INTERNATIONAL JOURNAL OF CARDIOLOGY AND CARDIOVASCULAR MEDICINE

ISSN 2517-570X

Obesity and Cardiovascular Disease

Shashi K. Agarwal

Center for Contemporary and Complementary Cardiology, 2227 US Highway 1, Suite 309,, North Brunswick, United States

CitationCitation COPIED

Agarwal SK. Obesity and Cardiovascular Disease. Int J Cardiol Cardiovasc Med. 2021 Feb;4(1):138.

Abstract

Cardiovascular diseases (CVD) are the leading cause of global morbidity and mortality. Besides imparting a tremendous amount of human suffering, they also inflict huge direct and indirect financial costs on the worldwide society. With the ready availability of affordable therapeutics globally, and the lack of newer innovations, lifestyle interventions are gaining importance to further control this epidemic. Obesity, a lifestyle factor, is consistently and strongly related to a higher risk of CVD incidence and mortality. Therefore, maintenance of optimal weight has become an important goal in the quest for improved CVD health worldwide. This paper reviews the relationship between obesity and cardiovascular diseases.

Keywords

Obesity; Cardiovascular disease; Obesity paradox; BMI; Coronary artery disease

Introduction

Both excess weight and cardiovascular diseases are globally on the rise. Obesity inflicts a significant harmful effect on cardiovascular diseases. This results in an enormous amount of human suffering, many premature and untimely deaths, and huge financial costs. Attaining and maintaining an optimal body mass index (BMI) is therefore an important goal in reducing this obesity-related plague of CVD morbidity and mortality. This manuscript briefly reviews the global obesity epidemic and its direct and indirect effect on the number one killer in the world – cardiovascular diseases.

The obesity pandemic

Obesity, a growing global health problem [1], has become a dangerous pandemic [2]. According to the World Health Organization (WHO), in 2016, more than half of the world’s adult population had an elevated BMI, with 39% being overweight and 13% being obese [3]. According to them, there were more than 1.9 billion adults aged 18 years and older who were overweight in 2016 [4]. Children and adolescents are also experiencing excessive weight gain [5,6]. WHO reported that in 2016, 41 million children worldwide under the age of 5 were overweight or obese; while over 340 million children and adolescents aged 5–19 were overweight or obese [7]. The collaborative groups of the Global Burden of Disease Study examined data from 68.5 million children and adults between 1980 and 2015 from over 195 countries and territories and found that the prevalence rate of obesity had increased in most countries and had doubled in more than 70 countries [8]. This enormous increase in excess body weight was associated with 4 million deaths, with cardiovascular disease accounting for two-thirds of these deaths [8]. It is expected that by 2030, more than 2.16 billion people will be overweight and 1.12 billion obese in the world [9].

The obesity epidemic has been especially noticeable in the industrialized countries. Obesity in the US has increased from a prevalence of 36.5% in 2011–2014 [10], to a prevalence of 42.4% in 2017-2018 [11]. Severe obesity (body mass index (BMI) ≥ 40 kg/m2 ) and morbid obesity, (BMI ≥ 50 kg/m2 ) increased 4-fold, and >10-fold, respectively, during the last quarter-century [12]. Obesity is now the second leading cause of preventable premature death in the US, after smoking [13], and may soon become the first [14]. It is expected to negate the gain in US life expectancy which resulted largely from a decline in smoking [15]. In 2014, Europe had overall obesity prevalence in adults of 15.9% [16]. In Italy, the prevalence of obesity is 20% today and has risen from approximately 7% in the 1970s [17]. Spain is also struggling with excess body weight, with approximately 41% of children aged between 6 and 9 years being overweight/obese in 2015 [18]. Eastern Europe has alarming statistics – 55.5% of Hungarians aged 15 years and older are now overweight or obese [19]. In the Eastern Mediterranean Region, the prevalence of obesity has increased from 15.1% in 1980 to 20.7% in 2015 [20].

The obesity burden is also affecting the less developed countries [21-24]. In 2010–2012 the prevalence of overweight and obesity in Chinese adults was 30.1% and 11.9%, respectively [25]. In India, the prevalence of overweight and obesity is increasing rapidly [26-28], and it is estimated that by 2030, 27.8% of all Indians would be overweight, and 5.0% obese [29]. China, India, Pakistan, and Indonesia are now in the top 10 countries with the highest populations of obesity in the world [30]. Obesity has also been increasing at an alarming rate among African countries [31]. Eastern Sudan has a prevalence of 26.8% for overweight and 32.2% for obesity [32]. Uganda has a 17.8% prevalence of overweight [33], while in Ethiopia, overweight/ obesity increased significantly from 10.9% in 2000 to 21.4% in 2016 [34]. Africa’s child population is expected to become the largest child population among all continents in 2055, reaching 1 billion [35]. Unfortunately, these children are also rapidly becoming obese [36].According to UNICEF, WHO, and the World Bank, Southern Africa has the highest prevalence of overweight among children under 5 years (14.6%), followed by Central Asia (11.6%) and Northern Africa (11.0%) [37].

Obesity is growing irrespective of the age, population and ethnic groups, and socioeconomic status of the individuals [38]. It is expected to continue rising in the coming decades [39]. The overweight/obesity pandemic and its health-related ramifications have resulted in grave economic consequences, with the world spending billions of dollars on this disorder [40].

Anthropometric measurements for bodyweight

Astronomer and mathematician Alphonse Quetelet (Belgian mathematician, astronomer, and statistician) developed the Quetelet Index in 1832, which was subsequently termed the body mass index or BMI (weight (kg/height (m2 )) in 1972 by Ancel Keys (1904-2004) [41]. BMI is nowadays, a widely used measure to define bodyweight.42 BMI is categorized into several groups: < 18.5 kg/m2 (underweight), 18.5–24.9 kg/m2 (normal weight), and 25 to 29.9 kg/m2 , (overweight). Obesity is defined as a BMI exceeding 30 kg/m2 and is subclassified into class 1 (30–34.9 kg/m2 ), class 2 (35–39.9 kg/m2 ), and class 3 or severe obesity (≥ 40 kg/m2 ).2 A BMI >50 Kg/m2 is considered morbid obesity [42]. Asian populations differ from European populations in the percentage of body fat, and health risks [43], and the International Obesity Task Force recommends different BMI categories for them [44]. These are: underweight (<18.5 kg/m2 ), normal (between 18.5 and 23 kg/m2 ), overweight (between 23 and 25 kg/m2 ), obese (between 25 and 30 kg/m2 ), and severely obese (≥ 30 kg/m2 ).

Obesity and non-CVD health implications

Elevated BMI is associated with several chronic diseases [45]. These include: asthma [46], several cancers (including those of the esophagus, colon and rectum, liver, gallbladder and biliary tract, pancreas, breast, uterus, ovary, kidney, thyroid, and blood - leukemia) [47],depression (obese adolescents have a 40% greater risk of being depressed) [48], end-stage renal disease [49], gall bladder disease [50], gout [51], hyperuricemia [52], obstructive sleep apnea [53], osteoarthritis [54,55], nonalcoholic fatty liver disease [56], and poor quality of life [57]. Higher morbidity in obese individuals has also been reported in children and adolescents [58]. Obesity is associated with a rise in disabilityadjusted life-years [59] and increased all-cause mortality [60- 62]. Obesity is also a strong predictor of CVD risk and greatly influences its clinical course [63].

The CVD epidemic

CVDs include high blood pressure (HTN), coronary heart disease (CHD), stroke, heart failure (HF), cardiac arrhythmias, peripheral arterial disease (PAD), deep vein thrombosis (DVT), and atherosclerotic erectile dysfunction (ED) [64,65]. The present global prevalence of hypertension of 26% is projected to rise to 29% by the year 2025 [66]. HTN is an independent predisposing factor for several other CVDs and increases CVD mortality [67]. Coronary artery disease is the most prevalent CVD [68], with a global prevalence of 2%–3% [69]. CHD is the leading cause of death of all diseases, and was responsible for an estimated 8.92 million deaths, globally, in 2015 [70]. It is expected that 82% of the future increase in coronary heart disease mortality will occur in developing countries [71]. The primary cause of CHD is atherosclerosis which results from a diseased endothelium, lowgrade inflammation, lipid accumulation, and plaque formation within the intima of the vessel wall [72]. This can progress into a flow-limiting stenosis of the large epicardial coronary arteries, resulting in ischemia [55].Plaque rupture or erosion can provoke superimposed atherothrombosis and subsequent vessel occlusion, leading to a myocardial infarction, and even death [56]. Stroke is prevalent all over the world [73]. According to WHO, 15 million people worldwide suffer a stroke every year, and kill about 3 million women and 2.5 million men [74]. Stroke is the third most common cause of death globally and results in enormous disabilities in those who survive [75]. HF affected about 40 million people in the world in 2015 [76]. It is estimated that 2% of all adults have heart failure and the rates are increasing [77]. Heart failure severely reduces the quality of life [78]. The mortality can be as high as 10% each year [79]. Cardiac arrhythmias are extremely common [80]. Atrial fibrillation affects about 2% to 3% of the population [81] and puts the affected individuals at a greater risk for embolic stroke [82] and heart failure [83]. SCD is usually due to ventricular arrhythmias and accounts for almost half of all deaths due to CVD [84]. PAD is present in more than 200 million people in the world [85]. It is seen in 7–14 % of the general population [86]. PAD usually involves the legs and is an atherosclerotic disease [87] and results in about 52,500 deaths annually (2015 data) [88]. Epidemiological studies indicate that ED affects approximately 11% of men over 30 years of age and 37% of the men over 70 years of age [89]. Atherosclerosis of the pelvic and penile vasculature is the major underlying cause [90]. Erectile dysfunction is a strong predictor for other cardiovascular diseases, including coronary artery disease [91]. DVT of the lower extremities is a common venous disease and is associated with significant morbidity and exhibits a high rate of recurrence [92]. Venous thromboembolism is the third most common cause of vascular mortality worldwide, accounting for 5.4 million deaths annually [93].

