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Obstructive sleep apnea (OSA) has been strongly associated with several cardiovascular disorders during the past decade, and studies suggested that there might be a causal relationship. Recent studies have described several pathophysiologic mechanisms that are active in OSA and may participate in the development of cardiovascular disorders. Primarily, the repetitive respiratory events that occur in OSA cause hypoxia, hypercapnea, arousals, or disrupted sleep singly or in combination. These abnormal physiologic events result in increased sympathetic outflow, alterations in blood pressure control mechanisms, dysfunctional ventilatory regulation, and vascular alterations. As a consequence of the relative impact and the genetic predisposition, these pathophysiologic alterations may lead to or complicate a wide variety of cardiovascular disorders. Frequently, patients who have OSA present with complaints of excessive daytime sleepiness, chronic fatigue, snoring, morning headache, and nocturnal arousals. Difficult-to-control hypertension, recurrent exacerbations of congestive heart failure, and nocturnal angina are common cardiovascular manifestations of undiagnosed OSA. This article reviews the major cardiovascular disorders associated with OSA and the pathophysiologic mechanisms associated with their development.
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PMID:Cardiovascular disease and obstructive sleep apnea: implications for physicians. 1090 7

We report here a 9-year-old girl with fibromuscular dysplasia of many muscular arteries including both renal and internal carotid arteries, the celiac artery, superior mesenteric artery, and one external carotid artery. She suffered from severe renovascular hypertension with beginning secondary cardiac decompensation, typical angina abdominalis, and neurological signs, including severe headaches and hemianopsia. Surgery was performed for all major vessels and the outcome is good 2.5 years after the operation. The clinical presentation, differential diagnosis, and treatment options of fibromuscular dysplasia in childhood are discussed and the literature is reviewed.
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PMID:Multivisceral fibromuscular dysplasia in childhood: case report and review of the literature. 1099 May 61

Despite the proliferation of computer-based resources for patients, usefulness has been limited to date. Already, 17,000 biomedical Internet sites exist, and patients are increasingly finding support and knowledge on the Internet, but the accuracy of the information found is highly variable and difficult for patients to assess. Patients have also found value in electronic communication with physicians, although relatively few physicians routinely use email to communicate with patients on a regular basis. Nonetheless, patient-focused information technologies potentially will have profound effects on medical care. With advancing sophistication of technology, patients will increasingly be able to compare and choose doctors using the Internet and to access information that allows them to monitor and regulate the quality of their own care. Further, technologies will likely be developed to allow patients to increasingly manage their own care -- whether they are patients with chronic illnesses such as diabetes or congestive heart failure who use customized software to adjust drug dosages and other treatments or patients with such common illnesses as headache or gastrointestinal infection who access self-management programs that may even write prescriptions for them. Thoughtful analysis and policy development will be critical for ensuring that the benefits are maximized and potential harm minimized. Specific areas include assessing the effects on outcomes and the characteristics of patients and technologies that succeed with self-management, and developing policies regarding liability for Web-based medical transactions and the privacy of information provided to physicians by email and via interactive Web sites.
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PMID:The use of information technology in improving medical performance. Part III. Patient-support tools. 1110 58

Clinical trials continue to guide patient management. However, the hypotheses generally come from observational studies. Studies on women continue to be too little and too few, particularly in light of the fact that most elderly hypertensive patients are likely to be women. Attention has been drawn to the possibility that hypertension per se may engender symptoms such as headache for example, in addition to harder endpoints such as death. The MICROHOPE study, which was not a blood pressure-lowering study, showed that angiotensin converting enzyme inhibition with ramipril in diabetic patients provided the same beneficial effects previously published for the HOPE study. The doxazosin arm of the ALLHAT study was terminated by the data monitoring and safety board because the doxazosin-treated patients developed congestive heart failure at a greater rate than diuretic-treated patients. Two extensive studies testing two different classes of calcium antagonists against primarily diuretic-based treatment showed that the calcium antagonists were no less effective in terms of preventing hard endpoints. A small, but impressive cross-over study testing the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, pravastatin, against placebo showed that statin treatment lowers blood pressure in hypercholesterolemic patients with hypertension. Meta- analyses emphasized the value of blood pressure reduction in the elderly and added to the controversy and confusion about the role of calcium antagonists in the first-line treatment of hypertension. The point may be moot since with the current recommendations few hypertensive patients will be adequately treated with a single agent.
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PMID:Recent clinical trial highlights in hypertension. 1127 95

