Many see cardiovascular disease as primarily a disease of men and the elderly, but the truth is cardiovascular disease, our nation’s leading killer, is an equal opportunity stalker. It’s the No. 1 killer of men and women of all racial and ethnic backgrounds. And it often strikes people in the prime of their life.
Cardiovascular disease refers to diseases and conditions affecting the heart and blood vessels, principally high blood pressure, heart disease and stroke. About 960,000 Americans die from cardiovascular disease each year, accounting for more than 40 percent of all deaths.
However, as the Centers for Disease Control reports, “A consideration of deaths alone severely underestimates the burden of cardiovascular disease. About 58 million Americans (almost one-fourth the population) live with some form of this disease. Heart disease is the leading cause of permanent disability among working adults. Stroke alone accounts for disability among more than 1 million people nationwide. Among the 6 million hospitalizations each year attributed to cardiovascular disease, congestive heart failure is the single most frequent cause for people aged 65 years or older.
The estimated cost of cardiovascular disease in the United States in 1999 was $287 billion. This figure includes health expenditures and lost productivity resulting from illness and death. The use of expensive treatments such as drugs and surgical procedures, while often effective in delaying death, is likely to continue to increase the financial impact of this disease on the nation.
The clinical laboratory’s role in all this is to help clinicians in diagnosing cardiovascular disease as early as possible in all patients and especially those at high risk for acute cardiac events. With that information, physicians can help their patients choose the best course of therapy whether it’s lifestyle changes, medication or both. Researchers continue their work to find a cure but until they do, it’s fruits, vegetables, exercise and cardiac markers to the rescue. — Coleen Curran
Molecule key to cellular quality control
New research at the University of North Carolina, Chapel Hill, points to a key role played by a molecular probe in the way body cells maintain quality control when under stress.
The findings, published in the January issue of Nature Cell Biology, add new insights into molecular changes involved in heart attack, heart failure stroke and some common neurological disorders.
They also add important new knowledge to a fundamental biological problem — how do cells decide to deal with proteins with improperly folded structures, whether to spend time and energy trying to fix them or whether to rapidly get rid of them?
“If you have proteins that become misfolded, they do two things. One, they stick together. Two, they accumulate. And this is the bad thing because there are a lot of diseases that we now understand as misfolded protein accumulations,” said cardiologist Cam Patterson, M.D., associate professor of medicine at UNC-CH School of Medicine and director of the Program in Molecular Cardiology.
“Many of these neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease — these are all neurological diseases in which the primary pathology is an accumulation of misfolded proteins. But we’re now beginning to appreciate that in the hear, under stressful condition, misfolded proteins also accumulate and that it impairs cardiac function,”
In previous research, Patterson and his colleagues sought genes that might regulate the way myocardium (heart muscle) responds to stress. Last year, they were the first to clone the gene CHIP, whose protein apparently blocked the folding activity of other molecules known as heat shock proteins. “Heat shock proteins also make sure the protein ends up in the right place in the cell where it does what it’s supposed to do,” Patterson explained.
The study team hypothesized that CHIP is the protein co-chaperone that makes this triage decision. It apparently provides a direct molecular link between the protein folding and degradation pathway.
“Speaking from my perspective as a cardiovascular biologist and cardiologist, this provides us with an entirely new stress-response system to look at, another molecular pathway we can try to modulate to provide protection to cells during conditions where they’re being stressed,” Patterson said. “We don’t know enough about the system to describe exactly how we would modulate it right now. There is a lot more work to be done. We do have a promising pathway, one that’s of particular importance for diseases of the myocardium.”
Sprinter’s secret weapon helps failing hearts
The same protein that helped Maurice Greene become the “world’s fastest man” at this summer’s Olympic Games could one day help millions of Americans, who suffer from a common type of progressive heart failure.
This protein, parvalbumin, helps skeletal muscle fibers in the arms and legs contract and relax rapidly and efficiently, according to a new animal study by scientists at the University of Michigan Medical School. Olympic sprinters have high levels of parvalbumin in their skeletal muscle, which explain why they can run faster than the rest of us, according to Joseph M. Metzger, Ph.D., associate professor of physiology and internal medicine at the U-M Medical School. Parvalbumin works like a sponge helping skeletal muscle cells relax faster by soaking up calcium ions.
In a recent Journal of Clinical Investigation study, Metzger showed that parvalbumin also can improve heart function in laboratory rats. It restores normal relaxation rates in hearts with a condition that mimics the abnormally slow cardiac relaxation common in human heart failure.
“Although important and challenging scientific obstacles remain, our findings raise the intriguing possibility of one day using parvalbumin therapy to treat progressive heart failure in humans,” Metzger said.
Exacerbated by high-fat diets and not enough exercise, heart failure is a growing medical problem. About 40 percent of the time, heart failure is associated with a condition called diastolic dysfunction where the heart contracts normally, but doesn’t relax fast enough to allow the cardiac chambers to fill with blood before the next contraction.
“In a healthy, living heart all cells work together like an orchestra with one conductor,” Metzger said. “In a heart with diastolic dysfunction, the cells relax too slowly, so the heart pumps inefficiently and the body tissues are starved for oxygen.”
The gene for parvalbumin is found in every cell in the body, but it is not naturally activated or expressed in heart muscle cells. To test the protein’s ability to relax cardiac muscle, researchers used a common adenovirus to deliver human parvalbumin genetic material into heart cells of laboratory rats.
In three experiments, researchers found that:
- When human parvalbumin was injected into the left ventricle of the heart, cardiac relaxation speed was significantly faster than in control animals that did not receive the gene.
- Pressure measurements inside the left ventricle confirmed that rates receiving parvalbumin injections had a much faster relaxation time than control rats.
- Echocardiograms showed that the time interval from aortic valve closure to mitral valve opening in rats receiving parvalbumin was shorter than in control rats.
- Parvalbumin restored normal cardiac relaxation rates in an experimental animal model with the same type of slow relaxation found in human heart failure.
“This was a proof-of-principle short-term study,” Metzger said. “Since adenoviral vectors elicit an immune response after about six days, in animals, they aren’t suitable for this application in humans where parvalbumin must be expressed for long periods of time. There are many new adenoviral-related vectors in development, however, which could be just as effective without provoking an immune response.”
