Long-term interleukin-6 levels and subsequent risk of coronary heart disease: two new prospective studies and a systematic review.
<h4>Background</h4>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...
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Public Library of Science (PLoS)
2008
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oai:doaj.org-article:001404b6e23c41e6bbfe7de85d5cc2e62021-12-02T19:55:56ZLong-term interleukin-6 levels and subsequent risk of coronary heart disease: two new prospective studies and a systematic review.1549-12771549-167610.1371/journal.pmed.0050078https://doaj.org/article/001404b6e23c41e6bbfe7de85d5cc2e62008-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18399716/?tool=EBIhttps://doaj.org/toc/1549-1277https://doaj.org/toc/1549-1676<h4>Background</h4>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.<h4>Methods and findings</h4>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).<h4>Conclusions</h4>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.John DaneshStephen KaptogeAndrea G MannNadeem SarwarAngela WoodSara B AnglemanFrances WensleyJulian P T HigginsLucy LennonGudny EiriksdottirAnn RumleyPeter H WhincupGordon D O LoweVilmundur GudnasonPublic Library of Science (PLoS)articleMedicineRENPLoS Medicine, Vol 5, Iss 4, p e78 (2008) |
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EN |
| topic |
Medicine R |
| spellingShingle |
Medicine R John Danesh Stephen Kaptoge Andrea G Mann Nadeem Sarwar Angela Wood Sara B Angleman Frances Wensley Julian P T Higgins Lucy Lennon Gudny Eiriksdottir Ann Rumley Peter H Whincup Gordon D O Lowe Vilmundur Gudnason Long-term interleukin-6 levels and subsequent risk of coronary heart disease: two new prospective studies and a systematic review. |
| description |
<h4>Background</h4>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.<h4>Methods and findings</h4>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).<h4>Conclusions</h4>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. |
| format |
article |
| author |
John Danesh Stephen Kaptoge Andrea G Mann Nadeem Sarwar Angela Wood Sara B Angleman Frances Wensley Julian P T Higgins Lucy Lennon Gudny Eiriksdottir Ann Rumley Peter H Whincup Gordon D O Lowe Vilmundur Gudnason |
| author_facet |
John Danesh Stephen Kaptoge Andrea G Mann Nadeem Sarwar Angela Wood Sara B Angleman Frances Wensley Julian P T Higgins Lucy Lennon Gudny Eiriksdottir Ann Rumley Peter H Whincup Gordon D O Lowe Vilmundur Gudnason |
| author_sort |
John Danesh |
| title |
Long-term interleukin-6 levels and subsequent risk of coronary heart disease: two new prospective studies and a systematic review. |
| title_short |
Long-term interleukin-6 levels and subsequent risk of coronary heart disease: two new prospective studies and a systematic review. |
| title_full |
Long-term interleukin-6 levels and subsequent risk of coronary heart disease: two new prospective studies and a systematic review. |
| title_fullStr |
Long-term interleukin-6 levels and subsequent risk of coronary heart disease: two new prospective studies and a systematic review. |
| title_full_unstemmed |
Long-term interleukin-6 levels and subsequent risk of coronary heart disease: two new prospective studies and a systematic review. |
| title_sort |
long-term interleukin-6 levels and subsequent risk of coronary heart disease: two new prospective studies and a systematic review. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2008 |
| url |
https://doaj.org/article/001404b6e23c41e6bbfe7de85d5cc2e6 |
| work_keys_str_mv |
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