Combined, these diseases are the leading cause of morbidity and mortality in the world [94].They cause approximately onethird of all deaths worldwide [53]. They are associated with immense human suffering [95], and are one of the leading causes of disability-adjusted life years (DALYs) [96], and impart a huge financial burden globally [97]. It is expected that CVDs will continue to rise globally in the coming years [98]. 

Anthropometric measurements for CVD

Fat amount and fat distribution is more important for CVD risk and can be missed by BMI measurement alone [99]. Central obesity is associated with a higher CVD risk [100].In the EUROASPIRE III study, the prevalence rate of central obesity in CVD patients was 53% [101] Central obesity can be objectively ascertained by several anthropometric measurements [102- 104]. These include the waist circumference (WC), waist-hip ratio (WHR), and the weight height ratio (WHtR) [103,104]. WC should ideally be <102 cm in males and <88 cm in females when measured to the nearest 0.1 cm at the umbilical level in a standing position [105]. In the Asian populations, these numbers are <85 cm for males and, <80 cm for females [105]. Higher values indicate central obesity. Many researchers have also used another anthropometric measurement, WHR (normal is 0.85 or less for women and 0.9 or less for men) for determining central obesity [36]. The WHO advises that a WHR of more than 1.0 increases CVD risk [103]. The WHtR is calculated as WC divided by height. (< 0.5 indicates no central obesity) and ≥ 0.5 is considered to be consistent with central obesity) [104]. Bhatt and group found that central obesity was an indicator of metabolic disorders in 53% of CVD individuals [106]. Rost and group found that another measurement, the body adiposity index (BAI = [(hip circumference (cm)/height (m)1.5) − 18] × 100) and WHtR of males and WC and WHR of females were associated with an increased risk of CVD mortality [107]. It may be therefore prudent to monitor all these measurements, in patients to get a more reliable appraisal of central obesity and CVD risk [108].

Obesity and CVD

The EUROASPIRE III study (across all 22 participating countries in Europe) found a 35% prevalence rate of obesity based on BMI in CVD patients [101].Most of the available studies have used obesity in their research on the connection between excess body weight and CVDs.

Obesity deleteriously affects CVDs is several ways:

Obesity and HTN 

There is a strong relationship between obesity and HTN [45,109]. Weight gain is associated with an increase in arterial pressure [46] and this relationship appears to be linear [45]. Obesity may result in a 3.5-fold increase in the likelihood of being hypertensive, and obesity may be responsible for 60-70% of HTN in adults [110]. The increasing prevalence of HTN has therefore been linked to the global obesity epidemic [47]. The dramatic increase in body weight in children and adolescents may also explain the increasingly higher prevalence of HTN being noted in this population [111].Obese children are at a two-fold higher risk of developing HTN compared to normal-weight children [49]. Weight reduction is associated with a significant decrease in arterial pressure in hypertensives [50]. Obesity surgery also reduces arterial blood pressure [51]. Obesity increases renal sodium absorption, impairs natriuresis and these lead to extracellular volume expansion and elevated blood pressures [52].

Obesity and CHD

Obesity is an independent risk factor for CHD [57]. Weight gain increases the risk of CHD events and CHD mortality [58]. Coronary artery calcification (CAC) scores are associated with increased CVD events [59] and obesity is a risk factor for CAC, irrespective of metabolic disorders [60]. One recent study indicated that obese patients were twice as likely to have CHD after adjustment for demographics, smoking, physical activity, and alcohol intake [61]. Obesity also results in more complex, raised, and hi-grade atherosclerotic coronary artery lesions [62]. These plaques demonstrate greater macrophage infiltration and higher plaque instability [63]. Following coronary artery bypass grafting, obese patients show a higher incidence of deep sternal wound infections [112]. Obese patients with CHD, also exhibit higher risks of mortality and unsatisfactory neurological recovery following a cardiogenic arrest recovery [63]. Weight loss in obese CHD patients results in marked improvements in several CHD risk factors, (such as hypertension, C-reactive protein (CRP), lipids, and glucose) [113], a lower incidence of CHD events [114],and reduced CHD mortality [114].Cardiac rehabilitation is associated with weight loss, and in obese patients, it is associated with significant lowering of CRP levels [115]. Obesity increases several CHD risk-factors, including hypertension, hyperlipidemia, and diabetes mellitus, which contribute to the increased CHD noted in these patients [116]. They also show systemic chronic low-grade inflammation, and this contributes further to CHD related atherosclerosis [117].

Obesity and stroke 

Numerous studies have reported an association between an elevated BMI and stroke [135] and this association appears to be linear [118].Data from the Nurses’ Health Study indicate a >2-fold increase in the risk of ischemic stroke and 1.6-fold increase in the risk for total stroke among women with BMI ≥32 kg/m2 compared with women with BMI <21 kg/m2 [119]. The Physicians’ Health Study showed a significant increase in the risk of total, ischemic, and hemorrhagic stroke with increasing BMI [120]. Men with BMI ≥30 kg/m2 had a >2-fold risk increase for stroke [120]. In a study of >39,000 healthy women, those with BMI ≥ 35 kg/m2 had a 2-fold increase in the risk of total stroke and an almost 3-fold increase in the risk of ischemic stroke compared with women with BMI <20 kg/m2 [121]. For each 1-U increase in BMI, there is an increase of 4% in the risk of ischemic stroke [118,120]. This association is linear and affects both men and women, regardless of race [122]. Although the increase in ischemic stroke appears to be well established in obese individuals, the association of the latter with hemorrhagic stroke remains unclear [123]. In a study by Kurth and group, BMI was not a strong risk factor for hemorrhagic stroke [121]. In UK, women with higher BMI demonstrated an increased risk of ischemic stroke but showed a decreased risk of hemorrhagic stroke [124]. The increased risk of stroke results from a higher prevalence of HTN, AF, diabetes mellitus (DM), dyslipidemia, increased inflammation, and a proinflammatory state in obese patients [125,126].

Obesity and HF

 Obesity is a known independent risk factor for HF [127], and this relationship is incremental [128].Approximately 29–40% of all HF patients (both with reduced and preserved ejection fraction) are overweight and 30–49% are obese [129].However, >80% of HF patients with preserved ejection fraction are overweight or obese [130]. In the Framingham Heart Study of 5881 patients, there was an increase of HF prevalence of 5% in men and 7% in women for every 1-unit increase in BMI [131]. Morbid obesity is associated with a 5-fold higher risk of incident HF [132].Severely obese patients with BMI ≥ 40 kg/m2 , have higher rates of pump thrombosis and acute kidney injury following a left ventricular assist device (LVAD) implantation [133]. Obese heart transplant patients have earlier high-grade acute rejection and a higher 5-year mortality when compared to heart transplant patients who were normal weight or overweight [134].Bariatric surgeryrelated weight loss in HF patients improves ejection fraction and results in a significant reduction of their New York Heart Association classification [133]. Obesity is associated with HTN, DM, metabolic syndrome, and dyslipidemia, all of which are risk factors for CHD, and can lead to HF [134].Elevated BMI is known to induce deleterious left ventricular remodeling [135].

Obesity and cardiac arrhythmias

Atrial fibrillation is more common in obese patients [136] Wanahita et al. reviewed 5 population-based studies (78,602 patients), and found that obese patients had a nearly 50% increased risk of developing AF [137]. In the Women’s Health Study, patients who became obese had a 41% increased risk of developing AF compared to those who did not become obese [138]. In both studies the risk of AF escalated with increasing BMI [137,138]. In the Women’s Health Study, there was a 4.7% increase in AF risk with each 1 kg/m2 unit increase in BMI [138]. It is estimated that about 18% of cases of AF could be prevented by achieving an optimal body weight [139]. Sudden cardiac death (SCD) is an unexpected death that occurs within one hour of symptoms onset [140]. Structural heart disease or primary electrical abnormalities of the heart lead to pulseless electrical activity in the heart, ventricular fibrillation, ventricular tachycardia, or asystole, precipitating SCD [141]. SCD was increased in apparently healthy obese patients in the Framingham Heart Study [142,143]. Annual SCD rates are nearly 40 times higher than in a matched nonobese population [144]. Obesity results in atrial remodeling, with hemodynamic, structural, and electrical derangements of the atria [145], that are similar to the structural and electrical changes that have been identified in patients with structural disease [146-148]. The increased electrical ventricular irritability noted in obese patients may lead to more frequent and complex ventricular dysrhythmias, and this may explain the higher prevalence of sudden cardiac death in this population [149]. Weight loss in overweight animals has been shown to improve electrophysiologic, structural, and histologic cardiac characteristics [150].

