Cardiovascular Risk and Body-Fat Abnormalities in HIV-Infected Adults
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《新英格兰医药杂志》
To the Editor: In their review of metabolic and cardiovascular risk factors affecting patients infected with the human immunodeficiency virus (HIV), Grinspoon and Carr (Jan. 6 issue)1 recommend the guidelines of the National Cholesterol Education Program for lipid-lowering therapy in HIV-infected patients with hyperlipidemia. Prediction of coronary heart disease (CHD) with the use of the Framingham equation, however, is based on (and principally predictive for) outpatients free of disease.2 Estimation of the 10-year risk of CHD at any point is based on the person's past and expected future lipid levels (which are best assessed as the area under the curve, as shown in Figure 1). In many treated HIV-infected patients, however, hyperlipidemia does not follow the 10-year course seen in the population without HIV infection, because frequent changes in therapy3,4 may lower total cholesterol levels, increase high-density lipoprotein cholesterol levels, and reduce the risk of atherogenesis.5
Figure 1. Association of Hyperlipidemia and Prediction of the Risk of Coronary Heart Disease over Time.
The area under the curve for a person with normal lipid blood levels (thin line) and for another with hyperlipidemia (thick line) contributes to the prediction of the 10-year risk of coronary heart disease at a given point (indicated by the asterisk). Thus, intermittent hyperlipidemia associated with consecutive HIV-therapy regimens (dashed and dotted lines) and the resultant area under the curve differ substantially from risk estimates based on the presence of hyperlipidemia in patients without HIV infection.
It seems to be inappropriate simply to reduce risk estimates after treatment interventions for hyperlipidemia, as shown in Table 2 of the article by Grinspoon and Carr.1 Effective statin (or antihypertensive) therapy does not result in the same estimated 10-year risk of CHD as for persons with normal lipid levels or normal blood pressure without therapy. HIV-infected patients with hyperlipidemia and risk factors for CHD before receiving highly active antiretroviral therapy might benefit substantially from lipid-lowering therapy, which should be considered first.
Georg M.N. Behrens, M.D.
Hannover Medical School
30625 Hannover, Germany
behrens.georg@mh-hannover.de
References
Grinspoon S, Carr A. Cardiovascular risk and body-fat abnormalities in HIV-infected adults. N Engl J Med 2005;352:48-62.
Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation 1998;97:1837-1847.
Mocroft A, Ledergerber B, Viard JP, et al. Time to virological failure of 3 classes of antiretrovirals after initiation of highly active antiretroviral therapy: results from the EuroSIDA study group. J Infect Dis 2004;190:1947-1956.
Mocroft A, Youle M, Moore A, et al. Reasons for modification and discontinuation of antiretrovirals: results from a single treatment centre. AIDS 2001;15:185-194.
van der Valk M, Kastelein JJ, Murphy RL, et al. Nevirapine-containing antiretroviral therapy in HIV-1 infected patients results in an anti-atherogenic lipid profile. AIDS 2001;15:2407-2414.
The authors reply: Dr. Behrens notes that prediction of the risk of CHD with the use of the Framingham equation is based on outpatients free of disease. The estimates to which we refer,1 which are based on a large outpatient population of HIV-infected adults, indicate that estimating cardiovascular outcomes with the use of baseline risk factors yielded similar estimated and actual rates. Like Dr. Behrens, we emphasize that such modeling can provide only a relative estimate in the case of young patients with changing lipid levels. We used an estimate of a 25 percent reduction in total cholesterol level to calculate the risk of myocardial infarction in Table 2 of our article,2 as suggested by studies of the use of statins in patients with chronic infection and hyperlipidemia who were receiving antiretroviral therapy.3 Dr. Behrens is correct that our calculations assume that lipid levels will remain relatively constant — they remain stable for up to 96 weeks in HIV-infected patients receiving stable antiretroviral therapy.4 Although an area-under-the-curve approach may provide additional information about patients with changing lipid levels, the Framingham equation is useful to estimate risk, particularly among patients with chronically elevated but stable lipid levels.
Steven Grinspoon, M.D.
Massachusetts General Hospital
Boston, MA 02114
sgrinspoon@partners.org
Andrew Carr, M.D.
St. Vincent's Hospital
2010 Sydney, Australia
References
Law MG, D'Arminio Monforte A, Friis-M?ller N, et al. Cardio- and cerebrovascular events and predicted rates of myocardial infarction in the D:A:D Study. Presented at the 11th Conference on Retroviruses and Opportunistic Infections, San Francisco, February 8–11, 2004.
