Abstract

Background and Aims: Hypertension is one of the most important and complex risk factors for cardiovascular diseases. Identifying biomarkers in hypertension may lead to better strategies to understand the development of hypertension. Biomarker discovery through the use of peptidomics may also provide essential information for the prediction and prevention of premature CVD development. Methods and Results: We included 78 hypertensive (based on 24-hour ambulatory blood pressure) and 79 normotensive age (20–30-years old), sex and ethnicity (62% black and 48% white) matched participants from the African-PREDICT study. Urinary peptidomics were analysed with capillary electrophoresis time-of-flight mass spectrometry. Hypertension-specific peptide profiles were combined into a single summary multidimensional classifier. When comparing the peptide data between the normotensive and hypertensive groups, 354 peptides were nominally differentially expressed (Wilcoxon p-value less than 0.05). Nonetheless, only three peptides (ID10000 (SHANK1), ID8939 (unsequenced) and ID6841 (unsequenced)) remained significant after rigorous adjustments for multiple comparisons (maxT test) and were more abundant in the hypertensive compared to the normotensive group (all p-value less than 0.001). Furthermore, the 15 nominally most significant peptides (all p-value less than or equal to 0.0013) were combined into a unifying score which differed significantly between the groups (p-value less than 0.001) but had an insufficient prediction capability for hypertension. Conclusion: Apart from differential expression of single peptides in hypertensive adults, including ID10000 (SHANK1), no unifying urinary hypertension peptidomics profile was identified with a sufficient prediction capability. Our findings suggest that a downstream multimarker approach cannot reliably represent a complex multifactorial condition such as hypertension.

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