Obesity, metabolic syndrome, and coronary atherosclerosis.

Abstract

HomeCirculationVol. 105, No. 23Obesity, Metabolic Syndrome, and Coronary Atherosclerosis Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBObesity, Metabolic Syndrome, and Coronary Atherosclerosis Scott M. Grundy, MD, PhD Scott M. GrundyScott M. Grundy From The Center for Human Nutrition and the Departments of Clinical Nutrition and Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Tex. Search for more papers by this author Originally published11 Jun 2002https://doi.org/10.1161/01.CIR.0000020650.86137.84Circulation. 2002;105:2696–2698The relationship between obesity and coronary atherosclerosis (and coronary heart disease [CHD]) has been a subject of some dispute for many years. Data from early investigations suggested that obesity is not an important contributing cause of coronary atherosclerosis and CHD. For example, results of the Seven Countries Study1 revealed little correlation between body weight and incidence of CHD. Moreover, in the massive autopsy study called “The Geographic Pathology of Atherosclerosis,” edited by Henry C. McGill, Jr,2 the relationship between body weight and atherosclerosis was weak at best. This study included a detailed examination of arteries from a large number of autopsies carried out in New Orleans, Sao Paulo, Puerto Rico, Lima, and Santiago; by and large, the results uncovered no association between extent of arterial fatty streaks or raised atherosclerotic lesions in either the coronary arteries or the aorta for any measure of body weight, height, or obesity.3 It was noted that this study had the advantage of including several groups that differed greatly in geographic origin, ethnicity, CHD morbidity, and severity of atherosclerosis. Although the authors3 conceded that obesity is a factor contributing to risk factors for CHD such as hypertension, they surmised that the relationship between obesity and other risk factors is too weak for obesity to have a detectable effect on the severity of atherosclerosis.See p 2712In spite of these earlier negative findings, the Framingham Heart Study in the United States has consistently shown that increasing degrees of obesity are accompanied by greater rates of CHD.4,5 Even so, multivariate analysis of Framingham data strongly suggests that most of the relationship between body weight and CHD risk is mediated through the standard, major risk factors, ie, blood pressure, total cholesterol, HDL cholesterol, and diabetes.6 Their own data led Framingham investigators to question whether obesity is truly an independent risk factor for CHD. This is not to say that obesity is not a causative risk factor for CHD; certainly if obesity is a contributing cause of risk factors that are directly atherogenic, then obesity must belong in the chain of causality. In fact, if obesity induces several major risk factors, it could be a more significant cause of atherosclerotic disease than an individual risk factor.Beyond Framingham data, however, other prospective studies suggest that obesity is a risk factor for CHD independently of the standard risk factors.7,8 If so, part of the relationship between obesity and CHD risk could be mediated by the emerging risk factors. This group of risk factors, which are commonly found in obese persons, includes atherogenic dyslipidemia, insulin resistance, a proinflammatory state, and a prothrombotic state.9 Atherogenic dyslipidemia, or the lipid triad, consists of raised triglycerides, small LDL particles, and low HDL cholesterol. Raised triglycerides commonly reflect the presence of remnant lipoproteins, which are widely believed to be atherogenic; moreover, several lines of evidence suggest that small LDL particles have enhanced atherogenic properties, beyond normal-sized LDL.10,11 Although low serum HDL cholesterol is generally considered to be an independent risk factor, it is closely associated with other emerging risk factors. Thus, some of its apparent independence may in fact be due to its association with emerging risk factors, which are usually hidden in routine clinical work up.Three other