Is obesity a risk factor for carotid atherosclerotic disease?—opportunistic review

Citation: Ferreira, J.; Cunha, P.; Carneiro, A.; Vila, I.; Cunha, C.; Silva, C.; Longatto-Filho, A.; Mesquita, A.; Cotter, J.; Correia-Neves, M.; et al. Is Obesity a Risk Factor for Carotid Atherosclerotic Disease? —Opportunistic Review. J. Cardiovasc. Dev. Dis. 2022,9, 162. https:// doi.org/10.3390/jcdd9050162 Academic Editor: Fabio Angeli Received: 9 April 2022 Accepted: 8 May 2022 Published: 17 May 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). Journal of Cardiovascular Development and Disease Review Is Obesity a Risk Factor for Carotid Atherosclerotic Disease?—Opportunistic Review Joana Ferreira 1,2,3,* , Pedro Cunha 2,3,4 , Alexandre Carneiro 5, Isabel Vila 2,3,4, Cristina Cunha 2,3,4, Cristina Silva 2,3,4, Adhemar Longatto-Filho 2,4,6,7 , Amílcar Mesquita 8, Jorge Cotter 2,3,4, Margarida Correia-Neves 2and Armando Mansilha 9,10 1Vascular Surgery Department, Hospital de Trás-os-Montes, 5000-508 Vila Real, Portugal 2Life and Health Science Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal; [email protected] (P.C.); [email protected] (I.V.); [email protected] (C.C.); [email protected] (C.S.); [email protected] (A.L.-F.); [email protected] (J.C.); [email protected] (M.C.-N.) 3Center for the Research and Treatment of Arterial Hypertension and Cardiovascular Risk, Internal Medicine Department, Hospital da Senhora da Oliveira, 4835-044 Guimarães, Portugal 4Medicine Department, Hospital da Senhora da Oliveira, 4835-044 Guimarães, Portugal 5Radiology Department, Unidade Local de Saúde Alto Minho, 4904-858 Viana do Castelo, Portugal; alexandrelimacarneir[email protected] 6Department of Pathology (LIM-14), University of São Paulo School of Medicine, São Paulo 01246-903, Brazil 7Molecular Oncology Research Center, Barretos Cancer Hospital, São Paulo 14784-400, Brazil 8Vascular Surgery Department, Hospital da Senhora da Oliveira, 4835-044 Guimarães, Portugal; [email protected] 9Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal; [email protected] 10 Vascular Surgery Department, Hospital de São João, 4200-319 Porto, Portugal *Correspondence: [email protected]; Tel.: +351-962-958-421 Abstract: Obesity is a risk factor for coronary atherosclerosis. However, the influence of adipose tissue in carotid atherosclerosis is not completely understood. No systematic review/meta-analysis was previously performed to understand if obesity is a risk factor for carotid atherosclerosis. This paper aims to provide an opportunistic review of the association between obesity and carotid atherosclerosis and define the role of the different adipose tissue depots in the characteristics of carotid stenosis. The databases PubMed and Cochrane Library were searched on 15–27 April and 19 May 2021. A total of 1750 articles published between 1985 and 2019 were identified, 64 were preselected, and 38 papers ( 35,339 subjects ) were included in the final review. The most frequent methods used to determine obesity were anthropometric measures. Carotid plaque was mostly characterized by ultrasound. Overall obesity and visceral fat were not associated with the presence of carotid plaque when evaluated separately. Waist-hip ratio, however, was a significant anthropometric measure associated with the prevalence of carotid plaques. As it reflected the ratio of visceral and subcutaneous adipose tissue, the balance between these depots could impact the prevalence of carotid plaques. Keywords: obesity; visceral adipose tissue; subcutaneous adipose tissue; carotid atherosclerotic disease 1. Introduction The worldwide prevalence of obesity has increased in the past decades. Obesity is an independent risk factor for atherosclerosis, stroke, and cardiovascular disease [ 1 – 3 ]. Cardiovascular outcomes and mortality are more dependent on fat distribution than on the total amount of adipose tissue [ 1 ]. Previous studies demonstrated that a higher ratio of visceral adipose tissue (VAT) to subcutaneous adipose tissue (SAT) was associated with an increased risk of poor cardiovascular outcomes [ 1 ]. VAT is metabolically active and secret adipokines that cause vascular inflammation and insulin resistance [ 2 ]. Conversely, SAT is associated with a neutral or even beneficial metabolic impact [2]. J. Cardiovasc. Dev. Dis. 2022,9, 162. https://doi.org/10.3390/jcdd9050162 https://www.mdpi.com/journal/jcdd J. Cardiovasc. Dev. Dis. 2022,9, 162 2 of 33 Increased abdominal VAT/SAT ratio was inversely correlated with the extent and severity of coronary artery plaques, higher total mortality, and incidence of major adverse cardiac events (MACE) [1,2]. The influence of obesity on carotid atherosclerosis disease remains unclear [ 4 ]. No previous systematic review/metanalyses evaluated the relationship between obesity on carotid atherosclerosis. 2. Methods 2.1. Data Sources and Search The PubMed and Cochrane Library databases were searched on 15–27th of April and 19 May 2021. The query was as follows: (‘Carotid artery stenosis OR ‘Carotid artery atherosclerosis’) AND (‘visceral adipose tissue’ OR ‘visceral fat’ OR ‘fat tissue’ OR ‘Obesity’ OR ‘subcutaneous adipose tissue’ OR ‘subcutaneous fat’). This review was conducted according to established methods for reviews in cardiovascular medicine (PRISMA criteria). 2.2. Inclusion and Exclusion Criteria Studies were included in the current opportunistic review if they met the following criteria: (1) correlating general obesity, VAT, or SAT with the prevalence of carotid artery plaque, (2) evaluating the influence of general obesity, VAT/SAT on carotid artery symptomatology, (3) retrospective or prospective observational clinical studies, (4) performed in humans, (5) full-text available, (6) studies published in English, French, Spanish, and Portuguese. Other studies were excluded for the following reasons: (1) analyzing intima-media thickness, (2) performed in children, (3) studies reported only as abstracts or with incomplete data, letters, reviews, case reports, nonclinical studies, (4) reviews or meta-analysis. If the studies had overlapping subjects, the one with the largest sample size was included in the final analysis. No attempt was made to contact the authors of the included studies to enquire about missing or incomplete data. No studies were excluded because of concerns about missing data. 2.3. Data Extraction—Outcomes-Definitions After removing the duplicated articles, two authors (J.F. and A.C.) independently selected the full-text articles after screening the title and abstract. Disagreements were resolved by consensus. For each study, the