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Questioning the need for adding statins

Epidemiological studies suggest cardiovascular disease, including myocardial infarction and stroke, are increased 50% to 100% among HIV patients compared with non-HIV patients. Moreover, writes Dr Steven K Grinspoon, professor of medicine, Harvard Medical School, and director of Massachusetts General Hospital's Programme in Nutritional Metabolism in a Healio report, data suggest cardiovascular disease rates remain high in this population, even as rates of morbidity and mortality from HIV-related infections continue to improve with more effective ART.

Grinspoon notes that recent studies indicate that both traditional and non-traditional risk factors contribute to increased CVD in HIV. Traditional risk factors, including smoking, dyslipidemia and diabetes, are more common in the HIV population, but contribute only partially to the increased CVD risk. In addition, he says, recent imaging studies using advanced computed tomography angiography techniques demonstrate unique differences in coronary artery disease in the HIV population.

First, coronary lesions are more prevalent, even among HIV patients with low traditional risk factors who were carefully matched with non-HIV patients with similar risk factors, seen in 59% of HIV patients vs. 34% of non-HIV patients in one recent study. Coronary artery lesions among HIV patients are not only more prevalent, but they are non-calcified and more frequently demonstrate high-risk morphology. That includes positive remodelling and low-attenuation plaque – features that are associated with more vulnerable, rupture-prone plaque.

He says that molecular imaging studies using fluorodeoxyglucose-positron emission tomography to assess arterial inflammation also demonstrated increased uptake, consistent with more metabolically active plaque in the arterial surface. Both altered plaque morphology and increased arterial inflammation related most strongly to markers of immune activation, including sCD163, rather than traditional risk markers or even markers of generalised inflammation, such as C-reactive protein (CRP).

He writes that taken together, these studies suggest a novel paradigm of CVD in HIV, marked by increased immune activation, which may contribute in part to increased plaque inflammation among HIV patients. Immune activation occurs even among HIV patients on chronic ART with good immunological control as well as among elite controllers without measurable viremia who have never received ART. The mechanisms of increased immune activation are not entirely understood, but may in part relate to depletion of T cells in the gut, resulting in increased microbial translocation and increased lipopolysaccharide and subsequent immune activation. Cytomegalovirus and other chronic infections also may contribute to increased immune activation. Indeed, strategies to decrease immune activation related to microbial translocation in the gut may be useful against CVD and are being tested in current studies.

He asks "what do the unique data regarding CVD in HIV tell us about appropriate therapy for this group, and who should we target?" He says primary prevention is a critical but untested strategy for CVD among HIV patients. This strategy is important because CVD among HIV patients often is seen among asymptomatic patients, with minimal CVD risk factors. In addition, this disease often is marked by sudden cardiac death without prodrome, suggesting acute plaque rupture as a mechanism. He says a number of primary prevention strategies may be considered.

Minimisation of traditional risk factors (ie, lifestyle modification, counselling for smoking cessation and treatments for hypertension and diabetes) are critical, but he questions whether they are enough.

Recent studies suggest treatment with HMG-CoA reductase inhibitors, or "statins," may prevent CVD even among patients without increases in LDL cholesterol – in the JUPITER trial among non-HIV patients with low LDL but increased CRP, statins reduced CV events. Of note, this increase was much larger than predicted by the size of LDL reduction alone, suggesting additional effects on inflammatory and other pathways may have contributed to the overall beneficial effects.

Studies conducted among HIV patients show the significant potential of statins to lower LDL. In addition, statins have been shown to have positive effects on inflammatory and immune activation markers among HIV patients.

Grinspoon notes that these data suggest the potential utility of statins in the HIV population. But he questions whether the time is right to recommend statins for HIV patients. He says, however, that the data are promising enough to suggest the need for a large definitive trial. He notes that recently, the US National Heart, Lung and Blood Institute, in collaboration with the National Institute of Allergy and Infectious Diseases and Kowa Pharmaceuticals, funded a landmark study, REPRIEVE, to determine the efficacy of statins for the primary prevention of CVD in HIV patients. REPRIEVE will assess whether use of a statin results in reduced rates of MI, stroke and other CVD events in asymptomatic HIV patients, Grinspoon says.

[link url="http://www.healio.com/infectious-disease/hiv-aids/news/print/infectious-disease-news/%7Bfc312ddd-15d7-4b01-8550-47d13ef501e2%7D/novel-mechanism-and-potential-treatment-strategies-for-cvd-in-hiv-patients#"]Full Healio report[/link]

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