Obesity and aortic stenosis

An elevated BMI is positively related to aortic stenosis [151,152].In 2014, two studies reported high BMI was associated with an increased risk of aortic valve stenosis [153,154].In 2017, Larsson and group showed a dose-response positive relationship between self-reported elevated BMI and risk of aortic valve stenosis [151].A recent study published in 2020, found a similar relationship [152]. Calcific aortic valve disease in obese patients probably represents an atherosclerotic process, the latter being associated with traditional atherogenic risk factors and pathologically demonstrating lipoprotein deposition, chronic inflammation, and active leaflet calcification [155,156].

Obesity and PAD

High BMI increases the risk of developing PAD [157]. Four out of five people with PAD are overweight or obese [109].In the Framingham Heart Study (3,313 patients, 53% were women), each 5-point increase in BMI (equivalent to a change from being slightly overweight to being obese) made a person 40% more likely to develop PAD [158]. Obesity is causally associated with PAD after controlling for the potential intermediate factors like hypertension, dyslipidemia, and hyperglycemia [159]. PAD in obese patients is more ominous [160].It not only increases nonfatal coronary events but also doubles the overall mortality and cardiovascular mortality over ten years if PAD is accompanied by obesity, when compared to the general population [161]. PAD may progress to critical leg ischemia [162] and this increases the risk of hospitalizations and lower extremity amputation [159]. Many researchers have noted a J-shaped association or a U-shaped association of BMI with PAD [160]. Atherosclerotic plaques limiting the blood flow are usually the cause of PAD [161]. Obesity is associated with increased inflammation, which is a major factor in the development of atherosclerosis [162]. Obese patients often have associated DM [163], dyslipidemia [164] and/or hypertension [45], and these also help drive PAD in these patients

Obesity and ED

Obesity is an independent risk factor for ED [165]. Men experience an increased relative risk of 1.5 to 3.0 for ED if their BMI is more than 25 [166].In the European Male Ageing Study, ED was present in 36.7% of obese men while it affected only 24.8% of healthy weight men [167]. Similar findings were reported by Sarwer et al. [168] who found that 36% of men undergoing bariatric surgery had ED. Non-surgical weight improves erectile function in obese men [169]. Bariatric surgery-related weight loss also helps reverse erectile function [170]. Obesity, and in particular central obesity, reduces testosterone levels and is associated with atherosclerotic ED [171].

Obesity and venous disease

DVT of the lower extremities is a common venous disease and is associated with significant morbidity and is plagued with a high rate of recurrence [172,173]. Venous thromboembolism (VTE) is the third most common cause of vascular mortality worldwide and comprises DVT and pulmonary embolism (PE) In clinical practice, about two-thirds of VTE episodes manifest as DVT and one-third as PE with or without DVT. Immobilization is an important risk factor for DVT [174]. Obese individuals are more likely to have protracted hospital immobilization which is conducive for the development of DVT [175].They are also more likely to be less physically active, and physical activity aimed at the leg musculature, engaging the calf muscle pump, also help reduce post-thrombotic syndrome and venous ulceration [176,177]. A high BMI, in the INVENT consortium study evaluating 52,632 individuals, was associated with venous thromboembolism (DVT and PE combined) [178].Obesity is associated with an increased intravascular volume and high-volume lymphatic overload, and this combined with the reduced physical activity seen in obese patients, leads to venous insufficiency, edema, and increased VTE [179].

Obesity is associated with factors such as increased intraabdominal pressure, chronic low-grade inflammation, increased fibrinogen levels with impaired fibrinolysis, and elevated clotting factor levels. These further contribute to the increased risk for VTE in these individuals [180].

Obesity and CVD risk factors

Obesity is also associated with many CVD risk factors, such as DM [163],dyslipidemia [164], metabolic syndrome [181], obstructive sleep apnea [182], systemic inflammation [183], atherosclerosis [184], depression [185], and end-stage renal failure [186]. These further contribute to the CVD related morbidity and mortality seen in obese patients [187-189]

Obesity and CVD mortality

Obesity, is associated with increased CVD mortality [187- 189],both in young individuals [190], and adults [191].

CVD benefits of weight loss

Weight loss is inevitably paralleled by an improvement of other cardiometabolic risk factors [192-194]. Weight loss helps reduce several major cardiovascular events [195]. Bariatric weight loss procedures demonstrate significant CVD risk reduction and mortality reduction, while often eliminating numerous comorbidities and improving the patient’s quality of life [196].

Obesity Paradox

Despite the clear evidence that obesity results increase the risk of CVD morbidity and mortality, there exists a phenomenon called the ‘obesity paradox’ The latter has been coined as clinical observations reveals that there is often a better cardiovascular survival in obese patients when compared with normal weight and underweight individuals. The obesity paradox has been noted in HTN [197], CAD [133], AF [153], pulmonary arterial hypertension [198], ST-elevation myocardial infarction [199], and HF [200]. Studies have found that patients demonstrating the obesity paradox have increased lean mass, despite the obesity, and a better cardiorespiratory fitness [201], and these may explain the phenomenon. Other mechanisms may also be involved [202-207].

Conclusion

Obesity is not only an important but an urgent global health issue. Elevated BMI is directly associated with increased CVD risk. Obesity increases several cardiovascular risk factors, which may also play a role. Central obesity, a stronger predictor of CVD health, maybe missed by BMI measurement alone. Hence WC, WHR, and WHtR should also be used to determine the risk in obese patients. Studies have demonstrated that weight loss, including that following bariatric surgery, improves CVD risk and positively modulates CVD morbidity and mortality. There are several ancillary health benefits also. Health care providers should aggressively counsel overweight and obese patients on weight reduction. The lifestyle changes associated with weight reduction may also help stem several other chronic diseases and increase the patient’s overall physical and emotional health.

References

1. World Health Organization Obesity and overweight. 2016. (Ref)

2. NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: A pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults. Lancet. 2017 Dec;390(10113):2627- 2642. (Ref)

3. Obesity and overweight Who.int (2019). (Ref)

4. World Health Organization Health Topics. Obesity and Overweight. (2018). (Ref)

5. Skinner AC, Skelton JA. Prevalence and trends in obesity and severe obesity among children in the united states, 1999– 2012. JAMA Pediatr. 2014 Jun;168(6):561–566. (Ref)

6. Fryar CD, Carroll MD, Ogden CL. Prevalence of overweight, obesity, and severe obesity among children and adolescents aged 2–19 years: United States, 1963–1965 through 2015– 2016. Natl Cent Heal Stat (US) Div Heal Nutr Exam Surv. 2018 Sep:93–95. (Ref)

7. WHO Obesity and Overweight. (Ref)

8. GBD 2015 Obesity Collaborators. Afshin A, Forouzanfar M, Reitsma MB, Sur P, et al. Health Effects of Overweight and Obesity in 195 Countries over 25 Years. N Engl J Med. 2017 Jul;377(1):13–27. (Ref)

9. Kolahi AA, Moghisi A, Soleiman Ekhtiari Y. Socio-demographic determinants of obesity indexes in Iran: findings from a nationwide STEPS survey. Health Promot Perspect. 2018 Jul;8(3):187–194. (Ref)

10. OECD. Obesity and the economics of prevention: fit not fat. Key facts - United States, update 2014. Paris: OECD Publishing; 2014. (Ref)

11. Hales CM, Carroll MD, Fryar CD, Ogden CL. Prevalence of Obesity and Severe Obesity Among Adults: United States, 2017-2018. NCHS Data Brief. 2020 Feb;(360):1-8. (Ref)

12. Piché ME, Tchernof A, Després JP. Obesity phenotypes, diabetes, and cardiovascular diseases. Circ Res. 2020;126(11):1477– 1500. (Ref)

13. Mokdad AH, Marks JS, Stroup DF, Gerberding JL. Actual causes of death in the United States, 2000. JAMA. 2004 Mar;291(10):1238–1245. (Ref)

14. Sturm R, Well KB. Does obesity contribute as much to morbidity as poverty or smoking? Public Health. 2001 May;115(3):229-235. (Ref)

15. Preston SH, Vierboom YC, Stokes A. The role of obesity in exceptionally slow US mortality improvement. Proc Natl Acad Sci U S A. 2018 Jan;115(5):957–961. (Ref)

16. Eurostat European Health Interview Survey - Almost 1 adult in 6 in the EU is considered obese - Share of obesity increases with age and decreases with education level. Eurostat news release 20 October 2016. (Ref)

17. Organization for Economic Co-operation and Development (OECD) The heavy burden of obesity: the economics of prevention. Country note to the report the heavy burden of obesity: Italy. Paris: OECD Health Policy Studies, OECD Publishing; 2019. 

18. World Health Organization Childhood Obesity Surveillance Initiative: highlights 2015-17. (Ref)

19. Központi Statisztikai Hivatal Egészségi állapot és egészségmagatartás, 2016–2017. Budapest: Központi Statisztikai Hivatal; (2018). p. 23. 