subsequent data were collected: first author, year of publication, country of the research center, type of study design, total number of patients, age, men (percentages), aims, inclusion and exclusion criteria, and main conclusions (Tables 1–3). Concerning the adipose tissue, the following information was recorded: the method used to determine the overall obesity, the VAT, and SAT (Table 3). The information collected about carotid stenosis were: imaging methods used to determine the presence of carotid stenosis; the definition of carotid plaque; the grade of carotid stenosis; and if the carotid plaque was symptomatic (Table 3). J. Cardiovasc. Dev. Dis. 2022,9, 162 3 of 33 Table 1. Characteristics of the studies included in the opportunistic review. Study Year Country Type of Study Total Number of Patients Quality of Studies MINOR CRITERIA Bogousslavsky et al. [5] 1985 Switzerland Cross-sectional 477 3 Lakka et al. [6] 2001 Finland Longitudinal 774 12 Hunt et al. [7] 2002 USA Cross-sectional 750 14 Hegazi et al. [8] 2003 USA Cross-sectional 52 12 Czernichow et al. [9] 2005 France Cross-sectional 1014 13 Hadjiev et al. [10] 2003 Bulgaria Cross-sectional 500 14 De Souza et al. [11] 2005 Brazil Cross-sectional 144 14 Montalcini et al. [12] 2006 Italy Cross-sectional 313 14 Lear et al. [12] 2007 Canada Cross-sectional 794 14 Park et al. [13] 2007 Korea Cross-sectional 378 14 Irace et al. [14] 2009 Italy Cross-sectional 1842 12 Yu et al. [15] 2009 Hong Kong Cross-sectional 518 13 Terzis et al. [16] 2011 Greece Longitudinal 106 14 Kadoglou et al. [17] 2012 Greece Longitudinal 112 12 Solomon et al. [18] 2012 South Africa Cross-sectional 203 12 Rodríguez-Flores et al. [19] 2013 Mexico Cross-sectional 185 14 Maksimovic et al. [20] 2013 Serbia Cross-sectional 657 14 Galarza-Delgado et al. [21] 2013 Mexico Cross-sectional 124 14 Cuspidi et al. [22] 2013 Italy Cross-sectional 3752 12 Chiquete et al. [23] 2014 Mexico Cross-sectional 533 12 Irie et al. [24] 2014 Japan Cross-sectional 179 12 Yan et al. [25] 2014 China Cross-sectional 911 12 Yuan et al. [26] 2016 USA Cross-sectional 1315 12 Pan et al. [27] 2016 China Cross-sectional 474 12 Radmard et al. [28] 2016 Iran Cross-sectional 191 12 Sandfort et al. [29] 2016 USA Longitudinal 106 12 Mitevska et al. [30] 2017 Macedonia Cross sectional 60 14 Higuchi et al. [31] 2017 Japan Cross-sectional 980 12 Mancusi et al. [32] 2017 Italy Cross-sectional 8815 14 Nishizawa et al. [33] 2017 Brazil Cross-sectional 240 12 Omisore et al. [34] 2018 Nigeria Cross-sectional 162 14 Imahori et al. [35] 2018 Norway Cross-sectional 4906 12 Laugesen et al. [36] 2018 Denmark Cross-sectional 169 12 Yoshida et al. [37] 2018 Japan Cross-sectional 352 14 Scicali et al. [38] 2018 Italy Cross-sectional 276 12 Rovella et al. [4] 2018 Italy Cross-sectional 390 12 Geraci et al. [39] 2019 Italy Cross-sectional 468 14 Haberka et al. [40] 2019 Poland Cross-sectional 391 14 J. Cardiovasc. Dev. Dis. 2022,9, 162 4 of 33 Table 2. Study aims, inclusion and exclusion criteria, methods to study adipose tissue. Study Age (Years) Men (%) Aims Criteria Method Used to Determine Inclusion Exclusion Overall Obesity VAT SAT Bogousslavsky et al. [5] 62.1 363 (76.1%) Determine the relative importance of each cardiovascular risk factor according to the progression of local atheromatous obstruction Patients with atheromatous internal carotid artery occlusion or stenosis, compared with matched control subjects without internal carotid artery disease and with matched patients with coronary heart disease but without internal carotid artery disease Age < 50 years old, without anatomic verification of stenosis, with dissection, dysplasia, posttraumatic occlusion, or intake of oral contraceptives According to medical charts NA NA Lakka et al. [6] NA 774 (100%) Whether WHR and WC are directly related to a 4-year increase in the indicators of common carotid atherosclerosis independent of BMI and other risk factors for atherosclerosis Men, 42–60 years old, Complete information about anthropometric measures and carotid atherosclerosis Coronary heart disease, stroke, claudication BMI WC WHR HC WHR Hunt et al. [7] 42.2 ±15.9 289 (38.5%) The extent to which the presence or absence of carotid artery plaque was under genetic control Age: 40–60-year-old, that the proband has a living spouse who was willing to participate in the study, and that the proband has at least 6 first-degree relatives, excluding parents, who were at least 16 years of age and living in the San Antonio area NA BMI WC NA Hegazi et al. [8] 51 ±9 18 (35%) Examine the relationship between obesity and regional patterns of adiposity, insulin resistance, and five independent measures of subclinical atherosclerosis Volunteers with a prior diagnosis of Type 2 diabetes of known duration not longer than 5 years, age: 20–70 years, and stable weight, with overall good general health Insulin treatment, current use of tobacco, prior history of myocardial infarction, stroke, or peripheral vascular disease BMI DXA CT scan. CT scan. J. Cardiovasc. Dev. Dis. 2022,9, 162 5 of 33 Table 2. Cont. Study Age (Years) Men (%) Aims Criteria Method Used to Determine Inclusion Exclusion Overall Obesity VAT SAT Czernichow et al. [9] 59.4 ±4.7 504 (49.7%) Association of body composition assessed by bioimpedance analysis and anthropometric indicators of fat repartition with carotid structure and function Volunteers Women aged: 35–60 years Men aged: 35–60 years Disease likely to hinder participation or threaten 5 years survival. Extreme beliefs or behavior regarding diet Bioimpedance BMI WC WHR HC WHR Hadjiev et al. [10] 2003 NA This population-based biennial epidemiological survey has been designed to assess the prevalence of the multiple vascular risk factors, their distribution patterns, and outcomes among the Bulgarian urban population. Without signs and symptoms of cerebrovascular disease, aged 50–79 years were enrolled in the study NA BMI NA NA De Souza et al. [11] 34.0 ±11.7 0 (0%) Estimated the prevalence of atherosclerotic plaque in carotid arteries in systemic lupus erythematous patients and controls and verified possible associations between risk factors and carotid plaque Women fulfilled the update American College of Rheumatology criteria for systemic lupus erythematosus Controls excluded if they had an autoimmune disease BMI NA NA Montalcini et al. [12] 57.2 ±7.37 0 (0%) Investigate whether the subclinical carotid atherosclerosis prevalence is different in obese postmenopausal women with and without metabolic syndrome Postmenopausal, Caucasian, aged 45–75 years Diabetes cardiovascular disease arrhythmia