Effects of Lifestyle Modification and Metformin on Atherosclerotic Indices among HIV-Infected Patients with the Metabolic Syndrome.

Author(s): Fitch K, Abbara S, Lee H, Stavrou E, Sacks R, Michel T, Hemphill L, Torriani M, Grinspoon S

Affiliation(s): aMassachusetts General Hospital (MGH) Program in Nutritional Metabolism bMGH Cardiovascular Imaging Section cMGH Department of Physical Therapy dMGH Cardiovascular Division eMGH Division of Musculoskeletal Radiology fMGH Biostatistics Center.

Publication date & source: 2011-11-22, AIDS., [Epub ahead of print]

OBJECTIVE:: Metabolic abnormalities including diabetes, dyslipidemia, hypertension, and abdominal obesity occur commonly in HIV patients, are associated with increased coronary artery calcification (CAC), and contribute to increased cardiovascular disease (CVD) in this population. We hypothesized that lifestyle modification (LSM) and metformin would improve CVD indices in HIV patients with metabolic syndrome. DESIGN:: A randomized, placebo controlled trial to investigate LSM and metformin, alone and in combination, over one year, among 50 HIV-infected patients with metabolic syndrome. METHODS:: We assessed CAC, cardiovascular and metabolic indices. RESULTS:: Among the participants, duration of HIV-infection was 14 +/- 1 yr and duration of antiretroviral therapy was 6 +/- 1 yr. Metformin-treated subjects demonstrated significantly less progression of CAC (-1 +/- 2 vs. 33 +/- 17, P = 0.004, metformin vs. placebo) whereas the effect of LSM on CAC progression was not significant (8 +/- 6 vs. 21 +/- 14, P = 0.82, LSM vs. no LSM). Metformin had a significantly greater effect on CAC than LSM (P = 0.01). Metformin-treated subjects also demonstrated less progression in calcified plaque volume (-0.4 +/- 1.9 vs. 27.6 +/- 13.8 mm, P = 0.008) and improved HOMA-IR (P = 0.05) compared to placebo. Subjects randomized to LSM vs. no LSM showed significant improvement in HDL (P = 0.03), hsCRP (P = 0.05), and cardiorespiratory fitness. Changes in CAC among the 4 groups: 1) no LSM, placebo (43 +/- 30); 2) LSM, placebo (19 +/- 7); 3) no LSM, metformin (1 +/- 1); and 4) LSM, metformin (-4 +/- 6) were different (P = 0.03 for ANOVA and linear trend across groups), the majority of this effect was mediated by metformin. Results are mean +/- SEM. CONCLUSION:: Metformin prevents plaque progression in HIV-infected patients with the metabolic syndrome.