emerging risk factors that commonly accompany obesity are worthy of mention. One of these is insulin resistance and its companion, hyperinsulinemia. Several hypotheses have been put forward for a causative link between insulin resistance (or hyperinsulinemia) and CHD risk.12–14 Second, obese subjects typically carry a proinflammatory state that may predispose them to acute coronary syndromes. This state is characterized by elevations of serum high-sensitivity C-reactive protein (hs-CRP); in fact, increased levels of hs-CRP reflect high cytokine levels that may render otherwise stable atherosclerotic plaques vulnerable to plaque rupture.15,16 An excess of adipose tissue apparently secretes increased amounts of several cytokines that underlie the proinflammatory state.17–19 Finally, adipose tissue present in excessive quantities also releases increased amounts of plasminogen activator inhibitor-1 (PAI-1),20–22 which favors a prothrombotic state. This latter state not only may promote atherogenesis, it may also enhance the size of coronary thrombosis accompanying coronary plaque rupture. In view of these additional effects of obesity, it would not be surprising if obesity imparts risk for major coronary events beyond that predicted by the standard risk factors.Returning to the question of the impact of obesity on coronary atherosclerosis, the present issue of Circulation contains an article by McGill et al23 in which body fat was correlated with the severity of coronary atherosclerosis in the Pathological Determinants of Atherosclerosis in Youth (PDAY) study. This study included autopsies carried out in approximately 3000 persons aged 15 to 34 years dying of external causes. Gross atherosclerotic lesions were graded in the right coronary artery and in the left anterior descending coronary artery. Adiposity was estimated by body mass index (BMI) and by thickness of the panniculus adiposus. In young men, BMI was positively associated with both fatty streaks and raised atherosclerotic lesions in both coronary arteries. A thick panniculus adiposus was also significantly associated with greater lesions of the right coronary artery when BMI was >30 kg/m2. Thus, obesity appeared to be a contributor to coronary atherosclerosis in adolescent and young adult men. In young women, BMI was not associated with coronary atherosclerosis, but in those with a thick panniculus adiposus, there was a trend toward greater coronary lesions.In the PDAY study,23 a portion, but not all, of the association between adiposity and coronary atherosclerosis could be explained by the standard, major risk factors. The latter were estimated from postmortem blood for lipid concentrations (non-HDL cholesterol and HDL cholesterol), thiocyanate (for smoking), glycohemoglobin (for recent, average plasma glucose levels); also medial thickness of renal arteries was assessed to identify hypertension. With increasing adiposity, non-HDL cholesterol (LDL+VLDL cholesterol), glycohemoglobin, and prevalence of hypertension were higher, whereas HDL-cholesterol levels were lower. As might be expected smokers had less adiposity. When the authors adjusted their data for the presence of the standard risk factors, the effects of adiposity on coronary fatty streaks and raised lesions was diminished but not eliminated. The standard risk factors reduced the effect of adiposity on fatty streaks by an average of 15% and on raised lesions by 12%. Although the impact of standard risk factors on coronary lesions may have been underestimated, the findings nonetheless strongly suggest that obesity is a risk factor for coronary atherosclerosis beyond and independent of the standard risk factors, at least for young men.If obesity is an independent risk factor for coronary atherosclerosis over and above standard risk factors, this relationship implies that much of the influence of obesity is mediated through the emerging risk factors—insulin resistance, a proinflammatory state, and a prothrombotic state. In the PDAY study,23 higher levels of glycohemoglobin in persons who were more obese reflect the presence of insulin resistance. The