Metabolic Syndrome and Cardiovascular Disease

Trends indicate that the metabolic syndrome will become the leading risk factor for heart disease. Now more than ever you need an all–in–one reference that provides the tools and practical advice you need to: Identify at–risk patients Explain individual contributing factors Aid in patient education and motivation Direct comprehensive care and Choose the most appropriate interventions Comprehensively revised to reflect leading–edge research and now organized to facilitate easy access to essential information and clinically–relevant guidance , Metabolic Syndrome and Cardiovascular Disease, 2e offers this and more. Not only will you receive a solid understanding of the pathophysiology underlying the metabolic syndrome and cardiovascular disease but also the rationale for today’s most effective treatments. What’s new? Filled with timely new content, this updated edition covers: New discoveries that have changed our understanding of the pathogenesis and interrelationship of metabolic syndrome, cardiovascular disease (CHD), and type 2 diabetes mellitus (DM) The relevance of mitochondria and telomeres Sleep and its impact on cardiometabolic health The pivotal interplay between insulin and forkhead transcriptionfactors Calorie restriction research Bariatric surgery experiences and outcomes In addition, each chapter includes essential information on comorbidities, interventions, and pharmacotherapeutic options – an exclusive feature found only in the second edition!

Preface  viii List of Abbreviations  ix 1 The Metabolic Syndrome: A Relevant Concept?  1 2 Mitochondria  3 Background  3 Cellular respiration  6 Modulation of mitochondrial metabolic activity  9 Factors that affect mitochondrial number and activity  10 Peroxisome proliferator–activated receptor gamma coactivator–1  11 Mitochondrial production of prooxidant species  12 Mitochondria and nitric oxide  15 Mitochondrial calcium homeostasis  17 The mitochondrial permeability transition   18 Apoptosis   22 Causes for mitochondrial dysfunction   22 Implications of mitochondrial dysfunction   27 Mitochondrial dysfunction and cardiovascular disease   27 Mitochondrial dysfunction and metabolic disease   29 Conclusion   32 Bibliography   34 3 Telomeres   40 Telomere structure   40 Telomere function   41 Telomere shortening   41 Telomere dysfunction   42 Physiologic age   42 Gender differences   43 Telomerase   43 Cell senescence and apoptosis   46 Telomeres in aging   49 Risk factors for cardiometabolic disease   51 Telomeres  senescence  and chronic disease   54 Cardiovascular disease   54 Insulin resistance and type 2 DM   57 Conclusion   58 Bibliography   60 4 The FoxO Transcription Factors and Sirtuins   64 Forkhead transcription factors   64 Functions of FoxO   68 Cardiovascular forkhead effects   70 Metabolic forkhead effects   72 Histone acetylation and deacetylation   75 Sirtuin deacetylases   76 Sirtuin regulation   78 Antiinflammatory  cardiovascular  and myocyte sirtuin effects   80 Sirtuin effects on metabolism   81 Sirtuins and cell longevity   83 Forkhead deregulation and insulin resistance   85 Paradoxical effect of nutrition versus stress on cell death suppression   87 Conclusion   89 Bibliography   90 5 Insulin and Insulin–Like Growth Factor   96 Anabolism and catabolism   96 Control of plasma glucose   96 Insulin   97 Insulin receptor location   98 Metabolic insulin signaling   101 Insulin–mediated glucose uptake   103 Nutrient storage and metabolism   104 Vascular and antiinflammatory effects   106 Mitogenic action   107 Insulin–like growth factor   108 Insulin and IGF impact on cell longevity   111 Amylin   113 Glucagon   113 Conclusion   113 Bibliography  114 6 Oxidative Stress   120 Free radicals   120 Oxidases   120 Sources for free radicals   123 Endogenous antioxidants   124 Physiologic functions of oxidative stress   126 Mechanisms of oxidative damage   127 Cellular stress–sensitive pathways   127 Cellular targets of oxidative stress   128 Oxidative stress–related diseases   129 Endothelial dysfunction with oxidative stress   129 Cardiovascular disease   130 Insulin resistance and type 2 DM   131 Conclusion   133 Bibliography   134 7 Mental Stress   139 Stress responses   139 Central stress pathways   139 Peripheral stress pathways   140 Fight–flight–fright responses to acute