Levosimendan, a pyridazinone-dinitrile derivative, is a calcium sensitiser with additional action on adenosine triphosphate (ATP)-sensitive potassium channels. It is used intravenously (IV) for the treatment of decompensated cardiac failure. At therapeutic doses, levosimendan exhibits enhanced contractility with no increase in oxygen demands. It also produces antistunning effects without increasing myocardial intracellular calcium concentrations or prolonging myocardial relaxation. Levosimendan also causes coronary and systemic vasodilation. In patients with decompensated congestive heart failure (CHF), IV levosimendan significantly reduced the incidence of worsening CHF or death. IV levosimendan significantly increased cardiac output or cardiac index and decreased filling pressure in the acute treatment of stable or decompensated CHF in large, double-blind, randomised trials and after cardiac surgery in smaller trials. Levosimendan is well tolerated, with the most common adverse events (headache, hypotension, nausea) being secondary to vasodilation. It has not been shown to be arrhythmogenic. Levosimendan has shown no clinically important pharmacokinetic interactions with captopril, felodipine, beta-blockers, digoxin, warfarin, isosorbide-5-mononitrate, carvedilol, alcohol (ethanol) or itraconazole.
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PMID:Levosimendan. 1136 86

In the past decade, cases of babesiosis in humans have been reported with increasing frequency, especially in the northeastern United States. Babesia microti (in the United States) and bovine strains (in Europe) cause most infections in humans. Most cases are tick-borne, although cases of transfusion-associated and transplacental/perinatal transmission have also been reported. Factors associated with more severe disease include advanced age, previous splenectomy and immunodeficient states. Symptoms include high fever, chills, diaphoresis, weakness, anorexia and headache. Later in the course of the illness, the patient may develop jaundice. Congestive heart failure, renal failure and acute respiratory distress syndrome are the most common complications. Therapy using the combination of quinine sulfate and clindamycin was the most commonly used treatment; however, atovaquone suspension plus azithromycin was recently reported an equally effective and less toxic therapy. Exchange transfusion, together with antibabesial chemotherapy, may be necessary in critically ill patients.
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PMID:When to suspect and how to monitor babesiosis. 1138 11

The uses, pharmacology, clinical efficacy, dosage and administration, adverse effects, and drug interactions of hawthorn are discussed. Hawthorn (Crataegus oxyacantha) is a fruit-bearing shrub with a long history as a medicinal substance. Uses have included the treatment of digestive ailments, dyspnea, kidney stones, and cardiovascular disorders. Today, hawthorn is used primarily for various cardiovascular conditions. The cardiovascular effects are believed to be the result of positive inotropic activity, ability to increase the integrity of the blood vessel wall and improve coronary blood flow, and positive effects on oxygen utilization. Flavonoids are postulated to account for these effects. Hawthorn has shown promise in the treatment of New York Heart Association (NYHA) functional class II congestive heart failure (CHF) in both uncontrolled and controlled clinical trials. There are also suggestions of a beneficial effect on blood lipids. Trials to establish an antiarrhythmic effect in humans have not been conducted. The recommended daily dose of hawthorn is 160-900 mg of a native water-ethanol extract of the leaves or flowers (equivalent to 30-169 mg of epicatechin or 3.5-19.8 mg of flavonoids) administered in two or three doses. At therapeutic dosages, hawthorn may cause a mild rash, headache, sweating, dizziness, palpitations, sleepiness, agitation, and gastrointestinal symptoms. Hawthorn may interact with vasodilating medications and may potentiate or inhibit the actions of drugs used for heart failure, hypertension, angina, and arrhythmias. The limited data about hawthorn suggest that it may be useful in the treatment of NYHA functional class II CHF.
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PMID:Hawthorn: pharmacology and therapeutic uses. 1188 7

Levosimendan is one of the first agents of a new class of drugs known as calcium sensitizers. These drugs are believed to increase cardiac contractility by sensitizing cardiac myofibrils to calcium, and may therefore be of clinical benefit in the treatment of low-cardiac output states, particularly congestive heart failure. In addition to sensitizing troponin to intracellular calcium, levosimendan has been shown to inhibit phosphodiesterase III, which may contribute to its positive inotropic effect, and open adenosine triphosphate (ATP)-sensitive potassium channels (K(ATP)), which may produce vasodilation. Unlike currently available intravenous inotropes, levosimendan does not increase myocardial oxygen utilization, has not been shown to be proarrhythmic, and has been used effectively in the presence of beta-blocking medications. Levosimendan also has not been shown to impair ventricular relaxation, which was an initial concern with this class of drugs. Clinical studies of levosimendan have demonstrated short-term hemodynamic benefits of levosimendan over both placebo and dobutamine. While large-scale, long-term morbidity and mortality data are scarce, the Levosimendan Infusion versus Dobutamine in severe low-output heart failure (LIDO) study suggested a mortality benefit of levosimendan over dobutamine up to 180 days after treatment. Clinical studies comparing levosimendan with other positive inotropes, namely milrinone, are lacking. Levosimendan treatment appears to be well-tolerated, with the primary adverse events being headache and hypotension. No clinically significant drug-drug interactions have been reported with levosimendan to date. The clinical future of levosimendan will depend on the results of larger, ongoing clinical trials.
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PMID:Levosimendan: a unique approach to the treatment of heart failure. 1214 86

