Depression in seniors linked to low levels of vitamin D

Researchers in Holland have found that older people with low blood levels of vitamin D and high blood levels of the parathyroid hormone are more likely to be depressed.

About 13 percent of older individuals have symptoms of depression, and other researchers have suspected that vitamin D may be linked to depression and other psychiatric illnesses.

The researchers from Vrije Universiteit in Amsterdam say however that it is unclear whether these abnormalities are a cause or a consequence of depression.

Dr. Witte J. G. Hoogendijk and colleagues looked at 1,282 men and women, aged 65 to 95 years, taking part in a long-term study of aging.

They say other research has previously linked altered levels of vitamin D and parathyroid hormone with depression, but the relationship has never been systematically studied.

Their research revealed that almost 40 percent of the men and 57 percent of the women had low levels of vitamin D in their blood and among the 169 people suffering from minor depression, as well as the 26 with major depressive disorder, vitamin D levels were 14 percent lower than for people who were free from depression.

The researchers found that blood levels of the parathyroid hormone, which increase with vitamin D deficiency, were 5 percent higher in people with minor depression and 33 percent higher in those with major depression, relative to levels seen in seniors without depression.

The Dutch team say there are a number of ways that low vitamin D levels could affect mood because the vitamin plays a role in a number of neurological and hormonal processes.

They suggest that if vitamin D deficiency is a cause rather than a result of depression, vitamin supplements and increased exposure to sunlight could help treat the mood disorder.

The researchers say underlying causes of vitamin D deficiency such as less sun exposure as a result of decreased outdoor activity, different housing or clothing habits and decreased vitamin intake may be secondary to depression, but depression may also be the consequence of poor vitamin D status.

They say long-term studies with repeated assessments are needed to explore the question of whether decreased vitamin D levels and increased parathyroid hormone levels precede depression or follow it.

The research is published in the Archives of General Psychiatry, May 2008.

Obesity and heart failure risk

Heart specialists at Johns Hopkins and elsewhere report what is believed to be the first wide-scale evidence linking severe overweight to prolonged inflammation of heart tissue and the subsequent damage leading to failure of the body's blood-pumping organ.

The latest findings from the Multiethnic Study of Atherosclerosis (MESA), to be published in the May 6 issue of the Journal of the American College of Cardiology, appear to nail down yet one more reason for the estimated 72 million obese American adults to be concerned about their health, say scientists who conducted the research.

"The biological effects of obesity on the heart are quite profound," says senior study investigator Jo?Lima, M.D. "Even if obese people feel otherwise healthy, there are measurable and early chemical signs of damage to their heart, beyond the well-known implications for diabetes and high blood pressure."

He adds that there is "now even more reason for them to lose weight, increase their physical activity and improve their eating habits."

In the latest study, researchers conducted tests and tracked the development of heart failure in an ethnically diverse group of nearly 7,000 men and women, age 45 to 84, who were enrolled in the MESA study, starting in 2000.

Of the 79 who have developed congestive heart failure so far, 35 (44 percent) were physically obese, having a body mass index, or BMI, of 30 or greater. And on average, obese participants were found to have higher blood levels of interleukin 6, C-reactive protein and fibrinogen, key immune system proteins involved in inflammation, than non-obese adults.

A near doubling of average interleukin 6 levels alone accounted for an 84 percent greater risk of developing heart failure in the study population.

The researchers from five universities across the United States also found alarming links between inflammation and the dangerous mix of heart disease risk factors known as the metabolic syndrome. Its combined risk factors for heart disease and diabetes - high blood pressure, elevated blood glucose levels, excess abdominal fat and abnormal cholesterol levels, and particularly obesity - double a person's chances of developing heart failure.

"More practically, physicians need to monitor their obese patients for early signs of inflammation in the heart and to use this information in determining how aggressively to treat the condition," says Lima, a professor of medicine and radiology at the Johns Hopkins University School of Medicine and its Heart Institute.

All MESA study participants, who will be followed through to 2012, had no pre-existing symptoms of heart disease. Upon enrollment, they all underwent a physical exam, including weight and body measurements, blood analysis and an MRI scan to assess heart function.

"Our results showed that when the effects of other known disease risk factors - including race, age, sex, diabetes, high blood pressure, smoking, family history and blood cholesterol levels - were statistically removed from the analysis, inflammatory chemicals in the blood of obese participants stood out as key predictors of who got heart failure," says Lima.

The chemicals are all known to be part of the body's defensive response to disease. They are well-recognized for producing symptoms that stem from the widening of small blood vessels, including redness and fever, and the release of immune system cells that make blood vessels leak fluid into surrounding tissue, causing swelling and cell death. The inflammatory process eventually leads to cell damage and the buildup of scar tissue near the damaged areas.

In obese participants, interleukin 6, a chemical that activates white blood cells and drives inflammation, was higher than in non-obese participants.

