Thomas H Hauser1, Ninad Salastekar2, Ernst J Schaefer3, Tanvi Desai4, Harvey L Goldfine5, Kristen M Fowler6, Griffin M Weber7, Francine Welty1, Melvin Clouse8, Steven E Shoelson4, Allison B Goldfine9. 1. Division of Cardiovascular Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts2Harvard Medical School, Boston, Massachusetts. 2. Harvard Medical School, Boston, Massachusetts3Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts4Clinical Behavioral and Outcomes Research, Joslin Diabetes Center, Boston, Massachusetts. 3. Cardiovascular Nutrition Laboratory, Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts. 4. Harvard Medical School, Boston, Massachusetts4Clinical Behavioral and Outcomes Research, Joslin Diabetes Center, Boston, Massachusetts. 5. The Heart Center of MetroWest, Framingham, Massachusetts. 6. Clinical Behavioral and Outcomes Research, Joslin Diabetes Center, Boston, Massachusetts. 7. Harvard Medical School, Boston, Massachusetts7Division of Interdisciplinary Medicine and Biotechnology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts. 8. Harvard Medical School, Boston, Massachusetts3Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts. 9. Harvard Medical School, Boston, Massachusetts4Clinical Behavioral and Outcomes Research, Joslin Diabetes Center, Boston, Massachusetts8Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
Abstract
IMPORTANCE: Inflammation may contribute to pathological associations among obesity, diabetes mellitus, and cardiovascular disease. OBJECTIVE: To determine whether targeting inflammation using salsalate compared with placebo reduces progression of noncalcified coronary artery plaque. DESIGN, SETTING, AND PARTICIPANTS: In the Targeting Inflammation Using Salsalate in Cardiovascular Disease (TINSAL-CVD) trial participants were randomly assigned between September 23, 2008, and July 5, 2012, to 30 months of salsalate or placebo in addition to standard, guideline-based therapies. Randomization was computerized and centrally allocated, with patients, health care professionals, and researchers masked to treatment assignment. Participants were overweight and obese statin-using patients with established, stable coronary heart disease. INTERVENTIONS:Salsalate (3.5 g/d) or placebo orally over 30 months. MAIN OUTCOMES AND MEASURES: The primary outcome was progression of noncalcified coronary artery plaque assessed by multidetector computed tomographic angiography. Secondary outcomes were other measures of safety and efficacy. RESULTS:Two hundred fifty-seven participants were randomized to salsalate (n = 129) or placebo (n = 128). Their mean (SD) age was 60.8 (7.0) years, and 94.0% (236 of 251) were male. One hundred ninety participants (89 in the salsalate group and 101 in the placebo group) completed the study. Compared with baseline, there was no increase in noncalcified plaque volume in the placebo-treated patients and no difference in change between the salsalate and placebo groups (mean difference, -1 mm3; 95% CI, -11 to 9 mm3; P = .87). Salsalate treatment decreased total white blood cell, lymphocyte, monocyte, and neutrophil counts and increased adiponectin levels without change in C-reactive protein levels. Fasting glucose, triglycerides, uric acid, and bilirubin levels were decreased in the salsalate group compared with the placebo group, while hemoglobin levels were increased. Urinary albumin levels increased, with tinnitus and atrial arrhythmias more common, in the salsalate group compared with the placebo group. CONCLUSIONS AND RELEVANCE: Salsalate when added to current therapies that include a statin does not reduce progression of noncalcified coronary plaque volume assessed by multidetector computed tomographic angiography in statin-using patients with established, stable coronary heart disease. The absence of progression of noncalcified plaque volume in the placebo group may limit interpretation of the trial results. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00624923.
RCT Entities:
IMPORTANCE: Inflammation may contribute to pathological associations among obesity, diabetes mellitus, and cardiovascular disease. OBJECTIVE: To determine whether targeting inflammation using salsalate compared with placebo reduces progression of noncalcified coronary artery plaque. DESIGN, SETTING, AND PARTICIPANTS: In the Targeting Inflammation Using Salsalate in Cardiovascular Disease (TINSAL-CVD) trial participants were randomly assigned between September 23, 2008, and July 5, 2012, to 30 months of salsalate or placebo in addition to standard, guideline-based therapies. Randomization was computerized and centrally allocated, with patients, health care professionals, and researchers masked to treatment assignment. Participants were overweight and obese statin-using patients with established, stable coronary heart disease. INTERVENTIONS:Salsalate (3.5 g/d) or placebo orally over 30 months. MAIN OUTCOMES AND MEASURES: The primary outcome was progression of noncalcified coronary artery plaque assessed by multidetector computed tomographic angiography. Secondary outcomes were other measures of safety and efficacy. RESULTS: Two hundred fifty-seven participants were randomized to salsalate (n = 129) or placebo (n = 128). Their mean (SD) age was 60.8 (7.0) years, and 94.0% (236 of 251) were male. One hundred ninety participants (89 in the salsalate group and 101 in the placebo group) completed the study. Compared with baseline, there was no increase in noncalcified plaque volume in the placebo-treated patients and no difference in change between the salsalate and placebo groups (mean difference, -1 mm3; 95% CI, -11 to 9 mm3; P = .87). Salsalate treatment decreased total white blood cell, lymphocyte, monocyte, and neutrophil counts and increased adiponectin levels without change in C-reactive protein levels. Fasting glucose, triglycerides, uric acid, and bilirubin levels were decreased in the salsalate group compared with the placebo group, while hemoglobin levels were increased. Urinary albumin levels increased, with tinnitus and atrial arrhythmias more common, in the salsalate group compared with the placebo group. CONCLUSIONS AND RELEVANCE: Salsalate when added to current therapies that include a statin does not reduce progression of noncalcified coronary plaque volume assessed by multidetector computed tomographic angiography in statin-using patients with established, stable coronary heart disease. The absence of progression of noncalcified plaque volume in the placebo group may limit interpretation of the trial results. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00624923.
Authors: Ninad Salastekar; Tanvi Desai; Thomas Hauser; Ernst J Schaefer; Kristen Fowler; Stacey Joseph; Steven E Shoelson; Allison B Goldfine Journal: Diabetes Obes Metab Date: 2017-07-06 Impact factor: 6.577
Authors: Katrin Niisuke; Zsuzsanna Kuklenyik; Katalin V Horvath; Michael S Gardner; Christopher A Toth; Bela F Asztalos Journal: J Lipid Res Date: 2020-01-17 Impact factor: 5.922
Authors: Francine K Welty; Fabian Schulte; Abdulhamied Alfaddagh; Tarec K Elajami; Bruce R Bistrian; Markus Hardt Journal: FASEB J Date: 2021-04 Impact factor: 5.191
Authors: Abdulhamied Alfaddagh; Tarec K Elajami; Hasan Ashfaque; Mohamad Saleh; Bruce R Bistrian; Francine K Welty Journal: J Am Heart Assoc Date: 2017-12-15 Impact factor: 5.501