Interleukin-6 as a Predictor of the Risk of Cardiovascular Disease: A Meta-Analysis of Prospective Epidemiological Studies

Immunol Invest. 2018 Oct;47(7):689-699. doi: 10.1080/08820139.2018.1480034. Epub 2018 Jun 6.


Objective: The etiology of cardiovascular disease (CVD) is complex owing to the interactions of genetic variance with environmental factors. Inflammatory processes are now being increasingly implicated in the pathogenesis of CVD. This meta-analysis investigated the potential role of interleukin-6 (IL-6) as a risk factor for CVD development in healthy individuals.

Methods: Literature search was carried out in multiple electronic databases, and study selection followed a priori eligibility criteria. Meta-analyses of standardized mean differences were carried out to determine an overall effect size of the difference in IL-6 levels between CVD cases and non-CVD matched controls. Meta-regression analyses were performed to examine the relationship between the IL-6 levels in CVD cases and several explanatory variables.

Results: Seventeen studies enrolling 288738 healthy individuals with an average follow-up duration of 7.4 ± 4.1 years were found eligible. Overall, data of 5400 CVD cases and 14607 matched non-CVD controls are used in the present meta-analysis. Baseline IL-6 levels were significantly higher in CVD cases than in non-CVD controls (standardized mean difference [95% confidence interval]) of 0.14 [0.09, 0.20]/mean difference of 0.36 [0.28, 0.44] picogram per milliliter). Total cholesterol, LDL-cholesterol, and triglyceride levels were also significantly higher, and HDL-cholesterol levels were significantly lower in CVD cases in comparison with the controls. Systolic blood pressure and total cholesterol levels had a significantly positive relationship, whereas triglyceride levels had a significantly inverse relationship with the levels of IL-6.

Conclusion: Higher IL-6 levels in healthy individuals are associated with CVD risk, which is co-associated with hypertension and hypercholesterolemia.

Keywords: Atherosclerosis; cardiovascular diseases; interleukin-6; prospective epidemiological survey; risk factors.

Publication types

  • Meta-Analysis

MeSH terms

  • Cardiovascular Diseases / epidemiology*
  • Cardiovascular Diseases / immunology
  • Cholesterol / metabolism
  • Female
  • Follow-Up Studies
  • Humans
  • Hypercholesterolemia / epidemiology*
  • Hypertension / epidemiology*
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Male
  • Prospective Studies
  • Risk Factors
  • Up-Regulation


  • Interleukin-6
  • Cholesterol