OBESITY AND CARDIOVASCULAR DISEASE BAHAREH TAVANA MD SPORTS

OBESITY AND CARDIOVASCULAR DISEASE BAHAREH TAVANA, MD SPORTS AND EXERCISE MEDICINE SPECIALIST 1

• Definition of obesity • Adverse effects of obesity • Treatment • Cardiovascular Benefits of Weight Loss • Cardiovascular Effects of Anti-Obesity Pharmacotherapy 2

DEFINITION OF OBESITY: • Obesity is a chronic metabolic disorder defined as the presence of excessive body fat, or most accurately, excess weight for height. • overweight is defined as a BMI of 25 to 29. 9 kg/m 2 and obesity as a BMI of ≥ 30 kg/m 2 3

• BMI fails to consider body fat distribution • BMI is not a good index of visceral fat, which is the basis of metabolic disorders associated with increased cardiovascular risk. • Additionally BMI fails to account for lean-body mass which strongly correlates with reduced CHD risk. 4

• Recent evidence indicates that waist-to-hip ratio (WHR) or waist circumference (WC) measurements might be superior to traditional body size measurements as risk assessment tools • Raised WHR increases population-attributable risk from obesity by more than threefold compared with BMI. 5

• WHR ≥ 0. 85 for women and ≥ 0. 90 for men effectively constituted an additional risk factor for AMI • “Appleshaped” individuals, that have excess of abdominal fat, are at greater CVD risk than “pear-shaped” individuals with fat deposits in the lower body 6

• Adipose tissue is not simply a passive storehouse for fat, but an endocrine organ that is capable of synthesizing and releasing into the bloodstream a variety of molecules. • Of clinical consideration, circulating concentrations of angiotensin II, C-reactive protein (CRP), fibrinogen, and tumor necrosis factor a (TNF-a) are all related to BMI. 7

• approximately 30% of the total circulating concentrations of interleukin 6 (IL-6) originate from adipose tissue. • This is of importance because IL-6 modulates CRP production in the liver, and CRP may be a marker of a chronic inflammatory state that predisposes to acute coronary syndromes 8

• Obesity is strongly linked with the development of insulin resistance and metabolic syndrome, which increases the risk of both T 2 DM and CVD 9

• Epicardial adipose tissue and pericardial fat is now recognized as a quantifiable risk factor for CVD outcomes, including mortality, HF, and stroke, probably more so than other fat depots, such as hepatic fat. 10

ADVERSE EFFECTS OF OBESITY • Cardiac function • LV diastolic dysfunction • LV systolic dysfunction • Right ventricular failure 11

• Haemodynamics • Increased blood volume • Increased stroke volume • Increased arterial pressure • Increased left ventricular (LV) wall stress • Pulmonary artery hypertension 12

• Cardiac structure • LV concentric remodeling • LV hypertrophy (eccentric and concentric)* • Left atrial enlargement • Right ventricular hypertrophy 13

• Neurohumoral • Insulin resistance and hyperinsulinaemia • Leptin insensitivity and hyperleptinaemia • Reduced adiponectin levels • Sympathetic nervous system activation • Activation of the renin–angiotensin–aldosterone system • Overexpression of peroxisome proliferator-activator receptors • Reduced levels of atrial and brain natriuretic peptide 14

TREATMENT • Diet : There's no single rule that applies to everyone, but to lose weight at a safe and sustainable rate of 0. 5 to 1 kg a week, most people are advised to reduce their energy intake by 600 calories a day. • Exercise : 250 to 300 min of moderate intensity aerobic exercise per week. • Medication: Medication Pharmacological intervention as adjunct to diet and exercise is indicated for individuals with a BMI ≥ 30 or ≥ 27 kg/m 2 with at least one obesity-related comorbidity. 15

• Cognitive behavioural therapy (CBT): Getting psychological support from a trained healthcare professional may also help you change the way you think about food and eating. • Surgery (called bariatric surgery): BMI of 40 or more, or between 35 and 40 and another serious health condition that could be improved with weight loss, such as type 2 diabetes or high blood pressure and sleep apnea. 16

CARDIOVASCULAR BENEFITS OF WEIGHT LOSS • preferential loss of body fat without losing lean body mass seems to be beneficial, and associated with lower mortality in obese patients with CVD. • Among patients with already established CVD, the most effective strategy to reverse obesity-associated CVD risk factors is thought to be dietary modification combined with structured exercise programs, termed as cardiac rehabilitation • In obese patients with CHD, a 5– 10% weight loss through cardiac rehabilitation enhanced CRF, improved plasma lipids and glucose levels, reduced serum inflammatory markers, and tended to reduce mortality. 17

• Weight reduction may also have a positive impact on LV structure and function. • A loss of 8 kg reduced LV wall thickness in mildly obese hypertensive patients, and performed better than standard pharmacologic treatment. 18

CARDIOVASCULAR EFFECTS OF ANTI-OBESITY PHARMACOTHERAPY • Anti-obesity medications have been plagued in the past by high rates of CVD adverse effects • Agents withdrawn from the market due to unexpected CVD side effects include: - fenfluramine/dexfenfluramine (valvular abnormalities), - sibutramine (HR, BP and CVD event increases), - ephedrine (sympathetic activation and thermodysregulation), and - phenylpropanolamine (hemorrhagic stroke) 19

• Rimonabant was withdrawn due to neuropsychiatric side effects. • Orlistat, for years the only approved weight loss medication, has a relatively favorable CVD safety profile. . The phentermine/topiramate combination(sympathomimetic plus antiepileptic), approved by the FDA in 2012, is not recommended in patients with high CVD risk due to increased rates of tachycardia and palpitations and lack of robust long-term CVD safety data. 20

• The novel sustained-release combination of naltrexone (opioid antagonist) and bupropion (antidepressant), approved by both the FDA , has been associated with an improved lipid profile and a reduction of inflammatory biomarkers, but also with transient increases in BP, thus prompting further investigation of its CVD safety 21

• Recently, glucose-lowering medications which are increasingly prescribed in patients with T 2 DM, namely liraglutide (glucagon-like peptide 1 -receptor agonist) and the sodium/glucose cotransporter 2 inhibitors empagliflozin and canagliflozin, have shown the potential to induce weight loss and reduce CVD morbidity and mortality. . Liraglutide is now approved by both the FDA and EMA for the treatment of obesity in the absence of T 2 DM. 22

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