Exploration of biomarkers for subclinical atherosclerosis in an African population using a proteomics chip targeted at inflammation and cardiovascular disease

Abstract

Introduction: The evolving use of multiplex proteomic platforms provides an excellent tool for investigating associations between multiple proteins and subclinical atherosclerotic disease. In this study, we evaluated the impact of a multiplex protein panel, on carotid intima-media thickness (cIMT) as a marker of subclinical atherosclerosis. Purpose: We used a multiplex proteomic platform to identify possible associations between proteins and subclinical carotid atherosclerosis as measured by carotid ultrasound in an African population. Methods: In the Sympathetic Activity and Ambulatory Blood Pressure in Africans (SABPA) study, 92 proteins from the Proseek Multiplex CVD III 96×96 (Olink Bioscience, Sweden) were analyzed in 378 participants (mean age 44.7±9.6 years, 50.6% women, 10.8% with known cardiovascular disease). Carotid ultrasound was performed for measurements of the carotid intima-media thickness (cIMT, mean 0.663±0.127 mm) and calculation of cross-sectional wall area (CSWA, mean 13.5±4.4mm2), a measure of target organ damage. Possible associations between the proteins, and cIMT and CSWA, respectively, were explored using linear regression models. A two-sided Bonferroni corrected P-value of 0.05/92=5.4x10–4 was considered statistically significant in the crude analysis. Results: Of 18 proteins (1 standard deviation of change of ln-transformed values) that were Bonferroni-corrected (p≤5.4x10–4) significantly associated with cIMT and/or CWAS in crude analyses, the following remained significant after further adjustment for age, sex, waist circumference, systolic blood pressure, smoking and total cholesterol: growth-differentiation factor-15 (GDF15; β 0.017, p=0.050), E-selectin (SELE; β 0.019, p=0.017), carboxypeptidase A1 (CPA1; β 0.019, p=0.019), C-C motif chemokine 15 (CCL15; β 0.031, p<0.001), chitinase-3-like protein 1 (CHI3L1; β 0.021, p=0.007), the hemoglobin scavenger receptor (CD163; β 0.021, p=0.008) and osteoprotegerin (OPG; β 0.022, p=0.004). As for target-organ damage defined by CSWA, SELE (β 0.459, p=0.018), CCL15 (β 0.398; p=0.032) and CD163 (β 0.541, p=0.005) showed multivariate adjusted significant associations. Conclusion: In an African population, we could confirm five proteins (GDF15, SELE, CHI3L1, CD163 and OPG) associated with cIMT, but in addition identified two proteins (CPA1 and CCL15) with novel associations with cIMT and/or CSWA