HEALTH NEWS

Study Title:

Inflammation and Heart Attacks

Study Abstract

Background
Circulating inflammatory markers may more strongly relate to risk of fatal versus nonfatal cardiovascular disease (CVD) events, but robust prospective evidence is lacking. We tested whether interleukin (IL)-6, C-reactive protein (CRP), and fibrinogen more strongly associate with fatal compared to nonfatal myocardial infarction (MI) and stroke.

Methods and Findings
In the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), baseline inflammatory markers in up to 5,680 men and women aged 70–82 y were related to risk for endpoints; nonfatal CVD (i.e., nonfatal MI and nonfatal stroke [n = 672]), fatal CVD (n = 190), death from other CV causes (n = 38), and non-CVD mortality (n = 300), over 3.2-y follow-up. Elevations in baseline IL-6 levels were significantly (p = 0.0009; competing risks model analysis) more strongly associated with fatal CVD (hazard ratio [HR] for 1 log unit increase in IL-6 1.75, 95% confidence interval [CI] 1.44–2.12) than with risk of nonfatal CVD (1.17, 95% CI 1.04–1.31), in analyses adjusted for treatment allocation. The findings were consistent in a fully adjusted model. These broad trends were similar for CRP and, to a lesser extent, for fibrinogen. The results were also similar in placebo and statin recipients (i.e., no interaction). The C-statistic for fatal CVD using traditional risk factors was significantly (+0.017; p<0.0001) improved by inclusion of IL-6 but not so for nonfatal CVD events (p = 0.20).

Conclusions
In PROSPER, inflammatory markers, in particular IL-6 and CRP, are more strongly associated with risk of fatal vascular events than nonfatal vascular events. These novel observations may have important implications for better understanding aetiology of CVD mortality, and have potential clinical relevance.

From press release:

A new study shows that for elderly people at risk of cardiovascular disease, the presence of inflammatory markers in the blood can identify that an individual is at a higher risk of a fatal rather than a non-fatal heart attack or stroke.

Inflammation is an immune response to injury. However, inflammation is also thought to play a role in cardiovascular disease. Previous studies have shown an association between high levels of markers of inflammation in the circulation with a greater risk of a cardiovascular event, such as a heart attack or stroke. In this study, Naveed Sattar of the University of Glasgow and colleagues used data from an existing trial known as PROSPER (the Prospective Study of Pravastatin in the Elderly at Risk), which involved participants aged between 70 and 82 who had or were at risk of cardiovascular disease.

They examined if three inflammatory markers—interleukin-6 (IL-6), C-reactive protein (CRP) and fibrinogen—were each more strongly massociated with fatal cardiovascular events than with non-fatal cardiovascular events in the period of over three years in which the patients in the trial were monitored.

Using several statistical models, the researchers found that in this group of elderly patients increased levels of all three inflammatory markers, and in particular IL-6, were more strongly associated with a fatal heart attack or stroke than with a non-fatal heart attack or stroke. They also investigated the predictive value of these inflammatory markers—in other words, whether it was useful to include these markers in tools designed to distinguish between individuals with a high and a low risk of heart attacks, strokes and other cardiovascular events.

They report that adding IL-6 to the established risk factors in predictive tools—including lifestyle factors such as smoking, high blood pressure and high blood cholesterol, all of which greatly increase the risk of cardiovascular disease—could help better identify those individuals at a risk of a fatal stroke or heart attack, but not those at risk of a non-fatal cardiovascular event.

The findings of the study suggest inflammatory markers may be more strongly associated with fatal heart attacks and strokes than non-fatal cardiovascular events. The researchers acknowledge that these findings now need to be confirmed in younger populations and larger studies to demonstrate an outright association and the design of the current study cannot show whether the proposed association is a causal one. Nevertheless, the findings should stimulate further investigation into whether the application of inflammatory markers may help better predict the risk of deaths from cardiovascular disease, and whether novel treatments which dampen inflammation might help prolong life.

Study Information

Sattar N, Murray HM, Welsh P, Blauw GJ, Buckley BM, et al.
Are Markers of Inflammation More Strongly Associated with Risk for Fatal Than for Nonfatal Vascular Events?
PLOS
2009 June
Division of Cardiovascular and Medical Sciences, Faculty of Medicine, University of Glasgow, Glasgow, Scotland.