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      Acute insulin resistance in ST-segment elevation myocardial infarction in non-diabetic patients is associated with incomplete myocardial reperfusion and impaired coronary microcirculatory function

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          Abstract

          Background

          Insulin resistance (IR) assessed by the Homeostatic Model Assessment (HOMA) index in the acute phase of myocardial infarction in non-diabetic patients was recently established as an independent predictor of intrahospital mortality. In this study we postulated that acute IR is a dynamic phenomenon associated with the development of myocardial and microvascular injury and larger final infarct size in patients with ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (pPCI).

          Methods

          In 104 consecutive patients with the first anterior STEMI without diabetes, the HOMA index was determined on the 2 nd and 7 th day after pPCI. Worst-lead residual ST-segment elevation (ST-E) on postprocedural ECG, coronary flow reserve (CFR) determined by transthoracic Doppler echocardiography on the 2 nd day after pPCI and fixed perfusion defect on single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) determined six weeks after pPCI were analyzed according to HOMA indices.

          Results

          IR was present in 55 % and 58 % of patients on day 2 and day 7, respectively. Incomplete post-procedural ST-E resolution was more frequent in patients with IR compared to patients without IR, both on day 2 (p = 0.001) and day 7 (p < 0.001). The HOMA index on day 7 correlated with SPECT-MPI perfusion defect (r = 0.331), whereas both HOMA indices correlated well with CFR (r = -0.331 to -0.386) (p < 0.01 for all). In multivariable backward logistic regression analysis adjusted for significant univariate predictors and potential confounding variables, IR on day 2 was an independent predictor of residual ST-E ≥ 2 mm (OR 11.70, 95% CI 2.46-55.51, p = 0.002) and CFR < 2 (OR = 5.98, 95% CI 1.88-19.03, p = 0.002), whereas IR on day 7 was an independent predictor of SPECT-MPI perfusion defect > 20% (OR 11.37, 95% CI 1.34-96.21, p = 0.026).

          Conclusion

          IR assessed by the HOMA index during the acute phase of the first anterior STEMI in patients without diabetes treated by pPCI is independently associated with poorer myocardial reperfusion, impaired coronary microcirculatory function and potentially with larger final infarct size.

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          Most cited references52

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          Changes in collateral channel filling immediately after controlled coronary artery occlusion by an angioplasty balloon in human subjects.

          Transluminal coronary angioplasty can serve as a model for controlled coronary artery occlusion and reperfusion which enables assessment of short-term changes in collateral vessel filling in patients with severe atherosclerotic coronary artery disease. In 16 patients with isolated left anterior descending or right coronary artery disease (greater than or equal to 75% stenosis) and normal left ventricular function, collateral filling to the artery being dilated was visualized by contrast injection into the contralateral artery using a second arterial catheter. During balloon inflation, contralateral dye injection was performed as soon as the patient developed angina or ST-T changes or at 90 seconds in those patients without symptoms or signs of ischemia. Grades of collateral filling from the contralateral vessel were: 0 = none; 1 = filling of side branches of the artery to be dilated via collateral channels without visualization of the epicardial segment; 2 = partial filling of the epicardial segment via collateral channels; 3 = complete filling of the epicardial segment of the artery being dilated via collateral channels. At baseline angiography, nine patients had grade 0 collateral filling, seven had grade 1 and none had grade 2 or 3. During coronary occlusion by balloon inflation, collateral filling improved by one grade in eight patients, two grades in five patients, three grades in two patients and remained the same in one patient.(ABSTRACT TRUNCATED AT 250 WORDS)
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            Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis.