findings of this study23 thus support the hypothesis that the emerging risk factors, which are common in obese persons and are characteristic of the metabolic syndrome, are independently atherogenic.The failure to find a positive relationship between adiposity and coronary atherosclerosis in women may have two explanations. First, premenopausal women generally have a delay in progression of atherosclerosis; and second, excess adipose tissue in men, which tends to accumulate abdominally, carries a higher risk for atherosclerotic disease than it does in women.24 These 2 factors may be interrelated.Two important questions must be addressed. First, why did the Framingham Heart Study4,5 find a positive correlation between BMI and CHD risk, whereas no such relationship was found in the Seven Countries Study1? And second, why did the PDAY study23 find a positive correlation between adiposity and coronary atherosclerosis in men, whereas the large Geographic Pathology of Atherosclerosis did not2,3? Regarding both questions, the Seven Countries Study1 and the Geographic Pathology Study2,3 may have included populations in which susceptibility to the adverse effects of obesity may have been too variable to detect a definite relationship. If some populations are less sensitive to the influence of adiposity, then an adverse effect in other populations may have been missed in the analysis. This possibility raises the issue of differences in susceptibility in different groups. This issue is important because it has implications for the approach to the problem of obesity in different populations.One example of a difference in susceptibility appears to exist between men and women in the United States. As the PDAY study23 showed, adiposity has a greater effect on atherogenesis in men than in women. It is well known that men develop coronary atherosclerosis more rapidly than women.2 This difference in atherogenesis rates may be related in part to differences in body fat distribution. Men are more prone to abdominal obesity than are women; and abdominal obesity is widely held to have more impact on risk factors than does gluteofemoral adiposity, which is common in women. Whether abdominal obesity per se is a direct cause of risk factors or a reflection of an underlying metabolic abnormality of a more fundamental type is not certain, but the association with cardiovascular risk factors certainly is present.24Some populations as a whole appear to be more susceptible to the adverse effects of obesity than are others. For example, only moderate weight gain leads to a striking increase in risk for CHD in the South Asian population.25–27 Undoubtedly, there is individual variability in susceptibility in this population, but in aggregate, the risk is high. South Asians commonly develop insulin resistance when they experience only moderate weight gain.28 This propensity is seen in South Asians who have migrated to other regions or who have moved into urban settings and have become relatively affluent in their own countries. The increased risk for CHD in South Asians exceeds by about 2-fold that which can be explained by standard risk factors at least compared with other populations.29 This observation supports the concept that the emerging risk factors, which are secondary to overweight, also contribute to CHD risk. In the case of South Asians, insulin resistance seems to be the most important emerging risk factor.28,30 It might be noted that South Asians are prone both to premature CHD and to type 2 diabetes, both of which are related to a greater insulin resistance.30Indeed, there is racial and ethnic variability in susceptibility to the specific risk factors of the metabolic syndrome. The differences presented below represent impressions gleaned from limited information in the literature; to date systematic comparisons of susceptibility and patterns of the metabolic syndrome in different populations have not been carried out. In general, the white population of European origin appears to be more predisposed to atherogenic dyslipidemia than other populations. Blacks of African origin are prone to