The Cardiovascular System: Implications of Obesity on the Body System and Resolution of Disease Processes Following Bariatric Surgery

| January 1, 2017

by Derrick Cetin, DO, and Elie Nasr, BA

Bariatric Times. 2017;14(1):10–15.


Obesity has been associated with diseases of the cardiovascular system as multiple factors of the disease increase the susceptibility to cardiovascular disease and other comorbid conditions. Here, the authors review the potential mechanisms by which obesity can influence the structure and function of the heart, including hemodynamic factors, metabolic factors, and direct/other causes. Inflammatory changes in the patient with obesity represent other potential mechanisms for structural or endocrine effects on the heart. Weight loss efforts between 5 to 10 percent have been shown to improve the comorbidities associated with metabolic process that leads to increased cardio-metabolic risk. The authors review the literature on both surgical and nonsurgical weight loss as improving metabolic status, thus decreasing cardiovascular risk.


There are multiple health-related effects of obesity called comorbidities which are associated with increased morbidity, mortality, and decreased quality of life. In addition to being a major contributor to chronic illnesses, obesity is associated with diseases of the cardiovascular system. When the BMI is ≥ 30 kg/m2, there is an association with increased risk of heart failure, myocardial infarction, premature atherosclerosis, and reduced survival because of cardiovascular deaths.[1],[2] In 2009, the American Heart Association scientific advisory noted that the prevalence of coronary heart disease (CHD) and the associated risk factors are increased in patients with obesity. The scientific advisory was published to inform surgeons, consulting physicians, and anesthesiologists of the association with cardiac and pulmonary diseases, which may negatively impact the outcome of any noncardiac surgery.[3]

The association between the degree of obesity and the incidence of cardiovascular disease (CVD) was re-examined in 5,209 men and women in the original Framingham study. A 26-year retrospective analysis revealed that obesity was determined to be a significant independent risk factor for CVD, especially in women. The percent of desirable weight on initial examination, according to the Metropolitan Relative Weight, predicted a 26-year incidence of coronary disease, coronary death, and congestive heart failure. This finding was independent of age, cholesterol, systolic blood pressure, smoking, left ventricular hypertrophy, and impaired glucose intolerance.[4] In addition to being an independent risk factor, obesity is also associated with hypertension, diabetes, and dyslipidemia as noted from the findings of the National Health and Nutrition Examination Survey, 1999 to 2004. It was observed that with increasing overweight and obesity class, there is an increase in the prevalence of hypertension, type 2 diabetes mellitus (T2DM), dyslipidemia, and metabolic syndrome.[5] Obesity is an important determinant of CVD due to these associated risk factors. Additionally, there can be an increased cardio-metabolic risk due to the presence of metabolic syndrome which is a clustering of metabolic disorders driven by insulin resistance.

Metabolic Syndrome

It has been established that obesity is an independent risk factor for CVD. Moreover, it is a component of several cardiovascular risk factors combined to establish what is called metabolic syndrome. Hypertension, insulin resistance, and dyslipidemia are the cardiovascular risk factors that, combined with the increase in intra-abdominal fat that define the metabolic syndrome.[6]

The link between obesity and insulin resistance originates from the development of hypertrophied adipose depot in the intra-abdominal or visceral compartment.[7] The increased visceral fat is an active endocrine organ producing increased pro-inflammatory cytokines: leptin, resistin, TNF-α, IL-6, CRP, and PAI-1. Conversely, the production of the anti-inflammatory cytokine adiponectin is reduced. Due to the underlying insulin resistance, there is increased lipolysis of intra-abdominal fat producing increased flux of free fatty acids into the portal system. The result is the development of increased cardiometabolic risk from increased inflammation, endothelial dysfunction, insulin resistance, and atherogenic dyslipidemia.[8]

Factors Contributing to Cardiovascular Disease

There are multiple factors that increase the susceptibility to CVD to include metabolic dysregulation, abnormal cardiac remodeling, endothelial dysfunction, premature coronary disease, increased sympathetic tone and pulmonary hypertension, and arrhythmias.[9] In this section there will be a review of the potential mechanisms by which obesity can influence the structure and function of the heart to include hemodynamic factors, metabolic factors, and direct/other causes to include inflammation and the various adipokines.[10]