BMI NA NA J. Cardiovasc. Dev. Dis. 2022,9, 162 6 of 33 Table 2. Cont. Study Age (Years) Men (%) Aims Criteria Method Used to Determine Inclusion Exclusion Overall Obesity VAT SAT Lear et al. [3] 46.9 ±8.7 389 (48.6%) Hypothesized that the association between VAT and atherosclerosis is independent of total body fat, established risk factors, and measures of central adiposity Healthy men and women (between 30 and 65 years of age) matched for ethnicity and BMI Recent weight change, previous diagnosis of cardiovascular disease, significant comorbidity, had significant prosthetics or amputations, currently taking medications for cardiovascular risk factors Dual-energy X-ray absorptiometry, CT scan BMI CT scan WC WHR CT scan WHR Park et al. [13] 65.3 ±12.2 204 (54%) Elucidate the relationship between metabolic syndrome and cerebrovascular stenosis Consecutive patients with acute ischemic stroke (large artery atherosclerosis, small artery occlusion, cardiac embolism, and ischemic stroke of undetermined etiology) Strokes of other determined etiology (venous thrombosis, arterial dissection, or moyamoya disease and those with transient ischemic attack). Patients unable to stand with assistance, patients who had no relevant lesions on diffusion-weighted imaging, poor MR angiographic images, incomplete work up NA WC NA Irace et al. [14] 30–80 1002 (54.4%) Evaluate the contribution of generalized adiposity, to carotid atherosclerosis, in participants with or without metabolic syndrome Caucasians BMI < 18.5 kg/m2, age < 30 years BMI WC NA Yu et al. [15] 56.4 ±3.3 0 (0%) Determine the prevalence of carotid plaque and identity its associated risk factors Postmenopausal Chinese women aged 50–64 years Surgical menopause, presence of cardiovascular disease, cancer and renal failure BMI WC WHR WHR J. Cardiovasc. Dev. Dis. 2022,9, 162 7 of 33 Table 2. Cont. Study Age (Years) Men (%) Aims Criteria Method Used to Determine Inclusion Exclusion Overall Obesity VAT SAT Terzis et al. [16] 40.5 ±1.1 60 (56.6%) Assess associations between actual long-term changes in BMI since adolescence and early and advanced stages of subclinical atherosclerosis among a population of healthy young adults This longitudinal study was based on a cohort initially recruited consecutively from two Athens high schools in 1983, collecting data on cardiovascular risk factors from a population of consecutive adolescents aged 12–17 years Loss/change of contact information or decline to participate, or not alive BMI WC NA Kadoglou et al. [17] 65 ±7.7 86 (76.8%) Assess if apelin and visfatin correlate with carotid plaque echogenicity Aged 56–80 years and overweight (BMI > 25 kg⁄m2 fat-mass > 30%) and with unilateral or bilateral carotid atherosclerosis without indications for intervention, not receiving lipid-lowering treatment Cerebral hemorrhage, sources of cardioembolism, concurrent conditions, diseases interfering with the expression of inflammatory mediators during the previous 3 months BMI Bioimpedance WHR WHR Solomon et al. [18] 56.4 ±10.9 0 (0%) Ascertain the association between clinical obesity and atherosclerosis African black women and Caucasian women who met the American College of Rheumatology criteria for rheumatoid arthritis Infected with HIV BMI WC WHtR WHR WHR J. Cardiovasc. Dev. Dis. 2022,9, 162 8 of 33 Table 2. Cont. Study Age (Years) Men (%) Aims Criteria Method Used to Determine Inclusion Exclusion Overall Obesity VAT SAT Rodríguez-Flores et al. [19] NA 107 (57.8%) Analyze the relationship between cardiovascular risk factors, including obesity, with the severity of atherosclerosis in different arterial territories Cadavers of men and women aged 0 to 90 years Arteries were not taken for examination in the following circumstances: when tissues had suffered advanced damage that precluded their analysis when the cadaver arrived more than 36 h after death, or in cases with previously reported congenital heart disease BMI NA NA Maksimovic et al. [20] 65.3 ±8.4 412 (62.7%) Investigate the relationship between abdominal obesity, and other atherosclerotic risk factors in patients with symptomatic carotid atherosclerotic disease Subjects who had symptoms of cerebral ischemia and carotid stenosis of ≥50% Age < 18 years, malignant disease, rheumatoid arthritis, or previous endarterectomy NA WC NA Galarza-Delgado et al. [21] 55.5 ±13.1 13 (10.5%) Association between the presence of rheumatoid nodules and plaque of the carotid artery Met at least 4 American Colege of Rheumatology criteria for rheumatoid arthritis greater than 16 years Pregnant patient, History of carotid surgery BMI WC NA Cuspidi et al. [22] 53.3 ±12.6 1977 (52.7%) Risk of developing left ventricular hypertrophy and carotid atherosclerosis is different in men and women with metabolic syndrome Uncomplicated essential hypertension Previous clinically overt cardiovascular disease, secondary causes of hypertension, life-threatening conditions NA WC NA J. Cardiovasc. Dev. Dis. 2022,9, 162 9 of 33 Table 2. Cont. Study Age (Years) Men (%) Aims Criteria Method Used to Determine Inclusion Exclusion Overall Obesity VAT SAT Chiquete et al. [23] 69.2 211 (39.6%) Identify risk factors associated with moderate to severe carotid stenosis History of ischemic stroke or transient ischemic attack or at least two cardiovascular risk factors (Age ≥55 years, hypertension, dyslipidemia, smoking habits, obesity or diabetes) NA BMI NA NA Irie et al. [24] 65 ±7 147 (82%) Clarify the parameters related to the echogenicity of carotid plaque Age ≥40 years, Type 2 diabetes, presence of carotid plaques History of ischemic stroke, coronary heart disease, peripheral artery disease, elevated liver enzymes, renal insufficiency BMI NA NA Yan et al. [25] 68.1 (4.9) 370 (40.6%) Investigate the association of the metabolic syndrome components with subclinical atherosclerosis Age ≥60 years Patients with clinical stroke, coronary heart disease, or heart failure BMI WC NA Yuan et al. [26] 58.9 (9.7) 552 (42.0%) Assess relationships between anthropometric measures and adipose tissue volumes with subclinical cardiovascular disease in carotid arteries Type 2 diabetes Prior coronary artery procedures. Absence of coronary artery calcification BMI WC CT scan CT scan Pan et al. [27] NA 231 (48.7%) Identify risk factors associated with carotid atherosclerosis Relatively healthy populations residing in Northeast China Excessive alcohol consumption, severe hepatitis B or C, liver disease, mental illness, severe cardiac or pulmonary insufficiency, and cancer BMI WC NA J. Cardiovasc. Dev. Dis. 2022,9, 162 16 of 33 Table 3. Cont. Study Carotid Plaque Conclusion