hypertension when they gain weight; they also appear to be susceptible to type 2 diabetes, possibly due to a relatively low reserve for insulin secretion. On the other hand, they develop less atherogenic dyslipidemia than do whites with the same degree of weight gain. In the United States, Native Americans and Hispanics are especially susceptible to type 2 diabetes, but are less likely to develop hypertension than are blacks. East Asians likewise tend to express the metabolic syndrome first as insulin resistance and type 2 diabetes.31 Whereas people of South Asia and Southeast Asia also have a high frequency of insulin resistance and type 2 diabetes, they appear to be more susceptible to CHD than are East Asians.32 More systematic comparisons to verify these impressions would make an important contribution to our understanding of the metabolic syndrome. In addition, studies on patterns of cardiovascular disease and type 2 diabetes in different populations likely would shed light on the role of adiposity in the causation of coronary atherosclerosis.Because of the relation of obesity to CHD and type 2 diabetes, the rising prevalence of obesity in the United States is a cause of great concern. In the wake of this epidemic of obesity is a corresponding increase in prevalence of the metabolic syndrome. A recent report33 indicated that 20% to 25% of the adult US population has the metabolic syndrome. In some older groups, this prevalence approaches 50%. The public health consequences for the nation project to be enormous. For this reason, public health efforts to prevent obesity in the general public should be a high national priority. From a clinical viewpoint, attention should focus on those individuals who are susceptible to the development of risk factors and the metabolic syndrome. These individuals will need direct clinical intervention. In some cases, weight reduction and increased physical activity may be sufficient to eliminate their risk factors; in other cases, drug therapies may be required to control risk factors.The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.FootnotesCorrespondence to Scott M. Grundy, MD, PhD, The Center for Human Nutrition and the Departments of Clinical Nutrition and Internal Medicine, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Y3.206, Dallas, TX 75390-9052. E-mail [email protected] References 1 Keys A, Menotti A, Aravanis C, et al. The seven countries study: 2289 deaths in 15 years. Prev Med. 1984; 13: 141–154.CrossrefMedlineGoogle Scholar2 McGill HC Jr. The Geographic Pathology of Atherosclerosis. Baltimore, Md: Williams and Wilkins; 1986.Google Scholar3 Montenegro MR, Solberg LA. Obesity, body weight, body length, and atherosclerosis. Lab Invest. 1968; 18: 134–143.Google Scholar4 Hubert HB, Fenileib M, McNamara PM, et al. Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham heart study. Circulation. 1983; 67: 968–977.CrossrefMedlineGoogle Scholar5 Kim KS, Owen WL, Williams D, et al. A comparison between BMI and Conicity index on predicting coronary heart disease: the Framingham Heart Study. Ann Epidemiol. 2000; 10: 424–431.CrossrefMedlineGoogle Scholar6 Wilson PWF, D’Agostino RB, Levy D, et al. Prediction of coronary heart disease using risk factor categories. Circulation. 1998; 97: 1837–1847.CrossrefMedlineGoogle Scholar7 Rimm EB, Stampfer MJ, Giovannucci E, et al. Body size and fat distribution as predictors of coronary heart disease among middle-aged and older US men. Am J Epidemiol. 1995; 141: 1117–1127.CrossrefMedlineGoogle Scholar8 Eckel RH, Krauss RM. American Heart Association call to action: obesity as a major risk factor for coronary heart disease: AHA Nutrition Committee. Circulation. 1998; 97: 2099–2100.CrossrefMedlineGoogle Scholar9 Expert Panel on Detection Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 2001; 285: 2508–2509.CrossrefMedlineGoogle Scholar10 Austin MA. Small, dense low-density lipoprotein as a risk factor for coronary heart disease. Int J Clin Lab Res. 1994; 24: 187–192.CrossrefMedlineGoogle Scholar11 Krauss RM. Dense low density lipoproteins and coronary artery disease. Am J Cardiol. 