Anomalie metaboliche Insulino-resistenza Iperglicemia

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1 Anomalie metaboliche Insulino-resistenza Iperglicemia
Iperattività del sistema nervoso ortosimpatico Stile di vita sedentario Disfunzione endoteliale Perdita di massa muscolare Influenza di citochine (TNF-alpha, leptina..) Iperglicemia Aumento della concentrazione degli FFA Insulin resistance occurs in HF of both ischaemic and nonischaemic aetiology,43,44 but why it is so prevalent is not fully understood. Many mechanisms have been suggested, including sympathetic nervous system (SNS) overactivity, sedentary lifestyle, endothelial dysfunction, loss of skeletal muscle mass, and influence of cytokines such as TNF-alpha and leptin on peripheral insulin sensitivity. Patients with HF have persistent activation of their SNS.48 Excessive activation of the SNS may lead to insulin resistance. The complex interactions between the SNS and glucose metabolism are briefly summarized in Figure 2. In healthy subjects, acute SNS activation reduces insulin-induced stimulation of muscle glucose uptake by 25%.48 Furthermore, stimulation of b-receptors increases lipolysis resulting in raised plasma free fatty acid (FFA) levels.49 FFAs impair insulin-mediated glucose disposal in human skeletal muscle50 and can stimulate hepatic gluconeogenesis, 51 further potentiating hyperglycaemia. Catecholamines have also been shown to inhibit pancreatic insulin secretion in humans and stimulate hepatic gluconeogenesis and glycogenolysis, further worsening hyperglycaemia.52

2 The cardiotoxic triad: Myocardial ischemia Hypertension
Several mechanisms may explain the association between DM and HF: † Risk factors for HF are common in diabetics (for example hypertension and CHD). † DM may have a direct effect on the myocardium. † DM may activate neurohormonal systems. The cardiotoxic triad: Myocardial ischemia Hypertension Diabetic cardiomyopathy

3 Stratton IM. UKPDS 35. BMJ 2000;321:405–412

4 Kaplan-Meier estimates of the proportion of patients with hospitalization for CHF divided into classes of glycemia at baseline (log rank P<0.001) Held, C. et al. Circulation 2007

5 Scompenso cardiaco, diabete e prognosi
Analyses from Studies of Left Ventricular Dysfunction (SOLVD) trial have demonstrated that diabetes serves as an independent risk factor for progression from asymptomatic left ventricular dysfunction to symptomatic HF as well as a risk factor for all-cause mortality in patients with symptomatic HF Diabetes has long been shown to be an important factor of poor outcome after acute myocardial infarction or acute coronary syndromes. The first suggestion that diabetes may also be a predictor of poor clinical outcome in patients with HF came from a subgroup analysis of the SOLVDtreatment trials showing that all cause and cardiovascular mortalities were higher in diabetic than in nondiabetic patients Shindler DM et al. SOLVD Trials and Registry. Am J Cardiol 1996;77:1017

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7 C’e’ molto di non cardiaco che pesa sulla prognosi nello sc

8 on the behalf of the Heart Failure Association of the ESC (HFA)
EURObservational Research Program: The Heart Failure Pilot Survey (ESC-HF Pilot) Aldo P Maggioni, Ulf Dahlström, Gerasimos Filippatos, Ovidiu Chioncel, Marisa Crespo Leiro, Jaroslaw Drozdz, Friedrich Fruhwald, Lars Gullestad, Damien Logeart, Marco Metra, John Parissis, Hans Persson, Piotr Ponikowski, Mathias Rauchhaus, Adriaan Voors, Olav Wendelboe Nielsen, Faiez Zannad, Luigi Tavazzi on the behalf of the Heart Failure Association of the ESC (HFA) Disclosures: None

9 Comparison between Acute and Chronic HF: baseline characteristics
CHF pts (n. 3226) AHF pts (n. 1892) Age (years), mean±SD 67±13 70±13 Females, % 29.7 37.3 Ischemic etiology, % documented by coronary angiography, % 40.4 84.9 50.7 64.0 SBP (mmHg), mean±SD 125±20 133±29 HR (bpm), mean±SD 72±14 88±24 Treated hypertension, % 58.3 61.8 Diabetes mellitus, % 29.0 35.1 History of Atrial Fibrillation, % 38.6 43.7 Chronic kidney dysfunction, % 18.5 26.0 ICD, % 13.3 6.0 CRT, % 1.1 0.4 CRT-D, % 8.7 2.9

10 EuroHeart Failure Survey Other Concomitant Diagnoses
pts Female 47% Mean age 71 yrs % Cleland JF et Al, European Heart Journal (2003) 24, 442–463

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13 Copyright © The American College of Cardiology.
From: Heart Failure–Associated Hospitalizations in the United States J Am Coll Cardiol. 2013;61(12): doi: /j.jacc Figure Legend: Annual age- and sex-adjusted rates of hospitalizations in the United States with a diagnosis of heart failure (HF) in the primary versus secondary position are shown. Date of download: 3/19/2013 Copyright © The American College of Cardiology. All rights reserved.

14 Copyright © The American College of Cardiology.
From: Heart Failure–Associated Hospitalizations in the United States J Am Coll Cardiol. 2013;61(12): doi: /j.jacc No DM! Figure Legend: Bars represent the percent of all heart failure–related hospitalizations that were related to a given diagnosis for a 3-year period. Values of p< for each diagnosis across all years. COPD = chronic obstructive pulmonary disease. Date of download: 3/19/2013 Copyright © The American College of Cardiology. All rights reserved.

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22 Non considerato il DM

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26 Dati UOC Fermo 2011 2012 RICOVERI SC 257 256 UOMINI 64% 61% DEG. MEDIA
8,2 7.2 ETA’ MEDIA 74,9 75 DECESSI 6% PAZ CON DM 21% 15% 58% 66% 10,4 8,3 77,4 4% 5%

27 CONCLUSIONI DM E SC sono frequentemente associati
Il peso della comorbilità DM nelle ospedalizzazioni è importante ma non sufficientemente indagato Il DM è un importante determinante prognostico Nella riduzione delle riospedalizzazioni è importante un attento controllo metabolico del diabete

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29 Domenico Gabrielli

30 Association of noncardiac morbidities with death in CHF patients
Braunstein JB et Al. J Am Coll Cardiol 2003;42:1226 –33