20. GBD 2015 Eastern Mediterranean Region Obesity Collaborators. Burden of obesity in the Eastern Mediterranean Region: findings from the Global Burden of Disease 2015 study. Int J Public Health (Ref)2018 May; 63(Suppl 1):165-176. (Ref)

21. NCD Risk Factor Collaboration (NCD-RisC) Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19·2 million participants. Lancet. 2016 Apr;387(10026):1377-1396. (Ref)

22. Monteiro CA, Conde WL, Popkin BM. Income-Specific Trends in Obesity in Brazil: 1975–2003. Am J Public Health. 2007 Oct;97:1808–1812. (Ref)

23. Bleich SN, Vercammen KA, Zatz LY, Frelier JM, Ebbeling CB, et al. Review Interventions to prevent global childhood overweight and obesity : a systematic review. LANCET Diabetes Endocrinol. 2018 Apr;6(4):332-346. (Ref)

24. Laws R, Campbell KJ, van der Pligt P, Russel G, Lynch J, et al. The impact of interventions to prevent obesity or improve obesity related behaviours in children (0-5 years) from socioeconomically disadvantaged and/or Indigenous families: a systematic review. BMC Public Health. 2014 Aug;14:779. (Ref)

25. Bureau of Disease Prevention and Control National Health and Family Planning Commission of the PRC. Report on Chinese Residents’ Chronic Diseases and Nutrition (2015) People’s Medical Publishing House; Beijing, China: 2016. 

26. International Institute for Population Sciences. National Family Health Survey (NFHS-2), India, 1998–99. (2000). 

27. International Institute for Population Sciences. National Family Health Survey (NFHS-3), India, 2005–06. International Institute for Population Sciences (2009).

28. International Institute for Population Sciences. National Family Health Survey (NFHS-4) 2015–16 India. International Institute for Population Sciences (IIPS) and ICF (2017).5–7. 

29. Kelly T, Yang W, Chen CS, Reynolds K, He J. Global burden of obesity in 2005 and projections to 2030. Int J Obes (Lond). 2008 Sep;32(9):1431-1437.(Ref)

30. Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014 Aug;384(9945):766-781. (Ref)

31. Swinburn BA, Sacks G, Hall KD, McPherson K, Finegood DT, et al. The global obesity pandemic: Shaped by global drivers and local environments. Lancet. 2011 Aug;378(8793):804–814. (Ref)

32. Omar SM, Taha Z, Hassan AA, Al-Wutayd O, Adam I. Prevalence and factors associated with overweight and central obesity among adults in the Eastern Sudan. PLoS One. 2020 Apr;15(4):e0232624. (Ref)

33. Kirunda BE, Fadnes LT, Wamani H, van den Broeck J, Tylleskär T. Population-based survey of overweight and obesity and the associated factors in peri-urban and rural Eastern Uganda. BMC Public Health. 2015 Nov;15:1168. (Ref)

34. Ahmed KY, Abrha S, Page A, et al. Trends and determinants of underweight and overweight/obesity among urban Ethiopian women from 2000 to 2016. BMC Public Health. 2020 Aug;20(1):1276. (Ref)

35. data.unicef.org – accessed January 2, 2021.

36. Klingberg S, Draper CE, Micklesfield LK, Benjamin-Neelon SE, van Sluijs EM, et al. Childhood obesity prevention in Africa: a systematic review of intervention effectiveness and implementation. Int J Environ Res Public Health. 2019 Apr;16(7):1212. (Ref)

37. UNICEF, WHO, World Bank Group. Levels and Trends in Child Malnutrition: UNICEF, WHO, World Bank Group joint child malnutrition estimates. 2016. 

38. GBD 2017 Risk Factor Collaborators. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990, 2013, 2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018 Nov;392(10159):1923-1994. (Ref)

39. Foreman KJ, Marquez N, Dolgert A, Fukutaki K, Fullman N, et al. Forecasting life expectancy, years of life lost, and all-cause and cause-specific mortality for 250 causes of death: reference and alternative scenarios for 2016-40 for 195 countries and territories. Lancet. 2018 Nov;392((10159)):2052–2090. (Ref)

40. Smith KB, Smith MS. Obesity statistics. Prim Care. 2016 Mar;43(1):121-135. (Ref)

41. Eknoyan G. Adolphe quetelet (1796-1874) - the average man and indices of obesity. Nephrol Dial Transplant. 2008 Jan;23(1):47-51. (Ref)

42. World Health Organization. Body mass index - BMI. 2018. (Ref)

43. WHO Expert Consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet. 2004 Jan 10;363(9403):157- 163. 

44. World Health Organization, International Obesity Task Force. The Asian-Pacific perspective: Redefining obesity and its treatment. Geneva, Switzerland: WHO Western Pacific Region, 2000. (Ref)

45. Doll S, Paccaud F, Bovet P, Burnier M, Wietlisbach V. Body mass index, abdominal adiposity and blood pressure: consistency of their association across developing and developed countries. Int J Obes Relat Metab Disord. 2002 Jan;26(1):48-57. (Ref)

46. Must A, Spadano J, Coakley EH, Field AE, Colditz G, et al. The disease burden associated with overweight and obesity. JAMA. 1999 Oct;282(16):1523-1539. (Ref)

47. Francischetti EA, Genelhu VA. Obesity-hypertension: an ongoing pandemic. Int J Clin Pract. 2007 Feb;61(2):269-280. (Ref)

48. Yan W, Li X, Zhang Y, Niu D, Mu K, et al. Reevaluate secular trends of body size measurements and prevalence of hypertension among Chinese children and adolescents in past two decades. J Hypertens. 2016 Dec;34(12):2337-2343. (Ref)

49. Willig AL, Casazza K, Dulin-Keita A, Franklin FA, Amaya M, et al. Adjusting adiposity and body weight measurements for height alters the relationship with blood pressure in children. Am J Hypertens. 2010 Aug;23(8):904–910. (Ref)

50. Lavie CJ, Milani RV. Obesity and cardiovascular disease: the Hippocrates paradox? J Am Coll Cardiol. 2003 Aug 20;42(4):677-679. (Ref)

51. Sjöström, K. Narbro, C.D. Sjöström, Karason K, Larsson B, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007 Aug;357(8):741-752. (Ref)

52. Parto P, Lavie CJ, Arena R, Bond S, Popovic D, et al. Body habitus in heart failure: Understanding the mechanisms and clinical significance of the obesity paradox. Future Cardiol. 2016 Nov;12(6):639–653. (Ref)

53. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, et al. Heart Disease and Stroke Statistics-2016 Update: A Report from the American Heart Association. Circulation. 2016 Jan 26;133(4):e38- 360. (Ref)

54. Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature. 2011 May;473(7347):317-325. (Ref)

55. Ganz P, Abben RP, Barry WH. Dynamic variations in resistance of coronary arterial narrowings in angina pectoris at rest. Am J Cardiol. 1987 Jan;59(1):66-70. (Ref)

56. Bentzon JF, Otsuka F, Virmani R, Falk E. Mechanisms of plaque formation and rupture. Circ Res. 2014 Jun;114(12):1852- 1866. (Ref)

57. Wilson PW, D’Agostino RB, Sullivan L, et al. Overweight and obesity as determinants of cardiovascular risk: the Framingham experience. Arch Intern Med. 2002 Sep;162(16):1867-1872. (Ref)

58. Yarnell JW, Patterson CC, Thomas HF, Sweetnam PM. Comparison of weight in middle age, weight at 18 years, and weight change between, in predicting subsequent 14 year mortality and coronary events: Caerphilly Prospective Study. J Epidemiol Community Health. 2000 May;54(5):344-348. (Ref)

59. Pletcher MJ, Tice JA, Pignone M, Browner WS. Using the coronary artery calcium score to predict coronary heart disease events: a systematic review and meta-analysis. Arch Intern Med. 2004 Jun 28;164(12):1285-1292. (Ref)

60. Chang Y, Kim B, Yun KE, Cho J, Zhang Y, et al. Metabolically healthy obesity and coronary artery calcification. J Am Coll Cardiol. 2014 Jun 24;63(24):2679-2686. (Ref)

61. Ndumele CE, Matsushita K, Lazo M, Bello N, Blumenthal RS, et al. Obesity and Subtypes of Incident Cardiovascular Disease. J Am Heart Assoc. 2016 Jul;5(8):e003921. (Ref)

62. Garcia-Labbé D, Ruka E, Bertrand OF, Voisine P, Costerousse O, et al. Obesity and coronary artery disease: evaluation and treatment. Can J Cardiol. 2015 Feb;31(2):184-194. (Ref)

63. De Rosa R, Vasa-Nicotera M, Leistner DM, et al. Coronary atherosclerotic plaque characteristics and cardiovascular risk factors - insights from an optical coherence tomography study. Circ J. 2017;81(8):1165–1173. (Ref)

64. WHO. About cardiovascular diseases. World Heal. Organ. 2018. (Ref)

65. https://www.who.int/cardiovascular_diseases/about_cvd/ en/ - accessed October 29, 2020. (Ref)

66. Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, et al. et al. Global burden of hypertension: analysis of worldwide data. Lancet. 2005 Jan;365(9455):217-223. (Ref)

67. Lee JH, Kim SH, Kang SH, Cho JH, Cho Y, et al. Blood pressure control and cardiovascular outcomes: real-world implications of the 2017 ACC/AHA Hypertension Guideline. Sci Rep. 2018  Sep;8(1):13155. (Ref)