Grinspoon S, Carr A. Cardiovascular risk and body-fat abnormalities in HIV-infected adults. N Engl J Med 2005;352:48-62.
Calza L, Manfredi R, Chiodo F. Statins and fibrates for treatment of hyperlipidaemia in HIV-infected patients receiving HAART. AIDS 2003;17:851-859.
Opravil M, Hirschel B, Lazzarin A, et al. A randomized trial of simplified maintenance therapy with abacavir, lamivudine, and zidovudine in human immunodeficiency virus infection. J Infect Dis 2002;185:1251-1260.
Figure 1. Association of Hyperlipidemia and Prediction of the Risk of Coronary Heart Disease over Time.
The area under the curve for a person with normal lipid blood levels (thin line) and for another with hyperlipidemia (thick line) contributes to the prediction of the 10-year risk of coronary heart disease at a given point (indicated by the asterisk). Thus, intermittent hyperlipidemia associated with consecutive HIV-therapy regimens (dashed and dotted lines) and the resultant area under the curve differ substantially from risk estimates based on the presence of hyperlipidemia in patients without HIV infection.
It seems to be inappropriate simply to reduce risk estimates after treatment interventions for hyperlipidemia, as shown in Table 2 of the article by Grinspoon and Carr.1 Effective statin (or antihypertensive) therapy does not result in the same estimated 10-year risk of CHD as for persons with normal lipid levels or normal blood pressure without therapy. HIV-infected patients with hyperlipidemia and risk factors for CHD before receiving highly active antiretroviral therapy might benefit substantially from lipid-lowering therapy, which should be considered first.
Georg M.N. Behrens, M.D.
Hannover Medical School
30625 Hannover, Germany
behrens.georg@mh-hannover.de
References
Grinspoon S, Carr A. Cardiovascular risk and body-fat abnormalities in HIV-infected adults. N Engl J Med 2005;352:48-62.
Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation 1998;97:1837-1847.
Mocroft A, Ledergerber B, Viard JP, et al. Time to virological failure of 3 classes of antiretrovirals after initiation of highly active antiretroviral therapy: results from the EuroSIDA study group. J Infect Dis 2004;190:1947-1956.
Mocroft A, Youle M, Moore A, et al. Reasons for modification and discontinuation of antiretrovirals: results from a single treatment centre. AIDS 2001;15:185-194.
van der Valk M, Kastelein JJ, Murphy RL, et al. Nevirapine-containing antiretroviral therapy in HIV-1 infected patients results in an anti-atherogenic lipid profile. AIDS 2001;15:2407-2414.
The authors reply: Dr. Behrens notes that prediction of the risk of CHD with the use of the Framingham equation is based on outpatients free of disease. The estimates to which we refer,1 which are based on a large outpatient population of HIV-infected adults, indicate that estimating cardiovascular outcomes with the use of baseline risk factors yielded similar estimated and actual rates. Like Dr. Behrens, we emphasize that such modeling can provide only a relative estimate in the case of young patients with changing lipid levels. We used an estimate of a 25 percent reduction in total cholesterol level to calculate the risk of myocardial infarction in Table 2 of our article,2 as suggested by studies of the use of statins in patients with chronic infection and hyperlipidemia who were receiving antiretroviral therapy.3 Dr. Behrens is correct that our calculations assume that lipid levels will remain relatively constant — they remain stable for up to 96 weeks in HIV-infected patients receiving stable antiretroviral therapy.4 Although an area-under-the-curve approach may provide additional information about patients with changing lipid levels, the Framingham equation is useful to estimate risk, particularly among patients with chronically elevated but stable lipid levels.
Steven Grinspoon, M.D.
Massachusetts General Hospital
Boston, MA 02114
sgrinspoon@partners.org
Andrew Carr, M.D.
St. Vincent's Hospital
2010 Sydney, Australia
References
Law MG, D'Arminio Monforte A, Friis-M?ller N, et al. Cardio- and cerebrovascular events and predicted rates of myocardial infarction in the D:A:D Study. Presented at the 11th Conference on Retroviruses and Opportunistic Infections, San Francisco, February 8–11, 2004.
Grinspoon S, Carr A. Cardiovascular risk and body-fat abnormalities in HIV-infected adults. N Engl J Med 2005;352:48-62.
Calza L, Manfredi R, Chiodo F. Statins and fibrates for treatment of hyperlipidaemia in HIV-infected patients receiving HAART. AIDS 2003;17:851-859.
Opravil M, Hirschel B, Lazzarin A, et al. A randomized trial of simplified maintenance therapy with abacavir, lamivudine, and zidovudine in human immunodeficiency virus infection. J Infect Dis 2002;185:1251-1260.