HAART lipodystrophy syndrome and cardiovascular risk

The Big Heart Disease Lie

Cardiovascular Disease can be Reversed

Get Instant Access

The fat redistribution and disturbances in glucose and fat metabolism resemble a clinical situation that is known as the "metabolic syndrome" in HIV-negative patients. This condition includes symptoms such as central adipositas, insulin resistance and hyperinsulinemia, hyperlipidemia (high LDL, Lp(a) hypertriglyceridemia and low HDL) and hypercoagulopathy. Given the well-established cardiovascular risk resulting from this metabolic syndrome, there is growing concern about a potential therapy-related increased risk of myocardial infarction in HIV patients. These fears are further sustained by reports of arterial hypertension on HAART, a high rate of smoking among HIV patients and increased levels of tissue plasmino-gen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) in patients with lipodystrophy. Although many of the, mainly retrospective, studies dealing with this issue are inconclusive, data from a large international study (D:A:D study) provide evidence for an increased relative risk of myocardial infarction during the first 7 years of HAART (Friis-Meller 2003). The incidence of myocardial infarction increased from 1.39/1,000 patient years in those not exposed to HAART, to 2.53/1,000 patient years in those exposed for < 1 year, to 6.07/1,000 patient years in those exposed for > 6 years (RR compared to no exposure: 4.38 [95 % CI 2.39 to 8.04], p = 0.0001). After adjustment for other potential risk factors, there was a 1.17-fold [1.11 to 1.24] increased risk of myocardial infarction per additional year of combined ART exposure. It is, however, of note that older age, male gender, smoking, diabetes mellitus, and pre-existing coronary artery disease were still associated with a higher risk of sustaining cardiovascular events than HAART in this study. Although the CHD risk profile in D:A:D patients worsened over time, the risk of myocardial infarction decreased over time after controlling for these changes. More recently, further analyses of the D:A:D cohort proposed an independent contribution of protease inhibitor therapy to the development of coronary heart disease. After adjustment for exposure to the other drug class and established cardiovascular risk factors (excluding lipid levels), the relative rate of myocardial infarction per year of protease-inhibitor exposure was 1.16 (95% confidence interval [CI], 1.10 to 1.23), whereas the relative rate per year of exposure to non-nucleoside reverse-transcriptase inhibitors was 1.05 (95% CI, 0.98 to 1.13). Adjustment for serum lipid levels further reduced the effect of exposure to each drug class to 1.10 (95% CI, 1.04 to 1.18) and 1.00 (95% CI, 0.93 to 1.09), respectively (Friis-Moller 2003). Data of the SMART study revealed that episodic antiretroviral therapy guided by the CD4 cell count significantly increased the risk of opportunistic disease or death from any cause, as compared with continuous antiretroviral therapy. Surprisingly, the hazard ratio for the drug conservation group vs. the viral suppression group was 1.6 (95% CI, 1.0 to 2.5; P=0.05) for fatal or non-fatal cardiovascular disease. These data may provide evidence for the role of the immune system and/or viral replication in the occurence of cardiovascular events in HIV-patients (El Sadr 2007). Several other studies used ultrasonography to measure the thickness of the carotid intima media or endothelial function to predict the cardiovascular risk. Some of these investigations found abnormal test results (e.g. reduced flow-mediated dilation) that correlated either with the use of protease inhibitors or the presence of dyslipidemia (Currier 2003). While there is some indication of an increased rate of coronary artery disease during HAART, the benefit of suppressed viral replication and improved immune function resulting in reduced morbidity and mortality, clearly argues for the use of antiretroviral drugs according to current international guidelines. It seems obvious however, that pre-existing cardiovascular risk factors in individual patients need to be considered more carefully before starting or switching HAART.

Recommendations such as the National Cholesterol Education Program (NECP) have been proposed for non-HIV-infected patients with similar risk constellations. These guidelines are being proposed by some authors for HIV patients as well (Dube 2003, Schambelan 2002, Grinspoon 2005). According to these recommendations, the overall cardiovascular risk in HIV-infected patients can be determined from specific risk factors by using the Framingham equation. Prediction of coronary heart disease using this equation, however, may have some limitations. A 10-year CHD risk estimation at any time point is determined by the individual's past and expected future lipid levels (best assessed as area under the curve). Hyperlipidemia in many treated HIV patients, however, does not follow the 10-year time course seen in the "normal population" due to frequent therapy changes that may lower total cholesterol, increase HDL, and improve atherogenic risk. Thus, the validity of this calculation for the long-term cardiovascular risk assessment in young patients with changing lipid levels and medication regimens requires further studies. Clearly, more clinical studies are necessary to assess whether these recommendations are also applicable in the presence of HIV and to determine the clinical value of lipid lowering drug therapy in these patients. Most importantly, the information about drug interactions of lipid lowering and antiretroviral drugs is still incomplete. The accumulation of pre-existing and drug-related risk factors will get more clinical attention, because, by improving the HIV-associated morbidity and mortality, HAART consequently increases an additional relevant cardiovascular risk factor: the age of patients who are effectively treated with antiretroviral drugs.

Was this article helpful?

0 0
Supplements For Diabetics

Supplements For Diabetics

All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.

Get My Free Ebook


Post a comment