Dr. Ron’s Research Review – June 1, 2011

This week’s research review focuses on the recent controversy over niacin to prevent heart attacks.

NIH stops study of niacin to prevent heart attacks Link

There was a small increase in strokes in the high-dose niacin users - 28 among those 1,718 people given Niaspan, compared with 12 among the 1,696 placebo users.

Low levels of high-density lipoprotein (HDL) cholesterol are associated with in- creased atherothrombotic events, including stroke. Niacin is a safe and effective means of raising HDL. (Keener and Sanossian 2008)

Niacin has pleiotropic effects on cardiovascular risk profiles by raising high-density lipoprotein-cholesterol (HDL-C), reducing triglycerides, low-density lipoprotein-cholesterol (LDL-C), lipoprotein (a) and markers of inflammation. (Wierzbicki 2011)

The epidemiological association of high HDL-C and reduced cardiovascular disease (CVD) events is well established from studies such as Framingham Heart Study with a 1% increase being associated with a 1% reduction in risk (but which is often misstated as 2–3% excluding the units of per mg⁄dl of HDL-C) (Wierzbicki 2011)

Vasodilatation of the peripheral vessels (e.g. flushing) might be crucially important in the early primary prevention of atherosclerosis by niacin. Only the hypothesis of “vasa vasorum hypoxia” provides a logical explanation for the early development of atherosclerosis deep in the arterial wall, between the media and intima at the branching sites of arteries. (Tuohimaa and Jarvilehto 2010)

Dr. Ron


Articles

What does the future hold for niacin as a treatment for hyperlipidaemia and cardiovascular disease?

            (Ahmed 2010) Download

Statin therapy is widely used in treatment and prevention of cardiovascular disease (CVD). It is well established that statin therapy is not associated with significant increase in high-density lipoprotein cholesterol (HDL-c) or significant decrease in triglyceride level. Importantly, emerging evidence has suggested that low HDL-c and high triglyceride are strong risk factors associated with CVD. Niacin is a unique lipid-lowering medication with a capacity to lower low-density lipoprotein cholesterol (LDL-c), triglyceride and increase HDL-c. In this context, there is considerable interest in trials involving niacin as monotherapy and in association with statins. Recent trials showed that the combination of statin and niacin is an effective treatment not only for dyslipidaemia (high LDL-c, high triglyceride and low HDL-c) but also for carotid intima-media thickness, one of the important features of atherosclerosis. Furthermore, niacin is distinguished by its unique capacity to effectively lower lipoprotein (a) [Lp(a)] levels. Flushing is the only factor that limits the wide use of niacin. The combination of statin and niacin has potential as a future treatment of atherogenic dyslipidemias; however, further evidence is needed. Importantly, the impact of niacin and statin on insulin sensitivity is not yet known. This article projects the potential benefits of current and possible future niacin clinical trials.

Niacin for stroke prevention: evidence and rationale

            (Keener and Sanossian 2008) Download

Low levels of high-density lipoprotein (HDL) cholesterol are associated with increased atherothrombotic events, including stroke. Niacin is a safe and effective means of raising HDL, yet its role in stroke prevention is not well characterized. The purpose of the study is to determine the role of niacin in stroke prevention. A search of the PUBMED database using the keywords niacin, stroke, atherosclerosis, and/or carotid artery was undertaken to identify studies for review. National guidelines from the American Heart Association and National Cholesterol Education Program were reviewed. Treatment of low serum HDL (<40 mg/dL) is an identified goal of dyslipidemic therapy. Niacin is effective in raising HDL levels and reducing cardiovascular events in individuals with high vascular risk and can be used for treatment of stroke patients with low serum HDL. Niacin can be used safely in combination with statins, the first-line dyslipidemic treatment for secondary stroke risk reduction, with increased efficacy. Studies are needed to better define the role for niacin in secondary stroke prevention. Treatment of stroke patients with extended-release (ER) of niacin, alone or in combination with statins, should be considered in stroke patients with atherosclerotic mechanisms with low serum HDL-C levels.

Niacin in the prevention of atherosclerosis: Significance of vasodilatation

         (Tuohimaa and Jarvilehto 2010) Download

There is a rising interest towards the old drug, nicotinic acid (niacin, vitamin B(3)), because at pharmacological concentrations it has a beneficial effect on HDL cholesterol. Its use, however, was limited due to its adverse effect, flushing. When the mechanism of flushing was solved, a combination of niacin and DP1 receptor antagonist or prostaglandin inhibitor is used, there has been a comeback of niacin with extensive clinical trials. This paper argues that the new strategy with niacin for the prevention of atherosclerosis should be re-evaluated, because vasodilatation of the peripheral vessels might be crucially important in the early primary prevention according to our "vasa vasorum hypoxia" hypothesis.

Niacin: the only vitamin that reduces cardiovascular events        

(Wierzbicki 2011) Download


References

Ahmed, M. H. (2010). "What does the future hold for niacin as a treatment for hyperlipidaemia and cardiovascular disease?" J Cardiovasc Med (Hagerstown) 11(11): 858-60.

Keener, A. and N. Sanossian (2008). "Niacin for stroke prevention: evidence and rationale." CNS Neurosci Ther 14(4): 287-94.

Tuohimaa, P. and M. Jarvilehto (2010). "Niacin in the prevention of atherosclerosis: Significance of vasodilatation." Med Hypotheses 75(4): 397-400.

Wierzbicki, A. S. (2011). "Niacin: the only vitamin that reduces cardiovascular events." Int J Clin Pract 65(4): 379-85.