Similarly, a near tripling of average levels of C-reactive protein in study participants increased the chance of heart failure by 36 percent.

C-reactive protein levels are widely known to rise dramatically and speed up the early stages of inflammation when cells swell up with fluid, leading to widespread arterial damage.

One-fifth higher than average blood levels of fibrinogen, best known for its role in blood clotting but also a major player in muscle scarring, bumped up the risk of heart failure by 37 percent.

When the inflammatory protein levels were included in the scientists' statistical analysis, the heightened risk from obesity disappeared.

"What this tells us is that both obesity and the inflammatory markers are closely tied to each other and to heart failure," says lead researcher Hossein Bahrami, M.D., M.P.H.

Each year, nearly 300,000 Americans die from heart failure.

Bahrami says study results also point to inflammation as a possible catalyst in metabolic syndrome. Increased blood levels of albuminuria, a chemical more known for its association with impaired kidney function and metabolic syndrome boosted risk of a progressively weakening heart nearly tenfold among MESA participants.

Bahrami, a senior cardiology research fellow at Hopkins, says "the basic evidence is building the case that inflammation may be the chemical route by which obesity targets the heart, and that inflammation may play an important role in the increased risk of heart failure in obese people, especially those with the metabolic syndrome."

He notes that previous studies, also done at Hopkins, have shown that even moderate exercise to lose abdominal fat dramatically offsets the harmful effects of metabolic syndrome on heart function.

Bahrami says the team's next steps are to determine how, over a longer timeframe, heart function changes with levels of inflammatory markers, and to see if alterations to the immune system proteins halts or speeds up disease.

BMI is calculated from a person's weight and height and serves as a good indicator of overall body fatness (where a person's weight in kilograms is divided by the square of height in meters; or using weight in pounds, divided by the height in inches squared, multiplied by a metric conversion factor of 703.)

MESA is funded by the National Heart, Lung and Blood Institute, a member of the National Institutes of Health.

Besides Lima and Bahrami, other Hopkins investigator involved in this study were David Bluemke, M.D., Ph.D., and Moyses Szklo, M.D., Dr.P.H. Study co-authors were Richard Kronmal, Ph.D., from the University of Washington in Seattle; Alain Bertoni, M.D., M.P.H., from Wake Forest University in Winston-Salem, N.C.; Donald Lloyd-Jones, M.D., Sc.M., from Northwestern University in Chicago; and Eyal Shahar, M.D., M.P.H., from the University of Arizona.

http://www.hopkinsheart.org/ and http://content.onlinejacc.org/

Study identifies new mechanism linking activation of key heart enzyme and oxidative stress

A study, led by University of Iowa researchers, reveals a new dimension for a key heart enzyme and sheds light on an important biological pathway involved in cell death in heart disease.

The study, published in the May 2 issue of Cell, has implications for understanding, and potentially for diagnosing and treating, heart failure and arrhythmias.

The UI researchers and colleagues from Vanderbilt University in Nashville, Tenn., focused on calmodulin kinase II, or CaM kinase II, a well-studied enzyme critical to many fundamental processes including heartbeat and thought.

Scientists know that CaM kinase's activity is sustained by adding a phosphate group -- a process known as phosphorylation. The new study proves that oxidation -- adding oxygen -- also can sustain the enzyme's activity, and like phosphorylation, the mechanism can be reversed to inactivate the kinase.

"Our results suggest that oxidation of CaM kinase is a dynamic and reversible process that may direct cell signaling in health and disease," said Mark Anderson, M.D., Ph.D., UI professor of internal medicine and molecular physiology and biophysics and senior study author. "Because CaM kinase activity is involved in arrhythmias, hypertrophy and heart cell death, this work also provides new insights into a disease pathway in heart that may lead to development of new drugs to treat heart disease."

In patients with heart failure, the level of angiotensin II -- a signaling molecule that promotes oxidation and cell death -- is elevated. Using a specially created antibody, the researchers found that angiotensin II also increases the amount of oxidized CaM kinase.

In addition, by replacing the cell's normal CaM kinase with a CaM kinase unable to be oxidized, the scientists were able to block angiotensin-induced cell death. Scientists hope this discovery might lead to therapies that prevent cell death by blocking CaM kinase oxidation.

Currently, "angiotensin-blockers" are a mainstay for treating patients with sick hearts, but they work indirectly by targeting receptors on the cell surface. Anderson, who also is the Potter-Lambert Chair in Cardiology and director of the UI Division of Cardiovascular Medicine, suggested that by understanding the signaling mechanisms that occur inside the cell, it might be possible to inhibit the angiotensin pathway more directly. This approach may also preserve some of the good effects mediated by the cell surface receptor.

