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The Effect of ART on Inflammation, Coagulation and Vascular Injury in START..... "Immediate ART led to reductions at 8 months of 12-21% in D-dimer,
IL-6, SAA, sICAM and sVCAM levels compared with deferral of ART.".....likely reducing risk for comorbidities
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from Jules: however the highest possible CD4 is more protective so immediate HAART at the highest CD4 has the most protective effect, a CD4 of 1000 is likely more protective than a CD4 of 600
Reported by Jules Levin
CROI 2017 Feb 14-16 Seattle, WA
Jason V. Baker1,2, Shweta Sharma3, Birgit Grund4, Adam Rupert5, Julia A. Metcalf6, Mauro Schechter7, Paula Munderi8, Inka Aho9, Sean Emery10, Abdel Babiker11,
Andrew Phillips12, Jens Lundgren13, Jim Neaton3 and H. Clifford Lane6 for the INSIGHT START (Strategic Timing of AntiRetroviral Treatment) Study Group
1Department of Medicine, University of Minnesota, Minneapolis, USA; 2Division of Infectious Diseases, Hennepin County Medical Center, Minneapolis, USA; 3Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, USA; 4School of Statistics, University of Minnesota, Minneapolis, USA;
5Leidos Biomedical Research Inc., Frederick, Maryland, USA; 6National Institute of Allergy and Infectious Diseases, Division of Clinical Research, Bethesda, MD; 7Projeto Praca Onze, Universidade Federal do Rio de Janeiro, Brazil; 8MRC/UVRI Uganda Research Unit, Entebbe, Uganda; 9Division of Infectious Diseases, Helsinki University Hospital, Finland;
10Kirby Institute, University of New South Wales, Sydney, Australia; 11MRC Clinical Trials Unit, University College London, London, UK; 12HIV Epidemiology & Biostatistics Group, University College London, UK; 13CHIP, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Denmark
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Markers of inflammation and endothelial dysfunction are associated with incident cardiovascular disease, all-cause mortality, and progression of coronary calcification in type 2 diabetic patients with microalbuminuria.
DOI: http://dx.doi.org/10.1016/j.jdiacomp.2015.11.005
Abstract
BACKGROUND:
We evaluated markers of inflammation and endothelial dysfunction and their associations with incident cardiovascular disease (CVD), all-cause mortality and progression of coronary artery calcium (CAC) in patients with type 2 diabetes (T2D) and microalbuminuria but without known coronary artery disease (CAD).
METHODS:
Prospective study including 200 patients receiving multifactorial treatment. Markers of inflammation (TNF-α, sICAM-1, sICAM-3, hsCRP, SAA, IL-1β, IL-6, IL-8) and endothelial dysfunction (thrombomodulin, sVCAM-1, sICAM-1, sICAM-3, sE-selectin, sP-selectin) were measured at baseline. Adjustment included traditional CVD risk factors, and full adjustment additionally NT-proBNP and CAC. The "SQRT method" assessed CAC progression after 5.8years, and cut-point was an annualised difference >2.5.
RESULTS:
Occurrence of CVD (n=40) and all-cause mortality (n=26) was traced after 6.1years. In adjusted and fully adjusted Cox models, TNF-α was a determinant of CVD and all-cause mortality (p≤0.007). Further, in adjusted and fully adjusted logistic regression, TNF-α was related to CAC progression (p≤0.042). Of the other biomarkers, sICAM-3 and thrombomodulin were also associated with both endpoints (p≤0.046), IL-1β with CVD endpoints (p=0.021), and sVCAM-1 and sICAM-1 with all-cause mortality (p≤0.005). Higher composite z-scores including all markers of inflammation and endothelial dysfunction were associated with CVD and all-cause mortality (p≤0.008).
CONCLUSIONS:
In patients with T2D and microalbuminuria without known CAD and receiving multifactorial treatment, biomarkers of inflammation and endothelial dysfunction were independently associated with CVD, all-cause mortality and CAC progression. Especially TNF-α was a robust determinant, even after adjusting for NT-proBNP and CAC.
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The percent change (95% CI) at month 8 within the immediate and deferred ART groups is presented for 7 biomarkers, by subgroups of gender, and tertiles of baseline HIV RNA levels and the baseline CD4:CD8 ratio. The numbers
presented to the right of each subgroup within each panel are the differences between the immediate and deferred ART groups for the percent change from baseline to the month 8 visit. For example, for males, the percent
change from baseline in D-dimer was 17.9% lower in the immediate compared to the deferred ART arm (-18.4% in the immediate minus -0.6% in the deferred).
a Adjusted for baseline biomarker level
* Significant interaction (p < 0.05) between subgroup and study arm. HIV RNA and CD4:CD8 ratio interactions with study arm are 1dF tests with the continuous variable.
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