Evaluation Method Definition Grade Symptomatic Park et al. [13] Magnetic resonance Degree of luminal narrowing of ≥50% NA Symptomatic None of the metabolic syndrome components were shown to be associated with extracranial internal carotid artery stenosis Irace et al. [14] US doppler Localized lesion encroaching the lumen of thickness at least 1.3 mm, no spectral broadening or only in the deceleration phase of systole and systolic peak velocity less than 120 cm/s. Stenosis was defined as spectral broadening throughout systole and/or peak flow velocity of at least 120 cm/s NA NA Overweight and obesity, however, do not independently associate with carotid atherosclerosis Yu et al. [15] Ultrasound Plaque was defined as a focal wall thickening of at least 1.5 mm The degree of plaque at the six segments was graded according to the following criteria: grade 0, no observable plaque, grade 1, one small plaque < 30% of vessel diameter, grade 2, one medium plaque between 30% and 50% of the vessel diameter or multiple small number plaques, and grade 3, one large plaque > 50% vessel diameter or multiple plaques with at least one medium plaque Asymptomatic A high WHR was independently associated with the presence of plaque Terzis et al. [16] Ultrasound Plaque was defined as a focal structure encroaching into the arterial lumen of at least 0.5 mm or 50% of the surrounding IMT value, or a thickness of 1.5 mm as measured from the media-adventitia interface to the intima-lumen interface NA Asymptomatic The presence of atheromatous plaques was independently associated with BMI J. Cardiovasc. Dev. Dis. 2022,9, 162 17 of 33 Table 3. Cont. Study Carotid Plaque Conclusion Evaluation Method Definition Grade Symptomatic Kadoglou et al. [17] US doppler Localized thickening of the vessel wall of more than 2.5 mm Classification of carotid stenosis according to the recommendations of the Society of Radiologists in Ultrasound Symptomatic (35 patients) Asymptomatic (51 patients) Increased fat mass correlated with carotid plaque vulnerability, as expressed by the gray scale median score Solomon et al. [18] Ultrasound Focal structure that encroaches into the arterial lumen of a least 0.5 mm or 50% of the surrounding intima-media thickness value or demonstrates a thickness of >1.5 mm as measured from the media-adventitia interface to the intima-lumen interface NA NA WHR was significantly related to carotid artery plaque in African Caucasian women, whereas none of the obesity measures were associated with carotid artery plaque in black women Rodríguez-Flores et al. [19] Histopathological study Classification of atherosclerosis lesions according to the American Heart Association NA NA BMI did not independently predict the risk of development of advanced lesions Maksimovic et al. [20] Ultrasound NA Classification of carotid stenosis according to NASCET Symptomatic Patients with and without abdominal obesity did not significantly differ, either in the degree of carotid stenosis or in the degree of its clinical manifestation J. Cardiovasc. Dev. Dis. 2022,9, 162 18 of 33 Table 3. Cont. Study Carotid Plaque Conclusion Evaluation Method Definition Grade Symptomatic Galarza-Delgado et al. [21] Ultrasound Focal structure that invades the lumen of the artery by at least 0.5 mm or 50% of the value of intima-media thickness, or when the thickness is equal to or greater than 1.5 mm when measured from the adventitia-media interphase to the intima-arterial lumen interphase NA NA Presence of plaque was associated with abdominal circumference Cuspidi et al. [22] Ultrasound NA NA Asymptomatic No association was found between abdominal obesity and carotid plaque Chiquete et al. [23] US doppler NA Classification of carotid stenosis according to NASCET Symptomatic (30 patients) Asymptomatic (503 patients) There was no association between obesity and carotid stenosis ≥50% or between obesity and symptomatic carotid stenosis Irie et al. [24] Ultrasound Focal structure encroaching into the arterial lumen or demonstrating a thickness >1.0 mm as measured from the media–adventitia interface to the intra-lumen interface NA Asymptomatic The presence of echolucent carotid plaques with low gray-scale median values was related to high BMI Yan et al. [25] US doppler Focal encroachment of internal carotid artery walls on either side NA Asymptomatic There was no significant association between abdominal obesity or overweight/obesity with carotid plaques Yuan et al. [26] CT scan Calcium mass score NA NA No association was found between BMI, WC, and VAT, SAT determined on CT scan and carotid calcification J. Cardiovasc. Dev. Dis. 2022,9, 162 19 of 33 Table 3. Cont. Study Carotid Plaque Conclusion Evaluation Method Definition Grade Symptomatic Pan et al. [27] Ultrasound NA NA NA In females, the prevalence of carotid atherosclerosis was significantly higher in obese than in the control group Radmard et al. [28] Ultrasound Localized thickening of >1.2 mm, not involving the whole circumference of the artery NA NA Subjects with the highest amount of VAT were more prone to have more than one carotid plaque in comparison with participants showing the highest values of SAT or other conventional anthropometric indices Sandfort et al. [29] Magnetic resonance NA Total wall volume measurements NA Obesity was associated with the progression of carotid atherosclerosis in a lowto moderate-risk population treated with optimal statin therapy Mitevska et al. [30] US doppler Detection of an IMT > 1.3 mm or a focal structure emerging from the wall of at least 0.5 mm or 50% of the surrounding IMT value Carotid stenosis greater than 60% was considered significant Asymptomatic Multivariate analysis showed that obesity was not an independent predictor for the presence of carotid plaques Higuchi et al. [31] US doppler NA Stenosis was regarded as significant if stenosis rate ≥70 Asymptomatic Visceral fat ≥100 cm2was independently associated with cervical plaque. BMI and WHR were not Mancusi et al. [32] Ultrasound IMT ≥1.5 mm NA Asymptomatic Obesity was associated with a modestly increased prevalence of carotid plaques Nishizawa et al. [33] Autopsy The largest atheroma plaque in the carotid artery was determined to calculate the stenosis index The stenosis index was calculated by subtracting the lumen area from the outer area, dividing the difference by the outer area, and multiplying the result by 100 NA Visceral fat was not associated with carotid artery stenosis index J. Cardiovasc. Dev. Dis. 2022,9, 162 20 of 33 Table 3. Cont. Study Carotid Plaque Conclusion Evaluation Method Definition Grade Symptomatic Omisore et