The Metabolic Syndrome
2003; Lippincott Williams & Wilkins; Volume: 108; Issue: 13 Linguagem: Inglês
10.1161/01.cir.0000089506.12223.f1
ISSN1524-4539
AutoresPeter W.F. Wilson, Scott M. Grundy,
Tópico(s)Lipoproteins and Cardiovascular Health
ResumoHomeCirculationVol. 108, No. 13The Metabolic Syndrome Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessReview ArticlePDF/EPUBThe Metabolic SyndromeA Practical Guide to Origins and Treatment: Part II Peter W.F. Wilson, MD and Scott M. Grundy, MD, PhD Peter W.F. WilsonPeter W.F. Wilson From the Framingham Heart Study of the National Heart, Lung, and Blood Institute, Boston, Mass. and Scott M. GrundyScott M. Grundy From the Framingham Heart Study of the National Heart, Lung, and Blood Institute, Boston, Mass. Originally published30 Sep 2003https://doi.org/10.1161/01.CIR.0000089506.12223.F1Circulation. 2003;108:1537–1540In this second part of discussing the components of the metabolic syndrome, we will discuss lipids and blood pressure criteria.Low HDL Cholesterol and Elevated TriglyceridesBackgroundIt is appropriate to consider jointly the effects of low HDL cholesterol (HDL-C) and high triglyceride levels as components of the metabolic syndrome (MetS). In observational studies, each of these factors is related to greater risk of coronary heart disease,1,2 and clinical trials have been undertaken to prevent outcomes.3 Persons with high triglycerides often have low HDL-C levels and small, dense LDL particles. Estrogen therapy and excessive alcohol intake may disrupt this pattern, as each may cause simultaneous increases in HDL and triglyceride levels.A variety of environmental and genetic factors have been related to HDL-C and triglyceride levels in certain populations. For instance, lower HDL-C levels are found in cigarette smokers, obese persons, inactive individuals, and those who use androgens or 17 nor-derivatives of progesterone.4,5 Genetic variants of lipoprotein lipase, hepatic lipase, cholesterol ester transfer protein, and peroxisome proliferator-activated receptors (PPAR)-α have been shown to have effects on HDL-C and triglyceride levels in populations,6–10 contributing to the development of the MetS.How Do You Make the Diagnosis?Lipid levels are best obtained in a person's usual, healthy state.11,12 Blood concentrations after a recent illness such as influenza, diarrhea, or a systemic disease accompanied by weight loss may reduce lipoprotein cholesterol levels, and physicians should be aware that it may be advisable to defer lipoprotein testing until acute illnesses have passed and the patient has recovered. A low HDL-C level (<40 mg/dL in men and 20% by Framingham scoring. Such patients will have an LDL goal <100 mg/dL. Most of the remaining patients with MetS will be at high enough risk to have an LDL goal of <130 mg/dL. If drug therapy is required to achieve the goals of therapy, the statins will represent first-line therapy.However, in many patients with MetS, statin therapy alone will not correct abnormalities in triglycerides and low HDL. Especially when the MetS occurs in high-risk patients, consideration can be given to adding a second lipid-lowering drug, eg, nicotinic acid or fibric acid. Unfortunately, the combination of statin+fibrate carries increased risk for severe myopathy. With this combination, it is prudent to avoid high doses of statins. Furthermore, clinicians should be selective in the use of combined therapy in patients at high risk. A clinical advisory reviewed selection of patients and reasonable precautions when statin therapy is used.18Blood Pressure ≥130/85 mm HgBackgroundObesity and weight gain in middle age are positively correlated with blood pressure levels and highly related to the prevalence and incidence of hypertension in the population setting.19,20 This fact, coupled with the demonstration that reduction of blood pressure to levels <130/85 mm Hg in patients with diabetes and other persons at high risk of cardiovascular disease is efficacious, has led to including high blood pressure as part of the MetS. Trials and summary reports