Editorial Comment: Fish Oil to Keep the Cardiologist Away?

July 1, 2007

Elevated fasting triglyceride levels and low levels of high-density lipoprotein cholesterol (HDL-C) are the hallmarks of HIV-associated dyslipidemia. Despite the perception of many HIV-infected patients and their clinicians, low-density lipoprotein cholesterol (LDL-C) levels among persons infected with HIV-even those receiving antiretroviral therapy––tend to be lower than those in uninfected controls.1,2 During antiretroviral therapy, increases in all lipid parameters are common; however, it is dramatic rises in triglyceride levels that for a number of reasons can be of the most concern.

Elevated fasting triglyceride levels and low levels of high-density lipoprotein cholesterol (HDL-C) are the hallmarks of HIV-associated dyslipidemia. Despite the perception of many HIV-infected patients and their clinicians, low-density lipoprotein cholesterol (LDL-C) levels among persons infected with HIV-even those receiving antiretroviral therapy––tend to be lower than those in uninfected controls.1,2 During antiretroviral therapy, increases in all lipid parameters are common; however, it is dramatic rises in triglyceride levels that for a number of reasons can be of the most concern.

Foremost, hypertriglyceridemia can be an independent risk factor of cardiovascular disease (CVD), albeit to a lesser extent than high LDL-C or low HDL-C levels. Of all the aspects of the metabolic syndrome, elevated triglyceride levels are the most common in HIV-infected patients and can develop in concert with other CVD risk factors, including abdominal obesity, hypertension, insulin resistance and glucose intolerance, and low HDL-C and high LDL-C levels. Furthermore, severe elevations in triglyceride levels have been associated with pancreatitis, although this appears to be a rare cause of this complication in HIV-infected persons.

The most recent National Cholesterol Education Program guidelines on the management of dyslipidemias in the general population recognize the risk posed by hypertriglyceridemia but recommend that lipid-lowering therapy first target high LDL-C levels if present and reserve therapy to reduce triglyceride levels for those persons with fasting levels exceeding 500 mg/dL. If after LDL-C goals are achieved the fasting triglyceride levels are 200 mg/dL or higher, then attention turns to reducing triglyceride levels.

Treatment of hypertriglyceridemia has largely been limited to fibrinic acid derivatives. Both gemfibrozil and fenofibrate are commonly used to treat hypertriglyceridemia in HIV-infected and -uninfected patients. However, there are some drawbacks to fibrates, the most significant of which is their overlapping toxicity with statins. Thus, there has been growing interest among HIV-infected patients and their clinicians in the use of omega-3 fatty acids (fish oil) to treat HIV-associated hypertriglyceridemia.

As reviewed by Metroka and colleagues,3 fish oil has been shown to reduce fasting and postprandial triglyceride levels. In addition, epidemiological and clinical trials indicate that omega-3 fatty acids can reduce the incidence of CVD.4,5 The anti-inflammatory properties of fish oil also make it an interesting agent for study in HIV infection––a disease state that is proinflammatory. In their review, Metroka and colleagues highlight clinical studies of persons with and without HIV infection who were given fish oil alone and in combination with statins and fibrates.

The data, as these authors correctly report, do support a role for fish oil in the treatment of hypertriglyceridemia in HIV-infected patients. Reductions in triglyceride levels of 25% to 45% among HIV-infected patients have been demonstrated––with the magnitude of the change appearing to be dose-dependent––and tolerability overall has been quite good. Furthermore, fish oil is perceived by many to be a natural alternative medicine and dietary supplement and, therefore, may be more acceptable to patients than fibrate therapy.

Some questions regarding the use of fish oil remain. Most important is whether treatment of moderate elevations in triglyceride levels (ie, 200 to 500 mg/dL) alters CVD risk sufficiently to justify pharmacological therapy. In addition, the optimal dose of the fatty acids in fish oil––docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)––remains unclear because a wide range of doses of these 2 fatty acids has been studied. Since the effect of fish oil on triglyceride levels appears to be dose-dependent, patients with more severe hypertriglyceridemia may require higher doses. However, the long-term safety of fish oil, which can be immunosuppressive when given at high doses to HIV-infected persons, also requires investigation.

Last, it is not known to what extent elevations in LDL-C levels during fish oil treatment may negate any of the CVD risk–reduction benefits of this therapy. Despite these concerns, the efficacy and safety data are compelling and make using omega-3 fatty acids as an alternative to fibrates hard to resist.

David Alain Wohl, MD
Associate Professor
AIDS Clinical Research and Treatment Unit
University of North Carolina
Chapel Hill

No potential conflict of interest relevant to this commentary was reported by Dr Wohl.

References:

References


1.

Savès M, Chene G, Ducimetiere P, et al. Risk factors for coronary heart disease in patients treated for human immunodeficiency virus infection compared with the general population.

Clin Infect Dis.

2003;37:292-298.

2.

Wohl D, Currier J, Scherzer R, et al. Gender and race/ethnicity differences in dyslipidemia among HIV-infected patients participating in the fat redistribution and metabolic change cohort study. 13th Conference on Retroviruses and Opportunistic Infections; February 5-8, 2006; Denver. Abstract 750.

3.

Metroka CE, Truong P, Gotto AM Jr. Treatment of HIV-associated dyslipid-emia: a role for omega-3 fatty acids?

AIDS Reader.

2007;17:362-364, 367-373.

4.

Bucher HC, Hengstler P, Schindler C, Meier G. N-3 polyunsaturated fatty acids in coronary heart disease: a meta-analysis of randomized controlled trials.

Am J Med.

2002;112:298-304.

5.

Albert CM, Campos H, Stampfer MJ, et al. Blood levels of long-chain n-3 fatty acids and the risk of sudden death.

N Engl J Med.

2002;346:1113-1118.