68. Roth GA, Johnson C, Abajobir A, Abd-Allah F, Ferede Abera S, et al. Global, regional, and national burden of cardiovascular diseases for 10 causes, 1990 to 2015. J Am Coll Cardiol. 2017 Jul;70:1-25. (Ref)

69. Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, et al. American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2019 Update: A Report From the American Heart Association. Circulation. 2019 Mar;139(10):e56-e528. (Ref)

70. GBD 2015 Mortality Causes of Death Collaborators (October 2016). “Global, regional, and national life expectancy, allcause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015”. 2016 Oct;388(10053):1459- 1544. (Ref)

71. https://www.who.int/cardiovascular_diseases/ publications/atlas_cvd/en/ - accessed November 5, 2020. (Ref)

72. Hansson G.K. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005 Apr;352(16):1685-1695. (Ref)

73. Ganz P, Abben RP, Barry WH. Dynamic variations in resistance of coronary arterial narrowings in angina pectoris at rest. Am J Cardiol. 1987 Jan;59(1):66-70. 55. (Ref)

74. Bentzon JF, Otsuka F, Virmani R., Falk E. Mechanisms of plaque formation and rupture. Circ. Res. 2014;114:1852–1866. 56 

75. Feigin VL, Roth GA, Naghavi M, Parmar P, Krsihnamurthi R, Chugh S, et al. Global burden of stroke and risk factors in 188 countries, during 1990-2013: a systematic analysis for the Global Burden of Disease study 2013. Lancet Neurol. 2016 Aug;15(9):913-924. (Ref)

76. https://www.who.int/cardiovascular_diseases/resources/ atlas/en/. Accessed November 21, 2020. (Ref)

77. Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, et al. Turner MB. Heart disease and stroke statistics—2012 update: A report from the American Heart Association [comparative study]. Circulation. 2012 Jan;125(1):e2–e220. (Ref)

78. GBD 2015 Disease and Injury Incidence and Prevalence Collaborators (October 2016). Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 388 (10053):1545–1602. (Ref)

79. Metra M, Teerlink JR (October 2017). Heart failure. Lancet. 2017 Apr;390 (10106):1981-1995. (Ref)

80. Juenger J, Schellberg D, Kraemer S, Haunstetter A, Zugck C, et al. Health related quality of life in patients with congestive heart failure: comparison with other chronic diseases and relation to functional variables. Heart. 2007 Mar;87 (3):235– 241. (Ref)

81. Neubauer S. The failing heart--an engine out of fuel. N Engl J Med. 2007 Mar;356(11):1140-1151. (Ref)

82. American Heart Association About Arrhythmia. (Ref)

83. Zoni-Berisso M, Lercari F, Carazza T, Domenicucci S. Epidemiology of atrial fibrillation: European perspective. Clin Epidemiol. 2014 Jun;6:213–220. (Ref)

84. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, et al. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur. Heart J. 2016 Oct;37:2893–2962. (Ref)

85. Anter E, Jessup M, Callans DJ. Atrial fibrillation and heart failure treatment considerations for a dual epidemic. Circulation. 2009 May;12;119(18):2516-2525. (Ref)

86. Mehra R. Global public health problem of sudden cardiac death. J Electrocardiology. 2007 Nov;40(6 Suppl):S118–S122. (Ref)

87. Fowkes FG, Rudan D, Rudan I, Aboyans V, Denenberg JO, et al. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. Lancet. 2013 Oct;382(9901):1329-1340. (Ref)

88. Alzamora MT, Fore´s R, Baena-Dı´ez JM, Pera G, Toran P, et al. The peripheral arterial disease study (PERART/ARTPER): prevalence and risk factors in the general population. BMC Public Health. 2010 Jan;10:38. (Ref)

89. Aboyans V, Ricco JB, Bartelink MEL, Bjorck M, Brodmann M, et al. Desormais I. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS): document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteriesEndorsed by: the European Stroke Organization (ESO)The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS) Eur Heart J. 2018 Mar;39(9):763– 816. (Ref)

90. GBD 2015 Mortality and Causes of Death, Collaborators. (October 8, 2016). Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016 Oct;388(10053):1459-1544. (Ref)

91. Rosen RC, Fisher WA, Eardley I, Niederberger C, Nadel A, et al. The multinational men’s attitudes to life events and sexuality (males) study: I. prevalence oSf erectile dysfunction and related health concerns in the general population. Curr Med Res Opin. 2004 ;20:607–617. (Ref)

92. Richardson D, Vinik A. Etiology and treatment of erectile failure in diabetes mellitus. Curr Diab Rep. 2002 Dec;2(6):501- 509. (Ref)

93. Uddin SMI, Mirbolouk M, Dardari Z, Dardari Z, Feldman DI, Cainzos-Achirica M, et al. Erectile dysfunction as an independent predictor of future cardiovascular events. Circulation. 2018 Jul;138:540–542. (Ref)

94. Heit JA. Epidemiology of venous thromboembolism. Nat Rev Cardiol. 2015 Aug;12:464-474. (Ref)

95. Abuduhalike R, Sun J, Mahemuti A. Correlation Study of the Long-Term Prognosis of Venous Thromboembolism and Inflammatory Gene Polymorphisms. Int J Gen Med. 2020 Dec;13:1559-1566 (Ref)

96. Roth GA, Johnson C, Abajobir A, Abd-Allah F, Abera SF, et al. Global, Regional, and National Burden of Cardiovascular Diseases for 10 Causes, 1990 to 2015. J Am Coll Cardiol. 2017 Jul 4;70(1):1-25.(Ref).

97. Mozaffarian D, Benjamin E, Go A, et al. Heart disease and stroke statistics-2016 update. A report from the American Heart Association. Circulation. 2016;133:0. 53

98. Arija V, Villalobos F, Pedret R, Vinuesa A, Jovan D, et al. Physical activity, cardiovascular health, quality of life and blood pressure control in hypertensive subjects: randomized clinical trial. Health Qual Life Outcomes. 2018 Sep;16(1):184. (Ref)

99. Bourne RR. Global, regional, and national disability-adjusted life-years (DALYs) for 359 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018 Nov;392:1859-1922. (Ref)

100.Bloom D, Cafiero E, Jané-Llopis E, Abrahams-Gessel S, Bloom L, et al. The Global Economic Burden of Non-Communicable Diseases. Geneva: World Econ. Forum. 2011;  (Ref)

101.Sniderman AD, Furberg CD. Age as a modifiable risk factor for cardiovascular disease. Lancet. 2008 May. 371:1547–1549. (Ref)

102.Piché ME, Poirier P, Lemieux I, Després JP. Overview of epidemiology and contribution of obesity and body fat distribution to cardiovascular disease: an update. Prog Cardiovasc Dis. Jul-Aug 2018;61(2):103-113. (Ref)

103.Coutinho T, Goel K, de Sá DC, Kragelund C, Kanaya AM, et al. Central obesity and survival in subjects with coronary artery disease: a systematic review of the literature and collaborative analysis with individual subject data. J Am Coll Cardiol. 2011 May;57(19):1877-1886. (Ref)

104.Dirk De B, Dallongeville J, Heidrich J, Kotseva K, Reiner Z, et al. Management of overweight and obese patients with coronary heart disease across Europe. Eur J Cardiovasc Prev Rehabil. 2010 Aug;17(4):447‐454. (Ref)

105.World Health Organization. Waist Circumference and WaistHip Ration: Report of a WHO Expert Consultation. World Health Organization; Geneva, Switzerland: 2008 December. (Ref)

106.Wakabayashi I. Necessity of Both Waist Circumference and Waist-to-Height Ratio for Better Evaluation of Central Obesity. Metabolic Syndrome and Related Disorders. 2013 Jun;11(3):189–194. (Ref)

107.Hsieh S D, Yoshinaga H, Muto T. Waist-to-height ratio, a simple and practical index for assessing central fat distribution and metabolic risk in Japanese men and women. Int J Obes Relat Metab Disord. 2003 May;27(5):610-616. (Ref)

108.https://www.hsph.harvard.edu/obesity-prevention-source/ waist-circumference-guidelines-for-different-ethnicgroups/. Accessed January 2, 2021. (Ref)

109.Bhatt DL, Steg PG, Ohman EM, Hirsch AT, Ikeda Y, et al. International prevalence, recognition, and treatment of cardiovascular risk factors in outpatients with atherothrombosis. JAMA. 2006 Jan;295(2):180-189. (Ref)

110.Rost S, Freuer D, Peters A, Thorand B, Holle R, et al. New indexes of body fat distribution and sex‐specific risk of total and cause‐specific mortality: a prospective cohort study. BMC Public Health. 2018 Apr;18(1):427. (Ref)

111.Myint PK, Kwok CS, Luben RN, Wareham NJ, Khaw KT. Body fat percentage, body mass index and waist‐to‐hip ratio as predictors of mortality and cardiovascular disease. Heart. 2014;100:1613–1619. (Ref)

112.Doll S, Paccaud F, Bovet P, Burnier M, Wietlisbach V. Body mass index, abdominal adiposity and blood pressure: Consistency of their association across developing and developed countries. Int J Obes Relat Metab Disord. 2002;26:48–57. 45 

113.AlMarri EA, Al-Hamad J. Prevalence of obesity  among hypertensive patients in Primary Care Clinic, Security Forces Hospital, Riyadh, Saudi Arabia 2017-2018: A prospective cross-sectional study. J Family Med Prim Care. 2020;9(4):1885-1890. (Ref)

