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Since the introduction of HAART leading to a notable extension of life expectancy in patients with HIV infection, questions related to comorbidities and long-term adverse effects of antiretroviral drugs have recently emerged.An increasing concern is mounting, particularly about the increased risk of coronary artery disease in HIV-infected patients, as initially described in two large prospective studies [1,2].Several of the traditional risk factors for coronary artery disease are frequently reported in HIV-positive individuals, including factors related to the patients' characteristics (such as cigarette smoking, drug addiction, and premature ageing) and factors associated with HIV infection itself and antiretroviral drugs (such as dyslipidaemia, insulin resistance, diabetes mellitus, central adiposity, arterial hypertension, and direct effects of the virus or antiretroviral agents on the vascular system). Moreover, some data suggest that endothelial dysfunction, impaired fibrinolysis, and increased inflammation are more common in HIV-positive patients than in general population and may contribute to an increased cardiovascular risk [3,4].To the best of our knowledge, HIV and HAART may contribute to an increased risk of cardiovascular diseases in three principal ways: HIV infection can identify a subgroup of the general population with a greater prevalence of traditional risk factors unrelated to HIV or HAART (e.g., male sex, advancing age, higher smoking rate, alcoholism, or drug addict); HIV infection and HAART can indirectly favour the occurrence of traditional risk factors (e.g., hyperlipidaemia, insulin resistance, diabetes mellitus, fat redistribution, or hypertension); and HIV and HAART can directly affect the pathogenesis of atherosclerotic disease (e.g., through inflammation and endothelial dysfunction) [3–5].The body of our knowledge suggests that all three above-mentioned mechanisms are plausible, contemporaneously affecting the risk of coronary artery disease in HIV-infected patients. However, experimental and clinical data are often still conflicting today, and several questions remain as to epidemiology, pathogenesis, prevention, and treatment of cardiovascular diseases and related risk factors, which will be discussed in this review.Even though initial case reports suggested an increased frequency of myocardial infarction in protease inhibitor-treated patients [6–8], data from large retrospective and observational studies demonstrate that considerable controversy exists until now about the association of HAART with increased incidence of coronary heart disease.Several retrospective studies have demonstrated a significantly increased incidence of myocardial infarction and cardiovascular complications in HIV-infected patients compared with HIV-uninfected persons. Current exposure to protease inhibitors was often significantly associated with a greater risk of myocardial infarction regardless of traditional cardiovascular risk factors, such as increased age, tobacco smoking, and metabolic disturbances [9–15].Similarly, large, prospective, cohort studies have documented an increased incidence of myocardial infarction and cerebrovascular diseases in association with a prolonged exposure to combination antiretroviral therapies. Really, the major limitation of some prospective studies is that the information about cardiovascular endpoints has been retrospectively ascertained and their conclusions are sometimes unreliable.The Data Collection on Adverse Events of Anti-HIV Drugs (DAD) study is a prospective, observational study of 11 previously established cohorts comprising 23 468 HIV-infected patients followed in 21 countries in Europe, United States, and Australia. The authors showed that the incidence of myocardial infarction increased significantly with increasing exposure to combination antiretroviral therapy, and the adjusted risk rate per year of exposure ranged from 0.32 for no HAART use to 2.93 for at least 6 years of HAART use. Other factors that also independently predicted myocardial infarction in the DAD study were increased age, current or past smoking, previous cardiovascular diseases, male sex, hypercholesterolaemia, hypertriglyceridaemia, and diabetes mellitus .