Iron, Insulin and Coronary Heart Disease Emphasis on the Generation of Sudden Death and Occult Diabetes (And Why Donating Blood Can Reduce Cardiovascular Death)
Authors:   Complutense University of Madrid, Department of Experimental Endocrinology - Human Physiology January, 2019, Jara Guerrero Juan Ariel 
Published: January 2021

Dysregulated glucose metabolism promote inflammation in monocytes and macrophages from patients with atherosclerotic coronary artery disease. Men with metabolic syndrome are at increased risk for sudden cardiac death, and the incident sudden death is not explained by obesity or traditional cardiovascular risk factors (Kurl, 2016), but the ingested nutritional iron. Individuals with increased abdominal adiposity exhibit an increased risk of heart failure, in spite of there are oweweigtht or not (Cavalera, 2014), because the insulin resistance contribute to increased myocardial fibrosis in the absence of hypertension (Quilliot, 2005). Iron overload, and plasma viscosity contributes to cardiovascular risk in the general population, particularly in men (Van der A, 2005; Junker, 1998). Iron influences glucose metabolism, even in the absence of significant iron overload, and its reduction may alleviate coronary heart disease and reduced or prevent their complications: High stored or free iron levels (measured by serum ferritin or catalytic iron concentrations) elevate risk for development of coronary atherosclerosis, because labile iron accelerates endothelial dysfunction and originates oxidative injury that promotes systemic and vascular inflammation, phrothrombotic conditions and insulin resistance (Williams, 2002). High serum ferritin is strongly and independently associated with acute myocardial infarction and constitutes a novel risk factor in acute sudden event (Holay, 2012). Iron plays a direct and causal role in diabetes pathogenesis mediated both by β-cell failure and insulin resistance (Simcox, 2013). In the general population, body iron stores are positively associated with the development of glucose intolerance, type 2 diabetes and gestational diabetes. In this way, blood donation significant drops in the incidence of cardiovascular events, as well as in procedures such as percutaneous transluminal coronary angioplasty and coronary artery bypass grafting (Holsworth, 2013): frequent blood donations decreased iron stores in healthy volunteers, improving insulin sensitivity and hemodynamic parameters. Iron and oxygen-derived free radicals are important in the pathogenesis of postischemic reperfusion injury and contributes substantially to endothelial dysfunction in acute coronary syndromes (Chekanov, 2002; Duffy, 2001) , and a high iron diet potentially increase ischemic damage induced by transient ischemia and early reperfusion (García-Yébenes, 2012) in animals and humans. Iron, hyperinsulinemia, and hyperglycemia act in concert to up regulate free-radical reactions (Facchini, 2000) and this metal excess accelerated the development of atherosclerosis and its accumulation may promotes illness, particularly, ischemic cardiovascular diseases. Insulin resistance in macrophages promotes formation of a necrotic core in atherosclerotic plaques by enhancing macrophage apoptosis, and exposure it to circulating blood in the event of plaque rupture can precipitate thrombosis, leading to unstable angina pectoris, myocardial infarction and sudden death (Rask.Madsen, 2012, rev). In humans phlebotomy slows progression of peripheral vascular disease and blood donation lowers significantly the risk of myocardial infarction (Salonen, 1998), particularly in insulin-resistant subjects. On the contrary, exogenous iron into healthy individuals provoked endothelial dysfunction accompanied by increased generation of superoxide radical in whole blood (Vinchi, 2014, rev). A causal relationship between pre-diabetes and cardiovascular disease exist (Ford, 2010, rev). Humans lack effective mechanisms to excrete excess iron, and excessive dietary iron uptake cause iron deposition in heart, and pancreas (Kulaksis, 2008) leading to sudden death and occult diabetes mellitus. Iron play an underappreciated role in the development of insulin resistance and insulin resistance-induced heart failure. In a chronic and acute way, Insulin resistance is an early and major factor in the development of heart failure and acute iron induced insulin resistance in cardiomyocytes (Sung, 2019). 1- Introduction 2- Catalytic Iron; Irreversible Oxidizer 3- Excess Hemoglobin and Cardiocerebrovascular Pathology 4- Free Iron as a promoter of Ischemic Heart Disease 5- Excess Ferritin and pathogenesis of Endothelial Dysfunction 6- Hyperinsulinemia as a Sudden Death Promoter. The determining role of Iron 7- Iron accumulated in excess and pathogenesis of Diabetes: High hemoglobin versus High Ferritin 8- Iron and atherosclerosis. The evidence 9- Blood Donation. Cardiovascular Pathology Protector