Hemodynamic factors. Evidence suggests that obesity is associated with changes in the heart that lead to subclinical left ventricular (LV) systolic and diastolic dysfunction, which are precursors to clinical heart failure. Obesity is associated with risk factors (hypertension, sleep apnea, diabetes, and hyperlipidemia) that can cause heart failure. Longstanding obesity and increasing BMI have been linked to congestive heart failure (CHF) as noted in the Framingham study.[11] During a follow up of 5,881 participants (mean of 14 years), CHF developed in 258 women and 238 men. After adjustment for the established risk factors, CHF was noted in seven percent of women and five percent of men for each one-unit increment of the BMI.[11] In the Atherosclerosis Risk in Communities (ARIC) study, 13,730 participants that had a BMI of 18.5kg/m2 or greater and no CVD at baseline were followed for a median of 23 years. This study compared the association of higher BMI with incident heart failure (HF), coronary heart disease (CHD), and stroke before and after adjusting for CVD risk factors (i.e., hypertension, T2DM, and hyperlipidemia). During the study period, there were 2,235 HF events, 1,653 CHD events, and 886 strokes. After controlling for smoking, age, physical activity, demographics, and alcohol intake, a higher BMI had the strongest association of HF noted in the CVD subtypes. Severe obesity had a nearly four-fold higher risk of incident HF compared with a nearly two-fold higher risk for incident CHD and stroke. The conclusion of the study was that the association higher BMI and HF was stronger than for those in the other CVD subtypes. Furthermore the higher BMI and incident HF was largely unexplained by the traditional CVD risk factors. An emphasis on weight management was stressed for HF management and prevention.

Obesity increases metabolic demand by causing a greater increase in fat-free mass compared to fat mass, despite the fact that adipose tissue comprises a greater portion of the total body weight. A significant volume of fluid is present in the interstitial space of adipose tissue, which is about 10 percent of the tissue wet weight.[12] Despite the increase in cardiac output with total fat mass, the perfusion per unit of adipose tissue decreases with increasing obesity.[13] This is because the blood flow is regulated by β1 adreno-receptors that mediate vasodilation, whereby skeletal muscle blood flow is regulated by mainly by β2-receptors.[14] Therefore, the blood flow is actually lower in adipose tissue than in skeletal muscle even though adipose tissue comprises a greater portion of the total body weight and contains a larger portion of fluid.[15] The net result is an increase in blood flow and an increased total blood volume produced by obesity.

The increase in total blood volume is associated with a concomitant increased cardiac output mostly from an increase in the cardiac stroke volume.[16] In turn, the left ventricular filling pressure increases disproportionately incrementally due to the Frank-Starling curve being shifted to the left. At any given level of activity, the cardiac workload is increased for subjects with obesity because of with the increased venous return that occurs during exercise.[16] With the volume overload that occurs with increased blood return to the heart, there is left ventricle chamber dilation. Eccentric hypertrophy is a process by which new sarcomeres lengthen in series with existing sarcomeres to dilate the chamber radius of the heart. Eccentric hypertrophy is an adequate, compensatory response to the early volume overload.[18]

There is an increased prevalence of left ventricular hypertrophy (LVH) in individuals with obesity which is associated with left ventricular diastolic dysfunction.[17] Diastolic dysfunction is an abnormality of the myocardium to return to the unstressed length and force.[18] It is due to an incremental increase in left ventricle filling pressures and volume (preload) with concomitant chamber dilation. Progressive chamber dilation leads to increased wall stress with subsequent increases of myocardial mass and LVH of the eccentric concentric type. The development of the eccentric concentric type of LVH results from an increased wall thickness relative to chamber size. In contrast, concentric eccentric LVH, chamber enlargement is more prominent than the increase in wall thickness. Left ventricular diastolic dysfunction may progress as a result of increased stiffness and/or decreased ventricular relaxation as the ventricular chamber is unable to accept an adequate volume during diastole.[18] At this point, there is usually development of left ventricular systolic dysfunction and left ventricular failure. The processes of increased filling pressures, stroke volume, and cardiac output are adequate, compensatory changes up to the point of dysfunction of the left ventricle with ensuing heart failure. Left ventricular failure can lead to pulmonary venous hypertension, pulmonary artery hypertension, which in turn results in right ventricular hypertrophy, and right ventricular failure.[19]

