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Obesity is considered a pandemic of the present century and is associated with severe noncommunicable chronic diseases, especially cardiovascular diseases, which remain the leading cause of death in the world. Visceral adiposity is a usual localization for ectopic fat depots and increases the risk of cardiovascular diseases. Endothelial dysfunction in obesity explains atherosclerosis and higher risk of incident coronary artery disease. Further microvascular disease caused by chronic inflammatory state increases cytokines and reduces the nitric oxide, and chronic inflammation has been characterized by the imbalance between proinflammatory and procoagulant and anti-inflammatory and anticoagulant activities of the endothelium to generate a procoagulant state. An important topic is the gut microbiota that influences the progression of atherosclerosis. Some studies have shown the influence of gut dysbiosis and progression of atherosclerosis and cardiovascular disease. Additionally studies talking about overweight and obesity with coronary artery disease are explained by levels of blood pressure, cholesterol, and glucose; however, another important causative factor is the ectopic fat deposition, especially pericardial and epicardial spaces, which may further contribute to the burden of coronary atherosclerosis. So, diagnosis of cardiovascular diseases in obesity requires a lot of knowledge to suspect, diagnose, and to treat.
*Address all correspondence to: doctorpedroparra@gmail.com
1. Introduction
Obesity is a disorder characterized by a disproportionate increase in body weight in relation to height, mainly due to the accumulation of fat, is considered a pandemic of the present century. It is associated with several noncommunicable chronic diseases, namely metabolic syndrome, type 2 diabetes mellitus (T2DM), cardiovascular diseases (CVD), obstructive sleeping apnea, osteoarthropathies, and cancer [1].
It is estimated that 39–49% of the world’s population (2.8–3.5 billon people) are overweight. Among adult men, the prevalence of obesity in the Hispanic, black, and white is higher than in Asians, respectively. In women, the prevalence of obesity behavior is almost the same as the men. The black women have the most prevalence following the Hispanic, white, and Asian. In addition, children and adolescents are also affected; between 2 and 19-year-olds, 17% are obese and the males and females are equally [2, 3].
Knowing that the obesity is a complex disease, the prevalence is based on racial/ethnic and sex factors. For example, among adult men, the prevalence of obesity in the Hispanic, black, and white is higher than in Asians, respectively. In women, the prevalence is almost the same as the men. The black women have the most prevalence following the Hispanic, white, and Asian showing there is a socioeconomic inequality structure as well. In addition, children and adolescents are also affected; between 2 and 19-year-olds 17% are obese and the males and females are equally [2].
In general terms, the trends in obesity prevalence around the world are getting up constantly, which means it highlights the significant impact that the obesity will continue to have on CVD the incidence, prevalence, and deaths globally.
At this time, obesity is linked to numerous diseases of the cardiovascular system: stroke, venous thromboembolic disease and pulmonary hypertension, cardiovascular disease, heart failure, arrhythmias such as atrial fibrillation, and sudden cardiac death [4].
2. Visceral adiposity, liver fat, and cardiovascular risk
There is a strongly correlation between overall obesity and abdominal obesity; although, there are two kinds of patients: either the ones with overall obesity but not abdominal obesity.
Abdominal obesity is linked to increased cardiovascular diseases. Along these lines, there still exists underdiagnosis to classify the CVD risk among obese patients. Trying to unmask and making a good clinical patient evaluation, organizations, expert panels, and a lot of evidence support have shown and recommended the waist circumference (WC) measurements with body mass index (BMI) applied in the clinical practice may add critical information and successful prediction of cardiovascular risk and mortality focusing on visceral adiposity.
Fortunately imaging techniques can be used to quantify adipose tissue and ectopic fat depots volumes. The National Library of Medicine described the adipose tissue as a storage of energy in the form of triacylglycerols and ectopic fat depots and is defined by excess adipose tissue in locations not classically associated with adipose tissue storage, some fat depots are more linked to risk factors for disease than others. Techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) are extraordinary and the most advanced in the study of human body composition and of its relationship with CVD risk. However, other techniques such as bio-impedance body composition are more available in the practice [5].
