Hypotheses, rationale, design, and methods for evaluation of ischemic preconditioning assessed by sequential exercise tests in diabetic and non-diabetic patients with stable coronary artery disease – a prospective study

Abstract

BackgroundIschemic preconditioning is a powerful mechanism of myocardial protection and in humans it can be evaluated by sequential exercise tests. Coronary Artery Disease in the presence of diabetes mellitus may be associated with worse outcomes. In addition, some studies have shown that diabetes interferes negatively with the development of ischemic preconditioning. However, it is still unknown whether diabetes may influence the expression of ischemic preconditioning in patients with stable multivessel coronary artery disease.Methods/DesignThis study will include 140 diabetic and non-diabetic patients with chronic, stable coronary artery disease and preserved left ventricular systolic function. The patients will be submitted to two sequential exercise tests with 30-minutes interval between them. Ischemic parameters will be compared between diabetic and non-diabetic patients. Ischemic preconditioning will be considered present when time to 1.0 mm ST-segment deviation is greater in the second of two sequential exercise tests. Exercise tests will be analyzed by two independent cardiologists.DiscussionIschemic preconditioning was first demonstrated by Murry et al. in dog’s hearts. Its work was reproduced by other authors, clearly demonstrating that brief periods of myocardial ischemia followed by reperfusion triggers cardioprotective mechanisms against subsequent and severe ischemia. On the other hand, the demonstration of ischemic preconditioning in humans requires the presence of clinical symptoms or physiological changes difficult to be measured. One methodology largely accepted are the sequential exercise tests, in which, the improvement in the time to 1.0 mm ST depression in the second of two sequential tests is considered manifestation of ischemic preconditioning.Diabetes is an important and independent determinant of clinical prognosis. It's a major risk factor for coronary artery disease. Furthermore, the association of diabetes with stable coronary artery disease imposes worse prognosis, irrespective of treatment strategy. It’s still not clearly known the mechanisms responsible by these worse outcomes. Impairment in the mechanisms of ischemic preconditioning may be one major cause of this worse prognosis, but, in the clinical setting, this is not known.The present study aims to evaluate how diabetes mellitus interferes with ischemic preconditioning in patients with stable, multivessel coronary artery disease and preserved systolic ventricular function.

Type 2 diabetes mellitus and myocardial ischemic preconditioning in symptomatic coronary artery disease patients

“…This was a prospective study that included patients with symptomatic CAD followed by the Medicine, Angioplasty, or Surgery Study (MASS) research group. The study design and protocol have been published elsewhere [ 36 ]. Briefly, patients were enrolled who had angina symptoms, multivessel CAD, preserved left systolic ventricular function, and a recent, positive ischemic treadmill stress test.…”

“…The sample size calculation has been previously published elsewhere [ 36 ]. Briefly, it was determined by the analysis of studies with similar methodologies that included only diabetic patients [ 38 ] and studies that included only nondiabetic patients [ 21 ].…”

Using nationwide ‘big data’ from linked electronic health records to help improve outcomes in cardiovascular diseases: 33 studies using methods from epidemiology, informatics, economics and social science in the ClinicAl disease research using LInked Bespoke studies and Electronic health Records (CALIBER) programme

“…[29][30][31][32] However, despite their potential advantages, large prospective clinical cohorts are lacking across all disease areas, and only a handful exist for CAD. [214][215][216][217] There is a stark contrast between the significant scientific interest in and the lack of clinically useful novel biomarkers. New technologies such as mass spectrometry and nuclear magnetic resonance spectroscopy for measuring metabolites (metabolomics) or proteins (proteomics) have the potential to provide early insight into the aetiology of CAD and, thus, better predictive performance.…”

Expressão do precondicionamento isquêmico em pacientes com diabetes mellitus tipo 2 e doença arterial coronariana

“…Dentre pacientes portadores de doença coronariana estável em seguimento ambulatorial no Instituto do Coração da Faculdade de Medicina da Universidade de São Paulo, foram selecionados aqueles portadores de sintomas estáveis, doença coronariana multiarterial, função sistólica ventricular esquerda preservada e angina ou teste ergométrico recente e positivo para isquemia miocárdica, conforme publicado anteriormente (46) . (47) .…”