114.Must A, Spadano J, Coakley EH, Field AE, Colditz G, et al. The disease burden associated with overweight and obesity. JAMA. 1999;282:1523–1529. 46 

115.Messerli FH, Ventura HO, Reisin E, Dreslinski GR, Dunn FG, et al. Borderline hypertension and obesity: two prehypertensive states with elevated cardiac output. Circulation. 1982 Jul;66(1):55-60. (Ref)

116.Francischetti EA, Genelhu VA. Obesity-hypertension: an ongoing pandemic. Int J Clin Pract. 2007 Feb;61(2):269–80. 47 

117.Yan W, Li X, Zhang Y, Niu D, Mu K, et al. Reevaluate secular trends of body size measurements and prevalence of hypertension among Chinese children and adolescents in past two decades. J Hypertens. 2016 Dec;34(12):2337-2343. (Ref)

118.Willig AL, Casazza K, Dulin-Keita A, Franklin FA, Amaya M, et al. Adjusting adiposity and body weight measurements for height alters the relationship with blood pressure in children. Am J Hypertens. 2010;23(8):904–910. 49 

119.Lavie CJ, Milani RV. Obesity and cardiovascular disease: the Hippocrates paradox? J Am Coll Cardiol, 42 (2003), pp. 677- 679. 50 

120.Sjöström, K. Narbro, C.D. Sjöström, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med, 357 (2007), pp. 741-752. 51 

121.Parto P., Lavie C.J., Arena R., Bond S., Popovic D., Ventura H.O. Body habitus in heart failure: Understanding the mechanisms and clinical significance of the obesity paradox. Future Cardiol. 2016;12(6):639–653. doi: 10.2217/fca-2016-0029. 52 

122.Wilson PW, D’Agostino RB, Sullivan L, et al. Overweight and obesity as determinants of cardiovascular risk: the Framingham experience. Arch Intern Med. 2002;162:1867– 72. 57 

123.Yarnell JW, Patterson CC, Thomas HF, Sweetnam PM. Comparison of weight in middle age, weight at 18 years, and weight change between, in predicting subsequent 14 year mortality and coronary events: Caerphilly Prospective Study. J Epidemiol Community Health 2000;54:344-8. 58 

124.Pletcher MJ, Tice JA, Pignone M, Browner WS. Using the coronary artery calcium score to predict coronary heart disease events: a systematic review and meta-analysis. Arch Intern Med. 2004;164:1285–1292. 59 

125.Chang Y, Kim B, Yun KE, et al. Metabolically healthy obesity and coronary artery calcification. J Am Coll Cardiol. 2014;63:2679–2686. 60.

126.Ndumele CE, Matsushita K, Lazo M, Bello N, Blumenthal RS, et al. Obesity and Subtypes of Incident Cardiovascular Disease. J Am Heart Assoc. 2016 Jul 28;5(8). 61

127.Garcia-Labbé D, Ruka E, Bertrand OF, Voisine P, Costerousse O, Poirier P. Obesity and coronary artery disease: evaluation and treatment. Can J Cardiol. 2015 Feb;31(2):184-94. 62

128.De Rosa R, Vasa-Nicotera M, Leistner DM, et al. Coronary atherosclerotic plaque characteristics and cardiovascular risk factors - insights from an optical coherence tomography study. Circ J. 2017;81(8):1165–1173. doi:10.1253/circj.CJ17-0054. 63

129.Buschmann K, Wrobel J, Chaban R, Rösch R, Ghazy A, et al. Body Mass Index (BMI) and Its Influence on the Cardiovascular and Operative Risk Profile in Coronary Artery Bypass Grafting Patients: Impact of Inflammation and Leptin. Oxid Med Cell Longev. 2020 Jun;2020:5724024. (Ref)

130.Sung CW, Huang CH, Chen WJ, Chang WT, Wang CH, et al. Obese cardiogenic arrest s urvivors with significant coronary artery disease had worse in-hospital mortality and neurological outcomes. Sci Rep. 2020 Oct 29;10(1):18638. (Ref)

131.Ades PA, Savage PD, Toth MJ, Harvey-Berino J, Schneider DJ, et al. High-calorie-expenditure exercise: a new approach to cardiac rehabilitation for overweight coronary patients. Circulation. 2009 May;119:2671–2678. (Ref)

132.Eilat-Adar S, Eldar M, Goldbourt U. Association of intentional changes in body weight with coronary heart disease event rates in overweight subjects who have an additional coronary risk factor. Am J Epidemiol. 2005 Feb;161:352–358. (Ref)

133.Sierra-Johnson J, Romero-Corral A, Somers VK, LopezJimenez F, Thomas RJ, et al. Prognostic importance of weight loss in patients with coronary heart disease regardless of initial body mass index. Eur Cardiovasc Prev Rehabil. 2008 Jun:15(3)336-340.  (Ref)

134.Lavie CJ, Morshedi-Meibodi A, Milani RV. Impact of cardiac rehabilitation on coronary risk factors, inflammation, and the metabolic syndrome in obese coronary patients. J Cardiometab Syndr. 2008 Aug;3(3):136-140.  (Ref)

135.Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, et al. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association scientific statement on obesity and heart disease from the obesity committee of the council on nutrition, physical activity, and metabolism. Circulation. 2006 Feb;113(6):898-918. (Ref)

136.Rexrode KM, Hennekens CH, Willett WC, Colditz GA, Stampfer MJ, et al. A prospective study of body mass index, weight change, and risk of stroke in women. JAMA. 1997 May;277(19):1539-1545. (Ref)

137.Kurth T, Gaziano JM, Berger K, Kase CS, Rexrode KM, et al. Body mass index and the risk of stroke in men. Arch Intern Med. 2002 Dec;162: 2557–2562. (Ref)

138.Kurth T, Gaziano JM, Rexrode KM, Kase CS, Cook NR, et al. Prospective study of body mass index and risk of stroke in apparently healthy women. Circulation. 2005 Apr;111(15):1992-1998. (Ref)

139.Strazzullo P, D’Elia L, Cairella G, Garbagnati F, Cappuccio FP, et al. Excess body weight and incidence of stroke: metaanalysis of prospective studies with 2 million participants. Stroke. 2010;41: e418–426. (Ref)

140.Rodriguez BL, D’Agostino R, Abbott RD, Kagan A, Burchfiel CM, et al. Risk of hospitalized stroke in men enrolled in the Honolulu Heart Program and the Framingham Study: a comparison of incidence and risk factor effects. Stroke. 2002 Jan;33(1):230-236. (Ref)

141.Chasman DI, Albert CM. Genetic Obesity and the Risk of Atrial Fibrillation: Causal Estimates from Mendelian Randomization. Circulation. 2017 Feb;135(8):741-754. (Ref)

142.Gaman M, Dobrica E, Pascu EG, Cozma MA, Elena-Epingeac M, et al. Cardio metabolic risk factors for atrial fibrillation in type 2 diabetes mellitus: focus on hypertension, metabolic syndrome and obesity. J Mind Med Sci. 2019 Feb;6:157-161. (Ref)

143.Lin TY, Chiu CJ, Kuan CH, Chen FH, Shen YC, et al. (Ref) IL-29 promoted obesity-induced inflammation and insulin resistance. Cell Mol Immunol. 2020 Apr;17(4):369-379. (Ref)

144.Hagg S, Fall T, Ploner A, Magi R, Fischer K, et al. European Network for Genetic and Genomic Epidemiology Consorium. Adiposity as a cause of cardiovascular disease: a Mendelian randomization study. Int J Epidemiol 2015 Apr;44(2):578– 586. (Ref)

145.Hu G, Jousilahti P, Antikainen R, Katzmarzyk PT, Tuomilehto J. Joint effects of physical activity, body mass index, waist circumference, and waist-to-hip ratio on the risk of heart failure. Circulation. 2010 Jan;121:237–244. (Ref)

146.Bozkurt B, Aguilar D, Deswal A. Contributory risk and management of comorbidities of hypertension, obesity, diabetes mellitus, hyperlipidemia, and metabolic syndrome in chronic heart failure: A scientific statement from the American Heart Association. Circulation. 2016 Dec;134(23):e535–e578. (Ref)

147.Lewis GA, Schelbert EB, Williams SG. Biological phenotypes of heart failure with preserved ejection fraction. J Am Coll Cardiol. 2017 Oct;70(17):2186–2200. (Ref)

148.Kenchaiah S, Evans JC, Levy D. Obesity and the risk of heart failure. N Engl J Med. 2002 Aug;347(5):305–313. (Ref)

149.Khan SS, Ning H, Wilkins JT. Association of body mass index with lifetime risk of cardiovascular disease and compression of morbidity. JAMA Cardiol. 2018;3(4):280–287. (Ref)

150.Lee AY, Tecson KM, Lima B. Durable left ventricular assist device implantation in extremely obese heart failure patients. Artif Organs. 2019 Mar;43(3):234–241. (Ref)

151.Lavie CJ, Mehra MR, Ventura HO. Body composition and advanced heart failure therapy: Weighing the options and outcomes. JACC Heart Fail. 2016 Oct;4(10):769-771. (Ref)

152.Yang TWW, Johari Y, Burton PR. Bariatric surgery in patients with severe heart failure. Obes Surg. 2020. (Ref)

153.Lavie CJ, Milani RV, Ventura HO. Obesity and cardiovascular disease: risk factor, paradox, and impact of weight loss. J Am Coll Cardiol. 2009 May;53(21):1925-1932. (Ref)

154.Alpert MA. Obesity cardiomyopathy: pathophysiology and evolution of the clinical syndrome. Am J Med Sci. 2001 Apr;321(4):225-236. (Ref)

155.Wang TJ, Parise H, Levy D, et al. Obesity and the risk of newonset atrial fibrillation. JAMA, 292 (2004), pp. 2471-2477) T.J. 