            The effect of different classes of antihypertensive drugs on incident diabetes mellitus is controversial because traditional meta-analyses are hindered by heterogeneity across trials and the absence of trials comparing angiotensin-converting-enzyme (ACE) inhibitors with angiotensin-receptor blockers (ARB). We therefore undertook a network meta-analysis, which accounts for both direct and indirect comparisons to assess the effects of antihypertensive agents on incident diabetes. We undertook a systematic review up to Sept 15, 2006, and identified 48 randomised groups of 22 clinical trials with 143,153 participants who did not have diabetes at randomisation and so were eligible for inclusion in our analysis. 17 trials enrolled patients with hypertension, three enrolled high-risk patients, and one enrolled those with heart failure. The main outcome was the proportion of patients who developed diabetes. Initial drug therapy used in the trials (and the number of patients with diabetes of the total number at risk) included: an ARB (1189 of 14,185, or 8.38%), ACE inhibitor (1618 of 22,941, or 7.05%), calcium-channel blocker (CCB, 2791 of 38,607, or 7.23%), placebo (1686 of 24,767, or 6.81%), beta blocker (2705 of 35,745, or 7.57%), or diuretic (998 of 18,699, or 5.34%). With an initial diuretic as the standard of comparison (eight groups), the degree of incoherence (a measure of how closely the entire network fits together) was small (omega=0.000017, eight degrees of freedom). The odds ratios were: ARB (five groups) 0.57 (95% CI 0.46-0.72, p<0.0001); ACE inhibitor (eight groups) 0.67 (0.56-0.80, p<0.0001); CCB (nine groups): 0.75 (0.62-0.90, p=0.002); placebo (nine groups) 0.77 (0.63-0.94, p = 0.009); beta blocker (nine groups) 0.90 (0.75-1.09, p=0.30). These estimates changed little in many sensitivity analyses. The association of antihypertensive drugs with incident diabetes is therefore lowest for ARB and ACE inhibitors followed by CCB and placebo, beta blockers and diuretics in rank order.
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              Insulin resistance as estimated by homeostasis model assessment predicts incident symptomatic cardiovascular disease in caucasian subjects from the general population: the Bruneck study.

              The purpose of this study was to evaluate whether insulin resistance is associated to cardiovascular disease (CVD) and to understand whether this association can be explained by traditional and novel CVD risk factors associated with this metabolic disorder. We examined a sample representative of the population of Bruneck, Italy (n = 919; aged 40-79 years). Insulin-resistant subjects were those with a score in the top quartile of the homeostasis model assessment (HOMA) for insulin resistance (HOMA-IR). Risk factors correlated with insulin resistance included BMI, A1C, HDL cholesterol, triglycerides, blood pressure, high-sensitivity C-reactive protein (hsCRP), fibrinogen, oxidized LDL, vascular cell adhesion molecule-1 (VCAM-1), and adiponectin. Subjects without CVD at baseline were followed up for 15 years for incident CVD, a composite end point including fatal and nonfatal myocardial infarction and stroke, transient ischemic attack, and any revascularization procedure. During follow-up, 118 subjects experienced a first symptomatic CVD event. Levels of HOMA-IR were higher at baseline among subjects who developed CVD (2.8) compared with those remaining free of CVD (2.5) (P < 0.05). Levels of HOMA-IR also were significantly correlated (P < 0.05) with most CVD risk factors we evaluated. In Cox proportional hazard models, insulin-resistant subjects had an age-, sex-, and smoking-adjusted 2.1-fold increased risk (95% CI 1.3-3.1) of incident symptomatic CVD relative to non-insulin-resistant subjects. After sequential adjustment for physical activity and classic risk factors (A1C, LDL cholesterol, and hypertension) as well as BMI, HDL cholesterol, triglycerides, and novel risk factors, including fibrinogen, oxidized LDL, hsCRP, VCAM-1, and adiponectin, the association between HOMA-IR and incident CVD remained significant and virtually unchanged (hazard ratio 2.2 [95% CI 1.4-3.6], P < 0.001). HOMA-estimated insulin resistance is associated with subsequent symptomatic CVD in the general population independently of all classic and several nontraditional risk factors. These data suggest that insulin resistance may be an important target to reduce CVD risk.
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                Author and article information

                Contributors
                Journal
                Cardiovasc Diabetol
                Cardiovasc Diabetol
                Cardiovascular Diabetology
                BioMed Central
                1475-2840
                2014
                5 April 2014
                : 13
                : 73
                Affiliations
                [1 ]Department of Cardiology, Clinical Centre of Serbia, Ul. Koste Todorovica 8, 11000 Belgrade, Serbia
                [2 ]School of Medicine, University of Belgrade, Belgrade, Serbia
                [3 ]Center for Medical Biochemistry, Clinical Centre of Serbia, School of Pharmacy, University of Belgrade, Belgrade, Serbia
                [4 ]Department of Nuclear medicine, Clinical Centre of Serbia, Belgrade, Serbia
                [5 ]Institute of Medical Statistics and Informatics, School of Medicine, University of Belgrade, Belgrade, Serbia
                [6 ]Institute for Gerontology and Palliative Care, Belgrade, Serbia
                [7 ]Serbian Academy of Sciences and Arts, University of Belgrade, Belgrade, Serbia
                Article
                1475-2840-13-73
                10.1186/1475-2840-13-73
                4234386
                24708817
                37a19ff2-5d93-4de7-b2bd-beee0e20aa84
                Copyright © 2014 Trifunovic et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 20 February 2014
                : 2 April 2014
                Categories
                Original Investigation

                Endocrinology & Diabetes
                insulin resistance,acute myocardial infarction,st-e resolution,coronary microcirculation,infarct size

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