Hypertension and OMICS, quo vadis

Arterial hypertension is present in more than 1 billion people worldwide [1,2]. Hypertension is among the world's greatest health-economical burdens, leading to major target organ damage, cardiovascular disease, chronic kidney disease, dementia and death. More sophisticated blood pressure (BP) assessment tools have been developed. BP assessment is currently nearly always done by each healthcare provider at patient visits. Regular community BP check events now occur. However, in the majority of the population, the underlying pathogenesis of hypertension is still not completely discovered. For this reason, we still use the term 'Essential Hypertension' in more than in 90% of our patients. In this issue, Mischak et al. (pp. 000–000) studied the urinary peptidome in subsets of 4228 individuals without end-organ damage. The data were retrieved from the Human Urinary Proteome Database general population (discovery) or type 2 diabetic (validation) cohorts. Participants were divided based on SBP and DBP into hypertensive (SBP ≥140 mmHg and/or DBP ≥90 mmHg, N = 1004) and normotensive (SBP < 120 mmHg and DBP < 80mmHg without antihypertensive treatment, N = 283) groups. Differences in urinary peptide abundance between the two groups were further investigated using an external cohort (n = 210 hypertensive and 210 normotensive) of participants without end-organ damage, who were partially matched for age, BMI, estimated glomerular fraction rate, sex and the presence of diabetes. The association of the urinary peptides with BP was compared with peptide biomarkers of chronic diseases, and bioinformatic analyses were conducted to look into the underlying molecular mechanisms. Within a discovery-validation study design, the investigators determined consistent, significant peptide changes between hypertensive and normotensive participants. The investigators identified 83 hypertension-associated peptides of both collagen and noncollagen origin. They further analysed the data for correlations with the continuous standardized BP variables and in protein-protein interaction bioinformatics analyses. Unfortunately, the epidemiologic design leaves open questions, as some of the groups differ by over 30 years of age, people with diabetes are used as the validation set for a group of the mostly nondiabetic training set, and effects on the peptidome of antihypertensive medications were not considered. These aspects weaken the study and require cautious interpretation. Nevertheless, the peptidome data are well analysed biochemically and the data analyses provide important food for thought. Among the hypertension-associated peptides identified in this study, the collagen-derived peptides were the most prominent, because fibrosis is a key factor in the process of the arterial wall stiffening. The authors' major conclusion is that urinary peptidomics will not become a diagnostic tool, but can contribute to understanding early mechanisms in the new onset of essential hypertension. A few years ago, Arnett and Claas [3] wrote a primer on the genomics, transcriptomics, proteomics, and metabolomics of BP and hypertension. Omics approaches may lead to better diagnostics than currently exist, potentially predicting the severity of hypertension or target-organ damage associated with hypertension. Omics may personalize antihypertensive therapy for optimal response in the future. Proteomics is the study of the full complement of proteins produced or modified by a biological system. Omics methods might be used directly in the clinic to predict and stratify risk, aid diagnosis, and guide treatment decisions. Indirect clinical impacts include new clinical measures that derive from omics research but that do not involve omics measures in the clinical setting. Although even the indirect impact of omics in the context of BP and hypertension is currently negligible, it is via this route that omics may have the greatest potential impact. For example, given the potentially lifelong effect of genetic variants, genetic risk scores might be used to predict hypertension and related cardiovascular disease before it develops. Although no pharmacogenomics or pharmacometabolomics prescribing regimens for hypertension have been developed to date, this is another area of intense research and optimism [4]. Given that the pathogenesis of preeclampsia remains largely unknown and the diagnosis can be difficult, proteomic explorations of this hypertensive disorder may uncover novel pathophysiological mechanisms and diagnostic markers [5,6]. Application of omics in resistant hypertension may eventually be informative for better defining the pathological mechanisms of resistant hypertension. In-depth analysis of the pathophysiological mechanisms of hypertension and resistant hypertension is needed to identify more effective targets for controlling in these individuals' BP [7]. Resistant arterial hypertension is considered as difficult to control BP, in which multiple systems are in disarray, including vascular, cardiogenic, renal, neurogenic and endocrine mechanisms that interact in a complex but integrated manner to achieve BP homeostasis. Multiple proteins and metabolites are thought to regulate BP control, but these are deranged in resistant hypertension. As we move into the era of diagnostic omic approaches, this technique may assist us to interpret the omic results and provide us in-depth information about which pathways are not operating correctly, resulting in resistant hypertension and consequently in target organ damage, including cardiovascular and renal diseases. This insight in the pathobiology of BP control addressed by omics may lead to more selective antihypertensive therapy. This may result in regression of target damage and reduction in cardiovascular events and reduce the progression of chronic kidney disease. The kidney is not only an organ of key relevance to BP regulation and the development of hypertension, but it also acts as the tissue mediator of genetic predisposition to hypertension. The identity of kidney genes, pathways and related mechanisms underlying the genetic associations with BP has started to emerge through integration of genomics with kidney transcriptomics, epigenomics, and other omics [8]. Polygenic risk scores derived from genome-wide association studies and refined on kidney omics hold the promise of enhanced diagnostic prediction, whereas kidney omics-informed drug discovery is likely to contribute new therapeutic opportunities for hypertension and hypertension-mediated kidney damage. In conclusion, the future will tell us if omics applied to hypertension will reveal more pathological mechanisms, the mechanisms of target organ damage, specifically on the cardiovascular system, the kidney and the brain. There are still several needs to reveal in the omics domain, including the need for ethnic stratification. With the growing ageing population, omics will contribute to understanding beyond SBP increase in the elderly and the very elderly of age-related changes in the cardiovascular system, the kidney and brain function regarding cognitive decline and dementia. ACKNOWLEDGEMENTS Conflicts of interest There are no conflicts of interest.