VSports在线直播 - Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The . gov means it’s official. Federal government websites often end in . gov or . mil. Before sharing sensitive information, make sure you’re on a federal government site. VSports app下载.

Https

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. V体育官网.

. 2008 Apr 8;5(4):e78.
doi: 10.1371/journal.pmed.0050078.

Long-term interleukin-6 levels and subsequent risk of coronary heart disease: two new prospective studies and a systematic review

John Danesh  1 , 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
Affiliations

Long-term interleukin-6 levels and subsequent risk of coronary heart disease: two new prospective studies and a systematic review

John Danesh et al. PLoS Med. .

Abstract

Background: 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 VSports手机版. 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. .

Methods and findings: 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) V体育安卓版. .

Conclusions: Long-term IL-6 levels are associated with CHD risk about as strongly as are some major established risk factors, but causality remains uncertain V体育ios版. These findings highlight the potential relevance of IL-6-mediated pathways to CHD. .

PubMed Disclaimer

Conflict of interest statement (VSports手机版)

Competing Interests: The authors have declared that no competing interests exist.

Figures (VSports)

Figure 1
Figure 1. QUOROM Flow Diagram Summarising the Search Strategy for Meta-analysis of IL-6 and CHD Outcomes in Generally Healthy Populations
Figure 2
Figure 2. Risk of CHD by Fifths of Baseline Circulating IL-6 Levels in a Pooled Analysis of Participants without Known CHD at Baseline in the Reykjavik Study and the BRHS
Fifths were calculated on the basis of the distribution of controls in the combined dataset. CIs were calculated using floating variances. Sizes of data markers are proportional to the inverse of the variance of the odds ratios. Adjusted for cohort, age, sex, recruitment period, and town of recruitment.
Figure 3
Figure 3. Odds Ratios for CHD per 2 SD Increase in Several Inflammatory Markers and Established Cardiovascular Risk Factors Shown with Progressively Increasing Degrees of Correction for Within-person Variability in a Pooled Analysis of Participants without Known Coronary Disease at Baseline in the Reykjavik Study and the BRHS
(A) Baseline exposure adjusted for baseline confounders. (B) Usual exposure adjusted for baseline confounders. (C) Usual exposure adjusted for usual confounders. Sizes of data markers are proportional to the inverse of the variance of the odds ratios. Baseline (A) refers to measured values just at the initial examination. Usual (B and C) refers to an estimate of the long-term average values by employing data on repeat measurements from the Reykjavik Study (see Methods). Odds ratios are adjusted for cohort, age, sex, period and town of recruitment, smoking status, history of diabetes, total cholesterol, loge triglycerides, systolic blood pressure, and body mass index.
Figure 4
Figure 4. Summary of 17 Prospective Studies Reporting Adjusted Associations of CHD Risk per 2 SD Increase in Baseline IL-6 Levels and Usual IL-6 Levels, with Both Adjusted Only for Baseline Levels of Several Established Risk Factors
(A) Baseline exposure adjusted for baseline confounders. (B) Usual exposure adjusted for baseline confounders. Baseline refers to measured values just at the initial examination. Usual refers to an estimate of the long-term average values. The correction for regression dilution (see Methods) in the two current studies (filled squares) was done using study-specific regression dilution ratios of 0.35 in Reykjavik study and 0.41 in the BRHS. A regression dilution ratio of 0.4 was assumed for other studies (empty squares) where such regression dilution ratio coefficients were unavailable. The odds ratio for a 1 SD increase in baseline and usual IL-6 levels are 1.26 (1.19–1.35) and 1.83 (1.56–2.14), respectively. Unshaded data markers were used in the second plot of this figure to indicate that correction for regression dilution involved use of coefficients from external studies, in contrast with the cohort-specific data on IL-6 variability available for the Reykjavik Study and BRHS. Sizes of data markers indicate the weight of each study in the analysis. Adjustment for within-person variability in levels of IL-6 and possible confounders requires access to individual participant data, currently available only in the Reykjavik Study and BRHS. +, adjusted for age and sex; ++, adjusted for age, sex, and smoking status; +++, adjusted for age, sex, smoking status, and other established CHD risk factors; FINRISK, Finnish National Risk Factor Survey; HPFUS, Health Professionals' Follow-up Study; MONICA, MONItoring of trends and determinants in Cardiovascular disease; PRIME, Prospective Epidemiological Study of Myocardial Infarction; WHIOS, Women's Health Initiative Observational Study; WOSCOPS, West of Scotland Coronary Prevention Study.
See this image and copyright information in PMC

References

    1. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005;352:1685–1695. - PubMed
    1. Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO, III, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation. 2003;107:499–511. - PubMed
    1. Kerr R, Stirling D, Ludlam CA. Interleukin 6 and haemostasis. Br J Haematol. 2001;115:3–12. - PubMed
    1. Le JM, Vilcek J. Interleukin 6: a multifunctional cytokine regulating immune reactions and the acute phase protein response. Lab Invest. 1989;61:588–602. - PubMed
    1. Woodward M, Rumley A, Tunstall-Pedoe H, Lowe GD. Associations of blood rheology and interleukin-6 with cardiovascular risk factors and prevalent cardiovascular disease. Br J Haematol. 1999;104:246–257. - PubMed

Substances