1995; 75: 53B–57B.CrossrefMedlineGoogle Scholar12 Laws A, Reaven GM. Insulin resistance and risk factors for coronary heart disease. Bailliere’s Clin Endocrinol Metab. 1993; 7: 1063–1078.CrossrefMedlineGoogle Scholar13 Haffner SM. Epidemiology of insulin resistance and its relation to coronary artery disease. Am J Cardiol. 1999; 84: 11J–14J.MedlineGoogle Scholar14 Smiley T, Oh P, Shane LG. The relationship of insulin resistance measured by reliable indexes to coronary artery disease risk factors and outcomes: a systematic review. Can J Cardiol. 2001; 17: 797–805.MedlineGoogle Scholar15 Morrow DA, Ridker PM. C-reactive protein, inflammation, and coronary risk. Med Clin North Am. 2000; 84: 149–161.CrossrefMedlineGoogle Scholar16 Blake GJ, Ridker PM. Novel clinical markers of vascular wall inflammation. Circ Res. 2001; 89: 763–771.CrossrefMedlineGoogle Scholar17 Chambers JC, Eda S, Bassett P, et al. C-reactive protein, insulin resistance, central obesity, and coronary heart disease risk in Indian Asians from the United Kingdom compared with European whites. Circulation. 2001; 104: 145–150.LinkGoogle Scholar18 Festa A, D’Agostino R Jr, Williams K, et al. The relation of body fat mass and distribution to markers of chronic inflammation. Int J Obes Relat Metab Disord. 2001; 25: 1407–1415.CrossrefMedlineGoogle Scholar19 Tchernof A, Nolan A, Sites CK, et al. Weight loss reduces C-reactive protein levels in obese postmenopausal women. Circulation. 2002; 10: 564–569.Google Scholar20 Sakkinen PA, Wahl P, Cushman M, et al. Clustering of procoagulation, inflammation, and fibrinolysis variables with metabolic factors in insulin resistance syndrome. Am J Epidemiol. 2000; 152: 897–907.CrossrefMedlineGoogle Scholar21 Mavri A, Alessi MC, Bastelica D, et al. Subcutaneous abdominal, but not femoral fat expression of plasminogen activator inhibitor-1 (PAI-1) is related to plasma PAI-1 levels and insulin-resistance and decreases after weight loss. Diabetologia. 2001; 44: 2025–2031.CrossrefMedlineGoogle Scholar22 Mertens I, Van der Planken M, Corthouts B, et al. Visceral fat is a determinant of PAI-1 activity in diabetic and non-diabetic overweight and obese women. Horm Metab Res. 2001; 33: 602–607.CrossrefMedlineGoogle Scholar23 McGill HC Jr, McMahan CA, Herderick EE, et al. Obesity and atherosclerosis in youth. Circulation. 2002: 105: 2712–2718.LinkGoogle Scholar24 Larsson B, Svardsudd K, Welin L, et al. Abdominal adipose tissue distribution, obesity and risk of cardiovascular disease and death: 13-year follow-up of participants in the study of men born in 1913. Br Med J. 1984; 288: 1401–1404.CrossrefMedlineGoogle Scholar25 McKeigue PM, Ferrie JE, Pierpoint T, et al. Association of early-onset coronary heart disease in South Asian men with glucose intolerance and by hyperinsulinemia. Circulation. 1993; 87: 152–161.CrossrefMedlineGoogle Scholar26 Dhawan J. Coronary heart disease in Asian Indians. Curr Opin Lipidol. 1996; 7: 196–198.CrossrefMedlineGoogle Scholar27 Venkatramana P, Reddy PC. Association of overall and abdominal obesity with coronary heart disease risk factors: comparison between urban and rural Indian men. Asia Pac J Clin Nutr. 2002; 11: 66–71.CrossrefMedlineGoogle Scholar28 Chandalia M, Abate N, Garg A, et al. Relationship between generalized and upper body obesity to insulin resistance in Asian Indian men. J Clin Endocrinol Metab. 1999; 84: 2329–2335.MedlineGoogle Scholar29 Miller GJ, Beckles GL, Maude GH, et al. Ethnicity and other characteristics predictive of coronary heart disease in a developing community: principal results of the St James Survey, Trinidad. Int J Epidemiol. 1989; 18: 808–817.CrossrefMedlineGoogle Scholar30 McKeigue PM. Metabolic consequences of obesity and body fat pattern: lessons from migrant studies. Ciba Found Symp. 1996; 201: 54–64.MedlineGoogle Scholar31 Chan JC, Ng MC, Critchley JA, et al. Diabetes mellitus-a special medical challenge from a Chinese perspective. Diabetes Res Clin Pract. 2001; 54 (suppl 1): S19–S27.CrossrefMedlineGoogle Scholar32 Lee J, Heng D, Chia KS, et al. Risk factors and incident coronary heart disease in Chinese, Malay and Asian Indian males: the Singapore Cardiovascular Cohort Study. Int J Epidemiol. 