Metabolic factors. In obesity there are changes in mitochondrial uncoupling and in myocardial energy metabolism with a switch in fatty acids becoming the key source of energy supply of the heart rather than glucose. Fatty acids become the prominent source of acetyl Co A for the TCA cycle. As a result of the change of the ratio of fatty acid oxidation to glucose oxidation and decreased mitochondrial oxidative metabolism, there is increased oxygen consumption for every ATP produced.[10] The increased oxygen consumption is associated with decreased cardiac efficiency with eventual decreased cardiac function and heart failure.[10] This shift of glucose to fatty acid utilization is also seen in the diabetic heart.

Increased accumulation of intramyocellular triglycerides and lipid metabolites such as ceramides has been associated with increased cardiomyocyte apoptosis in Zucker fatty rats.[20] The heart has a limited capacity to store triglycerides given the increased fatty acid supply which predisposes the heart to toxic lipid byproducts.[21] The lipotoxic metabolites, in severe cases, disturb the function of the heart leading to primarily a dilated cardiomyopathy.[22] It remains to be determined whether reduced lipolysis of myocardial triglycerides is responsible for the lipotoxic obesity cardiomyopathy.

Although the cardiac consequences of impaired insulin resistance are not well understood, reversal of insulin resistance with insulin sensitizers will increase myocardial glucose utilization, decrease fatty acid utilization, and reduce following myocardial ischemia.[23],[24] The role of insulin resistance and T2DM in causing cardiovascular disease and potential mechanisms which lead to cardiac dysfunction has been reviewed.[25] The exact role of insulin resistance and T2DM in the adult with obesity is controversial. The most likely explanation is that there are many synergistic and untoward effects on cardiac function and metabolism.[10]


In this section, the inflammatory changes as potential mechanisms for structural or endocrine effects on the heart will be reviewed. The inflammatory changes are due to the secretion of adipokines that originate in visceral fat or adipose tissue. Release of these bioactive mediators have many effects including body weight homeostasis and the development of insulin resistance.[26] Adaptations and alterations in cardiac function that occur with the accumulation of visceral adiposity, can occur even in an individual without any comorbidities.[10]

The dysregulation of adipokine signaling plays a role in the maladaptation of the heart and skeletal muscle.[26] Normally, non-adipose tissue and organs are protected from lipid overload by storing excess fatty acids in the form of triglycerides. This is regulated by the central and peripheral effects of leptin, which is one of the many adipokines secreted by visceral fat that can produce the abnormal changes in cardiac function and structure.[27] It is the normal physiologic secretion that is responsible for the central and peripheral regulation of lipid overload in non-adipose organs. With increased visceral fat, there is an overproduction of leptin which leads to leptin resistance promoting lipotoxicity of the heart.[28] Leptin resistance occurs as a result of receptors in the brain, especially the hypothalamus, to not receive the peripheral signal. It is thought that leptin resistance occurs as a result of leptin not being able to cross the blood brain barrier. Similarly, leptin deficiency or low levels occurring after weight loss can have the same effect on the central leptin receptors. Overall, the lack of leptin or leptin resistance is responsible for the accumulation of lipids in the non-adipose tissues suspected in the development of lipotoxic cardiomyopathy (lipid induced cardiac dysfunction) and increased apoptosis.[29] In summary, leptin mediates multiple effects that can produce heart failure occurring if too much or too little is produced by visceral fat.[29]

Adiponectin is another bioactive mediator produced by adipocytes, circulates in higher concentrations compared to lower levels in obese individuals. Hence, there is an independent negative predictor of adiponectin with increased visceral adiposity. The primary mechanism of adiponectin is glucose regulation through inhibition of hepatic glucose production. In skeletal muscle adiponectin also stimulates both glucose and fatty acid oxidation. In addition to being an insulin sensitizer, adiponectin appears to exert anti-inflammatory and anti-atherogenic effects and protects cardiovascular tissues under conditions of stress.[30] Adiponectin appears to exert its beneficial effects by inhibiting endothelial signaling through a Camp-dependent pathway modulating the inflammatory response.[31]

