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Original research article
Inflammation markers and risk of developing hypertension: a meta-analysis of cohort studies
  1. Ahmad Jayedi1,
  2. Kazem Rahimi2,3,
  3. Leonelo E Bautista4,
  4. Milad Nazarzadeh2,5,
  5. Mahdieh Sadat Zargar6,
  6. Sakineh Shab-Bidar7
  1. 1Food (salt) Safety Research Center, Semnan University of Medical Sciences, Semnan, Iran
  2. 2George Institute for Global Health, University of Oxford, Oxford, UK
  3. 3Deep Medicine, Oxford Martin School, University of Oxford, Oxford, UK
  4. 4Department of Population Health, School of Medicine, University of Wisconsin at Madison, Wisconsin, USA
  5. 5Collaboration Center of Meta-Analysis Research, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran
  6. 6Nursing Care Research Center, Semnan University of Medical Sciences, Semnan, Iran
  7. 7Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
  1. Correspondence to Dr Sakineh Shab-Bidar, Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran 14155/6117, Iran; s_shabbidar{at}


Objective To systematically assess the association of circulating inflammation markers with the future risk of hypertension.

Methods We did a systematic literature search of PubMed and Scopus, from database inception to July 10, 2018. Prospective and retrospective cohort studies evaluating the association of circulating C reactive protein (CRP), high-sensitive CRP (hs-CRP), interleukin 6 (IL-6) and IL-1β to the risk of developing hypertension in the general population were included. The relative risks (RRs) for the top versus bottom tertiles of circulating biomarkers were calculated using a fixed-effects/random-effects model. A potential non-linear dose-response association was tested.

Results Fourteen prospective cohort studies, two retrospective cohort studies and five nested case-control studies involving 142 640 participants and 20 676 cases were identified. The RR for the third versus first tertiles of circulating CRP was 1.23 (95% CI 1.11 to 1.35; I2=59%, n=12). The association remained unchanged after adjustment for body mass index. The RRs for other biomarkers were as follows: hs-CRP (RR 1.20, 95% CI 1.02 to 1.37; I2=74%, n=7), IL-6 (RR 1.51, 95% CI 1.30 to 1.71; I2=0%, n=5), and IL-1β (RR 1.22, 95% CI 0.92 to 1.51; I2=0%, n=3). A non-linear dose-response meta-analysis demonstrated that the risk of hypertension increased linearly with increasing circulating inflammation markers, even within the low-risk and intermediate-risk categories.

Conclusions Higher levels of circulating CRP, hs-CRP and IL-6, but not IL-1β, were associated with the risk of developing hypertension. The association persisted in subgroups of studies defined by major sources of heterogeneity.

  • inflammatory markers
  • hypertension
  • meta-analysis

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  • Contributors AJ designed the research, screened articles, extracted and analysed data, and wrote the paper; MSZ screened articles, extracted data and wrote the paper; KR, LEB and MN critically revised the manuscript and contributed to the interpretation of the results; SS-B wrote paper, revised the manuscript, and had primary responsibility for the final content.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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