Associations of Adiposity, Circulating Protein Biomarkers, and Risk of Major Vascular Diseases

Figures

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  Figure 1.. Flow Diagram A flow diagram to show participants whose data were used to estimate observational and genetic associations of body mass index, proteomics, and cardiovascular disease in the China Kadoorie Biobank (CKB). The excluded participants (n = 24 672) were enriched for cases as part of a case-control study, leaving 75 736 individuals with similar characteristics to the underlying CKB data set. BMI indicates body mass index; CHD, coronary heart disease; CVD, cardiovascular disease; GWAS indicates genome-wide association study.

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  Figure 2.. Associations of Observational and Genetically Instrumented Body Mass Index (BMI) With Proteins and Proteins With Vascular Events A, Adjusted SD differences (95% CI) of protein biomarkers per 1-SD higher observational BMI (calculated as weight in kilograms divided by height in meters squared) for 30 protein biomarkers with false-discovery rate–corrected P < .05. B, Corresponding estimates per 1-SD higher genetically elevated BMI. The observational estimates were adjusted for age, age squared, sex, region, smoking, alcohol use, education, household income, self-rated health, systolic blood pressure, diabetes, statin treatment, prior kidney disease, and fasting time. The mendelian randomization estimates were adjusted for age, age squared, sex, region, the first 12 principal components, education, smoking status, and alcohol use. The SD for BMI in the whole China Kadoorie Biobank cohort was 3.4. C, Adjusted hazard ratios (HRs) with 95% CIs of vascular events (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes I00-I09, I16-I25, I27-I88, I95-I99, and I10-I15 [only if fatal]) per 1-SD higher protein biomarkers. Models were adjusted…

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  Figure 3.. Meta-analysis of Genetic Associations of Body Mass Index (BMI) With Proteins and Observational Associations of Proteins With Cardiovascular Disease (CVD) A, Genetic associations of BMI with selected proteins (estimates from individual studies are shown in eFigure 8 in the Supplement). B, Observational associations of selected proteins with cardiovascular disease (estimates from individual studies are shown in Figure 4). Diamonds denote pooled estimates from meta-analyses, and open boxes denote estimates in the China Kadoorie Biobank (CKB). For C-reactive protein (CRP) and fibrinogen, outcomes estimates were extracted from previous studies of the largest known sample sizes.33,34,35,36 No prospective studies were identified on TNF-related weak inducer of apoptosis (TWEAK) and CVD. IL6 indicates interleukin-6; IL8, interleukin-8; IL12, interleukin-12; HGF, hepatocyte growth factor; hs-CRP, high-sensitivity CRP; MCP1, monocyte chemoattractant protein–1; MCP3, monocyte chemotactic protein–3; SRMA, systematic review and meta-analysis; TRAIL, TNF-related apoptosis-inducing ligand.

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  Figure 4.. Meta-analysis of Observational Associations of Proteins With Cardiovascular Disease (CVD) Boxes represent the relative risks (RRs) of CVD per 1-SD higher protein for individual studies, with the size of the box inversely proportional to the variance of the logRR. Open boxes represent previously published studies,37,38,39,40,41,42,43,44,45,46,47,48 and the black box represents the China Kadoorie Biobank (CKB). Diamonds represent summary RRs for each protein. Blood pressure, diabetes, and/or lipids were adjusted for in all studies. ARIC indicates Atherosclerosis Risk in Communities; CHD, coronary heart disease; FINRISK, Finnish risk study; GP, general practitioner; HGF, hepatocyte growth factor; IL6, interleukin-6; IL18, interleukin-18; InCHIANTI, Invecchiare in Chianti; IS, ischemic stroke; MCP1, monocyte chemoattractant protein–1; MCP3, monocyte chemotactic protein–3; MDCS, the Malmö Diet and Cancer Study; MESA, Multi-Ethnic Study of Atherosclerosis; MI, myocardial infarction; MONICA-KORA, Myocardial Infarction Augsbourg–Cooperative Health Research in the Region Augsburg; PMRP, Personalized Medicine Research Project; PRIME, the Panitumumab Randomized Trial in Combination With…