Another pathway for systemic inflammation, is the production of C-reactive protein (CRP). Patients with obesity have elevated levels of high sensitivity CRP synthesized in the liver, in response to cytokines released by fat cells.[32] The synthesis of CRP is largely regulated by elevated circulating levels of IL-6, which is also secreted by adipose tissue. It has been shown that adipose tissue is a determinant of a chronic low-grade inflammatory state as reflected by levels of IL-6, TNF-∝, and CRP.[45] Increased production of these cytokines is responsible for the development of endothelial dysfunction by decreasing nitric oxide (NO) bioavailability, which in turn leads to vasoconstriction and increasing vascular resistance.[46] In the Women’s Health Study, CRP is a strong independent risk factor for cardiovascular disease.[32] As a marker of inflammation, CRP has been shown in multiple studies to predict future myocardial infarction, CVA, and sudden cardiac death.[33]

Neurohumoral Activation

Numerous studies indicate that patients with obesity have the potential for activation of the sympathetic nervous system, which in most cases is from the effects of sleep-disordered breathing.[48] Increased sympathetic tone may contribute to the findings of concentric LVH as a result of the effects of hypertension and increased cardiac contractility. Catecholamines may have direct hypertrophic effects that are independent of hemodynamic factors, which appears to be from activation of the renin-angiotension system in obesity. Another mechanism for activation of the rennin-angiotensin system is from the increased secretion of angiotensinogen from the adipocyctes. Angiotensin can cause sympathoexcitation, so that there are additive effects of the rennin-angiotensin and sympathetic activation. The sympathoexcitation is from the hemodynamic effects (vasoconstriction and hypertension) and cardiac remodeling that occurs in obesity.50

Improvement of Comorbidities with Weight Loss

Many studies have shown the benefits of weight loss on hypertension, T2DM, hyperlipidemia, and sleep apnea.[34] Bariatric surgery is associated with long-term improvement of these comorbidities as a result of achievement of durable weight loss compared to non-surgical approaches usually fraught by weight regain. If the benefits are maintained, as a result of sustained, durable weight loss, this translates into benefits for cardiac structure and function.[35]

Bariatric surgery. Bariatric surgeries have become highly prevalent procedures in the United States. According to the American Society for Metabolic and Bariatric Surgery (ASMBS), approximately 196,000 bariatric procedures were performed in 2015. Of these procedures, sleeve gastrectomy was performed most often (53.8%) followed by Roux-en-Y gastric bypass (23.1%), gastric banding (5.7%), and biliopancreatic diversion with duodenal switch (0.6%), with the remaining 13.6 and 3.2 percent being revisions and other surgeries, respectively. Each surgical procedure modifies gastrointestinal anatomy in a way that alters the volume of the stomach, the pathway that food takes, and/or nutrient absorption. When gastric banding is performed, a silicone band is placed around the proximal part of the stomach and is fixed in place via anterior plication sutures. Once the band has been placed, it can be adjusted or tightened by injecting fluid into the subcutaneous port it is connected to. A sleeve gastrectomy reduces gastric volume by up to 80 percent by resecting the stomach around a 30F endoscope beginning three centimeters from the pylorus and ending at the angle of His. A Roux-en-Y procedure creates a 15-20 mL pouch from the stomach and directly attaches it to the small intestine via the jejunum to create the Roux limb. The duodenal biliopancreatic limb is then anastomosed to the side of the Roux limb. In a biliopancreatic diversion, a distal gastrectomy is performed along with a long Roux-en-Y reconstruction and the enteroenterostomy is placed about 50 centimeters proximal to the ileocecal valve. The volume of the gastric remnant and the length of the alimentary limb can be modified to suit the patient’s weight loss goals.[36]