al. [34] Ultrasound Plaque was defined as focal thickening of at least 50% greater than that of the surrounding vessel wall, with a minimum thickness of at least 1.5 mm NA NA Carotid plaques were associated with obesity Imahori et al. [35] Ultrasound Localized protrusion of the vessel wall into the lumen of at least 50% compared with the adjacent intima-media thickness NA NA BMI, WC, and WHtR were not associated with the presence of carotid plaques. The main measure of central obesity (WHR) showed the strongest and most consistent association with plaque presence and with plaque area Laugesen et al. [36] Magnetic resonance NA Carotid artery plaque burden was measured as maximum wall thickness derived from the lumen area and total vessel area outlines, maximum wall area, and maximum normalized wall index Asymptomatic Obesity was associated with increased carotid plaque necrotic core volume and calcification Yoshida et al. [37] Ultrasound Localized elevated lesions with a maximum thickness of more than 1 mm NA NA Visceral adiposity is an independent predictor of atherosclerosis Scicali et al. [38] Ultrasound IMT greater than 1.5 mm NA Asymptomatic The presence of carotid plaque was associated with high WHR Rovella et al. [4] Histology Collected at carotid endarterectomy NA Symptomatic (265 patients) Asymptomatic (125 patients) Obesity is an independent risk factor for carotid plaque destabilization J. Cardiovasc. Dev. Dis. 2022,9, 162 21 of 33 Table 3. Cont. Study Carotid Plaque Conclusion Evaluation Method Definition Grade Symptomatic Geraci et al. [39] US doppler Focal structure encroaching into the arterial lumen of at least 0.5 mm or 50% of the surrounding carotid IMT value or carotid IMT > 1.5 mm NA Asymptomatic ABSI was the only anthropometric adiposity index independently associated with the presence of carotid atherosclerotic plaque Haberka et al. [40] US doppler Presence of plaques in the common carotid artery, bulb, and internal carotid artery Classification of carotid stenosis according to NASCET NA None of the obesity measurements revealed an association with carotid atherosclerosis severity J. Cardiovasc. Dev. Dis. 2022,9, 162 22 of 33 The quality of each study was assessed by one author (J. F.) using the MINORS (methodological index for non-randomized studies) criteria (see supplement material) [ 41 ]. Each item was scored as 0 (not reported), 1 (reported but inadequate), or 2 (re-ported and adequate). The global ideal score is 16 for non-comparative studies and 24 for comparative studies [41]. The final classification is presented in Table 1. 3. Results A total of 1750 articles were found, and after removing duplicates, 1201 articles were left, as shown in Figure 1[42–49]. J. Cardiovasc. Dev. Dis. 2022, 9, x FOR PEER REVIEW 25 of 37 The quality of each study was assessed by one author (J. F.) using the MINORS (methodological index for non-randomized studies) criteria (see supplement material) [41]. Each item was scored as 0 (not reported), 1 (reported but inadequate), or 2 (reported and adequate). The global ideal score is 16 for non-comparative studies and 24 for comparative studies [41]. The final classification is presented in Table 1. 3. Results A total of 1750 articles were found, and after removing duplicates, 1201 articles were left, as shown in Figure 1 [42–49]. Figure 1. Flow diagram for this opportunistic review that aims to analyze the correlation between obesity and carotid atherosclerosis. Of the 64 papers, 26 were rejected after reading the full text due to the following reasons: eight articles did not correlate obesity with carotid artery stenosis [42–49]; Nine did not determine the presence of carotid artery stenosis [50–58]; In four articles, intimaFigure 1. Flow diagram for this opportunistic review that aims to analyze the correlation between obesity and carotid atherosclerosis. Of the 64 papers, 26 were rejected after reading the full text due to the following reasons: eight articles did not correlate obesity with carotid artery stenosis [ 42 – 49 ]; Nine did not determine the presence of carotid artery stenosis [ 50 – 58 ]; In four articles, intimamedia thickness and carotid artery plaque were both correlated with obesity [59–62]; One J. Cardiovasc. Dev. Dis. 2022,9, 162 23 of 33 article excluded subjects with a history of obesity [ 63 ]; Two papers were a letter to the editor [ 52 , 64 ]; One study did not measure carotid artery stenosis or obesity [ 65 ]; One article defined carotid artery stenosis as calcification seen on radiographs [66]. The 38 studies included in this opportunistic review were published in 1985 (one article) and between 2001 and 2019. The studies were conducted in 32 different countries, the majority in Europe (18 papers), eight studies in North America, eight in Asia, two in South America, and two in Africa (Table 1). Analyzing the studies included in this opportunist review by regions, there was a higher number of papers describing a positive association between obesity and carotid plaque characteristics in the research work performed in Asia and Africa. However, just two papers were identified from Africa. The majority of papers included were from Europe, where 10 papers found a relationship and an equal number did not. - The majority of the studies (34) were cross-sectional, and four were longitudinal. - A total of 35,339 subjects (49.20% men) were included: 26,492 from Europe, 4239 from Asia, 3859 from North America, 384 from South America, and 365 from Africa (Table 1). Some studies only included a specific group of patients: Type 2 diabetes (5 papers), women (4), patients with an autoimmune disease (4), or hypertension (3) (Table 2). The authors used different methods to determine the quantity of adipose tissue and to characterize the atherosclerotic plaque. The most frequent method used to determine obesity was anthropometric measures: Thirty-three articles assessed overall obesity with BMI, 19 evaluated visceral obesity with WC, and 11 estimated the relationship between the visceral and subcutaneous adipose tissue with WHR (Table 2). Six authors used medical imaging to quantify the VAT and SAT: Four authors used CT scans [ 3 , 8 , 26 , 31 ], one author used ultrasound [ 40 ], and another MRI [ 28 ]. Other methods were used: bioimpedance (three papers) [ 9 , 17 , 37 ]; dual-energy X-ray absorptiometry (two) [ 3 , 36 ]; and DXA (one) [ 8 ] (Table 2). In one paper, omental, mesenteric, mesocolon, and perirenal fat were dissected after the autopsy and weighed [ 33 ]. The VAT was the sum of the omental, mesenteric, mesocolon, and perirenal fat [33]. The carotid plaque was