emphasized these opinions, and data from the Hypertension Optimal Treatment (HOT) study and the recommendations of the Joint National Committee on Hypertension reflect this intensive approach.How Do You Make the Diagnosis?Diagnosis is made by standard assessment of sitting blood pressure levels in subjects at rest. Persons on treatment with blood pressure medications should be considered to have satisfied the blood pressure ≥130/85 criterion even if measured blood pressure is 40 000 patients.22,23Impaired Fasting GlucoseBackgroundAge, excess adiposity, genetic predisposition, inadequate physical activity, and other factors promote insulin resistance, and the reference method to assess the severity of the abnormality is an insulin clamp study.24,25 Other tests can be made without indwelling catheters, including options such as the frequently sampled intravenous glucose tolerance test, fasting insulin, and postprandial insulin levels after an oral glucose load. Each approach has advantages, but determination of insulin levels and insulin resistance is characteristic of research protocols and is not integral to regular clinical care. Higher levels of insulin in the fasting and postchallenge state in nondiabetic individuals have been related to an increased risk of cardiovascular disease and later T2DM in several studies.26–30How Do You Make the Diagnosis?Measures of fasting glucose are important, and in the usual outpatient setting, a fasting level 110 to 126 mg/dL on 2 occasions is considered to be impaired fasting glucose according to the criteria of the American Diabetes Association, thus fulfilling one of the diagnostic criteria for the MetS. European experts included elevated fasting insulin levels in considering diagnosis of the MetS, but only fasting glucose data have been used for American criteria. The added utility of fasting insulin, postchallenge glucose and insulin levels, and glycosylated hemoglobin levels are all active areas of research but are not considered diagnostic criteria for the MetS at the present.How Do You Treat Glucose Levels in the MetS?Most individuals with the MetS have hyperglycemia. They may not have definite impaired fasting glucose and may happen to have elevated glucose levels after eating. An improvement in lifestyle habits and certain medications may lessen the risk of progression from impaired fasting glucose to frank T2DM, and the results of 2 clinical trials completed in the past 2 years are especially important. In the first of these trials, European investigators had patients with impaired fasting glucose follow their usual lifestyle or alter their habits to reduce fat, increase fiber, and exercise regularly. After 1 year, the subjects in the lifestyle intervention group experienced a 4.2-kg weight loss (versus 0.8 kg in controls), a 5-mm Hg systolic blood pressure decrement (versus 3 mm Hg controls), a 2 mg/dL increase in HDL-C (versus a 1 mg/dL increase among controls), an 18 mg/dL decrease in triglycerides (versus a 1 mg/dL decrease in controls), and an 11% rate of new T2DM over 4 years (versus 23% in controls).30 The overall 58% (23% versus 11% absolute rates) decreased risk of new T2DM was particularly striking in this investigation. The second trial was conducted in the United States and enrolled subjects with elevated fasting and postload plasma glucose levels. The study included 3 arms of therapy: lifestyle changes, metformin, and troglitazone. The troglitazone intervention was stopped early because of liver toxicity. In comparisons with placebo users, the persons who followed the lifestyle prescription experienced a 58% lower progression rate to T2DM and the metformin users had a 31% lower development of T2DM.31SummaryThe MetS as currently defined by the ATP III panel includes 5 components. The background for their inclusion in the syndrome, measurement of the factors, and the appropriate interventions are described in this review. The factors are highly interrelated, and the utility of this diagnostic entity is under critical evaluation as new and existing data are evaluated concerning the role of the syndrome in the development of cardiovascular and metabolic outcomes.This article is Part II of a 2-part article. Part I appeared in the September 23, 2003, issue of Circulation (Circulation. 