156.Wanahita N, Messerli FH, Bangalore S, Gami AS, Somers VK, et al. Atrial fibrillation and obesity—results of a meta-analysis. Am Heart J. 2007 Dec;155(2):310-315. (Ref)

157.Tedrow UB, Conen D, Ridker PM. The long- and short-term impact of elevated body mass index on the risk of new atrial fibrillation. The WHS (Women’s Health Study) J Am Coll Cardiol. 2010 May;55(21):2319–2327. (Ref)

158.Miyasaka Y, Barnes ME, Gersh BJ, Cha SS, Bailey KR, et al. Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota 1980 to 2000, and implications on the projections for future prevalence. Circulation. 2006 Jul;114(2):119-125. (Ref)

159.Kuriachan VP, Sumner GL, Mitchell LB. Sudden cardiac death. Curr Probl Cardiol. 2015 Apr;40(4):133-200. (Ref)

160.Yow AG, Rajasurya V, Sharma S. Sudden Cardiac Death. [Updated 2020 Aug 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020. (Ref)

161.Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, et al. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 199 7 American Heart Association scientific statement on obesity and heart disease from the obesity committee of the council on nutrition, physical activity, and metabolism. Circulation. 2006 Feb;113(6):898-918. (Ref)

162.Messerli FH, Nunez BD, Ventura HO, Snyder DW. Overweight and sudden death: increased ventricular ectopy in cardiomyopathy of obesity. Arch Intern Med. 1987 Oct;147(10):1725-1728. (Ref)

163.Kannel WB, Plehn JF, Cupples LA. Cardiac failure and sudden death in the Framingham Study. Am Heart J. 1988 Apr;115(4):869-875. (Ref)

164.Munger TM, Dong YX, Masaki M, Oh JK, Mankad SV, et al. Electrophysiological and hemodynamic characteristics associated with obesity in patients with atrial fibrillation. J Am Coll Cardiol. 2012 Aug;60(9):851-860. (Ref)

165.Dimitri H, Ng M, Brooks AG, et al. Atrial remodeling in obstructive sleep apnea: implications for atrial fibrillation. Heart Rhythm. 2012 Mar;9(3):321-327. (Ref)

166.Medi C, Kalman JM, Spence SJ, Kuklik P, Stiles MK, et al. Atrial electrical and structural changes associated with longstanding hypertension in humans: implications for the substrate for atrial fibrillation. J Cardiovasc Electrophysiol. 2011 Dec;22(12):1317-1324.  (Ref)

167.Kistler PM, Sanders P, Dodic M, Spence SJ, Samuel CS, et al. Atrial electrical and structural abnormalities in an ovine model of chronic blood pressure elevation after prenatal corticosteroid exposure: implications for development of atrial fibrillation. Eur Heart J 2006 Dec; 27(24):3045-3056. (Ref)

168.Messerli FH, Nunez BD, Ventura HO, Snyder DW. Overweight and sudden death: increased ventricular ectopy in cardiomyopathy of obesity. Arch Intern Med. 1987 Oct;147(10):1725-1728. (Ref)

169.Mahajan R, Lau DH, Brooks AG, et al. Electrophysiological, electroanatomical, and structural remodeling of the atria as consequences of sustained obesity. J Am Coll Cardiol. 2015 Jul;66(1):1-11. (Ref)

170.Larsson SC, Wolk A, Håkansson N, Bäck M. Overall and abdominal obesity and incident aortic valve stenosis: two prospective cohort studies. Eur Heart J. 2017 Jul;38(28):2192- 2197. (Ref)

171.Larsson SC, Bäck M, Rees JMB, Mason AM, Burgess S. Body mass index and body composition in relation to 14 cardiovascular conditions in UK Biobank: a Mendelian randomization study. Eur Heart J. 2020 Jan;41(2):221-226. (Ref)

172.Martinsson A, Ostling G, Persson M, Sundquist K, Andersson C, et al. Carotid plaque, intima-media thickness, and incident aortic stenosis: a prospective cohort study. Arterioscler Thromb Vasc Biol. 2014 Oct;34(10):2343–2348. (Ref)

173.Eveborn GW, Schirmer H, Lunde P, Heggelund G, Hansen JB. Assessment of risk factors for developing incident aortic stenosis: the Tromso Study. Eur J Epidemiol. 2014 Aug;29(8):567-575. (Ref)

174.Stewart BF, Siscovick D, Lind BK, Gardin JM, Gottdiener JS, et al. Clinical factors associated with calcific aortic valve disease. J Am Coll Cardiol. 1997 May;29:630–634. (Ref)

175.Freeman RV, Otto CM. Spectrum of calcific aortic valve disease: pathogenesis, disease progression, and treatment strategies. Circulation. 2005 Jun;111(24):3316-3326. (Ref)

176.Lu B, Zhou J, Waring ME, Parker DR, Eaton CB. Abdominal obesity and peripheral vascular disease in men and women: a comparison of waist-to-thigh ratio and waist circumference as measures of abdominal obesity. Atherosclerosis. 2010 Jan;208(1):253-257. (Ref)

177.Bhatt DL, Steg PG, Ohman EM, et al. International prevalence, recognition, and treatment of cardiovascular risk factors in outpatients with atherothrombosis. JAMA. Jan 11 2006;295(2):180-189. 109. 

178.Murabito JM, Evans JC, Nieto K, Larson MG, Levy D, et al. Prevalence and clinical correlates of peripheral arterial disease in the Framingham Offspring Study. Am Heart J. 2002 Jun;143(6):961-965. (Ref)

179.Huang Y, Xu M, Xie L, Wang T, Huang X, et al. Obesity and peripheral arterial disease: a Mendelian randomization analysis. Atherosclerosis. 2016 Apr;247:218–224. (Ref)

180.Biancari F. Meta-analysis of the prevalence, incidence and natural history of critical limb ischemia. J Cardiovasc Surg (Torino). 2013 Dec;54(6):663–669. (Ref)

181.Ankle Brachial Index Collaboration, Fowkes FG, Murray GD, Butcher I, et al. Ankle brachial index combined with Framingham Risk Score to predict cardiovascular events and mortality: a meta-analysis. JAMA. 2008 Jul;300(2):197-208. (Ref)

182.Hicks CW, Yang C, Ndumele CE, Folsom AR, Heiss G. et al. Association s of Obesity With Incident Hospitalization Related to Peripheral Artery Disease and Critical Limb Ischemia in the ARIC Study. J Am Heart Assoc. 2018 Aug;7(16):e008644. (Ref)

183.Huang Y, Xu M, Xie L, Wang T, Huang X, et al. Obesity and peripheral arterial disease: A Mendelian randomization analysis. Atherosclerosis. 2016 Apr;247:218–224. 179. 

184.Desormais I, Aboyans V, Guerchet M, Ndamba-Bandzouzi B, Mbelesso P, et al. EPIDEMCA investigators. Body mass index and peripheral arterial disease, a “U-shaped” relationship in elderly African population - the EPIDEMCA study. Vasa. 2020 Jan;49(1):50-56. (Ref)

185.Simon F, Oberhuber A, Floros N, Düppers P, Schelzig H, et al. Pathophysiology of chronic limb ischemia. Gefasschirurgie. 2018;23(Suppl 1):13–18. (Ref)

186.Gregor MF, Hotamisligil GS. Inflammatory mechanisms in obesity. Annu Rev Immunol. 2011;29:415-445. (Ref)

187.Banerjee S, Talukdar I, Banerjee A, Gupta A, Balaji A, et al. Type II diabetes mellitus and obesity: Common links, existing therapeutics and future developments. J Biosci. 2019 Dec;44(6):150. (Ref)

188.Feingold KR. Obesity and Dyslipidemia. 2020 Nov 2. In: Feingold KR, Anawalt B, Boyce A, et al. editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000. (Ref)

189.Derby CA, Mohr BA, Goldstein I, Feldman HA, Johannes CB, et al. Modifiable risk factors and erectile dysfunction: can lifestyle changes modify risk? Urology. 2000 Aug;56(2):302- 306. (Ref)

190.Chitaley K, Kupelian V, Subak L, Wessells H. Diabetes, obesity and erectile dysfunction: field overview and research priorities. J Urol. 2009 Dec;182(6 Suppl):S45-50. (Ref)

191.Han TS, Tajar A, O’Neill TW, Jiang M, Bartfai G, et al. Impaired quality of life and sexual function in overweight and obese men: the European Male Ageing Study. Eur J Endocrinol. 2011 Jun;164(6):1003–1011. (Ref)