stress   142 Sequelae of sustained passive stress   142 Inflammatory effects of stress pathways   143 Vascular and lipoprotein effects of stress pathways   143 Stress impact on body weight   146 Metabolic effects of stress pathways   146 Depression and other mood disturbances   149 Conclusion   152 Bibliography   153 8 Sleep   159 Stages of sleep   159 Cardiovascular parameters during normal sleep   160 Function of sleep   161 Sleep duration   164 Circadian rhythm   165 Examples of circadian regulation   166 Neurohormonal modulation of wakefulness   168 Neurohormonal modulation of sleep   170 Sleep–arousal transitions   172 Sleep deficit   174 Pathophysiologic effects of sleep debt   175 Sleep debt and risk of cardiometabolic disorder   177 Sleep disorders   179 Conclusion   182 Bibliography   183 9 Inflammation   192 Immune responses   192 Selected participants in the inflammatory response   193 C–reactive protein   198 The renin–angiotensin–aldosterone system and inflammation   199 Inflammation and chronic diseases   202 Inflammation  endothelial and vascular dysfunction   202 Inflammation and atherosclerosis   205 Acute inflammation  carbohydrate metabolism  and dyslipidemia   210 Chronic inflammation and the metabolic syndrome   213 Causes for systemic inflammation   215 Conclusion   218 Bibliography   219 10 Adipose Tissue and Overweight   228 Energy storage   228 Diverse fat depots   230 Adipose tissue as immune organ   234 Adipose tissue as endocrine organ   236 Adipokines with beneficial cardiometabolic effect   237 Adipokines with detrimental cardiometabolic effect   244 Obesity comorbidities and cardiovascular disease   250 Obesity  insulin resistance  and diabetes   252 Conclusion   254 Bibliography   255 11 Weight Loss and Diet   266 Homeostatic responses to weight gain and weight loss   266 Adipose weight loss effects   267 Antiinflammatory  vasculoprotective  and metabolic effects of weight loss   267 Dietary intervention for weight loss   269 Calorie restriction   270 Surgical intervention   277 Diet   279 Exercise as adjunct to weight loss   289 Conclusion   289 Bibliography   291 12 Skeletal Muscle and Exercise   303 Myocyte structure and function   303 Metabolic adaptations in skeletal muscle   305 Energy sensors   311 Skeletal muscle in inflammation   317 Skeletal muscle in insulin resistance   318 Exercise effect on inflammation and oxidative stress   320 Exercise effect on metabolism in obesity  322 Exercise effect and cardiovascular health   322 Exercise and insulin resistance   325 Exercise and mortality   328 Exercise recommendation   331 Conclusion   332 Bibliography   334 13 Lipids  Atherogenic Dyslipidemia  and Therapy   347 Apolipoproteins   347 Lipoproteins   347 Apo A–containing lipoproteins   348 Apo B–containing lipoproteins   355 Apolipoproteins C  D  and E   360 The triglyceride lipase family   360 The normal metabolism of free fatty acids   363 Inflammation and hepatic insulin resistance   365 Atherogenic dyslipidemia in insulin resistance   369 Lipid–lowering therapy   372 The HMG CoA reductase inhibitors   374 Nicotinic acid   387 The fibric acid derivatives   388 Bile acid sequestrants   391 Ezetimibe   391 CETP inhibition   391 Conclusion   392 Bibliography   393 14 The Endothelium  Cardiovascular Disease  and Therapy   409 Endothelial function  409 Nitric oxide synthase and eNOS  409 Endothelial NO synthesis  410 Specific enhancers of NO synthesis   413 Functions of nitric oxide   415 Shear stress and vascular function   418 Mechanisms of endothelial dysfunction   420 Insulin  insulin resistance  and endothelial dysfunction   424 Implications of endothelial dysfunction   428 Assessment of endothelial function   430 Hypertension   432 Cardiomyopathy   434 Coronary and peripheral vascular disease   440 Pharmacologic antagonism of the  renin–angiotensin–aldosterone system and endothelin–1   443 Beta–adrenergic blockade   448 Phosphodiesterase–5 inhibitors  449 Conclusion   450 Bibliography   451 15 Insulin Resistance  Metabolic Syndrome  and Therapy   468 Diagnostic criteria for the metabolic syndrome   468 Prevalence of the metabolic syndrome   470 Insulin resistance   470 Causes of insulin resistance   474 Pathways toward insulin resistance   476 Pharmacologic therapy to improve insulin sensitivity   480 Conclusion   483 Bibliography   484 Index   491