Resolution of disease processes. The dramatic weight loss after bariatric surgery has been shown to be associated with significant benefits to patients including reduced CV risk factors, especially with regards to those with T2DM. A review of 73 CV risk factor studies, which included a total of 19,523 subjects (mean age 42 years, 76% female) showed postoperative improvement or resolution of hypertension, T2DM, and hyperlipidemia in 63 percent, 73 percent, and 65 percent of patients, respectively. The baseline prevalence of hypertension, T2DM, and hyperlipidemia were 44 percent, 24 percent, and 44 percent, respectively.37 Cardiac imaging techniques showed that 713 patients experienced significant improvements of left ventricular (LV) mass and isovolumic relaxation time postoperatively. LV mass regression was independent of postoperative systolic blood pressure changes. Researchers also found improvements in early/atrial (E/A) ratio which indicates reduced risk of diastolic dysfunction and, subsequently, of heart failure. Another systematic review examined 52 articles involving 16,867 patients (mean age 42 years, 78% female) with baseline prevalence of hypertension, diabetes, and dyslipidemia of 49 percent, 28 percent, and 46 percent, respectively.[38] The researchers reported an average excess weight loss of 52 percent (range 16% to 87%), and reductions of systolic blood pressure from 139 to 124 mmHg, diastolic blood pressure from 87 to 77 mmHg, fasting blood glucose from 125.99 mg/dL to 91.85 mg/dL, HbA1c from 7.45% to 5.98%, total cholesterol from 205 to 169 mg/dL, and triglycerides from 169 to 103 mg/dL at a mean follow-up of 34 months (range 3 to 155). These results, which illustrate significant decreases in the prevalence of hypertension, diabetes, and dyslipidemia, culminated in a 40-percent relative risk reduction in the 10-year CHD risk. The impacts of surgical weight loss on the structure and function of the CV system and related cardiac indices were recently further elucidated in a systematic review of 40 studies, which produced a set of 1,486 patients.[39] The aggregate studies showed decreases in LV mass index of 11.2% (95% CI 8.2, 13.1), an LV end-diastolic volume of 13.28 ml (95% CI 5.22, 21-34 ml), and a left atrial diameter of 1.967 mm (95% CI 0.980, 2.954). Also noted were increases in LV ejection fraction of 1.198% (95% CI -0.050, 2.347) and increases in E/A ratio of 0.189% (95% CI -0.113, 0.265). The improvements in the CV profiles of patients who undergo bariatric surgery can slow the progression of related diseases. Patients with established coronary artery disease can benefit from improved endothelial function and reduced risk of future cardiac events which can lead to a reduced number of CV deaths.[37] These results were reflected in the Utah Obesity Study which tracked the changes in 136 subjects who returned for five-year follow up following their RYGB procedure. These subjects’ coronary artery calcium scores were distinctly lower compared to their nonsurgical counterparts independent of traditional CV disease factors.[40] In an earlier analysis, carotid intima-media thickness (IMT) in post-gastroplasty subjects, measured at baseline and at 3 to 4 year intervals subsequently, demonstrated a rate of progression that was more in line with lean control subjects. In comparison, patients who continued to have obesity demonstrated a rate of progression that was three times higher.[41] A meta-analysis of 10 articles, totaling 314 patients, built upon these previous findings, elucidated the impacts of bariatric surgery on markers of subclinical atherosclerosis and endothelial function.[42] Patients who underwent surgical weight loss experienced a significant reduction of IMT (MD: -0.17mm; 95% CI: -0.290, 0.049; P=0.006) and improvement in flow-mediated dilation (FMD) (MD: 5.65%; 95% CI: 2.87, 8.03; P < 0.001). Nitroglycerin-mediated dilation (NMD) did not change (MD: 2.173%; 95% CI: -0.796, 5.142; P=0.151). These findings are in line with and support the previous understanding of the impacts of surgical weight loss. Improving markers associated with endothelial dysfunction, which is thought to be an important factor in the pathogenesis of subclinical atherosclerosis, can contribute to a reduction of CV risk.

It has been shown that substantial weight loss produces comparable structural changes in cardiac morphology and function in participants with and without CHF. The study included 14 patients with CHF and 39 without CHF, all were free from hypertension and underlying organic heart disease. Substantial weight loss in both groups produced comparable reductions in mean LV internal dimensions in diastole, LV mass/height index, and LV end-systolic wall stress. There were also improvements of the Doppler E/A ratio, E-wave deceleration time, and left atrial dimension. Linear regression analysis revealed that the duration of obesity to be the strongest predictor CHF 47.

