Are Markers of Inflammation More Strongly Associated with Risk for Fatal Than for Nonfatal Vascular Events?

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Citation: Naveed Sattar, Heather M. Murray, Paul Welsh, Gerard J. Blauw, Brendan M. Buckley, Stuart Cobbe, Anton J. M. de Craen, Gordon D. Lowe, J. Wouter Jukema, Peter W. Macfarlane, Michael B. Murphy, David J. Stott, Rudi G. J. Westendorp, James Shepherd, Ian Ford, Chris J. Packard (06/2009) Are Markers of Inflammation More Strongly Associated with Risk for Fatal Than for Nonfatal Vascular Events?. PLoS Med (Volume 6) (RSS)

doi: 10.1371/journal.pmed.1000099

Download: http://dx.doi.org/10.1371%2Fjournal.pmed.1000099

Tagged: Medicine (RSS)


Summary:

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Background

Cardiovascular disease (CVD)—disease that affects the heart and/or the blood vessels—is a common cause of death in developed countries. In the USA, for example, the leading cause of death is coronary heart disease (CHD), a CVD in which narrowing of the heart's blood vessels by “atherosclerotic plaques” (fatty deposits that build up with age) slows the blood supply to the heart and may eventually cause a heart attack (myocardial infarction). Other types of CVD include stroke (in which atherosclerotic plaques interrupt the brain's blood supply) and heart failure (a condition in which the heart cannot pump enough blood to the rest of the body). Smoking, high blood pressure, high blood levels of cholesterol (a type of fat), having diabetes, and being overweight all increase a person's risk of developing CVD. Tools such as the “Framingham risk calculator” take these and other risk factors into account to assess an individual's overall risk of CVD, which can be reduced by taking drugs to reduce blood pressure or cholesterol levels (for example, pravastatin) and by making lifestyle changes.

Why Was This Study Done?

Inflammation (an immune response to injury) in the walls of blood vessels is thought to play a role in the development of atherosclerotic plaques. Consistent with this idea, several epidemiological studies (investigations of the causes and distribution of disease in populations) have shown that people with high circulating levels of markers of inflammation such as interleukin-6 (IL-6), C-reactive protein (CRP), and fibrinogen are more likely to have a stroke or a heart attack (a CVD event) than people with low levels of these markers. Although these studies have generally lumped together fatal and nonfatal CVD events, some evidence suggests that circulating inflammatory markers may be more strongly associated with fatal than with nonfatal CVD events. If this is the case, the mechanisms that lead to fatal and nonfatal CVD events may be subtly different and knowing about these differences could improve both the prevention and treatment of CVD. In this study, the researchers investigate this possibility using data collected in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER; a trial that examined pravastatin's effect on CVD development among 70–82 year olds with pre-existing CVD or an increased risk of CVD because of smoking, high blood pressure, or diabetes).

What Did the Researchers Do and Find?

The researchers used several statistical models to examine the association between baseline levels of IL-6, CRP, and fibrinogen in the trial participants and nonfatal CVD events (nonfatal heart attacks and nonfatal strokes), fatal CVD events, death from other types of CVD, and deaths from other causes during 3.2 years of follow-up. Increased levels of all three inflammatory markers were more strongly associated with fatal CVD than with nonfatal CVD after adjustment for treatment allocation and for other established CVD risk factors but this pattern was strongest for IL-6. Thus, a unit increase in the log of IL-6 levels increased the risk of fatal CVD by half but increased the risk of nonfatal CVD by significantly less. The researchers also investigated whether including these inflammatory markers in tools designed to predict an individual's CVD risk could improve the tool's ability to distinguish between individuals with a high and low risk. The addition of IL-6 to established risk factors, they report, increased this discriminatory ability for fatal CVD but not for nonfatal CVD.

What Do These Findings Mean?

These findings indicate that, at least for the elderly at-risk patients who were included in PROSPER, inflammatory markers are more strongly associated with the risk of a fatal heart attack or stroke than with nonfatal CVD events. These findings need to be confirmed in younger populations and larger studies also need to be done to discover whether the same association holds when fatal heart attacks and fatal strokes are considered separately. Nevertheless, the present findings suggest that inflammation may specifically help to promote the development of serious, potentially fatal CVD and should stimulate improved research into the use of inflammation markers to predict risk of deaths from CVD.

Theoretical and practical relevance:

This study may bring a better understanding of risk factors for heart attacks and strokes.

The original author of this summary is PLOS Medicine. It is republished on AcaWiki under the Creative Commons Attribution license. http://www.plosmedicine.org/

This was published in an open access journal.