Research Questions:
Does immune dysregulation (e.g., elevated CRP, NLR, cytokines) predict incident CVD (MI, stroke, HF)?
Which immune biomarkers show strongest associations with specific CVD subtypes?
Do genetic variants (e.g., IL6R, TNF) modify immune-CVD relationships?
How do lifestyle factors (diet/exercise) interact with immune dysregulation on CVD risk?
Objectives:
Quantify associations between baseline immune biomarkers (CRP, IL-6, NLR, leukocyte counts) and CVD incidence using Cox regression.
Identify subtype-specific immune signatures via stratified analyses.
Test gene-immune interactions using polygenic risk scores and GWAS data.
Assess effect modification by lifestyle factors (physical activity, diet scores).
Scientific Rationale:
Chronic inflammation is implicated in atherosclerosis, but comprehensive population-level evidence linking multidimensional immune imbalance (cellular, humoral, genetic) to CVD is limited. The UK Biobank’s scale (>500k participants), longitudinal design (15+ years follow-up), and multi-omics data (genomics, proteomics, EHR-linked outcomes) provide a unique opportunity to:
Decipher which immune pathways most strongly drive CVD risk,
Identify high-risk subgroups via genetic/lifestyle interactions,
Generate mechanistic insights for targeted immunomodulatory therapies.
This addresses critical gaps in understanding immune-mediated CVD pathogenesis.