Surgical versus nonsurgical weight loss. The Surgical Treatment and Medications Potentially Eradicated Diabetes Efficiently (STAMPEDE) trial, a randomized, non-blinded control trial with 150 patients (50 T2DM patients in each of 3 arms) sought to reveal the effects of surgical weight loss on improving biomarkers associated with heightened CV risk and comparing them to an intensive diabetes-medication-only therapeutic approach.[43] The primary goal of the trial was to achieve an HbA1c of 6% or less by 12 months. This was achieved by 12% of subjects in the medication therapy group, 42% in the RYGB group (p=0.002), and 37% in the gastric sleeve group (p=0.008). The researchers measured changes in the cardio-metabolic biomarkers at five years which showed greater reductions in median hs-CRP, myeloperoxidase, median leptin, and plasminogen activator inhibitor-1 in the RYGB (39 patients) and gastric sleeve (36 patients) groups than in the medical therapy (25 patients) group. There were also favorable changes in the Apo A levels in the surgical groups compared to the medical group. The STAMPEDE trial was also able to show greater weight loss in gastric bypass and sleeve gastrectomy group versus medical therapy at 12 and 24 months; similar reduction in body weight, BMI, and body fat percentage between gastric bypass and sleeve gastrectomy groups; and a greater absolute reduction in percent truncal fat from baseline with gastric bypass versus sleeve gastrectomy.

The Swedish Obesity Subjects study showed similar results.[44] In this study, 1,471 patients underwent bariatric surgery and 1,444 patients who received conventional treatment. Analysis of patients at 15 years showed reduced all-cause mortality (hazard ratio of 0.76 between subjects who underwent bariatric surgery compared to those who received conventional treatments), reduced CV events (fatal and non-fatal), reduced cancer mortality, and reduced microvascular complications.


The association between the degree of obesity and the incidence of cardiovascular disease has been established in the Framingham study and other studies. Atherosclerotic cardiovascular disease is a very concerning long-term consequence of obesity. There are multiple factors that increase the susceptibility to CVD to include metabolic dysregulation, abnormal cardiac remodeling, endothelial dysfunction, premature coronary disease, increased sympathetic tone and pulmonary hypertension, and arrhythmias.[9] The strong association between obesity and heart failure is explained by the dual effects of obesity on cardiac structures (remodeling) as well as the effects of obesity on activation of the rennin-angiotensin system and sympathetic nervous system.

Weight loss efforts between 5 to 10 percent have been shown to improve the comorbidities associated with metabolic process that leads to increased cardio-metabolic risk. Unfortunately, weight loss is a difficult process with known compliance rates of 20 percent at one year and a significant number of individuals experiencing weight regain. The strong association between obesity and heart failure is explained by the effect of obesity on cardiac structure as well as the effect of obesity on blood vessels (double hit).

Bariatric surgery has been shown to be the most effective treatment for sustained weight loss in the patient with morbid obesity. The durable weight loss has been shown to improve overall metabolic status by improvements of hypertension, T2DM, sleep apnea, and hyperlipidemia in several studies. The improved metabolic status as a result of resolution of these cormorbidities, has been shown to decrease cardiovascular risk. Bariatric surgery is now being touted as a metabolic surgery with physiological benefits that exceed the durable weight loss. As result of the physiologic benefits, more patients are having the procedure that have class 2 obesity (BMI 35–39.9kg/m2) with comorbidities that have not been well controlled with medications and/or nutritional medical therapy.

In addition to the improvement of comorbidities, benefits that occur with weight loss include a decrease in the prevalence of the metabolic syndrome. There are enhanced metabolic changes that have been noted in several studies to include reductions in hs-CRP, leptin, and plasminogen activator inhibitor-1 and increases of adiponectin. Other cardiovascular benefits seen after bariatric surgery include reductions in LV mass, decreases in blood volume, BP, cardiac filling pressures, and increases in the ejection fraction and E/A ratio. Additionally, a relative risk reduction of 40 percent was noted when utilizing the Framingham risk score after bariatric surgery. Finally, in the Swedish Obesity Subjects study, mortality due to coronary heart disease was reduced by up to 56 percent and a continued risk reduction of 29 percent occurred for up to 10 years.


1. Berrington de Gonzalez A, Hartge P, Cerhan JR, et al. Body mass index and mortality among 1.46 million white adults. N Engl J Med. 2010;363:2211–2219.

2. Whitlock G, Lewington S, Sherliker P, et al. Body mass index and cause-specific mortality in 9000,000 adults: collaborative analyses of 57 prospective studies. Lancet. 2009;373:1083–1096.

