Impact of Insulin Resistance on Acetylcholine-Induced Coronary Artery Spasm in Non-Diabetic Patients

Abstract

PurposeCoronary artery spasm (CAS) and diabetes mellitus (DM) are implicated in endothelial dysfunction, and insulin resistance (IR) is a major etiological cause of type 2 DM. However, the association between CAS and IR in non-diabetic individuals has not been elucidated. The aim of the present study was to evaluate the impact of IR on CAS in patients without DM.Materials and MethodsA total of 330 eligible patients without DM and coronary artery disease who underwent acetylcholine (Ach) provocation test were enrolled in this study. Inclusion criteria included both hemoglobin A1c <6.0% and fasting glucose level <110 mg/dL without type 2 DM. Patients were divided into quartile groups according the level of homeostasis model assessment of insulin resistance (HOMA-IR): 1Q (n=82; HOMA-IR<1.35), 2Q (n=82; 1.35≤HOMA-IR<1.93), 3Q (n=83; 1.93≤HOMA-IR< 2.73), and 4Q (n=83; HOMA-IR≥2.73).ResultsIn the present study, the higher HOMA-IR group (3Q and 4Q) was older and had higher body mass index, fasting blood glucose, serum insulin, hemoglobin A1c, total cholesterol, and triglyceride levels than the lower HOMA-IR group (1Q). Also, poor IR (3Q and 4Q) was considerably associated with frequent CAS. Compared with Q1, the hazard ratios for Q3 and Q4 were 3.55 (95% CI: 1.79–7.03, p<0.001) and 2.12 (95% CI: 1.07–4.21, p=0.031), respectively, after adjustment of baseline risk confounders. Also, diffuse spasm and accompanying chest pain during Ach test were more strongly associated with IR patients with CAS.ConclusionHOMA-IR was significantly negatively correlated with reference diameter measured after nitroglycerin and significantly positively correlated with diffuse spasm and chest pain.

Cardiometabolic-Based Chronic Disease, Adiposity and Dysglycemia Drivers

“…The effects of insulin resistance on vascular biology include: 1) defects in glucose homeostasis, substrate oxidation, and mitochondrial function; 2) increased inflammation and oxidative stress; 3) alterations in lipids and lipoproteins; 4) impaired lipid storage in adipocytes via defects in both lipolysis and triacylglycerol synthesis; and 5) vasoregulation due to a reduction in endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) production (110,(93)(94)(95)(96)(97)(111)(112)(113)(114)(115)(116). Insulin resistance is also positively associated with acetylcholine-induced coronary artery spasm in patients without frank T2D (117).…”

Screening for Glucose Metabolism Disorders, Assessment the Disse Insulin Resistance Index and Hospital Prognosis of Coronary Artery Bypass Surgery

“…Myocardial dysfunction was noted and vascular function was impaired in patients with IR. High HOMA-IR level was associated with a decrease in global longitudinal stress and an increase in arterial stiffness [ 30 ], and HOMAIR positively correlates with the development of coronary spasm during acetylcholine provocation test [ 31 ]. An association of IR with the severity of coronary artery disease in patients with coronary artery disease has been demonstrated as well [ 17 ].…”

Type 2 Diabetes Complicated With Heart Failure: Research on Therapeutic Mechanism and Potential Drug Development Based on Insulin Signaling Pathway

“…VED can increase the whole systemic peripheral resistance and afterload through peripheral effects and aggravate the cardiac function impairment through central effects such as myocardial ischemia and inducible nitric oxide synthase (iNOS)-induced damaging effects ( Penna et al, 2006 ). Nemoto et al (2019) found that impaired endothelial function results in severe coronary artery stenosis as well as plaque vulnerability, while chronic hyperglycemia aggravates VED, resulting in more diffuse coronary artery lesions and worse clinical outcomes ( Kang et al, 2018 ). Meanwhile, coronary heart disease and infarction are precipitants of acute HF, and VED under hyperglycemia is highly likely to cause acute HF and seriously increases cardiac mortality (Driscoll et al, 2017).…”