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

Abstract

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.

HIV and Obesity Comorbidity Increase Interleukin 6 but Not Soluble CD14 or D-Dimer

“…31,50 sCD14 was found to increase with weight gain in virologically suppressed, predominately normal weight HIV+ participants between 0 and 48 weeks after antiretroviral initiation across nine countries. 29 In the Strategies for Management of Antiretroviral Therapy (SMART) Study, investigators did not detect an association between obesity and D-dimer in HIV+, 32 similar to our findings. Likewise, D-dimer was not associated with obesity in a cohort of uninfected participants.…”

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

“…In our study, women had significantly higher levels of sCD14 and D-dimer compared with men, and sCD14 levels were strongly correlated with age. Other studies have found that HIV-infected women had significantly elevated plasma levels of sCD14 compared with uninfected women 49 , and elevated D-dimer levels compared with HIV-infected men 50 . HIV-uninfected women have also been shown to have higher mean sCD14 compared with uninfected men 9 , perhaps suggesting that aging women in general may be at increased risk for developing CVD.…”

COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-Up

“…Nevertheless, it is yet unknown whether these hemostatic changes are a specific effect of SARS-CoV-2 or are a consequence of cytokine storm that precipitates the onset of systemic inflammatory response syndrome (SIRS), as observed in other viral disease (30)(31)(32)(33). Another consideration which has not yet been investigated is that the hemostatic changes seen with COVID-19 infection are related to liver dysfunction (34).…”