Using a wide range of scientific techniques and experimental methods, the team, led by Anderson and Jeffrey Erickson, Ph.D., a UI postdoctoral fellow, pinned down the details of the internal signaling mechanism.

Specifically, they showed that oxidation of two neighboring methionines -- sulfur-containing amino acids -- can sustain CaM kinase activity. Loss of these two methionines prevents activation by oxidation. They also found that they could return CaM kinase to its inactive state and inhibit heart cell death and dysfunction by using an enzyme called methionine sulfoxide reductase A (msrA), which reverses the methionine oxidation. Studies in worms, fruit flies and mice have shown that msrA increases lifespan, but, until now, the enzyme's targets in heart were unknown.

The UI team compared mice without the msrA enzyme to normal mice when the animals underwent disease stresses, including excess angiotensin or induced heart attacks. The mice without msrA were more likely to die than normal mice under these circumstances, and the levels of oxidized CaM kinase were much higher in mice that lacked the enzyme.

Anderson speculated that the findings could implicate msrA as a susceptibility gene for patients - potentially, variations in the gene might help explain why some people do so badly after a heart attack where others do well.

The study demonstrates a direct link between CaM kinase activation and oxidative stress, two processes that are implicated in a wide variety of physiological and disease states. These findings will likely have broad implications and applications in basic research, diagnostics and new therapeutic approaches and represent an example of translation science of the type supported and encouraged by the new Institute for Clinical and Translational Science at the UI.

"This study also is a great example of collaborative science," added Anderson. "We had to apply expertise from several different labs to tackle this problem. So, the ease with which we can collaborate across disciplines at the UI and between institutions was enormously beneficial."

The work involved researchers from the UI Roy J. and Lucille A. Carver College of Medicine's Departments of Internal Medicine, Radiation Oncology and Biochemistry; and Vanderbilt University.

In addition to Anderson and Erickson, the UI researchers included Peter Mohler, Ph.D., assistant professor of internal medicine; Douglas Spitz, Ph.D., professor of radiation oncology in the Free Radical and Radiation Biology Graduate Program; Robert Weiss, M.D., professor of internal medicine; Madeline Shea, Ph.D., professor of biochemistry; Mei-ling Joiner, Xiaoqun Guan, Ph.D.; William Kutschke; Jinying Yang; John Lowe; Susan O'Donnell; Nukhet Aykin-Burns, Ph.D.; Matthew Zimmerman, Ph.D.; and Kathy Zimmerman.

The researchers from Vanderbilt University included, Carmine Oddis, M.D.; Ryan Bartlett, Ph.D.; Amy-Joan Ham, Ph.D.; and Roger Colbran, Ph.D.

The study was funded in part by the National Institutes of Health, the Pew Charitable Trust and the UI Research Foundation.

http://www.uiowa.edu/

Short and long sleepers more likely to have metabolic syndrome

A study published in the May 1 issue of the journal SLEEP is the first known to report that short and long sleepers are more likely to have metabolic syndrome, or a combination of medical disorders that increase the risk of developing cardiovascular disease.

The study, authored by Martica H. Hall, PhD, associate professor of psychiatry at the University of Pittsburgh School of Medicine, and colleagues, focused on 1,214 adults between 30-54 years of age.

According to the results, the odds for having the metabolic syndrome increased by more than 45 percent in both short and long sleepers. Short sleep duration was common, with 20 percent of the sample reporting sleep durations of less than six hours per night. In contrast, only eight percent of the sample reported sleep durations of longer than eight hours per night.

"This relationship was strongest in the group of men and women who slept less than six hours per night. On average, the odds of having the metabolic syndrome were nearly doubled in men and women who slept less than six hours, compared to those who slept between seven and eight hours per night," said Dr. Hall.

Experts recommend that adults get between seven and eight hours of nightly sleep.

The American Academy of Sleep Medicine (AASM) offers the following tips on how to get a good night's sleep:

• Follow a consistent bedtime routine.
• Establish a relaxing setting at bedtime.
• Get a full night's sleep every night.
• Avoid foods or drinks that contain caffeine, as well as any medicine that has a stimulant, prior to bedtime.
• Do not bring your worries to bed with you.
• Do not go to bed hungry, but don't eat a big meal before bedtime either.
• Avoid any rigorous exercise within six hours of your bedtime.
• Make your bedroom quiet, dark and a little bit cool.
• Get up at the same time every morning.

Those who suspect that they might be suffering from a sleep disorder are encouraged to consult with their primary care physician or a sleep specialist.

SLEEP is the official journal of the Associated Professional Sleep Societies, LLC, a joint venture of the AASM and the Sleep Research Society.

SleepEducation.com, a patient education Web site created by the AASM, provides information about various sleep disorders, the forms of treatment available, recent news on the topic of sleep, sleep studies that have been conducted and a listing of sleep facilities.

http://www.aasmnet.org/