Long-Term Interleukin-6 Levels and Subsequent Risk of Coronary Heart Disease: Two New Prospective Studies and a Systematic Review

The relevance to coronary heart disease (CHD) of cytokines that govern inflammatory cascades, such as interleukin-6 (IL-6), may be underestimated because such mediators are short acting and prone to fluctuations. We evaluated associations of long-term circulating IL-6 levels with CHD risk (defined a...

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Vydané v:PLoS medicine Ročník 5; číslo 4; s. e78
Hlavní autori: Danesh, John, Kaptoge, Stephen, Mann, Andrea G, Sarwar, Nadeem, Wood, Angela, Angleman, Sara B, Wensley, Frances, Higgins, Julian P. T, Lennon, Lucy, Eiriksdottir, Gudny, Rumley, Ann, Whincup, Peter H, Lowe, Gordon D. O, Gudnason, Vilmundur
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States Public Library of Science 01.04.2008
Public Library of Science (PLoS)
Predmet:
Atherosclerosis
Blood pressure
Cardiovascular disease
Cardiovascular Disorders
Cardiovascular Medicine
Cholesterol
Cohort Studies
Confidence intervals
Coronary Disease - diagnosis
Coronary Disease - etiology
Coronary Disease - immunology
Cytokines
Female
Heart attacks
Humans
Inflammation
Interleukin-6 - blood
Ischemic Heart Disease
Male
Middle Aged
Prospective Studies
Risk Factors
Systematic review
Veins & arteries
United States > US
Prospective Studies
Coronary Disease
Humans
Middle Aged
Risk Factors
Female
Male
Inflammation
Cohort Studies
Interleukin-6
ISSN:1549-1676, 1549-1277, 1549-1676
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Shrnutí:The relevance to coronary heart disease (CHD) of cytokines that govern inflammatory cascades, such as interleukin-6 (IL-6), may be underestimated because such mediators are short acting and prone to fluctuations. We evaluated associations of long-term circulating IL-6 levels with CHD risk (defined as nonfatal myocardial infarction [MI] or fatal CHD) in two population-based cohorts, involving serial measurements to enable correction for within-person variability. We updated a systematic review to put the new findings in context. Measurements were made in samples obtained at baseline from 2,138 patients who had a first-ever nonfatal MI or died of CHD during follow-up, and from 4,267 controls in two cohorts comprising 24,230 participants. Correction for within-person variability was made using data from repeat measurements taken several years apart in several hundred participants. The year-to-year variability of IL-6 values within individuals was relatively high (regression dilution ratios of 0.41, 95% confidence interval [CI] 0.28-0.53, over 4 y, and 0.35, 95% CI 0.23-0.48, over 12 y). Ignoring this variability, we found an odds ratio for CHD, adjusted for several established risk factors, of 1.46 (95% CI 1.29-1.65) per 2 standard deviation (SD) increase of baseline IL-6 values, similar to that for baseline C-reactive protein. After correction for within-person variability, the odds ratio for CHD was 2.14 (95% CI 1.45-3.15) with long-term average ("usual") IL-6, similar to those for some established risk factors. Increasing IL-6 levels were associated with progressively increasing CHD risk. An updated systematic review of electronic databases and other sources identified 15 relevant previous population-based prospective studies of IL-6 and clinical coronary outcomes (i.e., MI or coronary death). Including the two current studies, the 17 available prospective studies gave a combined odds ratio of 1.61 (95% CI 1.42-1.83) per 2 SD increase in baseline IL-6 (corresponding to an odds ratio of 3.34 [95% CI 2.45-4.56] per 2 SD increase in usual [long-term average] IL-6 levels). Long-term IL-6 levels are associated with CHD risk about as strongly as are some major established risk factors, but causality remains uncertain. These findings highlight the potential relevance of IL-6-mediated pathways to CHD.
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ISSN:1549-1676
1549-1277
1549-1676
DOI:10.1371/journal.pmed.0050078