The abdominal adiposity can be divided into: obesity, subcutaneous, and visceral obesity. Overweight or obese patients with low levels of visceral adipose tissue (VAT) have been identified as having a more favorable cardiovascular risk profile, commonly known as metabolically healthy obese patients. Some recent data suggest that metabolically healthy obesity may be a transitory phenotype, the time of which may be variable by race, ethnicity, and gender. The relationship between visceral adipose tissue and cardiovascular risk is known, the first one being a clear accelerator for the development of cardiovascular diseases.
The concept called adipose tissue expandability refers to the ability of the adipocyte to be contained in the places where it normally lives. When this expansion capacity of adipose tissue is exceeded, it begins to be located in organs abnormally, developing diseases such as hepatic steatosis, which is directly related to a higher risk of developing cardiovascular events. Thus, it is important to identify that patients with increased visceral adiposity are the ones with the highest risk independent of weight.
Although the major known ectopic fat depot is the hepatic depot, there are other abnormal fat depots that contribute to the development of cardiovascular diseases. Some of these are: pericardial and epicardial depots despite being used many times in an undifferentiated way, they have a different anatomical locations and their relationship with cardiovascular diseases is different. The pericardial depot is located at the level of the pericardial sac and has been related to a high BMI, traditional cardiovascular risk (CVR) risk factors, and elevated atherogenic cholesterol. Additionally, the amount of pericardial fat has been associated with an increased risk of coronary heart disease, atherosclerosis, and heart failure adjusting for age, sex, BMI, and abdominal circumference; but not adjusting for traditional CVR factor and either when adjusting for levels of more atherogenic cholesterol particles [6].
VAT on the other hand represents the visceral fat contained between the external myocardium wall and the visceral lamina of the pericardium. It has been associated with a general CVR score and arterial stiffness in patients with CVD and DM2 [7].
Reports from multiple studies presented a high association between the pericardial depots and CVD. For example, a study of atherosclerosis showed the pericardial fat and a higher risk of all CVD causes, hard atherosclerotic CVD, and HF but not intra-thoracic fat [8]. Another study that analyzed all-cause mortality risk after adjustment for age, sex, lifestyle variables, lipids, glucose, and adipocytokines was higher by increment in pericardial fat, but it did not proof enough information to predict the events of CVD beyond traditional risk factors [9].
Epicardial adipose tissue (EAT) is the visceral fat layer located around the heart and is believed to be important for the buffering of the coronary arteries and in providing fatty acids as a source of energy for the cardiac muscle. Reviews have shown that this deposit may be considered highly insulin resistant and also indicator of cardiovascular risk because of the secretion of pro-inflammatory cytokines and carotid artery stiffness. In addition, this can produce sleep apnea severity in woman independently of BMI, and this last one is associated with higher CVD risk [10, 11].
Currently, the way to reduce the announced ectopic fat (adipose tissue depots) has been investigated. There are a lot of nonpharmacological strategies to be applied based on lifestyle interventions, some authors dare to say could be more effective than pharmacological therapies. One of those strategies are exercises such as aerobic in nature, which may reduce VAT unchanged on weight loss; and reports of losing VAT by only resistance and high-intensity raining are equivocal [12, 13]. Thus, exercise interventions not just can decrease the VAT, apparently have impact in reducing hepatic, epicardial, and pericardial fat. However, there is not enough information to support a significant reduction in epicardial fat with exercise as the caloric restriction strategy to reduce it [14].
The recommendation for physical activity of 150 min per week may be sufficient to reduce VAT with no further reduction with additional activity. It is very important to highlight that exercise can reduce VAT even in the absence of weight loss [15].
