Heart Hormone Paradox: The Curious Case of Adiponectin

What is the Goldilocks principle?

It refers to an amount that's not too much, not too little, but just right. Take alcohol: Moderate drinkers live longer than teetotalers or those who drink to excess. Other examples include salt, exercise, body weight and—as described at left—adiponectin levels in older people. Sometimes, the middle of the road is the place to be.

Why do some people have heart attacks while others don't? A major culprit is the highly individualized pattern of fat buildup in our blood vessels— the result of what we eat, what we do and our personal palette of body chemicals governing fat buildup (plaque). One of these signature substances is adiponectin, a bioactive hormone that our fat cells secrete into the bloodstream.

This article originally appeared in the spring/summer 2014 issue of the Wilf Family Cardiovascular Research Newsletter.In animals, adiponectin inhibits plaque formation in arteries, helps hold down inflammation in blood vessel walls and also boosts insulin sensitivity (helping clear vessel-damaging sugars from the blood).

Earlier studies had shown that in younger people, a high adiponectin level was a sign of overall good health. In 2004, for example, a major epidemiology study linked high levels of adiponectin to reduced heart-attack risk in healthy middle-aged men. Soon adiponectin was viewed as a biological marker of good cardiovascular health for everyone.

So in 2008, Einstein's Dr. Jorge Kizer received a surprise after seeing the results of his analyses of nearly 1,400 elderly people participating in the National Institutes of Health–funded Cardiovascular Health Study. He noticed that those with the highest adiponectin levels had higher rates of heart disease than people with lower levels. Soon Dr. Kizer, director of clinical cardiovascular research in Einstein's department of medicine, found himself drawn into the scientific debate dubbed the "adiponectin paradox."

Good or Bad?

Dr. Kizer studies molecules that influence cardiovascular health.These findings led Dr. Kizer and colleagues to pursue an investigation in the Cardiovascular Health Study cohort, where adiponectin was measured in almost 4,800 participants. This follow-up study was the largest to date examining the relationship between adiponectin and fatal events in older men and women (65 to 100 years old). The findings suggested an ideal level of adiponectin—not too high, not too low—for elderly people with no cardiovascular disease, heart failure or atrial fibrillation (irregular heartbeat).

"The highest risk of death was associated with the highest and lowest blood levels of adiponectin, while those in the middle had the lowest risk of death," explains Dr. Kizer, an associate professor of medicine (cardiology) and of epidemiology & population health.

Further findings added a twist to the curious case of adiponectin: in older people with heart failure or atrial fibrillation, only the highest levels were dangerous.

It turns out that in older people, increases in adiponectin reflect generally worsening health. Levels rise after a heart attack or as heart failure develops and also following other physical insults, including unintentional weight loss, muscle wasting and declining kidney function. "The sicker you are, the stronger the association between high adiponectin levels and risk of dying," says Dr. Kizer.

The adiponectin story highlights the complex ways in which biological molecules can act as markers and determinants of disease. Dr. Kizer and others will continue to research adiponectin's mechanisms—and what they mean for health as we age.