2001; 30: 983–988.CrossrefMedlineGoogle Scholar33 Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults. JAMA. 2002; 287: 356–359.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Béland-Bonenfant S, Paquette M, Fantino M, Bourque L, Saint-Pierre N, Baass A and Bernard S (2021) Montreal-FH-SCORE Predicts Coronary Artery Calcium Score in Patients With Familial Hypercholesterolemia, CJC Open, 10.1016/j.cjco.2020.09.007, 3:1, (41-47), Online publication date: 1-Jan-2021. Mazidi M, Kengne A, George E and Siervo M (2019) The association of red meat intake with inflammation and circulating intermediate biomarkers of type 2 diabetes is mediated by central adiposity, British Journal of Nutrition, 10.1017/S0007114519002149, 125:9, (1043-1050), Online publication date: 14-May-2021. Malik M, Malik M, Sukhera A, Khalid M, Waqas A, Qayyum W, Farooq Butt A, Baig A, Butt A and Malik F (2021) Metabolic Syndrome and Related Inflammation, Prevalence, and Predictive Value of C-Reactive Protein in South Asian Youths, Metabolic Syndrome and Related Disorders, 10.1089/met.2021.0016, 19:9, (483-490), Online publication date: 1-Nov-2021. Diaz-Canestro C and Xu A (2021) Impact of Different Adipose Depots on Cardiovascular Disease, Journal of Cardiovascular Pharmacology, 10.1097/FJC.0000000000001131, 78:6S, (S30-S39) Rinkūnienė E, Dženkevičiūtė V, Petrulionienė Ž, Majauskienė E, Ryliškytė L, Puronaitė R, Badarienė J, Navickas R and Laucevičius A (2021) Hypertriglyceridemia impact on arterial parameters in patients with metabolic syndrome, BMC Cardiovascular Disorders, 10.1186/s12872-021-02202-3, 21:1, Online publication date: 1-Dec-2021. Reinehr T (2020) Is Insulin Resistance a Treatment Target? Insulin Resistance, 10.1007/978-3-030-25057-7_17, (277-291), . Bijnen M, van de Gaar J, Vroomen M, Gijbels M, de Winther M, Schalkwijk C and Wouters K (2019) Adipose tissue macrophages do not affect atherosclerosis development in mice, Atherosclerosis, 10.1016/j.atherosclerosis.2018.12.010, 281, (31-37), Online publication date: 1-Feb-2019. Glad C, Svensson P, Nystrom F, Jacobson P, Carlsson L, Johannsson G and Andersson-Assarsson J (2018) Expression of GHR and Downstream Signaling Genes in Human Adipose Tissue—Relation to Obesity and Weight Change , The Journal of Clinical Endocrinology & Metabolism, 10.1210/jc.2018-01036, 104:5, (1459-1470), Online publication date: 1-May-2019. Morotti E, Giovanni Artini P, Persico N and Battaglia C (2019) Metformin metabolic and vascular effects in overweight/moderately obese hyperinsulinemic PCOS patients treated with contraceptive vaginal ring: a pilot study, Gynecological Endocrinology, 10.1080/09513590.2019.1613361, 35:10, (854-861), Online publication date: 3-Oct-2019. Vincent L, Leedy D, Masri S and Cheng R (2019) Cardiovascular Disease and Cancer: Is There Increasing Overlap?, Current Oncology Reports, 10.1007/s11912-019-0796-0, 21:6, Online publication date: 1-Jun-2019. Gordon S, Neufeld E, Yang Z, Pryor M, Freeman L, Fan X, Kullo I, Biesecker L and Remaley A (2019) DENND5B Regulates Intestinal Triglyceride Absorption and Body Mass, Scientific Reports, 10.1038/s41598-019-40296-0, 9:1, Online publication date: 1-Dec-2019. Li Y, Wang L, Xu J, Niu W, Shi H, Hu L, Zhang Y, Zhang M, Bao X, Zhang N and Sun Y (2019) Higher chromosomal aberration rate in miscarried conceptus from polycystic ovary syndrome women undergoing assisted reproductive treatment, Fertility and Sterility, 10.1016/j.fertnstert.2019.01.026, 111:5, (936-943.e2), Online publication date: 1-May-2019. Fisher E, Brzezinski R, Ehrenwald M, Shapira I, Zeltser D, Berliner S, Marcus Y, Shefer G, Stern N, Rogowski O, Halperin E, Rosset S and Shenhar-Tsarfaty S (2019) Increase of body mass index and waist circumference predicts development of metabolic syndrome criteria in apparently healthy individuals with 2 and 5 years follow-up, International Journal of Obesity, 10.1038/s41366-018-0312-x, 43:4, (800-807), Online publication date: 1-Apr-2019. Cheng B, Sheen L and Chang S (2018) Hypolipidemic effects of S -(+)-linalool