evaluated with ultrasound in 19 articles, with doppler ultrasound in 12 papers, and with MRI in three articles (Table 3). Two articles analyzed the histological composition of the carotid plaque (number of macrophages, foam cells, cap characteristics, and the quantity of lipids and calcium) [ 4 , 19 ]. One study determined the area of the cadavers of the largest atheroma plaque in the carotid artery of cadavers to calculate the stenosis index [33]. The carotid plaque was defined in most papers as a focal structure encroaching the vessel lumen or as a widening in the intima media-thickness (Table 3). However, there was no homogeneity in the definition, and different publications used different measures of intima-media thickness to define a plaque (Table 3). Sixteen articles only analyzed asymptomatic carotid plaques, six papers studied both symptomatic and asymptomatic, and two articles symptomatic. Fourteen articles did not specify if the carotid artery caused symptomatology. (Table 3). This opportunistic review included 1533 symptomatic and 19,799 asymptomatic patients. 3.1. Overall Obesity and the Prevalence of Carotid Plaques Overall obesity, determined by BMI, was not associated with the presence of carotid plaques in 15 papers, totaling 13,215 patients (Figure 2) [3,9,10,12,14,15,18,21,25,28,30,31,35,39,40]. Five studies (1363 patients) found, however, a positive association between the prevalence of carotid plaques and overall obesity (Figure 2) [5,11,16,27,34]. J. Cardiovasc. Dev. Dis. 2022,9, 162 24 of 33 J. Cardiovasc. Dev. Dis. 2022, 9, x FOR PEER REVIEW 27 of 37 atherosclerosis identified by ultrasound. However, there was no definition of atherosclerotic plaque [27]. The prevalence was significantly higher in obese females than in the control females. Obesity was defined as BMI ≥ 28 kg/m2 [27]. The study included 231 males, and no association was found for this gender [27]. Another study conducted on 144 women with systemic lupus erythematous found that the prevalence of carotid artery plaque was significantly associated with obesity, determined by BMI [11]. The oldest study included in this review included 477 patients who performed angiography or Doppler ultrasound and concluded that obesity was significantly more frequent in patients with internal artery occlusion or stenosis than in controls. Obesity was defined according to medical charts [5]. Two papers totaling 268 patients found that the prevalence of carotid plaques was associated with overall obesity determined by BMI [16,34]. However, one paper with 750 individuals concluded that the prevalence of carotid artery plaques was inversely related to BMI (Figure 2) [7]. Figure 2. Results of the studies that correlate overall obesity with the presence of the carotid atherosclerotic plaques. 3.2. Overall Obesity and the Characteristics of the Carotid Plaques Three papers suggested that overall obesity could be associated with carotid plaque instability (Figure 3) [4,24,36]. (1). Histological analysis of carotid plaques (390) concluded that obesity, defined as BMI ≥ 30 kg/m2 was an independent risk factor for carotid plaque destabilization, particularly in males [4]. Obesity was correlated with the presence of unstable carotid plaques, characterized by a high degree of inflammation, thinning, and rupture of the cap [4]. (2). One study analyzed the plaque echogenicity by gray-scale median using ultrasound and concluded that low gray-scale median values were related to high BMI [24]. Plaques with a low gray-scale median had a higher probability of causing embolization and symptoms. This research included 179 diabetic patients [24]. (3). One research paper found that obesity (BMI > 30.0 kg/m2) was associated with increased carotid plaque necrotic core volume and calcification independently of diabetes mellitus status [36]. The carotid plaque composition was assessed by magnetic resonance imaging. Obesity was determined by BMI [36]. The study included 78 patients with short-duration Type 2 diabetes mellitus and 91 sexand aged-matched control subjects [36]. Figure 2. Results of the studies that correlate overall obesity with the presence of the carotid atherosclerotic plaques. One of these was a prevalence study conducted on 474 healthy residents in Northeast China [ 27 ]. This study sought to determine the risk factors associated with carotid atherosclerosis identified by ultrasound. However, there was no definition of atherosclerotic plaque [ 27 ]. The prevalence was significantly higher in obese females than in the control females. Obesity was defined as BMI ≥ 28 kg/m 2 [ 27 ]. The study included 231 males , and no association was found for this gender [27]. Another study conducted on 144 women with systemic lupus erythematous found that the prevalence of carotid artery plaque was significantly associated with obesity, determined by BMI [11]. The oldest study included in this review included 477 patients who performed angiography or Doppler ultrasound and concluded that obesity was significantly more frequent in patients with internal artery occlusion or stenosis than in controls. Obesity was defined according to medical charts [5]. Two papers totaling 268 patients found that the prevalence of carotid plaques was associated with overall obesity determined by BMI [16,34]. However, one paper with 750 individuals concluded that the prevalence of carotid artery plaques was inversely related to BMI (Figure 2) [7]. 3.2. Overall Obesity and the Characteristics of the Carotid Plaques Three papers suggested that overall obesity could be associated with carotid plaque instability (Figure 3) [4,24,36]. (1). Histological analysis of carotid plaques (390) concluded that obesity, defined as BMI ≥30 kg/m2 was an independent risk factor for carotid plaque destabilization, particularly in males [ 4 ]. Obesity was correlated with the presence of unstable carotid plaques, characterized by a high degree of inflammation, thinning, and rupture of the cap [4]. (2). One study analyzed the plaque echogenicity by gray-scale median using ultrasound and concluded that low gray-scale median values were related to high BMI [ 24 ]. Plaques with a low gray-scale median had a higher probability of causing embolization and symptoms. This research included 179 diabetic patients [24]. (3). One research paper found that obesity (BMI > 30.0 kg/m 2 ) was associated with increased carotid plaque necrotic core volume and calcification independently of diabetes mellitus status [ 36 ]. The carotid plaque composition was assessed by magnetic resonance imaging. Obesity was determined by BMI [ 36 ]. The study included 