2003;108:1422–1424).This work is supported by NIH/National Heart, Lung, and Blood Institute contract N01-HC-38038; NIH grant AR/AG 41398; and a grant from Roche Laboratories.FootnotesCorrespondence to Peter W.F. Wilson, MD, Department of Cardiology, Boston University School of Medicine, 715 Albany St, Evans 204, Boston, MA 02118. E-mail [email protected] References 1 Hokanson JE, Austin MA. Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. J Cardiovasc Risk. 1996; 3: 213–219.CrossrefMedlineGoogle Scholar2 Wilson PWF, Larson MG, Castelli WP. Triglycerides, HDL-cholesterol and coronary artery disease: a Framingham update on their interrelations. Can J Cardiol. 1994; 10: 5B–9B.Google Scholar3 Rubins HB, Robins SJ, Collins D, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med. 1999; 341: 410–418.CrossrefMedlineGoogle Scholar4 Walden CE, Knopp RH, Wahl PW, et al. Sex differences in the effect of diabetes mellitus on lipoprotein triglyceride and cholesterol concentrations. N Engl J Med. 1984; 311: 953–959.CrossrefMedlineGoogle Scholar5 Wilson PWF. High-density lipoprotein, low-density lipoprotein and coronary artery disease. Am J Cardiol. 1990; 66 (suppl A): 7–10.CrossrefMedlineGoogle Scholar6 Vega GL, Clark LT, Tang A, et al. Hepatic lipase activity is lower in African American men than in white American men: effects of 5′ flanking polymorphism in the hepatic lipase gene (LIPC). J Lipid Res. 1998; 39: 228–232.CrossrefMedlineGoogle Scholar7 Gagne SE, Larson MG, Pimstone SN, et al. A common truncation variant of lipoprotein lipase (Ser447X) confers protection against coronary heart disease: the Framingham Offspring Study. Clin Genet. 1999; 55: 450–454.CrossrefMedlineGoogle Scholar8 Tai ES, Demissie S, Cupples LA, et al. Association between the PPARA L162V polymorphism and plasma lipid levels: the Framingham Offspring Study. Arterioscler Thromb Vasc Biol. 2002; 22: 805–810.LinkGoogle Scholar9 Couture P, Otvos JD, Cupples LA, et al. Absence of association between genetic variation in the promoter of the microsomal triglyceride transfer protein gene and plasma lipoproteins in the Framingham Offspring Study. Atherosclerosis. 2000; 148: 337–343.CrossrefMedlineGoogle Scholar10 Greiner DZ, Personius BE, Andrews TC. Effects of withdrawal of chronic estrogen therapy on brachial artery vasoreactivity in women with coronary artery disease. Am J Cardiol. 1999; 83: 247–249, A5.CrossrefMedlineGoogle Scholar11 Cooper GR, Myers GL, Smith J, et al. Blood lipid measurements: variations and practical utility. JAMA. 1992; 267: 1652–1660.CrossrefMedlineGoogle Scholar12 Cooper GR, Myers GL, Kimberly MM, et al. The effects of errors in lipid measurement and assessment. Curr Cardiol Rep. 2002; 4: 501–507.CrossrefMedlineGoogle Scholar13 Lobo RA, Carmina E. The importance of diagnosing the polycystic ovary syndrome. Ann Intern Med. 2000; 132: 989–993.CrossrefMedlineGoogle Scholar14 Reaven GM. Banting Lecture 1988: Role of insulin resistance in human disease. Diabetes. 1988; 37: 1595–1607.CrossrefMedlineGoogle Scholar15 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: 2486–2497.CrossrefMedlineGoogle Scholar16 Fletcher GF, Balady G, Blair SN, et al. Statement on exercise: benefits and recommendations for physical activity programs for all Americans. Circulation. 1996; 94: 857–862.CrossrefMedlineGoogle Scholar17 Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med. 2001; 345: 1583–1592.CrossrefMedlineGoogle Scholar18 Pasternak RC, Smith SC Jr, Bairey-Merz CN, et al. ACC/AHA/NHLBI Clinical Advisory on the Use and Safety of Statins. Circulation. 