and essential oil from Cinnamomum osmophloeum ct. linalool leaves in mice, Journal of Traditional and Complementary Medicine, 10.1016/j.jtcme.2017.02.002, 8:1, (46-52), Online publication date: 1-Jan-2018. Kandathil A, Abbara S, Hanna M, Minhajuddin A, Wehrmann L, Merchant A, Mills R and Fox A (2018) Atherosclerosis on CT Angiogram Predicts Acute Kidney Injury After Transcatheter Aortic Valve Replacement, American Journal of Roentgenology, 10.2214/AJR.17.19340, 211:3, (677-683), Online publication date: 1-Sep-2018. Tahara A, Kondo Y, Takasu T and Tomiyama H (2018) Effects of the SGLT2 inhibitor ipragliflozin on food intake, appetite-regulating hormones, and arteriovenous differences in postprandial glucose levels in type 2 diabetic rats, Biomedicine & Pharmacotherapy, 10.1016/j.biopha.2018.06.062, 105, (1033-1041), Online publication date: 1-Sep-2018. Daugherty A, Tall A, Daemen M, Falk E, Fisher E, García-Cardeña G, Lusis A, Owens A, Rosenfeld M and Virmani R (2017) Recommendation on Design, Execution, and Reporting of Animal Atherosclerosis Studies: A Scientific Statement From the American Heart Association, Arteriosclerosis, Thrombosis, and Vascular Biology, 37:9, (e131-e157), Online publication date: 1-Sep-2017.Daugherty A, Tall A, Daemen M, Falk E, Fisher E, García-Cardeña G, Lusis A, Owens A, Rosenfeld M and Virmani R (2017) Recommendation on Design, Execution, and Reporting of Animal Atherosclerosis Studies: A Scientific Statement From the American Heart Association, Circulation Research, 121:6, (e53-e79), Online publication date: 1-Sep-2017. Chun K, Im E, Kim B, Shin D, Kim J, Ko Y, Choi D, Jang Y and Hong M (2017) Incidence, Predictors, and Clinical Outcomes of New-Onset Diabetes Mellitus after Percutaneous Coronary Intervention with Drug-Eluting Stent, Journal of Korean Medical Science, 10.3346/jkms.2017.32.10.1603, 32:10, (1603), . Tune J, Goodwill A, Sassoon D and Mather K (2017) Cardiovascular consequences of metabolic syndrome, Translational Research, 10.1016/j.trsl.2017.01.001, 183, (57-70), Online publication date: 1-May-2017. Aslan M, Duzenli U, Esen R and Soyoral Y (2017) Serum prolidase enzyme activity in obese subjects and its relationship with oxidative stress markers, Clinica Chimica Acta, 10.1016/j.cca.2017.08.039, 473, (186-190), Online publication date: 1-Oct-2017. Jahan N and Shenoy S (2017) Relation of pedometer steps count & self reported physical activity with health indices in middle aged adults, Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 10.1016/j.dsx.2017.07.033, 11, (S1017-S1023), Online publication date: 1-Dec-2017. Hasin T, Iakobishvili Z and Weisz G (2017) Associated Risk of Malignancy in Patients with Cardiovascular Disease: Evidence and Possible Mechanism, The American Journal of Medicine, 10.1016/j.amjmed.2017.02.024, 130:7, (780-785), Online publication date: 1-Jul-2017. Andres A, Kooren J, Parker S, Tucker K, Ravindran N, Ito B, Huang C, Venkatraman V, Van Eyk J, Gottlieb R and Mentzer R (2016) Discordant signaling and autophagy response to fasting in hearts of obese mice: Implications for ischemia tolerance, American Journal of Physiology-Heart and Circulatory Physiology, 10.1152/ajpheart.00041.2016, 311:1, (H219-H228), Online publication date: 1-Jul-2016. Karastergiou K, Bredella M, Lee M, Smith S, Fried S and Miller K (2016) Growth hormone receptor expression in human gluteal versus abdominal subcutaneous adipose tissue: Association with body shape, Obesity, 10.1002/oby.21460, 24:5, (1090-1096), Online publication date: 1-May-2016. Dow C, Lincenberg G, Greiner J, Stauffer B and DeSouza C (2016) Endothelial vasodilator function in normal-weight adults with metabolic syndrome, Applied Physiology, Nutrition, and Metabolism, 10.1139/apnm-2016-0171, 41:10, (1013-1017), Online publication date: 1-Oct-2016. Han Y, Han H, Kim A, Choi J, Cho S, Park Y, Jung U and Choi M (2016) d -Allulose supplementation normalized the body weight and fat-pad mass in diet-induced obese mice via the regulation of lipid metabolism under isocaloric fed condition , Molecular Nutrition & Food Research, 10.1002/mnfr.201500771, 60:7, (1695-17