Congestive heart failure (CHF) is a clinical syndrome that features a failing heart together with signs and symptoms arising from renal retention of salt and water, mediated by attendant neurohormonal activation, and which prominently includes the renin-angiotensin-aldosterone system. More than this cardiorenal perspective, CHF is accompanied by a systemic illness whose features include an altered redox state in diverse tissues and blood, an immunostimulatory state with proinflammatory cytokines and activated lymphocytes and monocytes, and a wasting of tissues that includes muscle and bone. Based on experimental studies of aldosteronism and clinical findings in patients with CHF, there is an emerging body of evidence that secondary hyperparathyroidism is a covariant of CHF. The aldosteronism of CHF predisposes patients to secondary hyperparathyroidism because of a chronic increase in Ca 2+ and Mg 2+ losses in urine and feces, with a fall in their serum ionized levels and consequent secretion of parathyroid hormone. Secondary hyperparathyroidism accounts for bone resorption and contributes to a fall in bone strength that can lead to nontraumatic fractures. The long-term use of a loop diuretic with its attendant urinary wasting of Ca 2+ and Mg 2+ further predisposes patients to secondary hyperparathyroidism and attendant bone loss. Aberrations in minerals and micronutrient homeostasis that includes Ca 2+ , Mg 2+ , vitamin D, zinc and selenium appear to be an integral component of pathophysiologic expressions of CHF that contributes to its systemic and progressive nature. This broader perspective of CHF, which focuses on the importance of secondary hyperparathyroidism and minerals and micronutrients, raises the prospect that dietary supplements could prove remedial in combination with the current standard of care.
The US Food and Drug Administration's approval in March 2007 of aliskiren, the first commercially available direct renin inhibitor, for the treatment of hypertension met with great enthusiasm. Clinical trials have demonstrated it to be as effective as other commonly prescribed antihypertensive agents with few side effects. Preclinical studies in genetically manipulated rats have shown it to be effective in reversing angiotensin II-induced cardiac and renal damage. Despite the notable absence of human clinical data for this agent, many clinicians have touted aliskiren as the ideal agent to achieve additional suppression of the renin-angiotensin-aldosterone system (RAAS) as a means to reduce the morbidity and mortality of chronic diseases of the cardiovascular and renal systems. Clinical studies are ongoing and future studies are planned to prove its effectiveness in several chronic diseases known to be related to RAAS activation.
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