Effects of Aldosterone on Human Atherosclerosis: Plasma Aldosterone and Progression of Carotid Plaque.
ABSTRACT BACKGROUND: In animal models, aldosterone has adverse cardiac and vascular effects independent of blood pressure, and these are ameliorated by spironolactone or eplerenone (mineralocorticoid receptor antagonists). Both agents reduce mortality in human systolic heart failure. We studied the effect of plasma aldosterone on human carotid atherosclerosis. METHODS: The effect of plasma aldosterone on progression of carotid total plaque area (TPA) was studied using multiple linear regression, with variables that have previously been shown to maximally explain TPA variation (age, sex, total cholesterol, systolic blood pressure, diabetes, smoking, and medication for cholesterol and systolic blood pressure). RESULTS: Complete data were available in 848 patients with progression of plaque from baseline to the following year and in 571 for progression in the second year. In stepwise linear regression, plasma aldosterone was the only independent predictor of plaque progression in the first year (P = 0.005) and in the second year (P = 0.001). CONCLUSIONS: Plasma aldosterone is associated with progression of atherosclerosis. We are now planning to test the effects of mineralocorticoid receptor antagonism on plaque progression.
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ABSTRACT: At the early stage of chronic kidney disease (CKD), the systemic mineral metabolism and bone composition start to change. This alteration is known as chronic kidney disease-mineral bone disorder (CKD-MBD). It is well known that the bone turnover disorder is the most common complication of CKD-MBD. Besides, CKD patients usually suffer from vascular calcification (VC), which is highly associated with mortality. Many factors regulate the VC mechanism, which include imbalances in serum calcium and phosphate, systemic inflammation, RANK/RANKL/OPG triad, aldosterone, microRNAs, osteogenic transdifferentiation, and effects of vitamins. These factors have roles in both promoting and inhibiting VC. Patients with CKD usually have bone turnover problems. Patients with high bone turnover have increase of calcium and phosphate release from the bone. By contrast, when bone turnover is low, serum calcium and phosphate levels are frequently maintained at high levels because the reservoir functions of bone decrease. Both of these conditions will increase the possibility of VC. In addition, the calcified vessel may secrete FGF23 and Wnt inhibitors such as sclerostin, DKK-1, and secreted frizzled-related protein to prevent further VC. However, all of them may fight back the inhibition of bone formation resulting in fragile bone. There are several ways to treat VC depending on the bone turnover status of the individual. The main goals of therapy are to maintain normal bone turnover and protect against VC.TheScientificWorldJournal. 01/2014; 2014:637065.
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ABSTRACT: It has been proposed that cardiovascular risk could be markedly reduced by prescribing to all patients at risk a single daily pill. This concept is bad medicine, because each constituent has problems, and the problems are different for each patient. A key principle of Clinical Pharmacology is individualization of therapy. Patients are not all the same, so a single polypill cannot work for all of them. For patients with resistant hypertension, at least three different versions would be needed for patients with different causes of hypertension, and even then not all patients could take one.The Canadian journal of cardiology 01/2014; · 3.12 Impact Factor
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ABSTRACT: The first aldosterone blocker, spironolactone, initially was used as a diuretic but was accompanied by a significant amount of side effects that necessitated the withdrawal of the drug in a relevant number of patients. The discovery of the many receptor-mediated actions of aldosterone in several different organs greatly contributed to expand the indications of aldosterone blockers. Eplerenone was the second component of this class of drugs and differed from spironolactone because of its significantly better safety, albeit this was accompanied by a lower potency when used at equinumeric doses. Although these two drugs were being used in clinical practice, the epithelial sodium channel blockers, amiloride and triamterene, with a similar antialdosterone action, continued to be used in clinical practice in combination with thiazides and loop diuretics. New members of the third and fourth generation of mineralocorticoid receptor antagonists and aldosterone synthase inhibitors are in development. These new compounds, which include the new nonsteroidal mineralocorticoid-receptor antagonists and aldosterone synthase inhibitors, try to maintain adequate efficacy, avoiding the drawbacks of spironolactone and eplerenone. Ongoing studies will show the certainty of the capacities of these new compounds to override the virtues of the first mineralocorticoid-receptor spironolactone while avoiding the side effects leading so frequently to the withdrawal of the drug, including a significantly lower prevalence of hyperkalemia when chronic kidney disease is present.Seminars in Nephrology 01/2014; · 2.83 Impact Factor