Metabolic Syndrome and Obesity in Peripheral Arterial Disease

2. Metabolic Syndrome and Obesity in Peripheral Arterial Disease True Syndrome ? Mixture of unrelated phenotypes ? Fernando Botero, La famiglia

3. Metabolic Syndrome and Obesity in Peripheral Arterial Disease Syndrome is simply a clustering of factors that occur together more often than by chance alone and for which the cause is often uncertain. The metabolic syndrome fulfills these criteria Circulation october 20, 2009

4. Metabolic Syndrome and Obesity in Peripheral Arterial Disease Circulation october 20, 2009

5. Metabolic Syndrome and Obesity in Peripheral Arterial Disease Circulation october 20, 2009

6. Abdominal visceral fat area (cm2) Waist circumference correlates closely with visceral fat content Waist circumference (cm) Pouliot MC et al. Am J Cardiol 1994

7. Metabolic Syndrome and Obesity in Peripheral Arterial Disease Progression and outcomes of the metabolic syndrome. The metabolic syndrome arises largely out of abdominal obesity. With aging and increasing obesity, metabolic risk factors worsen. Many persons with the metabolic syndrome eventually develop type 2 diabetes. As the syndrome advances, risk for CV disease and its complications increase. Once diabetes develops, diabetic complications other than CV disease often develop. The metabolic syndrome encompasses each stage in the development of risk factors and type 2 diabetes. Grundy. JACC 2006

8. Metabolic Syndrome and Obesity in Peripheral Arterial Disease

9. Metabolic Syndrome and Obesity in Peripheral Arterial Disease: Inflammation and cytokines Pro-inflammatory cytokines including IL-1beta, IL-6, and tumor necrosis factor (TNF)-alpha are released from macrophages within the vessel wall during an inflammatory response. These cytokines mediate distant inflammatory effects, including activation of hepatic genes encoding acute phase reactants fibrinogen, CRP, and serum amyloid A. C-reactive protein induces synthesis of cytokines, CAMs, and tissue factor in monocytes and endothelial cells. Tissue factor activates the extrinsic coagulation cascade, providing a link between inflammation and thrombosis. Koh JACC 2005

10. Metabolic Syndrome and Obesity in Peripheral Arterial Disease: adiponectin Adiponectin is one of a number of proteins secreted by adipose cells that might couple regulation of insulin sensitivity with energy metabolism and serve to link obesity with insulin resistance. Adiponectin stimulates production of NO, reduces expression of adhesion molecules in endothelial cells, and decreasescytokine production. Plasma levels of adiponectin are negatively correlated with adiposity, and decreased plasma adiponectin levels are observed in patients with obesity and type II diabetes Koh JACC 2005

11. Metabolic Syndrome and Obesity in Peripheral Arterial Disease: link between inflammation and PAD McDermott JACC 2009

12. Metabolic Syndrome and Obesity in Peripheral Arterial Disease Patients with the metabolic syndrome are at twice the risk of developing CVD over the next 5 to 10 years as individuals without the syndrome. The risk over a lifetime undoubtedly is even higher. Furthermore, the metabolic syndrome confers a 5-fold increase in risk for type 2 diabetes mellitus. Conversely, little is known about the predictive role of MetS in peripheral arterial disease (PAD)

13. Metabolic Syndrome and Obesity in Peripheral Arterial Disease Much less information is available on the relationship between MetS and peripheral artery disease (PAD), with most data deriving from cross-sectional reports A prospective evaluations suggested that MetS is a predictor of end-stage PAD (lower-extremity amputation or revascularization) but that this risk increase is largely attributable to the impact of diabetes alone. Another recent analysis did not find a significant association of MetS with incident PAD, although a strong and independent relationship between MetS and cerebrovascular disease was noted.

14. Metabolic Syndrome and Obesity in Peripheral Arterial Disease • MetS is associated with an increased risk of future symptomatic PAD in women. This risk appears to be mediated largely by the effects of inflammation and endothelial activation. • (Conen Circulation. 2009;120:1041-1047.) • Women with MetS had a 62% increased risk of future PAD (hazard ratio 1.62, 95% confidence interval 1.10 to 2.38). • After multivariable adjustment, MetS remained significantly associated with PAD (adjusted hazard ratio 1.48, 95% confidence interval 1.01 to 2.18), with a 21% risk increase per additional MetS-defining trait (adjusted hazard ratio 1.21, 95% confidence interval 1.06 to 1.39).

15. Metabolic Syndrome and Obesity in Peripheral Arterial Disease Conen D et al. Circulation online Sept 2009

16. Metabolic Syndrome and Obesity in Peripheral Arterial Disease • The metabolic syndrome is associated with a 1.5-fold increase in risk of vascular events in PAOD patients. • Weight control reduces metabolic syndrome incidence and increases metabolic syndrome resolution during follow-up. • (Vleck ALM J Vasc Surg 2009;50:61-9) • The study population consisted of 461 patients with symptomatic PAOD Federation (IDF). The MetS was associated with an increased risk of vascular events (HR 1.51; 1.01-2.30, age- and gender-adjusted).

17. Metabolic Syndrome and Obesity in Peripheral Arterial Disease Vleck.Vasc Surg2009

18. Metabolic Syndrome and Obesity in Peripheral Arterial Disease The degree of peripheral arterial disease clinical manifestations was not related to metabolic syndrome score, but gangrene was significantly positively associated with increased fasting glucose, high-sensitivity C-reactive protein, and lower education. (Maksimovic. Angiology 2009; 60; 546) This cross-sectional study involved 388 consecutive patients with verified PAD.Metabolic syndrome was present in 59.8% of the patients with peripheral arterial disease.

19. Metabolic Syndrome and Obesity in Peripheral Arterial Disease: Maksimovic. Angiology 2009

20. Metabolic Syndrome and Obesity in Peripheral Arterial Disease • IDF-MEtS, but not rATP III-MetS, is an independent predictor of cardiovascular events. IDF-MEtScombined with an ABI<0.73 identifies a subgroup of claudicants at very high risk • (Brevetti Nutrition, Metabolism & Cardiovascular Diseases 2009 ) • 173 patients with intermittent claudication and ABI <0.90, in whom MetS was defined using the criteria of both Adults Treatment Panel III (rATP III) and International Diabetes Federation (IDF). IDF-MetS was independently associated with increased cardiovascular risk (HR 1.91, 95% CI 1.03-3.51, p=0.038).

21. Metabolic Syndrome and Obesity in Peripheral Arterial Disease Brevetti Nutr Metabol 2009

22. Metabolic Syndrome and Obesity in Peripheral Arterial Disease • In conclusion, similar to the previously noted relationship between MetS and incident coronary heart disease and stroke, several studies suggest a positive association with PAD. • Increased plasma levels of inflammatory markers were evident in subjects with MetS, and a strong influence of these factors on the relationship between MetS and PAD was noted, suggesting a possible pathophysiological role. • Prospective data from cohorts are greatly needed not only to corroborate the actual results but also to further elucidate mechanistic links between risk factor clustering and onset of this disease..

23. Linee Guida Prevenzione Cardiovascolare Fernando Botero, La coppia

24. Metabolic Syndrome and Obesity in Peripheral Arterial Disease Mattioli AV ESC 2009

25. Metabolic Syndrome and Obesity in Peripheral Arterial Disease Mc Dermott JACC 2009