Direct renin inhibition: an analysis of possible benefits.

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.

Exercise-induced asystole with syncope in a healthy young man.

Exercise-related syncope is frequently an ominous symptom associated with advanced cardiovascular disease. Asystole during or after exercise is a rare occurrence in persons with structural heart disease and is an even rarer cause of syncope in healthy persons. Herein we report on a healthy 40-year-old man who was hospitalized after a syncopal episode that followed playing basketball. He recalled several near-syncopal episodes after strenuous exercise over the past 6 months, during which time he used marijuana. A loss of sinoatrial activity and appearance of ventricular asystole occurred immediately after monitored exercise to suggest parasympathetic dominance, which could be related to long-term cannabinoid use.

Congestive heart failure is a systemic illness: a role for minerals and micronutrients.

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.

Secondary hyperparathyroidism and hypovitaminosis D in African-Americans with decompensated heart failure.

OBJECTIVE: We previously noted secondary hyperparathyroidism (SHPT) in African-American patients hospitalized during February, 2005 with either untreated or treated congestive heart failure (CHF) due to ischemic or idiopathic cardiomyopathy. Herein, we hypothesized that housebound African-American patients hospitalized during the period of June 1 through August 31, 2005, with CHF would have SHPT and hypovitaminosis D. METHODS: Twenty-five African-American patients with an ejection fraction (EF) less than 35% due to ischemic or dilated (idiopathic) cardiomyopathy were monitored: 20 were hospitalized with CHF, stratified on historical grounds as of 4 weeks' or longer duration or of 1 to 2 weeks' duration in 11 and 9 patients, respectively, despite medical care that included furosemide; serum parathyroid hormone (PTH) and 25(OH)D at the time of admission in these patients were compared to five asymptomatic outpatients seen during the summer with stable, compensated failure. RESULTS: Serum PTH was elevated (127 +/- 13; 82-243 pg/mL) in all patients with CHF of 4 weeks' or longer duration (normal, 12-65 pg/mL) and was elevated in three of nine patients (59 +/- 8; 18-99 pg/mL) with CHF of 1 to 2 weeks' duration. Ionized hypocalcemia (1.09 +/- 0.03 and 1.08 +/- 0.02 mmol/L; normal, 1.12-1.30) and hypomagnesemia (0.47 +/- 0.02 and 0.46 +/- 0.03 mmol/L; normal, 0.53-0.67) were respectively found in long- or short-duration CHF. No compensated patient had elevated PTH (42 +/- 5; 17-53). Hypovitaminosis D (< or =30 ng/mL) was universally present in patients with CHF of 4 weeks' or longer duration (15.1 +/- 1.4; 7.0-23.8 ng/mL) and was also prevalent in the other groups (20.3 +/- 5.1, 7.0-54.1 ng/mL in CHF of 1 to 2 weeks' duration and 23.1 +/- 4.9; 17.2-42.7 ng/mL in compensated failure). CONCLUSIONS: In African-American patients with CHF, hypovitaminosis D, aldosteronism, and loop diuretic treatment each exaggerate Ca and Mg losses to stress a fragile Ca balance leading to ionized hypocalcemia and hypomagnesemia with SHPT.