2002; 106: 1024–1028.LinkGoogle Scholar19 Wilson PW, D'Agostino RB, Sullivan L, et al. Overweight and obesity as determinants of cardiovascular risk: the Framingham experience. Arch Intern Med. 2002; 162: 1867–1872.CrossrefMedlineGoogle Scholar20 Wilson PW, Kannel WB, Silbershatz H, et al. Clustering of metabolic factors and coronary heart disease. Arch Intern Med. 1999; 159: 1104–1109.CrossrefMedlineGoogle Scholar21 Sowers JR, Bakris GL. Antihypertensive therapy and the risk of type 2 diabetes mellitus. N Engl J Med. 2000; 342: 969–970.CrossrefMedlineGoogle Scholar22 Selhub J, Bagley LC, Miller J, et al. B vitamins, homocysteine, and neurocognitive function in the elderly. Am J Clin Nutr. 2000; 71: 614S–620S.CrossrefMedlineGoogle Scholar23 Pasternak RC. The ALLHAT lipid lowering trial: less is less. JAMA. 2002; 288: 3042–3044.CrossrefMedlineGoogle Scholar24 Bergman RN. Lilly Lecture 1989. Toward physiological understanding of glucose tolerance: minimal-model approach. Diabetes. 1989; 38: 1512–1527.CrossrefMedlineGoogle Scholar25 Anderson RL, Hamman RF, Savage PJ, et al. Exploration of simple insulin sensitivity measurements derived from frequently sampled intravenous glucose tolerance (FSIGT) tests. The Insulin Resistance Atherosclerosis Study. Am J Epidemiol. 1995; 142: 724–732.CrossrefMedlineGoogle Scholar26 Eschwege E, Richard JL, Thibult N, et al. Coronary heart disease mortality in relation with diabetes, blood glucose and plasma insulin levels: the Paris Prospective Study, ten years later. Horm Metab Res. 1985; 15 (suppl): 41–46.Google Scholar27 Pyorala M, Miettinen H, Halonen P, et al. Insulin resistance syndrome predicts the risk of coronary heart disease and stroke in healthy middle-aged men: the 22-year follow-up results of the Helsinki Policemen Study. Arterioscler Thromb Vasc Biol. 2000; 20: 538–544.CrossrefMedlineGoogle Scholar28 Haffner SM, Stern MP, Hazuda HP, et al. Hyperinsulinemia in a population at high risk for non-insulin-dependent diabetes mellitus. N Engl J Med. 1986; 315: 220–224.CrossrefMedlineGoogle Scholar29 Haffner SM, Stern MP, Hazuda HP, et al. Cardiovascular risk factors in confirmed prediabetic individuals: does the clock for coronary heart disease start ticking before the onset of clinical diabetes? JAMA. 1990; 263: 2893–2898.CrossrefMedlineGoogle Scholar30 Tuomilehto J, Lindstrom J, Eriksson JG, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001; 344: 1343–1350.CrossrefMedlineGoogle Scholar31 Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002; 346: 393–403.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Ong K, Cochran B, Manandhar B, Thomas S and Rye K (2022) HDL maturation and remodelling, Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 10.1016/j.bbalip.2022.159119, 1867:4, (159119), Online publication date: 1-Apr-2022. Metz S, Krarup N, Bryrup T, Støy J, Andersson E, Christoffersen C, Neville M, Christiansen M, Jonsson A, Witte D, Kampmann U, Nielsen L, Jørgensen N, Karpe F, Grarup N, Pedersen O, Kilpeläinen T and Hansen T (2022) The Arg82Cys Polymorphism of the Protein Nepmucin Implies a Role in HDL Metabolism, Journal of the Endocrine Society, 10.1210/jendso/bvac034, 6:5, Online publication date: 1-May-2022. Ghizi A, de Almeida Silva M, Moraes F, da Silva C, Endringer D, Scherer R, Lenz D, de Lima E, Brasil G, Maia J, Bissoli N and de Andrade T (2021) Kefir improves blood parameters and reduces cardiovascular risks in patients with metabolic syndrome, PharmaNutrition, 10.1016/j.phanu.2021.100266, 16, (100266), Online publication date: 1-Jun-2021. Matsunaga A, Nagashima M, Yamagishi H and Saku K (2020) Variants of Lipid-Related Genes in Adult Japanese Patients with Severe Hypertriglyceridemia, Journal of Atherosclerosis and Thrombosis, 10.5551/jat.51540, 27:12, (1264-1277), Online publication date: 1-Dec-2020. Anton S, Cruz-Almeida Y, Singh A, Alpert J, Bensadon B, Cabrera M, Clark D, Ebner N, Esser K, Fillingim R, Goicolea S, Han S, Kallas H, Johnson A, Leeuwenburgh C, Liu A, Manini T, Marsiske M, Moore F, Qiu P, Mankowski R, Mardini M, McLaren C, Ranka S, Rashidi P, Saini S, Sibille K, Someya S, Wohlgemuth S, Tucker C, Xiao R and Pahor M (2020) Innovations in Geroscience to enhance mobility in older adults, Experimental Gerontology, 10.1016/j.exger.2020.111123, 142, (111123), Online publication date: 1-Dec-2020. Lamiquiz-Moneo I, Mateo-Gallego R, Fernández-Pardo