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, to be published May 6 in 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," said senior study
investigator Joao Lima. "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."
Lima said 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, ages 45 to 84, who were enrolled in the
MESA study that started in 2000.
Of the 79 who have developed congestive heart failure
so far, 35 (44 percent) were physically
obese, having a body mass index 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 nonobese 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, 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," said Lima, a professor of medicine and
radiology at the Johns Hopkins 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," Lima
said.
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 nonobese 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 scientists removed the effects of the
inflammatory protein levels from their
statistical analysis, the heightened risk from obesity
disappeared.
"What this tells us," said lead researcher Hossein
Bahrami, "is that both obesity and the
inflammatory markers are closely tied to each other and to
heart failure."
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 Johns
Hopkins, said, "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 Johns
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.
MESA is funded by the National Heart, Lung and Blood
Institute, a member of the National
Institutes of Health.
Other Johns Hopkins investigators involved in this
study were David Bluemke and Moyses Szklo.
Co-authors were Richard Kronmal, University of Washington;
Alain Bertoni, Wake Forest University;
Donald Lloyd-Jones, Northwestern University; and Eyal
Shahar, University of Arizona.
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