups," they concluded. Their analysis was based on a Markov decision model using published data to estimate 30-day mortality following bariatric surgery and the efficacy of surgery in reducing long-term death rates. The latter had two components: reduction in excess mortality associated with obesity, and research data on long-term mortality following bariatric surgery. Excess mortality estimates came from National Health Interview Survey data on some 400,000 participants from 1991 to 1996 linked to the National Death Index. Inputs on surgery efficacy were derived from a 2007 study of nearly 8,000 patients who had undergone gastric bypass and the same number of medically treated or untreated obese controls. That study found that the procedure cut death rates by half during about seven years of follow-up. (See Missing Link Found: Bariatric Surgery Reduces Mortality) Schauer and colleagues obtained rates of inhospital mortality following bariatric surgery from the 2005 National Inpatient Survey, then multiplied them by three to estimate 30-day mortality. The researchers explained that according to earlier research, inhospital death rates typically underestimate 30-day mortality by a factor of two to three. Their threefold correction factor represents "a conservative estimate that biases the model against gastric bypass surgery," they wrote. Schauer and colleagues tested this correction factor and other aspects of the model in sensitivity analyses. The biggest gains in life expectancy occurred in younger women with relatively high BMI values, the model showed. The age effect was less important than BMI at the time of surgery. A 35-year-old woman with BMI of 45 would gain about 3.2 years of extra life, whereas at 55, a similarly obese woman would gain about 2.5 extra years. But a 35-year-old woman with BMI of 55 could expect to live five more years with surgery, the model indicated. Men in general derived less survival benefit from bariatric surgery, particularly with advancing age at the time of the procedure. At 35, the difference in life expectancy gained was roughly 10%, but by age 75 it had grown to about 50%. The sensitivity analyses found that relatively large changes in most parameters used in the model did not affect the overall results substantially. The effect of 30-day mortality on whether or not surgery was beneficial for long-term survival was related to BMI and gender. For women with a BMI of 40, 30-day mortality of more than 5% would mean surgery was not helpful, but short-term mortality had to exceed 15% for surgery not to be preferable for those with BMI of 55 or more. These thresholds were about 10% higher for men. The efficacy of surgery in reducing mortality was less important for older men, the analysis also showed. A 75-year-man with a BMI of 35 could expect only a very slight gain in life span -- perhaps one or two months. "Younger patients have lower surgical risk and more time over which to realize the benefits of surgery. For older patients, the gain is smaller, and for some, gastric bypass surgery will decrease life expectancy," Schauer and colleagues wrote. However, they identified several potentially serious limitations to the analysis. The study of long-term mortality following bariatric surgery was conducted at a single center and was not randomized. Additionally, long-term complications, such as need for repeat surgery, were not addressed in the model. Certain other risks that might be heightened after bariatric surgery were excluded as well, and quality of life was not modeled. "The decision analysis presented here is a step forward in understanding optimal patient selection but also highlights some of the areas for which better data are needed," the researchers wrote.

Exercise May Aid Cognitive Function

By Charles Bankhead, Staff Writer, MedPage Today Published: January 12, 2010 Reviewed by Zalman S. Agus, MD; Emeritus Professor University of Pennsylvania School of Medicine and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner Earn CME/CE credit for reading medical news