Nesiritide, a recombinant human B-type natriuretic peptide, is the first in a new drug class for the treatment of decompensated heart failure. The drug binds to receptors in the vasculature, kidney, adrenal gland, and brain, and overcomes resistance to endogenous BNP present in patients with CHF. Nesiritide administration leads to a rapid and balanced vasodilatory effect, which results in a significant decrease in right and left ventricular filling pressures and systemic vascular resistance and at the same time in an increase in stroke volume and cardiac output without a change in heart rate. These early hemodynamic changes result in a rapid improvement in symptoms of heart failure. In addition, nesiritide lowers aldosterone, catecholamines, and endothelin-1 levels and its effect on the kidney leads to an increased natriuresis and diuresis without effect on serum potassium or renal function. Prior to its approval for clinical use, nesiritide was studied in 10 different clinical trials involving 941 patients with moderate and severe CHF, including elderly patients, patients with both systolic and diastolic dysfunction, and patients with arrhythmias, renal insufficiency, and acute ischemic syndrome. In comparative studies with available vasoactive therapies frequently used for treatment of patients with decompensated heart failure, nesiritide was proven comparable in efficacy to inotropic drugs such as dobutamine, but superior in safety. In a recent study, nesiritide was found to be more effective and better tolerated than the vasodilator, nitroglycerin. The most common side effects expected with the use of nesiritide are headaches and decrease in blood pressure. At the recommended dose of nesiritide, headache was reported during the first 24 hours of treatment in 8% of patients and symptomatic hypotension in 4% of patients, compared to 20% and 5% in nitroglycerin-treated patients.
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PMID:Nesiritide: a new drug for the treatment of decompensated heart failure. 1223 67

In well designed studies in patients with mild to moderate hypertension, combinations of the sustained-release (SR) formulation of the nondihydropyridine calcium channel antagonist verapamil 120 to 240 mg/day and the ACE inhibitor trandolapril 0.5 to 8 mg/day were significantly more effective in reducing sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP) from baseline than placebo. In most randomised studies, combinations of verapamil SR 120 to 240 mg/day and trandolapril 0.5 to 8 mg/day were significantly more effective in lowering sitting DBP and SBP than the corresponding monotherapies administered at the same dosage. Trandolapril/verapamil SR 2/180 mg/day provided significantly more effective 24-hour ambulatory blood pressure (BP) control than of the corresponding monotherapies. Moreover, trandolapril/verapamil SR reduced BP in patients inadequately controlled with either of the corresponding monotherapies. The antihypertensive efficacy of trandolapril/verapamil SR 2/180 mg/day was generally similar to that of other combinations of antihypertensive agents (metoprolol/hydrochlorothiazide, atenolol/chlorthalidone, lisinopril/hydrochlorothiazide, enalapril/hydrochlorothiazide) in patients with hypertension, including those with type 2 diabetes mellitus. Trandolapril/verapamil SR reduced BP in patients with hypertension and type 2 diabetes or primary renal disease, Black patients and elderly patients. Trandolapril/verapamil SR was more effective than the individual components administered as monotherapy in reducing proteinuria in patients with type 2 diabetes or primary renal disease. Trandolapril/verapamil SR had a neutral or beneficial effect on metabolic parameters (glucose, insulin, lipids) in patients with hypertension, including those with type 2 diabetes. Trandolapril/verapamil SR preserved left ventricular function in patients with heart failure. Fewer cardiac events occurred after therapy with trandolapril/verapamil SR than after trandolapril alone in post-myocardial infarction patients with congestive heart failure. The incidence of adverse events in recipients of trandolapril/verapamil SR was similar to that of the individual components, and that of other combination therapies. In placebo-controlled trials conducted in the US, headache, upper respiratory tract infections, cough, constipation, atrioventricular block (first degree) and dizziness were the most commonly reported adverse events in recipients of combinations of verapamil SR (120 to 240 mg/day) and trandolapril (0.5 to 8 mg/day). In conclusion, the fixed-dose combination of trandolapril/verapamil SR is an effective treatment for patients with hypertension, including those with type 2 diabetes. Trandolapril/verapamil SR tended to be more effective than monotherapy with either verapamil SR or trandolapril, and generally showed antihypertensive efficacy similar to that of other combination antihypertensive therapies. Current data support the use of trandolapril/verapamil SR as an alternative treatment when monotherapy with either agent is not effective. Data from large clinical trials currently being conducted will assist in fully defining the role of trandolapril/verapamil SR as a cardio- and renoprotective agent.
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PMID:Fixed combination trandolapril/verapamil sustained-release: a review of its use in essential hypertension. 1242 Nov 12


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