Correspondence

Hypertriglyceridemia

N Engl J Med 2008; 358:310-311January 17, 2008

Article

To the Editor:

Brunzell's Clinical Practice article on hypertriglyceridemia (Sept. 6 issue)1 does not give n−3 fatty acid supplementation fair representation. Clinical evidence, similar to or better than evidence in support of niacin, supports the use of n−3 fatty acids in the management of dyslipidemia.

In contrast to the review Brunzell cites, which questions the benefit of n−3 fatty acids,2 other systematic reviews3,4 of secondary-prevention trials showed the efficacy of n−3 fatty acids in reducing cardiovascular-related and overall mortality. According to a recent report, n−3 fatty acids in combination with a statin significantly reduced major coronary events in patients with known cardiovascular disease.5

In regard to niacin, there have been no randomized trials in which niacin alone reduced overall mortality. The findings in the observational portion of the Coronary Drug Project 9 years after the original trial are not conclusive.6 Many patients in the niacin group stopped taking the medication after the study ended, suggesting that factors other than niacin were responsible for the reduction in mortality.

Supplementation with n−3 fatty acids effectively reduces triglyceride levels and is safe, without serious side effects. It is a viable option in managing hypertriglyceridemia (especially in patients with moderate-to-high cardiovascular risk) and should not be dismissed from the clinician's armamentarium.

(The views expressed in this letter are those of the author and do not necessarily reflect the official positions of the Department of the Army and the Department of Defense.)

Robert Oh, M.D., M.P.H.
Tripler Army Medical Center, Honolulu, HI 96859
roboh98@gmail.com

Dr. Oh reports holding stock in Merck, Pfizer, and Teva Pharmaceuticals. No other potential conflict of interest relevant to this letter was reported.

6 References

1. 1

   Brunzell JD. Hypertriglyceridemia. N Engl J Med 2007;357:1009-1017
   Full Text | Web of Science | Medline

2. 2

   Twisselmann B. Risks and benefits of omega 3 fats: summary of responses. BMJ 2006;332:915-916
   CrossRef | Web of Science

3. 3

   Wang C, Chung M, Lichtenstein A, et al. Effects of omega-3 fatty acids on cardiovascular disease: evidence report/technology assessment number 94. Rockville, MD: Agency for Healthcare Research and Quality, 2004. (AHRQ publication no. 04-E009-1.)
   

4. 4

   Studer M, Briel M, Leimenstoll B, Glass TR, Bucher HC. Effect of different antilipidemic agents and diets on mortality: a systematic review. Arch Intern Med 2005;165:725-730
   CrossRef | Web of Science | Medline

5. 5

   Yokoyama M, Origasa H, Matsuzaki M, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet 2007;369:1090-1098[Erratum, Lancet 2007;370:220.]
   CrossRef | Web of Science | Medline

6. 6

   Canner PL, Berge KG, Wenger NK, et al. Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. J Am Coll Cardiol 1986;8:1245-1255
   CrossRef | Web of Science | Medline

To the Editor:

In his comprehensive review of hypertriglyceridemia, Brunzell recommends treatment when the triglyceride level exceeds 1000 mg per deciliter, in order to prevent triglyceride-induced pancreatitis. This conflicts with the 2001 National Cholesterol Education Program (NCEP) guidelines, which established a triglyceride level of 500 mg per deciliter as the threshold above which treatment should be administered to prevent triglyceride-induced pancreatitis.1 Many authorities endorse this recommendation.2

Ashok Malani, M.D.
University of Southern California, Los Angeles, CA 90089
drmalani@yahoo.com

Hussam Ammar, M.D.
Sanjay Mughal, M.D.
Heartland Regional Medical Center, St. Joseph, MO 64506

2 References

1. 1

   Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III): final report. Circulation 2002;106:3143-3421
   Medline

2. 2

   Mahley RW, Weisgraber KH, Farese RV Jr. Disorders of lipid metabolism. In: Larsen PR, Kronenberg HM, Melmed S, Polonsky KS, eds. Williams textbook of endocrinology. 10th ed. Philadelphia: Saunders, 2003:1642-705.
   

Author/Editor Response

The letters by Oh and by Malani et al. raise three questions. First, what is the efficacy of n−3 fatty acid supplements for decreasing deaths from coronary heart disease? Two articles are cited in my Clinical Practice article, one positive and one negative. Oh reports several additional articles, mostly positive. Other recent reports also address this issue.1,2 The use of n−3 fatty acid supplements remains controversial. There are good data to support the role of n−3 fatty acids in decreasing plasma triglyceride levels in some patients with hypertriglyceridemia. I recommend eating n−3–enriched fatty fish; an additional benefit is the reciprocal decrease in the amount of foods as entrées containing saturated fat and cholesterol.

Oh also questions the basis for the recommendations for nicotinic acid to treat patients with hyperlipidemia. The trials he mentions are those involving nicotinic acid monotherapy. In the Clinical Practice article, I recommend nicotinic acid in combination with other drugs that complement its effects, in particular, to selectively lower small, dense low-density lipoprotein (LDL) particles.3 As opposed to studies of n−3 fatty acid supplementation with variable results, all studies of nicotinic acid referenced in the article showed an association with a decrease in coronary artery disease.

Malani et al. call into question the triglyceride levels above which drug therapy is recommended to prevent triglyceride-induced pancreatitis. I recommend 1000 mg per deciliter as the threshold, whereas the Adult Treatment Panel III recommends 500 mg per deciliter. My colleagues and I performed a prospective trial to answer this question in the 1970s, as referenced in the Clinical Practice article. Triglyceride-induced pancreatitis occurred at plasma triglyceride levels above 2000 mg per deciliter and did not recur if triglyceride levels were maintained below 2000 mg per deciliter. The recommended level of less than 1000 mg per deciliter should be complemented by the recommendation to avoid specific drugs that raise triglyceride levels.

John D. Brunzell, M.D.
University of Washington, Seattle, WA 98195-6426
brunzell@u.washington.edu

3 References

1. 1

   Mozaffarian D, Rimm EB. Fish intake, contaminants, and human health: evaluating the risks and the benefits. JAMA 2006;296:1885-1889[Erratum, JAMA 2007;297:590.]
   CrossRef | Web of Science | Medline

2. 2

   Sachs FM, Campos H. Polyunsaturated fatty acids, inflammation, and cardiovascular disease: time to widen our view of the mechanisms. J Clin Endocrinol Metab 2006;91:398-400
   CrossRef | Web of Science | Medline

3. 3

   Zambon A, Hokanson JE, Brown BG, Brunzell JD. Evidence for a new pathological mechanism for coronary artery disease: hepatic lipase-mediated changes in LDL density. Circulation 1999;99:1959-1964
   Web of Science | Medline