Interleukin‐6 and <scp>d</scp>‐dimer levels are associated with vascular dysfunction in patients with untreated HIV infection

Baker, Jason V.; Quick, Harrison; Hullsiek, Katherine Huppler; Tracy, Russ; Duprez, Daniel; Henry, Keith; Neaton, James D.

doi:10.1111/j.1468-1293.2010.00835.x

Cited by 32 publications

(25 citation statements)

References 4 publications

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“…Among HIV-infected adults, D-dimer amounts add risk prediction to complex risk algorithms such as the VACS Index (Justice et al, 2012b). D-dimer levels are associated with important intermediate pathophysiological mechanisms such as endothelial damage and vascular dysfunction (Baker et al, 2010; Hileman et al, 2012). Finally, D-dimer levels are associated with in situ clot formation in SIV infected macaques (Pandrea et al, 2012).…”

Section: Hiv Also Causes a Hypercoagulable State Which Is Linked To mentioning

confidence: 99%

Systemic Effects of Inflammation on Health during Chronic HIV Infection

2013

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Combination antiretroviral therapy for HIV infection improves immune function and eliminates the risk of AIDS-related complications, but does not restore full health. HIV-infected adults have excess risk of cardiovascular, liver, kidney, bone and neurologic diseases. Many markers of inflammation are elevated in HIV disease and strongly predictive of the risk of morbidity and mortality. A conceptual model has emerged to explain this syndrome of diseases where HIV-mediated destruction of gut mucosa leads to local and systemic inflammation. Translocated microbial products then pass through the liver, contributing to hepatic damage, impaired microbial clearance and impaired protein synthesis. Chronic activation of monocytes and altered liver protein synthesis subsequently contribute to a hypercoagulable state. The combined effect of systemic inflammation and excess clotting on tissue function leads to end-organ disease. Multiple therapeutic interventions designed to reverse these pathways are now being tested in the clinic. It is likely that knowledge gained on how inflammation affect health in HIV disease could have implications for our understanding of other chronic inflammatory diseases and the biology of aging.

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Section: Hiv Also Causes a Hypercoagulable State Which Is Linked To mentioning

confidence: 99%

Systemic Effects of Inflammation on Health during Chronic HIV Infection

2013

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“…D-dimer levels decline following antiretroviral therapy (ART) initiation [1], [5], [6] and increase after stopping ART in treatment experienced patients [1], [4]. Correlations of D-dimer with HIV viremia and markers of endothelial dysfunction and microbial translocation [1], [4], [7], [8] have also been reported. This favors the hypothesis that HIV replication and microbial translocation are among the main determinants of the hypercoagulable state seen in HIV-infected persons.…”

Section: Introductionmentioning

confidence: 98%

Factors Associated with D-Dimer Levels in HIV-Infected Individuals

et al. 2014

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BackgroundHigher plasma D-dimer levels are strong predictors of mortality in HIV+ individuals. The factors associated with D-dimer levels during HIV infection, however, remain poorly understood.MethodsIn this cross-sectional study, participants in three randomized controlled trials with measured D-dimer levels were included (N = 9,848). Factors associated with D-dimer were identified by linear regression. Covariates investigated were: age, gender, race, body mass index, nadir and baseline CD4+ count, plasma HIV RNA levels, markers of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6]), antiretroviral therapy (ART) use, ART regimens, co-morbidities (hepatitis B/C, diabetes mellitus, prior cardiovascular disease), smoking, renal function (estimated glomerular filtration rate [eGFR] and cystatin C) and cholesterol.ResultsWomen from all age groups had higher D-dimer levels than men, though a steeper increase of D-dimer with age occurred in men. Hepatitis B/C co-infection was the only co-morbidity associated with higher D-dimer levels. In this subgroup, the degree of hepatic fibrosis, as demonstrated by higher hyaluronic acid levels, but not viral load of hepatitis viruses, was positively correlated with D-dimer. Other factors independently associated with higher D-dimer levels were black race, higher plasma HIV RNA levels, being off ART at baseline, and increased levels of CRP, IL-6 and cystatin C. In contrast, higher baseline CD4+ counts and higher high-density lipoprotein cholesterol were negatively correlated with D-dimer levels.ConclusionsD-dimer levels increase with age in HIV+ men, but are already elevated in women at an early age due to reasons other than a higher burden of concomitant diseases. In hepatitis B/C co-infected individuals, hepatic fibrosis, but not hepatitis viral load, was associated with higher D-dimer levels.

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“…Among uninfected persons and HIV-infected adults, biomarkers of monocyte activation (soluble CD14 [sCD14]) and altered coagulation (D-dimer) have been independently associated with increased risk for myocardial infarction, coronary heart disease, and all-cause mortality 4–10 . Cigarette smoking, a traditional risk factor for cardiovascular disease, is more prevalent among HIV-infected adults 11–14 .…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, elevated D-dimer has been independently associated with and predictive of incident CVD in HIV-infected persons in recent analyses 7, 18 . Elevated D-dimer levels have been associated with vascular dysfunction, indicated by impaired small artery elasticity (a marker of early vascular disease and future clinical risk) and increased plasma markers of endothelial function 4 . In a recent prospective study, sCD14 was associated with increased carotid artery intima-media thickness 26 ; however a cross-sectional study found dissimilar results 27 .…”

Section: Introductionmentioning

confidence: 99%

Elevated Soluble CD14 and Lower D-Dimer Are Associated With Cigarette Smoking and Heavy Episodic Alcohol Use in Persons Living With HIV

Cioe

Baker

Kojic

et al. 2015

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background Persons living with HIV (PLWH) are at increased risk for cardiovascular disease in part due to persistent inflammation and coagulation activation. Methods We examined whether smoking and heavy episodic alcohol use (defined as 5 or more drinks on one occasion) were associated with greater monocyte activation (sCD14) and coagulation (D-dimer) in participants in the Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (the ‘SUN’ Study), a prospective observational cohort. Results Using regression analysis (n = 689), current smoking compared with nonsmoking was associated with significantly elevated sCD14 (B= 135.57, 95%CI (84.95, 186.19), p < .001); whereas heavy alcohol use compared to non-heavy use was associated with significantly lower D-dimer levels (B= −.059, 95%CI (−.102, −.016), p = .007). Conclusions Smoking cessation should be encouraged by HIV care providers to improve mortality outcomes from all causes of death, particularly cardiovascular disease.

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Interleukin‐6 and d‐dimer levels are associated with vascular dysfunction in patients with untreated HIV infection

Cited by 32 publications

References 4 publications

Systemic Effects of Inflammation on Health during Chronic HIV Infection

Systemic Effects of Inflammation on Health during Chronic HIV Infection

Factors Associated with D-Dimer Levels in HIV-Infected Individuals

Elevated Soluble CD14 and Lower D-Dimer Are Associated With Cigarette Smoking and Heavy Episodic Alcohol Use in Persons Living With HIV

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