According to data from the National Health and Nutrition Examination Survey, central obesity has higher risk of cardiovascular mortality compared with patients with the same BMI but without central adiposity. This has been called normal weight central obesity and expected survival estimates were consistently lower for those with central obesity when controlled for age and BMI [16, 17].
The process to atherosclerosis begins with fatty streaks resulting in thickening of the intima arterial layer. Obesity is considered a storm, which accelerates this process by several mechanisms such as insulin resistance through adipocytokines, endothelial dysfunction, hypercoagulability, and inflammation. The VAT makes systemic and vascular inflammation that promotes atherogenesis. Further, insulin resistance has been associated to metabolic syndrome, proinflammatory, and prothrombotic states.
Endothelial dysfunction in obesity has two principal causes: diminished bioavailability of nitric oxide and increased oxidative stress. A good marker of early atherosclerosis is carotid intima media thickness [18].
Several prospective epidemiological studies demonstrate that obesity and higher risk of incident coronary artery disease (CAD) are strongly linked. Excess visceral fat rather than body weight has been linked to increased risk of cardiovascular events. BMI, higher measures of central adiposity, including WC and waist-to-hip ratio (WHR), were aligned with a higher risk of CAD and cardiovascular mortality independently of BMI [19, 20].
Another important concept is the duration of obesity and abdominal adiposity, expressed as excess BMI-years and WC-years, which are stronger predictors of CAD, highlighting these measurements must be evaluated together [21].
4.2 Microvascular disease and obesity
The chronic inflammatory conditions developed from the obesity are linked to abnormalities in the coronary microvasculature. Coronary microvascular disease is pathophysiologically associated with endothelial dysfunction and possibly to small vessel remodeling and also disturbing coronary blood flow; this microvascular disease is independently associated with higher BMI [22].
Obesity has implications in macrophages and adipocytes that generate a proinflammatory state that increases the cytokines and reduces the nitric oxide. All this cascade promotes endothelial dysfunction (Figure 1).
Figure 1.
OBESTITY and PROINFLAMATORY STATE.
Proinflamatory state:
IL1β, IL 6, Leptin, TNFα, PCR,
NO.
Endothelial Dysfunction:
ROS, angiotensinogen, calprotectin
NO, Ghrelin.
Metabolic disorders: Changes in glucose and lipid metabolism, insulin resistance, hypertension, atherosclerosis.
Normally the endothelium regulates vascular homeostasis; it is the natural inner lining of the vessels. Its layers are: tunica intima, tunica media, and the vascular smooth muscle cell (VSMC). But there is a combination-coordination of multiple factors such as blood flow, distribution of nutrients, hormones, and other macronutrients, and migration and proliferation of VSMC. The VSMC is an important component of vessel wall remodeling in response to injury, which controls coagulation and fibrinolysis activities, reduces vascular tone and regulates cellular and vascular adhesions, inhibits leukocyte adhesions, and modulates inflammatory activities and angiogenesis (Figure 2).
Figure 2.
Endothelial dysfunction and obesity.
Vasodilators: Apelin, H2S, NO, PGI2, IgF1.
Permeability: NO, VEGF, ROS, PGI2, PAI1, FGF, Leptin.
Anticoagulant factors: Anti thrombin III, Thrombomodulin.
Angiogenic factors: FGF, TGFβ, VEGF.
Vasoconstrictors: ROS, VCAM, PgH2, Ang II, Resistin.
Nevertheless, the endothelial dysfunction is usually characterized by the disrupt between secretion and release of vasoconstriction and vasodilation agents, pushing the vascular endothelial toward prothrombotic and proatherogenic effects [23].
Secondly, the distorted provokes that the leukocyte adhesion, activation of platelets, pro-oxidation of mitogens, impaired PGI2, coagulation, and nitric oxide (NO) productions are the features or ¨faulty physiological properties¨ resulted from a dysfunction of endothelium, as well decreased synthesis of EDHF, and vasoconstriction factors including Ang II and prostaglandin (PGH2), atherosclerosis, and thrombosis (Figure 3) [23].