J, López-Ariño C, Marco-Benedí V, Bea A, Ferraro L, Jarauta E, Cenarro A and Civeira F (2020) Glycerol kinase deficiency in adults: Description of 4 novel cases, systematic review and development of a clinical diagnostic score, Atherosclerosis, 10.1016/j.atherosclerosis.2020.10.897, 315, (24-32), Online publication date: 1-Dec-2020. Younis A, Younis A, Goldkorn R, Goldenberg I, Peled Y, Tzur B and Klempfner R (2019) The Association of Body Mass Index and 20-Year All-Cause Mortality Among Patients With Stable Coronary Artery Disease, Heart, Lung and Circulation, 10.1016/j.hlc.2018.02.015, 28:5, (719-726), Online publication date: 1-May-2019. Rippe J and Angelopoulos T (2017) The Role of Nutrition and Lifestyle in the Prevention and Treatment of Cardiovascular Disease Nutrition in Lifestyle Medicine, 10.1007/978-3-319-43027-0_7, (137-150), . Kim S, Kim M, Shim W and Park S (2017) Epicardial adipose tissue is related to cardiac function in elderly women, but not in men, Nutrition, Metabolism and Cardiovascular Diseases, 10.1016/j.numecd.2016.11.001, 27:1, (41-47), Online publication date: 1-Jan-2017. Chen H, Fajol A, Hoene M, Zhang B, Schleicher E, Lin Y, Calaminus C, Pichler B, Weigert C, Häring H, Lang F and Föller M (2016) PI3K-resistant GSK3 controls adiponectin formation and protects from metabolic syndrome, Proceedings of the National Academy of Sciences, 10.1073/pnas.1601355113, 113:20, (5754-5759), Online publication date: 17-May-2016. Lamiquiz-Moneo I, Blanco-Torrecilla C, Bea A, Mateo-Gallego R, Pérez-Calahorra S, Baila-Rueda L, Cenarro A, Civeira F and de Castro-Orós I (2016) Frequency of rare mutations and common genetic variations in severe hypertriglyceridemia in the general population of Spain, Lipids in Health and Disease, 10.1186/s12944-016-0251-2, 15:1, Online publication date: 1-Dec-2016. Hu S, Cui G, Huang J, Jiang J and Wang D (2016) An APOC3 3′UTR variant associated with plasma triglycerides levels and coronary heart disease by creating a functional miR-4271 binding site, Scientific Reports, 10.1038/srep32700, 6:1, Online publication date: 1-Dec-2016. Younis A, Younis A, Tzur B, Peled Y, Shlomo N, Goldenberg I, Fisman E, Tenenbaum A and Klempfner R (2016) Metabolic syndrome is independently associated with increased 20-year mortality in patients with stable coronary artery disease, Cardiovascular Diabetology, 10.1186/s12933-016-0466-6, 15:1, Online publication date: 1-Dec-2016. Brandão I, Ramalho S, Pinto-Bastos A, Arrojado F, Faria G, Calhau C, Coelho R and Conceição E (2015) Metabolic profile and psychological variables after bariatric surgery: association with weight outcomes, Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity, 10.1007/s40519-015-0199-7, 20:4, (513-518), Online publication date: 1-Dec-2015. Park J, Lee J and Ovbiagele B (2014) Nontraditional Serum Lipid Variables and Recurrent Stroke Risk, Stroke, 45:11, (3269-3274), Online publication date: 1-Nov-2014. Seung Won Yang and kim-jeyoung (2014) Correlation between the Stage of Change in Dance Exercise Behavior for Physical Strength, Risk Factors of Metabolic Syndrome, and Lifestyles in College Students, Official Journal of the Koeran Society of Dance Science, 10.21539/ksds.2014.31.2.251, 31:2, (251-263), Online publication date: 1-Jul-2014. Cui G, Li Z, Li R, Huang J, Wang H, Zhang L, Ding H and Wang D (2014) A Functional Variant in APOA5/A4/C3/A1 Gene Cluster Contributes to Elevated Triglycerides and Severity of CAD by Interfering With MicroRNA 3201 Binding Efficiency, Journal of the American College of Cardiology, 10.1016/j.jacc.2014.03.050, 64:3, (267-277), Online publication date: 1-Jul-2014. Satomi Y (2012) Lipidomics for Pharmaceutical Research Lipidomics, 10.1002/9783527655946.ch16, (319-328), Online publication date: 24-Oct-2012. Nagasaka R, Yamsaki T, Uchida A, Ohara K and Ushio H (2011) γ-Oryzanol recovers mouse hypoadiponectinemia induced by animal fat ingestion, Phytomedicine, 10.1016/j.phymed.2011.01.004, 18:8-9, (669-671), Online publication date: 1-Jun-2011. Codario R (2011) Obesity and the Metabolic Syndrome Type 2 