Inflammation may be a More Powerful Predictor of a Cardiovascular Event

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Inflammation may be a more powerful predictor of cardiovascular

trouble in women than unfavorable cholesterol levels, according to

new research. A large study conducted by Harvard scientists found

that women with high blood levels

of an inflammatory marker called C-reactive protein (CRP) face a

greater riskfor heart attack and stroke than women with high

cholesterol. Many of the women with high CRP levels had normal

cholesterol, which suggests that cholesterol testing alone does not

fully reveal which women are at risk.

 

The study also establishes the levels of CRP,as measured by an

inexpensive but highly sensitive blood test that correlates with

low, moderate, and high risk for a cardiovascular event.

As we go to press, a panel of health experts is considering the pros

and cons of routine CRP testing.

 

An important question remains unanswered: Although we

know that an elevated CRP is a sign of trouble, will reducing it

help lower cardiovascular risk and save lives?

While we wait for more information, there are several proven steps

that you can take to lessen your heart disease risk.

Not surprisingly, some have been shown to lower CRP levels.

 

Advances in understanding heart disease Some 15 years ago, health

experts began to entertain the idea that inflammation plays a role

in heart disease. Inflammation activates the immune system and is an

important part of the body's healing process. But it can go awry,

and may

injure tissue instead of helping to repair it. The inflammation

hypothesis was attractive because about half of all heart attacks

and strokes occur in people with normal cholesterol and blood

pressure.

 

We now know that atherosclerosis,the narrowing of coronary blood

vessels by fatty buildup, or plaque — is more than just an arterial

plumbing problem.

Inflammation, triggered by infection or irritation, accelerates

plaque formation and leaves plaques more vulnerable to the ruptures

that cause heart attack and stroke.

 

It also makes plaque surfaces stickier, allowing substances

that contribute to artery-clogging clots to latch on more easily.

C-reactive protein (CRP) levels and cardiovascular risk*CRP in

milligrams per liter (mg/L)

 

Level of cardiovascular risk

Less than 0.5 mg/L

 

Lowest

 

Less than 1 mg/L

 

Low

 

1–3 mg/L

 

Moderate

 

Greater than 3 mg/L

 

High (risk doubles)

 

* In men and women, independent of cholesterol levels

 

Source: Paul M. Ridker, M.D., Brigham and Women's Hospital, Boston

 

Until recently, researchers thought that CRP was merely a sign of

inflammation,not a direct player. Now, they suspect that CRP

activates changes that promote inflammation in coronary arteries.

 

Largest CRP study in women-

Several studies have linked elevated CRP to cardiovascular risk in

women, but the latest findings, published in the November 14, 2002,

New England Journal of Medicine, offer what may be the strongest

evidence yet.

 

Harvard Professor of Medicine Paul Ridker, M.D., and colleagues at

Boston's Brigham and Women's Hospital analyzed data collected from

nearly 28,000 women who were followed for eight years as part of the

Women's Health Study.

 

The researchers compared CRP and LDL cholesterol ( " bad cholesterol " )

levels, correlating them with cardiovascular events and death from

cardiovascular causes.

 

After accounting for factors such as age, smoking status, diabetes,

and hormoneuse, researchers found that 77% of all events took place

in women with LDL cholesterol levels below 160 mg/dL. Almost half

occurred in women with what is considered optimal or near-optimal

LDL, that is, below 130 mg/dL. Women with high CRP were about twice

as likely as those with high cholesterolto die from a heart attack

or stroke. Further, women with low cholesterol buthigh CRP were at

greater risk than those with high cholesterol and low CRP.

 

Questions remain-

 

Because no one knows yet whether lowering CRP will actually decrease

the incidence of cardiovascular disease, some clinicians are

skeptical aboutwidespread CRP testing. This spring, Brigham and

Women's researchers led by Dr.Ridker will begin a major effort to

settle the question.

 

They plan to enroll 15,000 men and women nationwide in a study

comparingrosuvastatin, a cholesterol-lowering drug not yet approved

for use in theUnited States, to a placebo. The trial will include

women over 60 and men over 55 who have low LDL (less than 130

mg/dL), elevated CRP (greater than 2 mg/L),and no apparent heart

disease.

 

Researchers would also like to know how to adjust for factors that

can interfere with the predictive ability of the CRP test. CRP

measures inflammation anywhere in the body, so anything that affects

inflammation, whether related to heart disease or not, can alter the

results.

 

That includes illness, infection, smoking, and injury, which raise

CRP, and the use ofanti-inflammatory agents such as aspirin, which

may lower it.

 

Timeline: Understanding CRP's role in women's heart disease risk

1998 Results from Harvard's Women's Health Study show that women

with high levels of CRP are more likely to have a heart attack than

women with low levels(Circulation, August 25, 1998).

 

2000 Harvard Medical School researchers show that high-sensitivity

CRP testingis a better indicator of heart attack risk in women than

measures of total cholesterol,

LDL, homocysteine, or lipoprotein (a)

(New England Journal of Medicine, March 23, 2000).

 

2002 University of Vermont researchers find that weight loss lowers

CRP inobese women (Circulation, Feb. 5, 2002).

 

In the Framingham Heart Study, higher body mass index is found to

correlate with higher CRP in women (Circulation,Sept. 3, 2002).

 

Once these concerns are addressed, high-sensitivity CRP testing may

eventually be performed routinely, along with cholesterol screening.

For now, doctors may want to test only people who are at risk for

heart disease due to factors other than cholesterol,

such as family history, high blood pressure, obesity, ordiabetes.

 

Perhaps more important, testing might identify more people who would

benefit from lifestyle strategies that reduce cardiovascular risk.

 

What should you do?

Women who have normal cholesterol levels but are otherwise at risk

for heart disease may want to ask their doctors about high-

sensitivity CRP testing. If a woman's CRP is high, her doctor may

recommend changes such as these:

 

Exercise 30 minutes per day on most days of the week. Several

studies have shown a strong correlation between CRP levels and

exercise. For example, data from a study of 14,000 men and women

participating in the ongoing NationalHealth and Nutrition

Examination Survey indicate that CRP drops with increased

physical activity.

 

In this study, vigorous exercisers had the lowest CRP.

 

Maintain a healthy weight. Fat cells produce substances that cause

inflammation and raise CRP. CRP rises with increasing body mass

index (weight-height ratio). Researchers have also found that losing

weight can reduce CRP.

 

Don't smoke, actively or passively. Smoking can irritate blood

vessels, causing inflammation and elevating CRP. It is the most

potent heart diseaserisk factor, raising risk by 250%. Even exposure

to other people's smoke is risky, contributing to 50,000 premature

deaths each year.