Figure 3.
Proinflamatory and anti-inflammatory state in obesity.
The major participating agents of endothelial dysfunction in obesity include: insulin resistance, oxidized form of low-density lipoprotein (oxLDL), adipose tissues related inflammation, and decreased NO bioavailability. Others such as elevated production of ROS and arginase, advanced glycation end products (RAGE), and phenotypic alterations in perivascular adipose tissue result in mild inflammation and elevated leptin with subsequent reduction of adiponectin secretions [24].
Further obesity generates a procoagulant state, which is explained by several mechanisms:
Adipose tissue in obesity secretes decreased levels of adiponectin, thereby facilitating the susceptibility of platelets aggregation with the subsequent increased PAI-1 production, which further inhibits fibrinolysis.
Macrophages found in adipose tissue also produce TF, which combines with the elevated liver secretion of FVII and FVIII to promote the possibility of coagulation abnormalities.
Inflammation has been characterized by the imbalance between proinflammatory and procoagulant, and anti-inflammatory and anticoagulant activities of the endothelium, leading to disturbance of the hemostatic system.
4.3 Endothelial dysfunction, epigenetic modifications, and vascular calcification
Epigenetic modifications such as DNA methylation and histone acetylation are described. Previous studies have recognized changes in expression of methyltransferase linked with hypomethylation of hypermethylated genomic regions. These findings are linked between epigenetic modifications and atherosclerosis.
Vascular calcification (VC) is one of the mechanisms that influences vascular remodeling due to the differentiation of vascular smooth muscle cells (VSMCs), alterations in elastin, collagen, and endothelial dysfunction. VC increases the chances of cardiovascular mortality and morbidity, especially in individuals with obesity, type 2 diabetes mellitus (T2DM), and chronic kidney disease [25]. Several studies have identified the correlation between ROS generation, particularly H2 O2 (hydrogen peroxide), and the progression of vascular calcification. An elevated level of ROS triggers MMP (matrix metalloproteinase) activity and alteration in collagen and elastin deposition [26].
4.4 How the gut microbiota affects on vascular endothelium
Gut microbiota is the collection of bacteria that inhabitat gastrointestinal tract and have many repercussions in health. Several studies have indicated that gut microbiota plays a contributing role in atherosclerosis through modulating inflammation and the secretion of microbial metabolites. Recent studies have shown the influence of gut disbiosis and progression of atherosclerosis and cardiovascular disease. Bacteria such as Akkermansia muciniphila promote barrier function and have attenuating effect against atherosclerosis [27].
Scientists have found that the relative abundance of Roseburia and Eubacterium was lower, while Collinsella was higher in atherosclerosis patients compared with healthy controls [28].
Variety of metabolites are derived from the gut microbiota, as well as co-metabolism of gut microbiota such as amines methylamines, polyamines, short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), and secondary bile acids (BAs). SCFAs are a group of well-established gut microbial metabolites that are critically involved in metabolic diseases [27].
Diet has an important role in biodiversity of microbiome and hemostasis for maintaining human health. Disbiosis has been associated with progression of various diseases including CVD, obesity, diabetes, nonalcoholic fatty liver disease, and some types of cancer.
4.5 Molecular endothelial dysfunction in obesity
There are many bioquimical makers of endothelial dysfunction: first MCP1 (monocyte chemotactic and activating factor). This protein is synthesized by several types of cells, including inflammatory and inflammation-mediated cells, monocytic cells, human tubular epithelial cells (TECs), and renal-mediated cells in response to various stimuli and when joint to chemokine receptor 2 (CCR2) initiates various monocyte-mediated proinflammatory signals and monocyte chemoattractant activities, facilitating monocytes migration to the subendothelium and combines with ox-LDL to form foam cells, forming a fatty streak and eventual atherosclerotic plaque (Figure 4) [29].