Diabetes, Pre-Diabetes, and the Metabolic Syndrome, 10.1007/978-1-60327-441-8_5, (67-92), . Bocci V (2010) The Clinical Application of Ozonetherapy OZONE, 10.1007/978-90-481-9234-2_9, (97-232), . Cicero A, Derosa G, Bove M, Imola F, Borghi C and Gaddi A (2009) Psyllium improves dyslipidaemia, hyperglycaemia and hypertension, while guar gum reduces body weight more rapidly in patients affected by metabolic syndrome following an AHA Step 2 diet, Mediterranean Journal of Nutrition and Metabolism, 10.1007/s12349-009-0056-1, 3:1, (47-54), Online publication date: 1-Apr-2010. Gündogan K, Bayram F, Capak M, Tanriverdi F, Karaman A, Ozturk A, Altunbas H, Gökce C, Kalkan A and Yazıcı C (2009) Prevalence of Metabolic Syndrome in the Mediterranean Region of Turkey: Evaluation of Hypertension, Diabetes Mellitus, Obesity, and Dyslipidemia, Metabolic Syndrome and Related Disorders, 10.1089/met.2008.0068, 7:5, (427-434), Online publication date: 1-Oct-2009. Rodríguez-Morán M, Guerrero-Romero F and Rascón-Pacheco R (2009) Dietary factors related to the increase of cardiovascular risk factors in traditional Tepehuanos communities from Mexico. A 10 year follow-up study, Nutrition, Metabolism and Cardiovascular Diseases, 10.1016/j.numecd.2008.08.005, 19:6, (409-416), Online publication date: 1-Jul-2009. Hazels Mitmesser S (2009) Cardiovascular Issues Nutrition and Exercise Concerns of Middle Age, 10.1201/9781420066029.sec8, (397-413), Online publication date: 10-Mar-2009. Vlek A, van der Graaf Y, Sluman M, Moll F and Visseren F (2009) Metabolic syndrome and vascular risk in patients with peripheral arterial occlusive disease, Journal of Vascular Surgery, 10.1016/j.jvs.2008.12.070, 50:1, (61-69), Online publication date: 1-Jul-2009. Mishra S, Yadav D, Gupta M, Mishra H and Sharma P (2008) Hyperinsulinemia predisposes to NAFLD, Indian Journal of Clinical Biochemistry, 10.1007/s12291-008-0030-6, 23:2, (130-135), Online publication date: 1-Apr-2008. Garcia-Portilla M, Saiz P, Benabarre A, Sierra P, Perez J, Rodriguez A, Livianos L, Torres P and Bobes J (2008) The prevalence of metabolic syndrome in patients with bipolar disorder, Journal of Affective Disorders, 10.1016/j.jad.2007.06.002, 106:1-2, (197-201), Online publication date: 1-Feb-2008. Jiamsripong P, Mookadam M, Alharthi M, Khandheria B and Mookadam F (2008) The Metabolic Syndrome and Cardiovascular Disease: Part 2, Preventive Cardiology, 10.1111/j.1751-7141.2008.00002.x, 11:4, (223-229), Online publication date: 1-Sep-2008. Wang J, Ban M, Kennedy B, Anand S, Yusuf S, Huff M, Pollex R and Hegele R (2008) APOA5 genetic variants are markers for classic hyperlipoproteinemia phenotypes and hypertriglyceridemia, Nature Clinical Practice Cardiovascular Medicine, 10.1038/ncpcardio1326, 5:11, (730-737), Online publication date: 1-Nov-2008. Wang J, Cao H, Ban M, Kennedy B, Zhu S, Anand S, Yusuf S, Pollex R and Hegele R (2007) Resequencing Genomic DNA of Patients With Severe Hypertriglyceridemia (MIM 144650), Arteriosclerosis, Thrombosis, and Vascular Biology, 27:11, (2450-2455), Online publication date: 1-Nov-2007. Alam I, Lewis K, Stephens J and Baxter J (2007) Obesity, metabolic syndrome and sleep apnoea: all pro-inflammatory states, Obesity Reviews, 10.1111/j.1467-789X.2006.00269.x, 8:2, (119-127), Online publication date: 1-Mar-2007. Martín Timón I, Secades I and Botella Carretero J (2007) El tabaquismo, la obesidad y la distribución de la grasa corporal se asocian de manera independiente con la resistencia a la insulina y con otros factores de riesgo cardiovascular, Revista Clínica Española, 10.1157/13100221, 207:3, (107-111), Online publication date: 1-Mar-2007. Pei W, Sun Y, Lu B, Liu Q, Zhang C, Zhang J, Jia Y, Lu Z, Hui R, Liu L and Yang Y (2007) Apolipoprotein B is associated with metabolic syndrome in Chinese families with familial combined hyperlipidemia, familial hypertriglyceridemia and familial hypercholesterolemia, International Journal of Cardiology, 10.1016/j.ijcard.2006.03.045, 116:2, (194-200), Online publication date: 1-Mar-2007. Fernndez Fresnedo G, Gmez Alamillo C, C.
Referência(s)