3. Poirier P, Alpert MA, Fleisher LA, et al. Cardiovascular evaluation and management of severely obese patient undergoing surgery. Circulation. 2009;120(1):86–95.

4. Hubert HB, Feinleib M, McNamara PM, Castelli WP. Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study. Circulation. 1983;67(5):968–977.

5. Nguyen NT, Magno CP, Lane KT, Hinojosa MW, Lane JS. Association of hypertension, diabetes, dyslipidemia, and metabolic syndrome with obesity: Findings from the National Health and Nutrition Examination Survey, 1999-2004. J Am Coll Surg. 2008;207(6):928–934.

6. Grundy SM. Metabolic syndrome: a multiplex cardiovascular risk factor. J Clin Endocrinol Metab. 2007;92(2):399–404.

7. Aldhahi W, Hamdy O. Adipokines, inflammation, and the endothelium in diabetes. Curr Diab Rep. 2003;3:293–298.

8. Kershaw EE1, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab. 2004;89(6):2548–2556.

9. Poirier P, et al. Bariatric surgery and cardiovascular risk factors: a scientific statement from the American Heart Association. Circulation. 2011;123:1683–1701.

10. Abel ED, Litwin SE, Sweeney G. Cardiac remodeling in obesity. Physiol Rev. 2008;88(2):389–419.

11. Kenchaiah S, Evans JC, Levy D, et al. Obesity and the risk of heart failure. N Engl Med. 2002;347:305–313.

12. Linde B, Chisolm G. The interstitial space of adipose tissue as determined by single injection and equilibration techniques. Acta Physiol Scand. 1975;95:383–390.

13. Lesser GT, Deutsch S. Measurement of adipose tissue blood flow and perfusion in man by uptake of 85Kr. J Appl Physiol. 1967;23:621–630.

14. Rosell S, Belfrage E. Blood circulation in adipose tissue. Physiol Rev. 1979;59:1078–1104.

15. Oberg B, Rosell S. Sympathetic control of consecutive vascular sections in canine subcutaneous adipose tissue. Acta Physiol Scand. 1967;71:47–57.

16. Kaltman AJ, Goldring RM. Role of circulatory congestion in Cardiorespiratory failure of obesity. Am J Med. 1976;60:645–653.

17. Messerli FH. Cardiomyopathy of obesity: a not-so-Victorian disease. N Engl J Med. 1986;314:378–380.

18. Zile MR, Brutsaert DL. New concepts in diastolic dysfunction and diastolic heart failure: Part I. Circulation. 2002;105:1387–1393.

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

20. Zhou YT, Grayburn P, Karim A, et al. Lipotoxic heart disease in obese rats: implications for human obesity. Proc Natl Acad Sci U S A. 2000;97(4):1784–1789.

21. Muoio DM, Newgard CB. Obesity-related derangements in metabolic regulation. Annu Rev Biochem. 2006;75:367–401.

22. Getz GS. Lipotoxicity: many roads to cell function and cell death. J Lipid Res. 2008;49:2101–2112.

23. Sidell RJ, Cole MA, Draper NJ, et al. Thiazolidinedione treatment normalizes insulin resistance and ischemic injury in the Zucker fatty rat heart. Diabetes. 2002;51:1110–1117.

24. Yue TL, Bao W, Gu JL, et al. Rosiglitazone treatment in Zucker diabetic Fatty rats is associated with ameliorated cardiac insulin resistance and protection from ischemia/reperfusion-induced myocardial injury. Diabetes. 2005;54:554–562.

25. Mensah GA, Mokdad AH, Ford E, et al. Obesity, metabolic syndrome, type 2 diabetes: emerging epidemics and their cardiovascular implications. Cardiol Clin. 2004;22:485–504.

26. Van Gaal LF1, Mertens IL, De Block CE. Mechanisms linking obesity with cardiovascular disease. Nature. 2006;444:875–880.

27. Unger RH. Minireview: weapons of lean body mass destruction: The role of ectopic lipids in the metabolic syndrome. Endocrinology. 2003;144(12):5159–5165.