Obesity increases morbidity and mortality especially when associated to hypertension and CAD [30].
Obesity is associated with overt atherosclerotic lesions even after accounting for the impact of these metabolic cardiovascular risk factors. The association of obesity with raised atherosclerotic lesions among men in the Pathobiological Determinants of Atherosclerosis in Youth study was present only for those with a thick abdominal panniculus, indicating the fundamental role of central adiposity in the development of atherosclerotic disease [31]. Chronic inflammation induced by obesity increases the likelihood of low-density lipoprotein oxidation, which promotes atherogenesis [32]. Other factors together increase atherosclerosis are insulin resistance and metabolic syndrome.
Endothelial dysfunction in obesity is principally caused by diminished bioavailability of nitric oxide in the setting of inflammation and oxidative stress [33].
A prospective study published by Whintlock et al. describes an increase of probability of mortality stroke in a range of 25–50 kg/m2, each 5 kg/m2 is associated with 40% higher stroke mortality. A prospective cohort study with 3.2 million person-year by follow-up from 1964 to 2015 concluded that overweight and obesity shortened longevity and increased lifetime risk [34].
There are important differences in obesity according to gender that must be taken into account, such as the impact of hormones in women against the development of atherosclerosis.
Before menopause, women generally have greater vagal than sympathetic tone, and lower levels of total cholesterol and LDL-C than men. Additionally, differences in glucose and lipid metabolism, sex hormones, and cytokine production are thought to explain why men are at an increased risk of CVD [35, 36]. This recalls the protective effect of estrogens in maintaining health and distribution of body fat. This is likely explained by the aforementioned differences in hormone-driven patterns of fat distribution, with men more likely to deposit visceral fat, compared with subcutaneous fat in women, considering that visceral fat has been associated with greater cardiometabolic risk [37, 38].
Obesity is characterized by an increased risk of diabetes, hypertension, and dyslipidemia, and independently associated with CVD. Several prospective epidemiological studies demonstrate that obesity is associated with higher risk of incident coronary artery disease [39]. There are controversies if obesity causes high risk of CVD or the complications of obesity are the cause of them. Some large prospective analyses have indicated that the link between obesity and CAD is mediated largely by hypertension, dyslipidemia, diabetes, and other comorbidities, whereas other prospective studies suggest a significant residual CAD risk in obesity even after accounting for these risk factors [40].
A meta-analysis of 21 studies including 1.8 million individuals suggested that approximately half of the associations of overweight and obesity with CAD are explained by levels of blood pressure, cholesterol, and glucose [41]. There are three mechanisms linked to metabolic syndrome, that is, production of adipocytokines, oxidative stress, and a prothrombotic state [42].
Other important causative factor is the ectopic fat deposition, especially pericardial and epicardial spaces, which may further contribute to the burden of coronary atherosclerosis [43].
Some studies of pathobiology have shown that arteries with intramyocardial course in perfect condition could have atherosclerosis in epicardial segment of the same artery. Thus, local production of adipocytokines by epicardial fat may modulates blood vessel biology through paracrine signaling or through vasa vasorum [44].
6. Diagnosis of coronary artery disease (CAD) in obesity
CAD has been associated with higher measures of central adiposity, including WC and WHR inclusive those with normal weight and BMI. The degree and duration of obesity expressed as excess BMI years and WC years are stronger predictors of CAD [21].
Many changes can occur in the patients with CAD. There are noninvasive and invasive modalities to assess CAD in patients with obesity. These will be described below.
6.1 Noninvasive CAD assessment
6.1.1 Electrocadiography
Obesity has the potential to affect the ECG in several ways: displacing the heart by elevating the diaphragm in the supine position, increasing the cardiac workload, and increasing the distance between the heart and the recording electrodes.
Several electrocardiographic changes are associated with obesity (Table 1).
Table 1.
Electrocardiographic changes in importance order.
More frequent ST-segment depression is seen in patients with overweight and CAD, and insulin concentration may be related to the development of the ST-segment depression over time [21].