78 patients with short-duration Type 2 diabetes mellitus and 91 sexand aged-matched control subjects [36]. J. Cardiovasc. Dev. Dis. 2022,9, 162 25 of 33 1 Figure 3. Summary of the studies that correlate overall obesity with the characteristics of the carotid atherosclerotic plaques. This opportunistic review identified three articles that found that obesity did not correlate with calcium score or carotid plaque score (Figure 3) [8,26,37]. (1). No association was found between BMI and calcium mass score of the carotid arteries determined with a CT scan [ 26 ]. This study was performed on 1315 diabetic patients [26]. (2). One study found that the measures of adiposity (BMI, the systemic fat mass, and the fat-free mass determined with DXA) were not significantly different in patients with higher plaques score [ 8 ]. For each segment, the degree of plaque was graded as follows: 0 = no plaque; 1 = 1 small plaque. <30% of vessel diameter; 2 = 1 medium plaque between 30% of vessel diameter or multiple small plaques; and 3 = 1 large plaque >50% of the vessel diameter or multiple plaques with at least 1 medium plaque [ 8 ]. The grades were summed across the right and left carotid arteries to create an overall measure of the extent of focal plaque [8]. This study included 52 patients [8]. J. Cardiovasc. Dev. Dis. 2022,9, 162 32 of 33 28. Radmard, A.R.; Poustchi, H.; Ansari, L.; Khorasanizadeh, F.; Yoonessi, A.; Taheri, A.P.H.; Rahmanian, M.S.; Jafari, E.; Malekzadeh, R.; Merat, S. Abdominal fat distribution and carotid atherosclerosis in a general population: A semi-automated methods using magnetic resonance imaging. Jpn. J. Radiol. 2016,34, 414–422. [CrossRef] 29. Sandfort, V.; Lai, S.; Ahlman, M.A.; Mallek, M.; Liu, S.; Sibley, C.T.; Turkbey, E.B.; Lima, J.A.C.; Bluemke, D.A. Obesity Is Associated with Progression of Atherosclerosis During Statin Treatment. J. Am. Heart Assoc. 2016,5, e003621. [CrossRef] 30. Mitevska, I.; Baneva, N.; Bosevski, M.; Kostovska, E. Prevalence of risk factors and asymptomatic carotid atherosclerosis in diabetic patients screened for silent myocardial ischemia by SPECT myocardial imaging. Nucl. Med. Ver. 2017 ,20, 3–9. [CrossRef] 31. Higuchi, S.; Kabeya, Y.; Kato, K. Visceral-to-subcutaneous fat ratio is independently related to small and large cerebrovascular lesions even in healthy subjects. Atherosclerosis 2017,259, 41–45. [CrossRef] [PubMed] 32. Mancusi, C.; Gerdts, E.; Losi, M.A.; D’Amato, A.D.; Manzi, M.V.; Canciello, G.; Trimarco, V.; De Luca, N.; Simonse, G.; Izzo, R. Differential effect of obesity on prevalence of cardiac and carotid target organ damage in hypertension (The Campania Salute Network). Int. J. Cardiol. 2017,244, 260–264. [CrossRef] [PubMed] 33. Nishizawa, A.; Suemoto, C.K.; Farias-Itao, D.S.; Campos, F.M.; Silva, K.C.S.; Bittencourt, M.S.; Grinberg, L.T.; Leite, R.E.P.; Ferretti-Rebustini, R.E.L.; Farfel, J.M.; et al. Morphometric measurements of systemic atherosclerosis and visceral fat: Evidence from na autopsy study. PLoS ONE 2017,12, e0186630. [CrossRef] 34. Omisore, A.; Famurewa, O.; Komolafe, M.; Asaleya, C.; Fawale, M.; Afolabi, B. Association of traditional cardiovascular risk factors with carotid atherosclerosis among adults at a teaching hospital in South-western Nigeria. Cardiovasc. J. Afr. 2018 ,28, 183–188. [CrossRef] 35. Imahori, Y.; Mathiesen, E.B.; Leon, D.A.; Hopstock, L.A.; Hughes, A.D.; Johnsen, S.H.; Jørgensen, L.; Emaus, N.; Morgan, K.E. The contribution of obesity to carotid atherosclerotic plaque burden in a general population sample in Norway: The Tromsø Study. Atherosclerosis 2018,273, 15–20. [CrossRef] [PubMed] 36. Laugesen, E.; Høyem, P.; Thrysoe, S.; Hansen, E.S.S.; Mikkelsen, A.F.S.; Kerwin, W.S.; Poulsen, P.L.; Hansen, T.K.; Kim, W.Y. Negative Carotid Artery Remodeling in Early Type 2 Diabetes Mellitus and Increased Carotid Plaque Vulnerability in Obesity as Assessed by Magnetic Resonance Imaging. J. Am. Heart Assoc. 2018,7, e008677. [CrossRef] 37. Yoshida, T.; Hashimoto, M.; Kawahara, R.; Yamamoto, H.; Tanaka, M.; Ito, H.; Masuda, I.; Hosoda, K.; Yamamoto, W.; Uozumi, R.; et al. Non-obese visceral adiposity is associated with the risk of atherosclerosis in Japanede patients with rheumatoid arthritis: A cross-sectional study. Rheumatol. Int. 2018,38, 1679–1689. [CrossRef] [PubMed] 38. Scicali, R.; Rosenbaum, D.; Pino, A. Na increased waist-to-hip ratio is a key determinant of a atherosclerotic burden in overweight subjects. Acta Diabetol. 2018,55, 741–749. [CrossRef] 39. Geraci, G.; Zammuto, M.; Gaetani, R.; Mattina, A.; D’Ignoto, F.; Geraci, C.; Noto, D.; Averna, M.; Cottone, S.; Mulè, G. Relationship of a Body Shape Index and Body Roundness Index With carotid atherosclerosis in arterial hypertension. Nitrition Metab. Cardiovasc. Dis. 2019,29, 822–829. [CrossRef] 40. Haberka, M.; Skilton, M.; Biedro´n, M.; Szostak-Janiak, K.; Partyka, M.; Matla, M.; G ˛asior, Z. Obesity, visceral adiposity and carotid atherosclerosis. J. Diabetes Its Complicat. 2019,33, 302–306. [CrossRef] 41. Buford, T.W.; Anton, S.D.; Judge, A.R.; Marzetti, E.; Wohlgemuth, S.E.; Carter, C.S.; Leeuwenburgh, C.; Pahor, M.; Manini, T.M. Models of accelerated sarcopenia: Critical pieces for solving the puzzle of age-related muscle atrophy. Ageing Res. Rev. 2010 ,9, 369–383. [CrossRef] [PubMed] 42. Puttonen, S.; Kivimäki, M.; Elovainio, M.; Pulkki-Råback, L.; Hintsanen, M.; Vahtera, J.; Telama, R.; Juonala, M.; Viikari, J.S.; Raitakari, O.T.; et al. Shift work in young adults and carotid artery intima–media thickness: The Cardiovascular Risk in Young Finns study. Atherosclerosis 2009,205, 608–613. [CrossRef] [PubMed] 43. Pearson, T.L. Cardiovascular risk in minority and underserved women in Appalachian Tennessee: A descriptive study. J. Am. Acad. Nurse Pract. 2010,22, 210–216. [CrossRef] [PubMed] 44. Varleta, P.; Concepción, R.; Vargas, P.; Casanova, H. Grosor íntima media carotídeo y asociación con factores de riesgo cardiovascular tradicionales y metabólicos. Ver. Med. Chile 2013,141, 695–703. [CrossRef] 45. Alkali, N.; Bwala, S.; Akano, A.; Osi-Ogbu, O.; Alabi, P.; Ayeni, O. Stroke risk factors, subtypes, and 30 day case fatality in Abuja, Nigeria. Niger. Med. J. 2013,54, 129–136. [CrossRef] 46. Rodríguez-Saldaña, J.; Rodriguez-Flores, M.; Cantú-Brito, C.; Aguirre-Garcia, J. A Pathological Study of the Epidemiology of Atherosclerosis in Mexico City. Cardiol. Res. Pr. 2014,2014, 2642058. [CrossRef] 47. Maddaloni, E.; Cavallari, I.; De Pascalis, M.; Keenan, H.; Park, K.; Manfrini, S.; Buzzetti, R.; Patti, G.; Di Sciascio, G.; Pozzilli, P. Relation of Body Circumferences to Cardiometabolic Disease in Overweight-Obese Subjects. Am. J. Cardiol. 