Examining Chronic Inflammatory Markers on Blood Pressure Measures in the Presence of Vitamin D Insufficiency Among Indigenous Cree Adults: Results from the Cross-sectional Multi-Community Environment-and-Health Study in , Quebec, Canada

Objective: High blood pressure (BP) is a risk factor for cardiovascular disease. Examining the role of inflammatory mediators on BP is important since vitamin D (VD) is a modifiable risk factor, which possibly modulates inflammatory cytokines. This study simulated what are known as average 'controlled direct effects (CDE)' of inflammatory markers, C reactive protein (CRP), tumour necrosis factor-α (TNF-α), and interlukin-6 (IL-6) on continuous BP measures, while fixing VD, an intermediate variable to specific level.

Design: Cross-sectional study.

Setting: We analysed data from the Multi-Community Environment-and-Health Study, 2005-2009, conducted in , Quebec, Canada.

Participants: This study recruited 1425 study Indigenous Cree participants from seven Cree communities. Only adults with serum VD levels, inflammatory markers and BP measures were included in this data analysis.

Primary And Secondary Outcomes Measures: Inflammatory markers examined the top 25th exposure percentiles. VD 'insufficiency' (ie, 25-hydroxyvitamin-D levels<50 nmol/L) defined by the Institute of Medicine. CDE for each inflammatory marker in the presence and absence of population VD insufficiency simulated the average direct effect change for systolic and diastolic BP (SBP and DBP) measures. All models were adjusted for exposure-and-mediator outcome relationship.

Results: Among 161 participants, 97 (60 %) were female. The prevalence of VD insufficiency was 32%. CDE estimates show in the presence and absence of population vitamin D insufficiency, inflammatory markers have a slightly different association on BP. TNF-α significantly and inversely associated with SBP in the presence of vitamin D insufficiency, fully adjusted model β = -13.61 (95% CI -24.42 to -2.80); however, TNF-α was not associated with SBP in the absence of vitamin D insufficiency. CRP, IL-6 were also not significantly associated with BP measures, although the magnitude of association was greater for those with elevated inflammation and VD insufficiency.

Conclusion: This novel analysis shows in the presence of VD insufficiency, inflammation (particularly TNF-α) may affect SBP. Additional research is needed to elucidate these findings, and the temporal relationship between these variables.