6.1.2 Treadmill stress test
Many patients with obesity fail to achieve 80–85% of the age-predicted heart rate needed for diagnostically valid results.
Chronotropic competence can be reduced in obesity, with a prior study showing that peak heart rate, heart rate recovery, and chronotropic index are lower in patients with obesity, regardless of fitness level [45].
6.1.3 Stress ecocardiography
Stress echocardiography is highly feasible in most cases for patients with obesity through either physiological stress (treadmill exercise) or pharmacological stress (dobutamine).
However, stress echocardiography is highly operator-dependent and can be limited in the presence of poor acoustic windows related to pulmonary disease, breast size, obesity, and respiratory motion. Contrast study in obesity patients is suggested because the sensitivity is better than without contrast. Contrasted images improved sensitivity and specificity (82% vs 70% and 78% vs. 67%, respectively) [46].
6.1.4 PET (positron emission tomography) rubidium
PET rubidium has a 91% sensitivity and 89% specificity and produces less irradiation exposure, better quality of images, a greater degree of diagnosis, reduces invasive examination, and low cardiac death rates in obesity [47].
Therefore, PET rubidium is the nuclear imaging technique of choice for patients with obesity.
Stress cardiac MRI and PET are likely the diagnostic techniques least affected by obesity.
The presence of ischemia predicted adverse events at 5 years of follow-up, regardless of whether scar was present. Lack of inducible ischemia is associated with a low annual major adverse coronary events (MACEs) rate of 0.3% at 2 years in patients with obesity [48].
6.1.6 CT calcium score
CAC (coronary artery calcium) is a marker of atherosclerosis that is predictive of cardiovascular events. This technique offers the possibility of determining the presence and extent of calcified coronary artery plaque. Some studies suggest that waist circumference (WC) and waist-to-hip ratio (WHR) provide more useful prognostic information than BMI on the likelihood of elevated CAC. This concept emphasizes the importance of abdominal obesity and pathophysiology of atherosclerosis [49].
6.1.7 Cardiac CT coronary angiography
CT coronary angiography is an alternative for the quantification of calcified or noncalcified plaque. This approach is useful in specific subset of symptomatic patients with obesity or when stress test is equivocal, uninterpretable stress test, or in cases when a discrepancy exists between clinical presentation and stress test results. This technique allows evaluation of luminal stenosis and plaque characterization and quantification [50].
One major challenge with CT coronary angiography is that image quality degrades as BMI increases; this degradation increases in background noise. In patients with overweight can reduce signal-to-noise ratio, and low vessel opacification may occur when contrast is inspected.
6.2 Invasive evaluation of CAD in obesity
6.2.1 Coronary angiography
Patients undergoing catheterization have potential difficulties: suboptimal radiographic visualization, vascular access laborious, bleeding, radial access is preferred in obesity patients because it has been associated with three times lower rate of complications than transfemoral access and higher radiation exposure to both patients with obesity and staff [51].
6.2.2 PCI and obesity
In the Cath PCI Registry after multivariable adjustment obesity was independently associated with a greater mortality rate and lower bleeding rate. Adequate anticoagulation is important in this subpopulation [52, 53]. Another study reported that patients with severe obesity have major risk of contrast-induced nephropathy. Dialysis and vascular complications, gastrointestinal bleeding, and MACE (Major Adverse Cardiovascular Events) are not statistically different [54].
6.2.3 Intravascular ultrasound
Several intravascular imaging techniques such as intravascular ultrasound, virtual histology intravascular ultrasound, and optical coherence tomography allow in vivo assessment of plaque burden, plaque morphology, and response to therapy.
Abdominal visceral adiposity independently predicted the presence and extent of noncalcified coronary plaque that also contained multiple features of plaque vulnerability [55].
The appropriate choice of test to assess CVD depends on local expertise, the relative strengths and weaknesses of each modality, and individual patient characteristics that contribute to the pretest likelihood of CVD and the risk/benefit ratio of using a given modality.
