Abstract 19277: Statin Therapy Lowers Myocardial Fibrosis Marker sST2 in Patients Living With HIV
Introduction: We have recently shown that patients living with HIV have higher soluble ST2 (sST2), galectin-3 and high sensitivity troponin T (hs-cTnT), than non-HIV controls and that hs-cTnT is associated with calcified coronary plaque in patients with HIV. The objective of the current study is to assess effects of statin therapy on these markers of myocardial fibrosis, injury and inflammation in HIV patients.
Hypotheses: Atorvastatin will reduce markers of myocardial fibrosis, injury and inflammation in HIV patients.
Methods: 40 HIV+ men and women participated in a 12-month randomized, double-blind placebo controlled trial of atorvastatin 40mg po qd (starting at 20mg po qd in first 3 months and escalating to 40mg po qd in final 9 months) vs. placebo. Serial sST2, galectin-3, hs-cTnT, sCD14, MCP-1, hs-IL6, hs-CRP and oxidized LDL by ELISA and coronary plaque volume on CT coronary angiography (CCTA) were measured.
Results: Atorvastatin lowered sST2 compared to the placebo group (change in statin group -0.310 [-4.195 to 2.075]ng/mL median[IQR] vs. 1.163 [0.624 to 4.715]ng/mL in the placebo group, p=0.04). The change in sST2 was significantly related to change in monocyte activation markers sCD14 (r=0.63, p<0.0001) and MCP-1 (r=0.52, p=0.0009), change in markers of generalized inflammation hs-IL6 (r=0.58, p=0.0002) and hs-CRP (r=0.83, p<0.0001), and change in oxLDL (r=0.49, p=0.002). No statistically significant differences were seen for changes in galectin-3 and hs-cTnT between groups. Significant progression of coronary plaque was seen in the placebo group and the change in calcified plaque volume over time was associated with change in hs-cTnT (r=0.74, p=0.0002).
Conclusions: sST2, a member of the IL-1 receptor family and a marker of fibrosis and inflammation, is lowered by atorvastatin in patients living with HIV. The reduction in sST2 is significantly associated with reduction in markers of monocyte activation and generalized inflammation, suggesting statins may exert effects on fibrosis via immunomodulatory mechanisms. Progression of calcified coronary plaque was seen with placebo and increases in calcified plaque were significantly related to hs-cTnT, a marker of myocardial injury.
Author Disclosures: J. Lo: Research Grant; Significant; National Institutes of Health. Consultant/Advisory Board; Modest; Gilead Sciences. C. Defilippi: None. R. Christenson: None. K. Fitch: None. S. Looby: None. E. Kim: None. M. Lu: None. U. Hoffmann: Research Grant; Significant; HeartFlow, Siemens Healthcare. S. Grinspoon: Consultant/Advisory Board; Modest; Navidea, Theratechnologies, Bristol Meyers Squibb, Merck, Gilead.
- © 2016 by American Heart Association, Inc.