Background-The mechanisms of simple faint remain elusive. We propose that postural fainting is related to excessive thoracic hypovolemia and splanchnic hypervolemia during orthostasis compared with healthy subjects. Methods and Results-We studied 34 patients 12 to 22 years old referred for multiple episodes of postural faint and 11 healthy subjects. Subjects were studied in the supine position and during upright tilt to 70°for 30 minutes and subgrouped into Sϩ, historical fainters who fainted during testing (nϭ24); SϪ, historical fainters who did not faint during testing (nϭ10); and control subjects. Supine venous occlusion plethysmography showed no differences between blood flows of the forearm and calf in Sϩ, SϪ, or control. Cardiac index, total peripheral resistance, and blood volume were not different. Using impedance plethysmography, we assessed blood redistribution during upright tilt. This demonstrated decreased thoracic blood volume and increased splanchnic, pelvic, and leg blood volumes for all subjects. However, thoracic blood volume was decreased in Sϩ compared with control volume, correlating well with the maximum upright heart rate. Splanchnic volume was decreased in the Sϩ and SϪ groups, correlating with the change in thoracic blood volume. Pelvic and leg volume changes were similar for all groups and uncorrelated to thoracic blood volume. Conclusions-Enhanced

Orthostatic hypotension (OH) occurs in 0.5% of individuals and as many as 7-17% of patients in acute care settings. Moreover, OH may be more prevalent in the elderly due to the increased use of vasoactive medications and the concomitant decrease in physiologic function, such as baroreceptor sensitivity. OH may result in the genesis of a presyncopal state or result in syncope. OH is defined as a reduction of systolic blood pressure (SBP) of at least 20 mm Hg or diastolic blood pressure (DBP) of at least 10 mm Hg within 3 minutes of standing. A review of symptoms, and measurement of supine and standing BP with appropriate clinical tests should narrow the differential diagnosis and the cause of OH. The fall in BP seen in OH results from the inability of the autonomic nervous system (ANS) to achieve adequate venous return and appropriate vasoconstriction sufficient to maintain BP. An evaluation of patients with OH should consider hypovolemia, removal of offending medications, primary autonomic disorders, secondary autonomic disorders, and vasovagal syncope, the most common cause of syncope. Although further research is necessary to rectify the disease process responsible for OH, patients suffering from this disorder can effectively be treated with a combination of nonpharmacologic treatment, pharmacologic treatment, and patient education. Agents such as fludrocortisone, midodrine, and selective serotonin reuptake inhibitors have shown promising results. Treatment for recurrent vasovagal syncope includes increased salt and water intake and various drug treatments, most of which are still under investigation.

Existing guidelines for the prevention and treatment of coronary artery disease focus on lowering low-density lipoprotein cholesterol (LDL-C) as the primary lipid target. However, there has been increasing interest in raising high-density lipoprotein cholesterol (HDL-C) due to strong evidence linking low HDL-C levels with an increased risk of atherosclerosis. Raising HDL-C levels with lifestyle changes and pharmacologic interventions appear to reduce the risk of coronary artery disease beyond that of lowering LDL-C alone. Niacin has a substantial HDL-C raising effect, and also may beneficially alter total cholesterol, LDL-C and triglyceride levels. Niacin also exhibits antioxidant, anti-inflammatory and other beneficial effects on atherosclerosis. Niacin is safe and effective to use in women, in patients with diabetes mellitus and/or metabolic syndrome, and when used in combination with statins. Niacin has the promise of being a powerful pharmacologic agent in the fight against atherosclerotic disease, although additional clinical studies are required to examine this further.

Nicotinic acid (niacin) is one of the oldest drugs used to treat dyslipidemia. In addition to modestly lowering low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a), niacin is currently the most effective available agent for raising high-density lipoprotein cholesterol (HDL-C). Despite its well-documented beneficial effects on lipids, the clinical use of niacin has been limited by its side effect profile, notably flushing. This sensation of cutaneous vasodilatation and burning has limited patient compliance and is a frequent cause of discontinuation of the drug. While pretreatment with nonsteroidal anti-inflammatory agents, such as aspirin, may reduce the incidence of flushing, present-day niacin still results in flushing in many patients. Recent studies have elucidated what we currently understand as the molecular mechanism that mediates niacin-induced flushing, specifically that niacin acting through its receptor stimulates the production of several prostaglandins, including prostaglandin (PG) I(2), PGE(2) and PGD(2). Laropiprant is a potent, highly selective prostaoid DP(1) receptor antagonist that decreases the incidence and intensity of niacin-induced flushing without affecting its beneficial lipid effects. Thus, laropiprant, when used in conjunction with niacin, can improve the tolerability of niacin and aid in medication compliance. This paper reviews the data suggesting the importance of raising HDL with niacin, describes the pharmacology of the drug, and examines the potential beneficial effects of combining niacin with laropiprant.