192.Sarwer DB, Spitzer JC, Wadden TA, Rosen RC, Mitchell JE, et al. Sexual functioning and sex hormones in persons with extreme obesity and seeking surgical and nonsurgical weight loss. Surg Obes Relat Dis. Nov-Dec 2013;9(6):997-1007. (Ref)

193.Kolotkin RL, Binks M, Crosby RD, Østbye T, Mitchell JE, et al. Improvements in sexual quality of life after moderate weight loss. Int J Impot Res. 2008;20:487–492. (Ref)

194.Reis LO, Favaro WJ, Barreiro GC, de Oliveira LC, Chaim EA, et al. Erectile dysfunction and hormonal imbalance in morbidly obese male is reversed after gastric bypass surgery: a prospective randomized controlled trial. Int J Androl. 2010 Oct;33(5):736-744. (Ref)

195.Corona G, Mannucci E, Ricca V, Lotti F, Boddi V, et al. The age-related decline of testosterone is associated with different specific symptoms and signs in patients with sexual dysfunction. Int J Androl. 2009 Dec;32(6):720-728. (Ref)

196.Heit JA. Epidemiology of venous thromboembolism. Nat Rev Cardiol. 2015 Aug;12(8):464–474. (Ref)

197.Brandjes DP, Büller HR, Heijboer H, Huisman MV, de Rijk M, et al. Randomised trial of effect of compression stockings in patients with symptomatic proximal-vein thrombosis. Lancet. 1997;349(9054):759-762. (Ref)

198.Al Sayegh F, Almahmeed W, Al Humood S, Marashi M, Bahr A, et al. Global Risk Profile Verification in Patients with Venous Thromboembolism (GRIP VTE) in 5 Gulf countries. Clin Appl Thromb Hemost. 2009 May-Jun;15(3):289-296. (Ref)

199.Padberg FT, Johnston MV, Sisto SA. Structured exercise improves calf muscle pump function in chronic venous insufficiency: A randomized trial. J Vasc Surg. 2004 Jan;39(1):79-87. (Ref)

200.Kahn SR, Shrier I, Shapiro S, Houweling AH, Hirsch AM, et al. Six-month exercise training program to treat postthrombotic syndrome: A randomized controlled two-centre trial. CMAJ. 2011 Jan;183(1):37-44.  (Ref)

201.Araki CT, Back TL, Padberg FT, Lee BC, Duran WN, et al. The significance of calf muscle pump function in venous ulceration. J Vasc Surg. 1994;20(6):872–879. (Ref)

202.Lindstrom S, Germain M, Crous-Bou M, Smith EN, Mornage PE, et al. Assessing the causal relationship between obesity and venous thromboembolism through a Mendelian Randomization study. Hum Genet. 2017 Jul;136(7):897–902. (Ref)

203.Sugerman HJ, Suggerman EI, Wolfe L, Kellum Jr JM, Schweitzer MA, et al. Risks and benefits of gastric bypass in morbidly obese patients with severe venous stasis disease. Ann Surg. 2001 Jul;234(1):41–46. (Ref)

204.Blokhin IO, Lentz SR. Mechanisms of thrombosis in obesity. Curr Opin Hematol. 2013 Sep;20(5):437-444. (Ref)

205.Jia W. Obesity, metabolic syndrome and bariatric surgery: A narrative review. J Diabetes Investig. 2020 Mar;11(2):294– 296. (Ref)

206.Roche J, Isacco L, Masurier J, Pereira B, Mougin F, et al. Are obstructive sleep apnea and sleep improved in response to multidisciplinary weight loss interventions in youth with obesity? A systematic review and meta-analysis. Int J Obes (Lond). 2020 Apr;44(4):753-770. (Ref)

207.Lumeng CN, Saltiel AR. Inflammatory links between obesity and metabolic disease. J Clin Invest. 2011 Jun; 121(6): 2111– 2117. (Ref)

208.Zhang T, Chen J, Tang X, Luo Q, Xu D, et al. Interaction between adipocytes and high-density lipoprotein: new insights into the mechanism of obesity-induced dyslipidemia and atherosclerosis. Lipids Health Dis. 2019 Dec;18(1):223. (Ref)

209.Mannan M, Mamun A, Doi S, Clavarino A. Prospective Associations between Depression and Obesity for Adolescent Males and Females- A Systematic Review and Meta-Analysis of Longitudinal Studies. PLoS One. 2016 Jun;11(6):e0157240. (Ref)

210.Hsu CY, McCulloch CE, Iribarren C, Darbinian J, Go AS. Body mass index and risk for endstage renal disease. Ann Intern Med. 2006 Jan;144(1):21-28. (Ref)

211.Hruby A, Manson JE, Qi L, Malik VS, Rimm EB, Sun Qi, et al. Determinants and consequences of obesity. Am J Public Health. 2016 Sep;106(9):1656–1662. (Ref)

212.Larsson B, Svärdsudd K, Welin L, Wilhelmsen L, Björntorp P, et al. Abdominal adipose tissue distribution, obesity, and risk of cardiovascular disease and death: 13 year follow up of participants in the study of men born in 1913. Br Med J (Clin Res Ed). 1984;288(6428):1401–1404. (Ref)

213.Song X, Jousilahti P, Stehouwer CDA, Söderberg S, Onat A, et al. Comparison of various surrogate obesity indicators as predictors of cardiovascular mortality in four European populations. Eur J Clin Nutr. 2013 Dec;67(12):1298-1302. (Ref)

214.Messerli FH, Nunez BD, Ventura HO, Snyder DW. Overweight and sudden death: increased ventricular ectopy in cardiopathy of obesity. Arch Intern Med. 1987 Oct;147(10):1725-1728. (Ref)

215.Dikaiou P, Björck L, Adiels M, Lundberg CE, Mandalenakis Z, et al. Obesity, overweight and risk for cardiovascular disease and mortality in young women. Eur J Prev Cardiol. 2020 Mar 2:2047487320908983. (Ref)

216.Abed HS, Wittert GA, Leong DP, Shirazi MG, Bahrami B, Middledorp ME, et al. Effect of weight reduction and cardiometabolic risk factor management on symptom burden and severity in patients with atrial fibrillation: a randomized clinical trial. JAMA. 2013 Nov;310(19):2050-2060. (Ref)

217.Pathak RK, Middeldorp ME, Lau DH, Mehta AB, Mahajan R, et al. Aggressive risk factor reduction study for atrial fibrillation and implications for the outcome of ablation: the arrest-AF cohort study. J Am Coll Cardiol. 2014 Dec;64(21):2222-2231. (Ref)

218.Pathak RK, Middeldorp ME, Meredith M, Mehta AB, Mahajan R, et al. Long-term effect of goal directed weight management in an atrial fibrillation cohort: a long-term follow-up study (legacy study). J Am Coll Cardiol. 2015 May;65(20):2159- 2169. (Ref)

219.Sierra-Johnson J, Wright SR, Lopez-Jimenez F, Allison TG. Relation of body mass index to fatal and nonfatal cardiovascular events after cardiac rehabilitation. Am J Cardiol. 2005 Jul;96(2):211-214. (Ref)

220.Eliasson B, Liakopoulos V, Franzén S, Naslund I, Svensson AM, et al. Cardiovascular disease and mortality in patients with type 2 diabetes after bariatric surgery in Sweden: a nationwide, matched, observational cohort study. Lancet Diabetes Endocrinol. 2015 Nov;3(11):847-854. (Ref)

221.Uretsky S, Messerli FH, Bangalore S. Obesity paradox in patients with hypertension and coronary artery disease. Am J Med. 2007 Oct;120(10):863–870. (Ref)

222.Sierra-Johnson J, Romero-Corral A, Somers V.K. Prognostic importance of weight loss in patients with coronary heart disease regardless of initial body mass index. Eur J Cardiovasc Prev Rehabil. (Ref) 2008;15(3):336–340. 133.

223.Lavie C.J., Milani R.V., Ventura H.O. Obesity and cardiovascular disease. Risk factor, paradox, and impact of weight loss. J Am Coll Cardiol. 2009;53(21):1925–1932. 153.

224.Agarwal MA, Shah M, Garg L, Lavie CJ. Relationship between obesity and survival in patients hospitalized for hypertensive emergency. Mayo Clin Proc. 2018;93(2):263–265. (Ref)

225.Neeland IJ, Das SR, Simon DN. The obesity paradox, extreme obesity, and long-term outcomes in older adults with STsegment elevation myocardial infarction: Results from the NCDR. Eur Heart J Qual Care Clin Outcomes. 2017 Jul;3(3):183-191. (Ref)

226.Horwich TB, Fonarow GC, Hamilton MA, MacLellan WR, Woo MA, et al. The relationship between obesity and mortality in patients with heart failure. J Am Coll Cardiol. 2001 Sep;38(3):789-795. (Ref)

227.Lavie AA, Kokkinos CJ, Parto PF, Pandey A, Ventura HO. The interaction of cardiorespiratory fitness with obesity and the obesity paradox in cardiovascular disease. Prog Cardiovasc Dis. 2017 May;60(1):30-44. (Ref)

228.Carbone S, Canada JM, Billingsley HE, Siddiqui MS, Elagizi A, Lavie CJ. Obesity paradox in cardiovascular disease: Where do we stand? Vasc Health Risk Manag. 2019 May;15:89-100. (Ref)