Action Points   Explain to patients that two different studies showed that physical activity in midlife or late in life may improve certain aspects of cognitive function. The studies differed in that one showed benefits only in women and with vigorous activity whereas the other study demonstrated benefits in men and women but was limited to moderately intense exercise. Almost any amount of moderate physical activity in mid- or late life reduced the odds of mild cognitive impairment by 30% to 40% in an ongoing cohort study, researchers reported. Men and women derived similar benefit, which was limited to moderate exercise -- not light or vigorous physical activity, investigators wrote in the January Archives of Neurology. "Our findings contribute to the growing body of literature that indicates the potentially beneficial relationship between physical exercise and cognition," Yonas E. Geda, MD, of the Mayo Clinic in Rochester, Minn., and colleagues concluded. "A future population-based cohort study is needed to confirm whether physical exercise is associated with decreased risk of incident mild cognitive impairment." Meanwhile, a small, separate interventional study described in the same journal showed that six months of high-intensity aerobic exercise was associated with significant improvement in executive function in older women at increased risk of cognitive decline, but not in older men. Mild cognitive impairment confers a five- to 10-fold increased risk of dementia compared with normal cognition. Observational studies have shown that physical activity may protect against dementia and Alzheimer's disease, and some evidence suggests that exercise for individuals with mild cognitive impairment offers some protection, too, the authors wrote. Geda and colleagues continued exploration of the association between physical activity and cognitive impairment with an evaluation of the effect of physical activity in midlife, approximately the age of onset for mild cognitive impairment. Data for the study came from the Mayo Clinic Study of Aging. The study included 1,324 participants who completed a standardized questionnaire about physical activity. Their median age was about 80, and none of the participants exhibited signs of dementia at baseline. Investigators assessed the frequency and intensity of physical activity as reported by each participant. Light exercise: bowling, leisurely walking, stretching, slow dancing, and golfing using a cart. Moderate exercise: brisk walking, hiking, aerobics, strength training, swimming, tennis doubles, yoga, martial arts, weight lifting, moderate use of exercise machines, and golfing without use of a cart. Vigorous exercise: jogging, backpacking, bicycling uphill, tennis singles, racquetball, skiing, and intense or extended use of exercise machines. The neuropsychologic evaluation consisted of nine tests that assessed memory, executive function, language, and visuospatial skills. A consensus panel classified each participant as having normal cognition (N=1,126) or mild cognitive impairment (N=198). The two groups differed significantly in several respects. Participants with mild cognitive impairment were more likely to be men, older, less educated, more likely to be depressed, and had more comorbidity (P<0.001 to P=0.02). Any frequency of moderately intense activity in midlife (ages 50 to 65) was associated with an odds ratio of 0.61 for mild cognitive impairment (95% CI 0.43 to 0.88, P=0.008). Moderate activity in later life was associated with an odds ratio of 0.68 (95% CI 0.49 to 0.93, P=0.02). More or less intense activity of any frequency or duration did not significantly affect the odds ratio for mild cognitive impairment. The authors noted several limitations of the study, including a cross-sectional design than could not assess causality, self-reported physical exercise data and relatively few subjects engaged in vigorous exercise in late life, which limited statistical power for that analysis. A prospective evaluation of high-intensity aerobic exercise for patients with existing mild cognitive impairment showed that women had improved executive function, but men did not. The study involved 17 women and 16 men ages 55 to 85. All had mild cognitive impairment by standardized assessment criteria, and all reported sedentary lifestyles at enrollment, Laura D. Baker, PhD, of the Veterans Affairs Puget Sound Health Care System in Seattle, and colleagues reported. Participants were randomized 2:1 to aerobic exercise or stretching activity (control) and followed for six months. Both groups engaged in their assigned, supervised activities four times a week for 45 to 60 minutes at each session. After two weeks, activity was supervised once a week. Participants assigned to aerobic exercise increased the duration and intensity of exercise over the first six weeks until they reached 75% to 85% of heart rate reserve, a level maintained for the remainder of the study. Cognitive function was assessed at baseline and after three and six months of follow-up, as were physical status and laboratory values. The results showed overall improvement in executive function among aerobic exercisers (P=0.04). Including gender as a predictive variable in the statistical model revealed significant interaction, reflecting a difference in response to the intervention for men and women (P=0.04). Aerobic exercise increased glucose disposal, and reduced fasting plasma levels of insulin, cortisol, and brain-derived neurotrophic factor in women, the researchers reported. Among men, aerobic exercise increased plasma levels of insulin-like growth factor I. Women on aerobic exercise demonstrated improvement in all four assessments of executive function, while men showed improvement in only one test. "Aerobic exercise is a cost-effective practice that is associated with numerous physical benefits," the authors concluded. "The results of this study suggest that exercise also provides a cognitive benefit from some adults with mild cognitive impairment." They also noted several limitations, including small sample size, exclusion of a number of subjects for medical reasons, and the fact that "the demands of the aerobic intervention are suited for a controlled trial, but may not be well-tolerated in less structured, less supervised population-based studies."

