Elsevier

Cardiology Clinics

Volume 28, Issue 3, August 2010, Pages 517-527
Cardiology Clinics

The Role of Aldosteronism in Causing Obesity-Related Cardiovascular Risk

https://doi.org/10.1016/j.ccl.2010.04.001Get rights and content

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Obesity and hypertension

There is a direct correlation between increasing body weight and risk of hypertension. Data from the National Health and Nutrition Examination Survey 1999–2004 indicate that the prevalence of hypertension increases progressively with increasing body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) from about 15% among people with a BMI less than 25 kg/m2 to approximately 40% among those with a BMI of 30 kg/m2 or greater.1 Analyses from the Framingham

Aldosterone and hypertension

Cross-sectional and prospective studies indicate that aldosterone, independent of renin-angiotensin II, has an important contribution in the development and severity of hypertension. In a prospective analysis done as part of the ongoing Framingham Offspring Study, serum aldosterone, plasma renin concentration, and the aldosterone/plasma renin ratio (ARR) were prospectively related to development of hypertension or to blood pressure progression (increase in severity).5 In this evaluation of more

Aldosterone and cardiorenal disease

A growing body of evidence links aldosterone excess to the development and progression of several cardiovascular disease processes separate from hypertension, including congestive heart failure, CKD, coronary artery disease, and stroke. In congestive heart failure, higher plasma aldosterone and angiotensin II levels predict increased mortality. Cross-sectional studies implicate aldosterone excess as a probable contributor to the development of CKD. In an evaluation of 2700 participants in the

Potential mechanisms of aldosterone-induced end-organ damage

A large body of experimental evidence has demonstrated that aldosterone excess in combination with high dietary salt intake induces perivascular inflammation and fibrosis.27 These effects occur in multiple organs, including the heart, kidney, and brain. In addition, human studies suggest a variety of other effects presumed to negatively affect cardiovascular risk, including suppression of nitric oxide activity, impairment of endothelial function, and stimulation of thrombogenic pathways.28

Obesity and aldosterone

The cause of the apparent increase in aldosterone excess and its role in contributing to the development of hypertension over the last several decades remain unexplained. Demonstration of this growing role of aldosterone in mediating hypertension and other cardiovascular complications has coincided with a progressive increase in worldwide rates of obesity, suggesting a possible causative relation between increasing body weight and stimulation of aldosterone release. Population-based

Obesity and blood pressure response to aldosterone blockade

If obesity contributes to aldosterone excess, it would be anticipated that aldosterone antagonists would be more effective in lowering blood pressure in obese subjects than in nonobese subjects. Although there is little, if any, direct data assessing this possibility, preliminary data suggestive of a preferential benefit of aldosterone blockade in relation to adiposity are emerging. In a retrospective analysis of the blood pressure response of spironolactone in patients with CKD, Khosla and

Potential mechanisms of adipocyte-derived hyperaldosteronism

Potential mechanisms by which adipocytes may contribute to excess aldosterone secretion include generalized stimulation of the renin-angiotensin-aldosterone system and, separately, release from adipocytes of secretagogues specific for aldosterone. Adipocytes appear to have all the components of the renin-angiotensin system (RAS) and thus may produce locally generated angiotensin II.54, 55, 56 As noted earlier, adipocytes may also produce aldosterone and thus may directly contribute to systemic

Summary

Obesity and aldosterone excess are common. Observational studies indicate that indices of adiposity such as BMI, waist circumference, and measure of visceral tissue correlate with aldosterone levels. In vitro studies suggest that adipocytes release factors that stimulate aldosterone secretion independent of renin-angiotensin II. These studies support the concept that obesity contributes to hyperaldosteronism. Aldosterone excess has been shown to have an important contribution in the development

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    Portions of this work were supported by the grant 5R01DK053867 from National Institute of Diabetes and Digestive and Kidney Diseases (K.S.).

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