7. Clinical management, treatment, and secondary cardiac disease
Obesity paradox refers to the fact that although obesity increases the risk of CVD for those who had already an CVD, excess weight is not a risk factor to develop adverse outcomes including death [56].
Although weight loss would be believed to significantly benefit cardiovascular outcomes, this benefit has only been shown in weight loss performed through bariatric surgery in which more than 10–15% of body weight is lost; therefore, that modest weight loss has not been shown to impact cardiovascular outcomes [57, 58].
To treat obesity requires a multidisciplinary management in which the eating pattern, amount of exercise, stress, sleep pattern are evaluated. So, it is not enough exercise and nutrition to evaluate all the factors related to weight gain together.
Some clinical trials demonstrate the cardiovascular impact of Mediterranean diet in reducing MACE in patients with high cardiovascular risk. However, lifestyle changes in diabetes patients have failed to show a significant reduction in MACE, only those with weight loss greater than 10% had significant results [59, 60].
Pharmacological treatment has impact on weight reduction as well. For example, liraglutide has been shown to reduce death by 13% and 22% from cardiovascular causes in patients with type 2 diabetes in LEADER trial [61].
Recently semaglutide at 2.4 mg dose in obese patients without diabetes has demonstrated a significant body weight reduction (14.9% vs. 2.4% with placebo). In total, 69% of body weight reduction ≥10% at 68 weeks and 50% body weight reduction ≥15% .
Further reduction in waist circumference, systolic blood pressure, and improvement of physical function [62].
Orlistat was approver in 1998 for the treatment of obesity and demonstrated 37% reduction in progression from prediabetes to diabetes and significant reduction of associated disease such as hypertension and blood lipid levels [63].
Naltrexone SR/Bupropion SR is another drug approved in the United States for the treatment of obesity and has cardiovascular security trial (LIGHT trial – Cardiovascular Outcomes Study of Naltrexone SR/Bupropion SR in Overweight and obese subjects with cardiovascular risk factors). Bupropion suppresses appetite transiently due to an endorphin-mediated mechanism of action. Naltrexone blocks the endorphin, which allows a long-term appetite suppression effect [64]. However, because of the early unanticipated termination of the trial, it is not possible to assess non-inferiority to the prespecified upper limit of 1.4. Consequently, the cardiovascular safety of this treatment remains uncertain and will require evaluation in a new adequately powered outcome trial.
Lorcaserine was approved in the obesity treatment but recently was removed for the Food and Drug Administration (FDA), due to a possible increased risk of cancer [65].
Finally, patients with body mass index greater than 35 kg/m2 with comorbidities or greater than 40 kg/m2 without them get benefit from bariatric surgery. Non-randomized prospective studies desmonstrated a reduction of cardiovascular death in this group of patients [66].
In conclusion, obesity patients have an important difference than patients with normal weight. First, the chronic inflammation is the principal cause of molecular and cellular changes that have been linked to development of chronic diseases and manifestations due to decreased expansibility of adipose tissue. Endothelial dysfunction is an important factor that contributes to vascular calcification and atherosclerosis. In addition, the intestinal microbiota plays an important role in the development and inflammation of atherosclerotic plaque. Obesity is linked to major risk of CVD and is directly proportional to the amount of excess weight, it can be explained by blood pressure, cholesterol, and glucose levels. Diagnosis must be evaluated according to the risk and the clinical probability of suffering an event, evaluating the expected changes at the electrocardiographic level that can lead to overdiagnosis. Finally, remember that there are currently multiple noninvasive studies for the early diagnosis of cardiovascular disease, which have allowed more timely diagnoses to be made in obese patients.
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Written By
Pedro Felipe Parra Velasco
Submitted: 18 May 2022Reviewed: 29 July 2022Published: 06 March 2023
Open access peer-reviewed chapter