Nursing Homes Overuse Antipsychotics

By Nancy Walsh, Contributing Writer, MedPage Today
Published: January 11, 2010
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner 

In 2006, a year after the FDA issued mortality warnings about prescribing antipsychotic drugs for the elderly, nearly 30% of nursing home residents received the medication -- despite the fact that a third of them had no indication for the drugs, a study revealed. In nursing homes where rates of antipsychotic drug use were highest, residents had a risk ratio of 1.37 (95% CI 1.24 to 1.51) for receiving at least one of them, compared with facilities where rates of prescribing were low, according to Yong Chen, MD, of the University of Massachusetts Medical School in Worcester, and colleagues.
This elevated risk associated with facility-level prescribing was seen for patients with dementia but no psychosis (RR 1.40, 95% CI 1.23 to 1.59), and in residents with neither psychosis nor dementia (RR 1.54, 95% CI 1.24 to 1.91), the researchers reported in the Jan. 11 Archives of Internal Medicine.
An unrelated study, also released today, indicated that office-based physicians were in fact cutting back on prescription of antipsychotics for dementia as a result of FDA warnings.
Recent research suggest that there's wide variation in use of antipsychotics among facilities, reflecting what the authors of the current study called "an institutional prescribing culture."
Previous work had suggested that facility-level factors contributed to this effect in Canada, but the extent to which these factors exist in the U.S. has been unclear.
So Chen and colleagues assessed a nationwide, cross-sectional sample of 16,586 U.S. residents newly admitted to 1,257 nursing homes.
The nursing homes were categorized into quintiles according to their rates of antipsychotic use, with prescribing rates in the previous year ranging from zero to 24.4% in quintile one to 43.8% to 100% in quintile five.
The sample included 972 patients with psychosis, 6,188 patients with dementia but no psychosis, and 9,426 with neither dementia nor psychosis.
Among residents with psychosis, 74.8% received at least one antipsychotic, as did 41.1% of those with dementia but no psychosis, and 16.4% of those with neither condition.
Compared with residents in quintile five facilities, those in quintile one were more likely to be:

• Older (>75 years, 75% versus 59%, P<0.001)
• Women (69.4% versus 60.9%, P<0.001)
• White (85% versus 71.9%, P<0.001)

Residents in quintile one also were more likely to be frail, as determined by the Changes in Health, End-stage disease and Symptoms and Signs (CHESS) score of 3 or higher (24.7% versus 14%, P<0.001), than those in quintile five.
They also had better Cognitive Performance Scale scores of 0 or 1 (39.2% versus 31.4%, P<0.001).
Conversely, compared with patients in quintile one nursing homes, those in quintile five facilities were more likely to have:

• Moderate or severe behavioral problems (23.5% versus 12.6%, P<0.001)
• Dementia (52.3% versus 41.4%, P<0.001)
• Psychosis (10.3% versus 4%, P<0.001)

Residents in quintile five had twice the unadjusted risk ratio of receiving antipsychotics compared with those in quintile one (RR 2, 95% CI 1.78 to 2.24), although this was reduced to 1.37 after adjusting for demographics, health status, and potential indication for antipsychotics.
When the investigators looked at individual patient characteristics, they found that antipsychotic medication users were:

• Younger (≤65, 13.7% versus 10.2%, P<0.001)
• Male (37.6% versus 34.1%, P<0.001)
• Less frail (CHESS score 0, 24.9% versus 17.6%, P<0.001)

Antipsychotic users also tended to have:

• Moderate and severe behavioral problems (32.3% versus 8.9%, P<0.001)
• Dementia (68.8% versus 36.9%, P<0.001)
• Psychosis (15.1% versus 2.1%, P<0.001)

The study confirms the existence of facility-level variation in prescribing, with the likelihood of a new resident being given an antipsychotic medication being "strongly and independently related to the facility-level antipsychotic prescribing rate, even after adjustment for clinical and sociodemographic characteristics," the investigators wrote.
Only a small proportion of residents receiving the drugs had diagnoses of schizophrenia, bipolar disorder, or aggressive behavioral symptoms of dementia, which suggests that managing behavioral problems is an important component of facility-level decisions regarding antipsychotic medication use.
The study also suggests that organizational culture plays an important role in medication prescribing in nursing homes, because in these settings, prescribing decisions often are made without direct contact between the prescriber and the patient.
Among the limitations of the study were its cross-sectional design, which precludes conclusions about causality, and the use of a sole data source: a single long-term-care pharmacy provider. They also pointed out that "we have excluded NHs with fewer than five residents. . . . and we further excluded short-stay residents because of their distinct characteristics from long-stay residents. Limiting our study sample therefore prevents us from extending the interpretation of our findings to smaller facilities."
They further pointed out that the "prevalence of psychoses in our sample was lower compared with that found in another study using medical records. Thus, we may have underestimated the prevalence of psychoses in this sample."
The investigators concluded that "safety concerns continue to persist in the use of antipsychotic medications in [nursing home] residents whose benefits from these agents are unclear."
They called for further research to clarify why this prescribing culture exists and to determine whether there are adverse health consequences for patients.