Niacin, either alone or in combination with a statin, safely and effectively addresses most lipid abnormalities in patients with mixed dyslipidemia. Therapeutically used for more than 50 years, niacin is the most effective clinically available agent for increasing high-density lipoprotein cholesterol (HDL-C) levels. In most patients, niacin increases HDL-C by 20–40%. Niacin also has beneficial effects on all known pro-atherogenic lipid parameters, including lowering low-density lipoprotein cholesterol(LDL-C), non-HDL-C and triglycerides. It is the only current lipid therapy that decreases Lp, an independent risk factor for atherosclerosis. Niacin also has favorable effects on lipid particle size; it reduces small, dense LDL while increasing cardio-protective HDL, as measured by either particle size (HDL) or by apolipoprotein profile (HDL containing apolipoprotein A-I without apolipoprotein A-II). These alterations in lipids are clinically meaningful, as treatment with niacin has been associated with significant reductions in cardiovascular events and morbidity and, in combination with statins, with regression of atherosclerotic cardiovascular disease.
Despite niacin’s numerous beneficial lipid effects, patient compliance to long-term therapy is challenged by flushing, a common side effect of niacin. The onset of flushing can occur rapidly and usually lasts about 1 h. It is a transient, non-allergic response, but it may result in patient discomfort.
Physiologically, niacin influences lipoprotein metabolism by decreasing triglyceride synthesis via multiple pathways.
Considering niacin’s beneficial effects on nearly all lipid parameters associated with cardiovascular risk, and recent demonstration of its vascular anti-inflammatory properties, strategies to minimize or eliminate flushing should be deemed important to increase patient compliance to niacin therapy. As attenuation to flushing rapidly develops, dose titration is important in reducing flushing in patients. As a result of niacin’s mechanism of action, flushing can be managed in three ways: controlling the absorption rate of niacin; preventing the production of prostaglandins; or simultaneously blocking the DP1, EP2 and EP4 receptors.
Educating patients about the benefits of niacin therapy may also increase the likelihood that patients are willing to tolerate any of the minor bothersome effects of flushing . One of the easiest ways that medical personnel can help improve their patients compliance with niacin therapy is to provide their patients with a clear understanding of the clinical benefits of niacin as well as what to expect and how to manage flushing. While improvements in lipid profiles are meaningful to physicians, patients may be more willing to tolerate the transient flushing symptoms that can occur if they realize that niacin reduces cardiovascular risk, as determined by both mortality and cardiovascular event rates, and that this benefit extends beyond the duration of active therapy. Patients should be counseled to take aspirin (325 mg) 30 min before a snack and extended-release niacin. The importance of continuing to take the final daily maintenance dose of niacin extended-release should be emphasized. If there is a period of discontinuation, the titration procedure has to be followed again, although it maybe possible to accelerate it at the discretion of the prescriber. Patients are also advised to avoid hot beverages, spicy foods and hot showers near the time of taking niacin.
Given niacin’s beneficial effects across a wide spectrum of the lipid profile, proven safety record and ability to be safely combined with statins, it should be regarded as an attractive option for the treatment of dyslipidemia.
The same receptor that is responsible for niacin’s decrease in free fatty acids is also likely the same receptor that is responsible for the flushing side effects. Therefore, it is currently difficult to separate the two effects, but flushing can be effectively managed in patients.
As tolerance to flushing develops rapidly, healthcare professionals should particularly address flushing during dose titration of niacin.
Obesity and Free Fatty Acids (FFA) – N.I.H.
Obesity is closely associated with (peripheral as well as hepatic) insulin resistance and with a low grade state of inflammation characterized by elevation of pro-inflammatory cytokines in blood and tissues. Both, insulin and inflammation, contribute to the development of type 2 diabetes mellitus, hypertension, atherogenic dyslipidemias and disorders of blood coagulation and fibrinolysis. All these disorders are independent risk factors for atherosclerotic vascular disease such as heart attacks, strokes and peripheral arterial disease.
The reason why obesity is associated with insulin resistance is not well understood. However, it can be demonstrated that free fatty acids cause both insulin resistance and inflammation in the major insulin target tissues (skeletal muscle, liver and endothelial cells) and thus are an important link between obesity, insulin resistance, inflammation and the development of type 2 diabetes millitus, hypertension, dyslipidemia, disorders of coagulation and atherosclerotic vascular disease.