Correspondence
Correction
Drug Treatment of Lipid Disorders
N Engl J Med 1999; 341:2020-2021December 23, 1999
- Article
To the Editor:
In his review of drug treatment for lipid disorders (Aug. 12 issue),1 Dr. Knopp notes that dietary intervention is an important first step in the treatment of patients with hyperlipidemia. We would like to remind readers not to overlook the benefits of physical activity in such patients. In addition to raising serum high-density lipoprotein (HDL) cholesterol concentrations, physical activity facilitates weight loss and has also been reported to reduce the risk of cardiovascular diseases, an effect that is independent of its effects on serum lipid concentrations in both men and women. For these reasons, physical activity along with dietary modification is recommended as the first line of therapy in the second report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.2
2 ReferencesJoan Dorn, Ph.D.
John Naughton, M.D.
State University of New York at Buffalo, Buffalo, NY 14214-3000Catarina Galletti, M.D.
University of Bologna, 40059 Bologna, Italy1
Knopp RH . Drug treatment of lipid disorders. N Engl J Med 1999;341:498-511
Full Text | Web of Science | Medline2
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults
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To the Editor:
In his discussion of fibrates, Dr. Knopp does not mention that these drugs often cause an increase in both serum urea and creatinine concentrations. In a review of articles that contained data on renal function in a total of 2643 patients taking fibrates,1 an increase in mean serum creatinine concentrations during therapy was reported in all five articles on fenofibrate and in all seven on bezafibrate, with increases occurring in 8 percent to 18 percent of patients taking fenofibrate and in 9 percent to 40 percent of those taking bezafibrate; three of four articles on ciprofibrate also reported increased serum creatinine concentrations (range, 6 percent to 16 percent of patients). In all cases, renal function returned to normal after discontinuation of the fibrate. No renal impairment was described in any of the eight articles reporting data on patients taking gemfibrozil.
Although the mechanisms leading to the increased serum urea and creatinine concentrations are unknown, this side effect is important for two reasons. First, awareness of this change may prevent unnecessary studies in patients in whom it develops. Second, high serum concentrations of homocysteine, an important cardiovascular risk factor, have recently been reported in patients taking either fenofibrate or bezafibrate.2 This increase has been ascribed to a fibrate-induced impairment of renal function, and it may counteract the benefits expected from the lipid-lowering action of fenofibrate, bezafibrate, and ciprofibrate. This might explain why gemfibrozil, which is devoid of renal side effects, is the only fibrate that has resulted in a significant reduction of major cardiac events in both primary-prevention trials3 and secondary-prevention trials.4
4 ReferencesNilufer Broeders, M.D.
Christiane Knoop, M.D.
Daniel Abramowicz, M.D.
Hôpital Erasme, B-1070 Brussels, Belgium1
Broeders N ,Knoop C ,Antoine M ,Abramowicz D . Fibrate-induced renal dysfunction: is gemfibrozil the only non-nephrotic agent? Transplantation 1999;67:Suppl:S170-S170 abstract.
CrossRef | Web of Science2
Dierkes J ,Westphal S ,Luley C . Serum homocysteine increases after therapy with fenofibrate or bezafibrate. Lancet 1999;354:219-220
CrossRef | Web of Science | Medline3
Frick MH ,Elo O ,Haapa K , et al. Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia: safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med 1987;317:1237-1245
Full Text | Web of Science | Medline4
Rubins HB ,Robins SJ ,Collins D , et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. N Engl J Med 1999;341:410-418
Full Text | Web of Science | Medline
Author/Editor Response
Dr. Knopp replies:
To the Editor: Dorn et al. make the worthy point that exercise is an important element in caring for patients with hyperlipidemia. However, substantial physical effort is required, such as five hours of aerobic exercise per week, to raise the serum HDL cholesterol concentration by 5 mg per deciliter (0.1 mmol per liter).1 Obese, inactive patients, in whom the beneficial effects of exercise on serum triglyceride and HDL concentrations would be the greatest, are least likely to engage in such activity. In general, my colleagues and I inquire about and encourage exercise. A specific recommendation of exercise can be beneficial when dietary and drug interventions have been maximally implemented and when the patient can clearly recognize the potential benefit of greater physical effort.
The mechanism and clinical importance of the increase in serum creatinine associated with the use of some fibric acid drugs are unclear. The effect appears to be entirely reversible. The studies in which increases in serum homocystine concentrations were reported in patients receiving fibric acid derivatives were not controlled.2,3 It is also unclear whether the reported increases in serum creatinine and homocystine concentrations are related.
There is an error in Table 2 of the article, on page 500, which lists risk factors for cardiovascular disease. In the right-hand column, the serum homocystine concentration should have been >10 μmol per liter, not >10 nmol per liter, as printed.
3 ReferencesRobert H. Knopp, M.D.
Northwest Lipid Research Clinic, Seattle, WA 981041
Thompson PD ,Cullinane EM ,Sady SP , et al. Modest changes in high-density lipoprotein concentration and metabolism with prolonged exercise training. Circulation 1988;78:25-34
CrossRef | Web of Science | Medline2
de Lorgeril M ,Salen P ,Paillard F ,Lacan P ,Richard G . Lipid-lowering drugs and homocysteine. Lancet 1999;353:209-210
CrossRef | Web of Science | Medline3
Dierkes J ,Westphal S ,Luley C . Serum homocysteine increases after therapy with fenofibrate or bezafibrate. Lancet 1999;354:219-220
CrossRef | Web of Science | Medline
- Citing Articles (1)
Citing Articles
1
Gerd Assmann, Heike Benecke, Albrecht Neiss, Paul Cullen, Helmut Schulte, Kurt Bestehorn. (2006) Gap between guidelines and practice: attainment of treatment targets in patients with primary hypercholesterolemia starting statin therapy. Results of the 4E-Registry (Efficacy Calculation and Measurement of Cardiovascular and Cerebrovascular Events including Physicians?? Experience and Evaluation). European Journal of Cardiovascular Prevention & Rehabilitation 13:5, 776-783
CrossRef
