Vericiguat in Patients With Metabolic Syndrome and Coronary Vascular Dysfunction

Coronary vascular dysfunction is one of the "final common pathways" for the impact of multiple cardiovascular risk factors. The investigators will conduct a randomized, double-blind placebo-controlled study in individuals with the metabolic syndrome and baseline coronary vascular dysfunction to evaluate the impact of vericiguat, a stimulator of soluble guanylyl cyclase, on coronary vascular function using non-invasive cardiac magnetic resonance imaging.

Inclusion Criteria:Age range 35-85 yearsPresence of the metabolic syndrome defined by the National Cholesterol Education Program, Adult Treatment Panel III (NCEP ATP III) definition, with at least three of the following five criteria:waist circumference > 40 inches (men) or >35 inches (women)blood pressure >130/80 mmHgfasting triglyceride (TG) level >150 mg/dLfasting high-density lipoprotein (HDL) cholesterol level <40mg/dL in men or <50mg/dL in womenFasting blood glucose >100 mg/dLEither one of the following:Men ≤ 40 or women ≤ 50 years of age with no history or symptoms of ischemic heart disease, orMen >40 or women >50 years of age with either one of the followinga coronary angiography within the past 24 months showing no significant coronary artery disease, defined as >50% stenosis of the left main coronary artery and/or >70% stenosis of another major coronary vessel, ora coronary artery calcium score obtained within the prior 24 months or if no prior calcium scan, one performed as a research study following consent with a score equal to 0IHE-induced %-change in coronary flow ≤13%Exclusion Criteria:Systolic blood pressure <110 mm HgCurrent or anticipated use of long-acting nitrates, soluble guanylate cyclase (sGC) stimulators, or phosphodiesterase type 5 (PDE5) inhibitorsHematocrit <30%Unable to understand the risks, benefits, and alternatives of participation so as to provide informed consentWomen who are pregnant.Women with reproductive capacity not using an acceptable form of contraceptionHistory of claustrophobiaInability to lie flat and still for 45 minutesPresence of non-magnetic resonance (MR)-compatible objects or devices, such as intra-orbital debris, intra-auricular implants, intra-cranial clips, an implanted defibrillator or a pacemakerHistory as a machinist, welder, metal worker or a similar activity that poses the risk of metal exposure to the eyes