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.