2016 ,118, 822–827. [CrossRef] 48. Masson, W.; Siniawski, D.; Toledo, G.; Vita, T.; Fernández, G.; Castillo, S.G.; Valle, J.; Cagide, A. Estimación de la «edad vascular» basada en el índice de masa corporal en una población en prevención primaria. Asociación con la aterosclerosis carotídea subclínica. Med. Clínica 2013,140, 255–259. [CrossRef] 49. Serena, J.; Segura, T.; Roquer, J.; García-Gil, M.; Castillo, J. The ARTICO study: Identification of patients at high risk of vascular recurrence after a first non-cardioembolic stroke. BMC Neurol. 2015,15, 1–7. [CrossRef] 50. Manchev, I.C.; Mineva, P.P.; Hadjiev, D.I. Prevalence of Stroke Risk Factors and Their Outcomes: A Population-Based Longitudinal Epidemiological Study. Cerebrovasc. Dis. 2001,12, 303–307. [CrossRef] J. Cardiovasc. Dev. Dis. 2022,9, 162 33 of 33 51. Kahraman, S.; Yilmaz, R.; Akinci, D.; Arici, M.; Altun, B.; Erdem, Y.; Yasavul, U.; Turgan, C. U-Shaped Association of Body Mass Index with Inflammation and Atherosclerosis in Hemodialysis Patients. J. Ren. Nutr. 2005,15, 377–386. [CrossRef] [PubMed] 52. Yasuda, T.; Matsuhisa, M.; Fujiki, N.; Sakamoto, F.; Tsuji, M.; Fujisawa, N.; Kimura, M.; Ishibashi, R.; Kaneto, H.; Yamasaki, Y.; et al. Is Central Obesity a Good Predictor of Carotid Atherosclerosis in Japanese Type 2 Diabetes with Metabolic Syndrome? Endocrime J. 2007,54, 695–702. [CrossRef] [PubMed] 53. Lajunen, T.; Vikatmaa, P.; Bloigu, A.; Ikonen, T.; Lepäntalo, M.; Pussinen, P.J.; Saikku, P.; Leinonen, M. Chlamydial LPS and high-sensitivity CRP levels in serum are associated with an elevated body mass index in patients with cardiovascular disease. Innate Immun. 2008,14, 375–382. [CrossRef] [PubMed] 54. De Michele, M.; Panico, S.; Iannuzzi, A.; Celentano, E.; Ciardullo, A.V.; Galasso, R.; Sacchetti, L.; Zarrilli, F.; Bond, M.G.; Rubba, P. Association of Obesity and Central Fat Distribution with Carotid Artery Wall Thickening in Middle-Aged Women. Stroke 2002 , 33, 2923–2928. [CrossRef] 55. Lind, L.; Siegbahn, A.; Ingelsson, E.; Sundstrom, J.; Arnlov, J. A Detailed Cardiovascular Characterization of Obesity Without the Metabolic Syndrome. Arter. Thromb. Vasc. Biol. 2011,31, e27–e34. [CrossRef] 56. Jackson, R.; Sidawy, A.; Amdur, R.; Macsata, R. Obesity is an Independent Risk Factor for Death and Cardiac Complications after Carotid Endarterectomy. J. Am. Coll Surg. 2012,214, 148–155. [CrossRef] 57. Abreu, T.; Ferreira, E.; Filho, S.; Sales, K.; Lopes, F.; Oliveira, A. Prevalence of carotid artery calcifications detected on panoramic radiographs and confirmed by Doppler ultrasonography: Their relationship with systemic conditions. Indian J. Dent. Res. 2015 , 26, 345–350. [CrossRef] 58. Yamauchi, T.; Kuno, T.; Takada, H.; Nagura, Y.; Kanmatsuse, K.; Takahashi, S. The impact of visceral fat on multiple risk factors and carotid atherosclerosis in chronic haemodialysis patients. Nephrol. Dial. Transpl. 2003,18, 1842–1847. [CrossRef] 59. Hwang, I.; Suh, S.; Seo, A.; Ahn, H.; Yim, E. Association between Metabolic Components and Subclinical Atherosclerosis in Korean Adults. Korean J. Fam. Med. 2012,33, 229–236. [CrossRef] 60. Novo, S.; Peritore, A.; Trovato, R.L.; Guarneri, F.P.; Di Lisi, D.; Muratori, I.; Novo, G. Preclinical atherosclerosis and metabolic syndrome increase cardioand cerebrovascular events rate: A 20-year follow up. Cardiovasc. Diabetol. 2013,12, 155. [CrossRef] 61. Wang, X.; Li, W.; Song, F.; Wang, L.; Fu, Q.; Cao, S.; Gan, Y.; Zhang, W.; Yue, W.; Yan, F.; et al. Carotid Atherosclerosis Detected by Ultrasonography: A National Cross-Sectional Study. J. Am. Heart Assoc. 2018,7, e00870. [CrossRef] [PubMed] 62. Sforza, E.; Boissier, C.; Martin, M.S.; Feasson, S.; Barthélémy, J.C.; Roche, F. Carotid artery atherosclerosis and sleep disordered breathing in healthy elderly subjects: The Synapse cohort. Sleep Med. 2013,14, 66–70. [CrossRef] [PubMed] 63. Yamamoto, M.; Egusa, G.; Hara, H.; Yamakido, M. Association of intraabdominal fat and carotid atherosclerosis in non-obese middle-aged men with normal glucose tolerance. Int. J. Obes. 1997,21, 948–951. [CrossRef] [PubMed] 64. Nejmanze, P. Differential Effects of Body Adiposity and Serum Lipids on Right and Left Carotid Artery Lesions. Stroke 2003 ,34, e185–e186. 65. Node, K.; Inoue, T.; Boyko, V.; Goldberg, I.; Fisman, E.Z.; Adler, Y.; Schwammenthal, E.; Matas, Z.; Behar, S.; Tenenbaum, A. Long-term effects of peroxisome proliferator-activated receptor ligand bezafibrate on N-terminal pro-B type natriuretic peptide in patients with advanced functional capacity impairment. Cardiovasc. Diabetol. 2009,8, 1–7. [CrossRef] [PubMed] 66. Friedlander, A.; Altman, L. Carotid artery atheromas in postmenopausal womem–Their prevalence on panoramic radiographs and their relationship to atherogenic risk factors. Am. Dent. Assoc. 2001,132, 1130–1136. [CrossRef] 67. Wang, H.; Chen, Y.; Eitzman, D. Imaging Body Fat–Techniques and Cardiometabolic Implications. Arterioscler. Thromb. Vasc. Biol. 2014,34, 2217–2223. [CrossRef] 68. See, R.; Abdullah, S.M.; McGuire, D.K.; Khera, A.; Patel, M.J.; Lindsey, J.B.; Grundy, S.M.; de Lemos, J.A. The Association of Differing Measures of Overweight and Obesity with Prevalent Atherosclerosis-The Dallas Heart Study. J. Am. Coll. Cardiol. 2007 , 50, 752–759. [CrossRef] 69. Shuster, A.; Patlas, M.; Pinthus, J.; Mourtzakis, M. The clinical importance of visceral adiposity: A critical review of methods for visceral adipose tissue analysis. Br. J. Radiol. 2012,85, 1–10. [CrossRef] 70. Há, E.; Bauer, R. Emerging Roles for Adipose Tissue in Cardiovascular Disease. Arter. Thromb. Vasc. Biol. 2018 ,38, e137–e144. [CrossRef] 71. Gao, Y.; Wang, Y.; Lu, C.; Zeng, C.; Chang, D.; Ju, S. Correlations between the abdominal fat related parameters and severity of coronary artery disease assessed by computed tomography. Quant. Imaging Med. Surg. 2018,8, 579–587. [CrossRef] [PubMed] 72. Figueroa, A.L.; Takx, R.A.; MacNabb, M.H.; Abdelbaky, A.; Lavender, Z.R.; Kaplan, R.S.; Truong, Q.A.; Lo, J.; Ghoshhajra, B.B.; Grinspoon, S.K.; et al. Relationship between measures of adiposity, arterial inflammation, and subsequent cardiovascular events. Circ. Cardiovasc. Imaging 2016,9, e004043. [CrossRef] [PubMed] 73. Imai, A.; Komatsu, S.; Ohara, T.; Kamata, T.; Yoshida, J.; Miyaji, K.; Takewa, M.; Kodama, K. Visceral abdominal fat accumulation predicts the progression of noncalcified coronary plaque. Atherosclerosis 2012,222, 524–529. [CrossRef] [PubMed] 74. Hansson, G.; Libby, P.; Tabas, I. Inflammation and plaque vulnerability. J. Intern. Med. 2015,278, 483–493. [CrossRef]