Atherosclerotic cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in the United States. Inflammation is increasingly accepted as a major contributor to the pathogenesis of coronary heart disease (CHD) . Atherosclerosis primarily affeects large and medium sized vessels including the aorta, carotid, and coronary arteries. Accepted clinical CHD risk factors include age, male gender, family history of premature CHD, hypertension, smoking, diabetes, elevated LDL and low HDL cholesterol. CHD is the major adverse consequence of the “metabolic syndrome” – a constellation of metabolic abnormalities including obesity, insulin resistance, hypertension, impaired glucose tolerance, or diabetes, hyperinsulinemia and dyslipidemia.
Autopsy data suggest that the aorta offers a valuable window for the study of atherosclerotic plaque burden. Until recently, the assessment of underlying atherosclerosis was limited to invasive angiographic methods (x-ray coronary angiography, intravascular ultrasound) or non-invasive or moderately invasive (transesopageal) ultrasound methods. More recently, non-invasive vascular imaging techniques, including CMR, offer the opportunity to identify, quantify, and characterize atherosclerosis of larger arteries such as the aorta [2-4].
A Specialized Center of Clinically Oriented Research (SCCOR) program in Vascular Injury, Repair, and Remodeling with the central theme “Metabolic Syndrome, Inflammation and Vascular Remodeling” is being directed by Dr. Francine Welty at BIDMC, with funding from the NHLBI. This parent study titled, “Targeting Inflammation using Salsalate or Lifestyle intervention in the Metabolic Syndrome and CardioVascular Disease – TINSAL-CVD” investigates whether primary targeting of inflammation as a therapeutic goal provides a new route to treat CHD utilizing MDCT of the coronary arteries to assess atherosclerosis with a primary hypothesis being that those randomized to the salsalate arm and lifestyle arm will have no progression of coronary soft plaque volume progression while those randomized to the placebo arm will have a 7% progression.
The ancillary CMR branch of the study involves applying CMR methods to characterize baseline aortic atherosclerosis and inflammation in those with the metabolic syndrome, to examine its relationship to novel inflammatory measures, and the response of the plaque and plaque components to treatment.
Warren J. Manning, MD
Reza Nezafat, Ph.D.