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  • Review Article
  • Published:

The pathophysiology of hypertension in patients with obesity

Nature Reviews Endocrinology volume 10, pages 364–376 (2014)Cite this article

Subjects

Key Points

  • The incidence of hypertension is substantially increased in the population of people with obesity and affected individuals have increased morbidity and mortality from cardiovascular disease (CVD) and chronic kidney disease

  • Adipokine alterations, insulin resistance, sympathetic nervous system and renin–angiotensin–aldosterone system activation, obstructive sleep apnoea, renal abnormalities, maladaptive immunity and gut microbiome changes all link hypertension to obesity

  • Hyperuricaemia associated with a high-fructose diet is emerging as a key factor in the development of hypertension associated with diet-induced obesity

  • Dysregulation of the dipeptidyl peptidase 4–incretin system contributes to the development of maladaptive immunity and associated hypertension in obesity

  • Estrogen-mediated CVD protection is compromised in individuals with obesity, thereby underscoring the greater CVD risks associated with obesity in premenopausal women compared with those in age-matched men with obesity

  • Adjunctive therapy with mineralocorticoid receptor antagonists and renal denervation is emerging as an additional therapeutic measure for management of obesity-related hypertension

Abstract

The combination of obesity and hypertension is associated with high morbidity and mortality because it leads to cardiovascular and kidney disease. Potential mechanisms linking obesity to hypertension include dietary factors, metabolic, endothelial and vascular dysfunction, neuroendocrine imbalances, sodium retention, glomerular hyperfiltration, proteinuria, and maladaptive immune and inflammatory responses. Visceral adipose tissue also becomes resistant to insulin and leptin and is the site of altered secretion of molecules and hormones such as adiponectin, leptin, resistin, TNF and IL-6, which exacerbate obesity-associated cardiovascular disease. Accumulating evidence also suggests that the gut microbiome is important for modulating these mechanisms. Uric acid and altered incretin or dipeptidyl peptidase 4 activity further contribute to the development of hypertension in obesity. The pathophysiology of obesity-related hypertension is especially relevant to premenopausal women with obesity and type 2 diabetes mellitus who are at high risk of developing arterial stiffness and endothelial dysfunction. In this Review we discuss the relationship between obesity and hypertension with special emphasis on potential mechanisms and therapeutic targeting that might be used in a clinical setting.

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Figure 1: Obesity contributes to the development of hypertension via the interaction of dietary, genetic, epigenetic and environmental factors.
Figure 2: Possible mechanisms of obesity-associated hypertension and therapeutic strategies.

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Acknowledgements

This work was supported by grants from the NIH (R01 HL73101-01A1 and R01 HL107910-01) and Veterans Affairs Merit System (0018) to J.R.S. and by an investigator-initiated grant from Boehringer Ingelheim Pharmaceuticals to V.G.D.

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  1. Internal Medicine, University of Missouri, Columbia School of Medicine, One Hospital Drive, Columbia, 65212, MO, USA

    Vincent G. DeMarco, Annayya R. Aroor & James R. Sowers

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V.G.D. and A.R.A. contributed equally in preparing all aspects of the manuscript. J.R.S. made substantial contributions to discussion of the content, and read and edited the manuscript before submission.

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DeMarco, V., Aroor, A. & Sowers, J. The pathophysiology of hypertension in patients with obesity. Nat Rev Endocrinol 10, 364–376 (2014). https://doi.org/10.1038/nrendo.2014.44

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