C-Reactive Protein

[Guest guest]

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 risk for

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 correlate 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? We do know that cholesterol-lowering drugs

called statins can reduce CRP and that aspirin appears to help prevent

cardiovascular disease in people with high CRP.

 

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 hormone

use, 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 cholesterol to

die from a heart attack or stroke. Further, women with low cholesterol but high

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 about

widespread 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 comparing

rosuvastatin, a cholesterol-lowering drug not yet approved for use in the United

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 of anti-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 testing

is 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).

 

2001 In a controlled trial, Harvard Medical School researchers find that

lovastatin reduces blood levels of CRP as well as heart attack risk in nearly

6,000 women and men who had neither high cholesterol nor known heart disease

(New England Journal of Medicine, June 28, 2001).

 

2002 University of Vermont researchers find that weight loss lowers CRP in obese

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, or

diabetes.

 

Widely accepted, testing could lead to a greater use of statins, which lower not

only LDL cholesterol but also CRP. 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 National

Health 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 (see Timeline, above).

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

causing inflammation and elevating CRP. It is the most potent heart disease risk

factor, raising risk by 250%. Even exposure to other people’s smoke is risky,

contributing to 50,000 premature deaths each year.

 

 

 

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