28. Flier JS. Obesity wars: Molecular progress confronts an expanding epidemic. Cell. 2004;116:337–350.

29. Unger RH. Hyperleptinemia: protecting the heart from lipid overload. Hypertension. 2005;45:1031–1034.

30. Lihn AS, Pedersen SB, Richelsen B. Adiponectin: action, regulation and association to insulin sensitivity. Obes Rev. 2005;6(1):13–21.

31. Ouchi N, Kihara S, Arita Y, et al. Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF- kappaB signaling through a Camp-dependent pathway. Circulation. 2000;102 (11):1296–1301.

32. Ridker PM, Buring JE, Shih J, Matias M, Hennekens CH. Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation. 1998;98(8):731–733.

33. Ridker PM. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation. 2003;107:363–369.

34. Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery- A systemic review of the literature and meta-analysis. JAMA. 2004;292(14):1724–1737.

35. Poirier P, Giles TD, Bray GA, et al. Obesity and cardiovascular disease: pathophysiology, evaluation, 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, Metabolism. Circulation. 2006;113:898–918.

36. Vest AR, Heneghan HM, Schauer PR, Young JB. Surgical management of obesity and the relationship to cardiovascular disease. Circulation. 2013;127(8):945–959.

37. Vest AR, Heneghan HM, Agarwal S, Schauer PR, Young JB. Bariatric surgery and cardiovascular outcomes: a systematic review. Heart. 2012;98(24):1763–1777.

38. Heneghan HM, Meron-Eldar S, Brethauer SA, Schauer PR, Young JB. Effect of bariatric surgery on cardiovascular risk profile. Am J Cardiol. 2011;108(10):1499–1507.

39. Aggarwal R, Harling L, Efthimiou E, et al. The effects of bariatric surgery on cardiac structure and function: a systematic review of cardiac imaging outcomes. Obes Surg. 2016;26(5):1030–1040.

40. Priester T, Ault TG, Adams TD, Hunt SC, Litwin SE. Abstract 481: Coronary calcium scores are lower 5 years after bariatric surgery: evidence for slowed progression of atherosclerosis? Circulation. 2009;120:S341–S342.

41. Karason K, Wikstrand J, Sjöström L, Wendelhag I. Weight loss and progression of early atherosclerosis in the carotid artery: a four-year controlled study of obese subjects. Int J Obes Relat Metab Disord. 1999;23(9):948–956.

42. Lupoli R, Di Minno MN, Guidone C, et al. Effects of bariatric surgery on markers of subclinical atherosclerosis and endothelial function: a meta-analysis of literature studies. Int J Obes (Lond). 2016;40(3):395–402.

43. Schauer PR, Kashyap SR, Wolski K, et al. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med. 2012;366(17):1567–1576.

44. Sjöström L, Narbro K, Sjöström CD, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007;357(8):741–752.

45. Yudkin JS, Stehouwer CD, Emeis JJ, Coppack SW. C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Arterioscler Thromb Vasc Biol. 1999;19(4):972–978.

46. Papanicolaou DA, Vgontzas AN. Interleukin-6: the endocrine cytokine. J Clin Endocrinol Metab. 2000;85(3):1331–1333.

47. Alpert MA, Terry BE, Mulekar M, et al. Cardiac morphology and left ventricular function in normotnesive morbidly obese patients with and without congestive heart failure, and effect of weight loss. Am J Cardiol. 1997;80:736–740.

48. Narkiewicz K, van de Borne PJ, Cooley RL, Dyken ME, Somers VK. Sympathetic activity in obese subjects with and without obstructive sleep apnea. Circulation. 1998;98:772–776.

49. Ruano M, Silvestre V, Castro R, et al. Morbid obesity, hypertensive disease and the rennin-angiontensin-aldosterone axis. Obes Surg. 2005;15(5):670–676.

50. Davy KP, Hall JE. Obesity and hypertension: two epidemics or one? Am J Physiol Regul Integr Comp Physiol. 2004;286(5):R803–813.

FUNDING: No funding was provided.

DISCLOSURES: The authors report no conflicts of interest relevant to the content of this manuscript. AUTHOR

AFFILIATION: Derrick Cetin, DO, and Elie Nasr, BA, are from Cleveland Clinic, Bariatric and Metabolic Institute, Cleveland, Ohio.

Tags: , , , , , ,

Category: Past Articles, Review

Comments are closed.