Markers of atherosclerosis and inflammation and mortality in patients with HIV infection

Abstract

Objective-HIV-infected patients are at increased risk for cardiovascular disease, which may be mediated in part by inflammation. Surrogate marker studies suggest an increased prevalence of vascular abnormalities in HIV infection. We examined the association of all-cause mortality in HIV-infected patients with carotid artery intima-media thickness (cIMT) and high-sensitivity Creactive protein (hsCRP).Design and Methods-Baseline risk factors, cIMT and hsCRP were prospectively measured in 327 HIV-infected participants. Follow-up time with median of 3.1 years was calculated from baseline to death or censored dated 7/31/07. Cox Proportional Hazards models were used to study risk factors associated with mortality.Results-Thirty eight (11.6 %) of participants have died since study enrollment. CIMT was significantly higher in those who died and decedents were significantly more likely to have cIMT above the 75 th percentile. Those who died had higher hsCRP than those alive and more had hsCRP values above 3 mg/L. CD4 count was lower and log 10 viral load was higher in decedents, but antiretroviral regimens were similar in both groups. CIMT and hsCRP levels were significantly associated with mortality (HR=2. 74, 95% CI 1.26 to 5.97, p=0.01; HR=2.38, 95% CI 1.15 to 4.9, p=0.02).Conclusions-Our study demonstrated a strong association of carotid IMT and hsCRP with allcause death in this HIV-infected population despite being similar with respect to exposure to antiretroviral medications. Together these surrogate markers may be indices of chronic inflammation and unfavorable outcomes in HIV-positive patients.

Efavirenz and ritonavir-boosted lopinavir use exhibited elevated markers of atherosclerosis across age groups in people living with HIV in Ethiopia

“…Charakida et al showed that cIMT and FMD were elevated in HIV-infected children, particularly those taking a protease inhibitor (PI)-containing regimen (Charakida et al, 2005). Increased cIMT has been widely reported in HIV-infected populations (Chironi et al, 2003;Hsue et al, 2009a;Hsue et al, 2004;Lorenz et al, 2008;Mercie et al, 2005;Oliviero et al, 2009;van Vonderen et al, 2009), is strongly associated with all-cause mortality in HIV patients (Mangili et al, 2011), and appears to be associated with both HIV infection and HAART regimen (Chironi et al, 2003;Lorenz et al, 2008). Protease inhibitors have been implicated as a mediator of increased cIMT (Maggi et al, 2004).…”

Microbial Translocation in the Pathogenesis of HIV Infection and AIDS

“…The reasons for this phenomenon are likely complex, although recent studies suggested that chronic inflammation and immune activation/senescence may contribute to the initiation and progression of atherosclerosis in HIV infection (37,(140)(141)(142). LPS represents an important source of inflammatory stimuli (143) and has been investigated in the setting of atherosclerosis (144).…”

Adiponectin Levels and Coronary Artery Disease among HIV-Infected Men

“…Other markers of inflammation and kidney reserve have already been shown to correlate with future cardiovascular risk including hsCRP, D-dimer, and cystatin C levels [4,25,[62][63][64]. Interestingly, inflammatory markers themselves (such as hsCRP) can down-regulate adiponectin production, potentially explaining some of the predictive capabilities of these markers [65].…”

“…As HIV patients are living longer, they are increasingly developing cardiovascular and metabolic diseases, similar to the aging general population [1][2][3][4]. Additionally, some studies suggest that HIV patients are experiencing accelerated vascular aging [5,6], although further data are needed.…”

“…Additionally, some studies suggest that HIV patients are experiencing accelerated vascular aging [5,6], although further data are needed. The exact risk factors for the higher risk of cardiovascular disease among HIV patients are unclear, but likely related to complex interactions between the virus itself, antiretroviral medications, increased immune activation, and metabolic changes [3,4,[7][8][9][10][11][12][13].…”