Cardiovascular disease is the leading cause of death in women at advanced age, who are affected a decade later compared to men. Cardiovascular risk factors in women are not properly investigated nor treated and events are frequently lethal. Both menopause and type 2 diabetes substantially increase cardiovascular risk in the female sex, promoting modifications on lipid metabolism and circulating lipoproteins. Lipoprotein subfractions suffer a shift after menopause towards a more atherogenic lipid profile, consisted of hypertriglyceridemia, lower levels of both total high density lipoprotein (HDL) and its subfraction HDL2, but also higher levels of HDL3 and small low-density lipoprotein particles. This review discusses the impact of diabetes and menopause to the lipid profile, challenges in lipoprotein subfractions determination and their potential contribution to the cardiovascular risk assessment in women. It is still unclear whether lipoprotein subfraction changes are a major driver of cardiometabolic risk and which modifications are predominant. Prospective trials with larger samples, methodological standardizations and pharmacological approaches are needed to clarify the role of lipoprotein subfractions determination on cardiovascular risk prediction and intervention planning in postmenopausal women, with or without DM.
Vaccarino V, Parsons L, Every NR, et al. Sex-based differences in early mortality after myocardial infarction: National Registry of Myocardial Infarction 2 participants. N Engl J Med. 1999;34:217–25. CrossRef
Cholesterol Treatment Trialists (CTT) Collaboration, Baigent C, Blackwell L, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376:1670–81. CrossRef
Schaefer EJ, Lamon-Fava S, Cohn SD, et al. Effects of age, gender, and menopausal status on plasma low density lipoprotein cholesterol and apolipoprotein B levels in the Framingham Offspring Study. J Lipid Res. 1994;35:779–92. PubMed
Li Z, McNamara JR, Fruchart JC, et al. Effects of gender and menopausal status on plasma lipoprotein subspecies and particle sizes. J Lipid Res. 1996;37:1886–96. PubMed
Berneis K, Rizzo M. LDL size: does it matter? Swiss Med Wkly. 2004;134:720–4. PubMed
Aguilar-Salinas CA, Melzer OA, Reyna LS, et al. Effects of estrogen/medrogestone therapy on the apoprotein B-containing lipoproteins in postmenopausal women with type 2 diabetes mellitus under satisfactory and non-satisfactory glycemic control. Isr Med Assoc J. 2001;3:137–43. PubMed
World Health Organization. The 10 leading causes of death in the world, 2000 and 2012. In: The top 10 causes of death. Geneva: World Health Organization; 2014. http://www.who.int/mediacentre/factsheets/fs310/en/. Accessed 09 Feb 2016.
Frink RJ. Gender gap, inflammation and acute coronary disease: are women resistant to atheroma growth? Observations at autopsy. J Invasive Cardiol. 2009;21:270–7. PubMed
National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). 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. Circulation. 2002;106(25):3143–421.
Zhijuan L, Jianxin C, Liping W, et al. Analysis of high risk factors and characteristics of coronary artery in premenopausal women with coronary artery disease. Int J Clin Exp Med. 2015;8:16488–95.
National Heart, Lung and Blood Institute. What are the signs and symptoms of heart disease? In: Heart disease in women. National Heart, Lung and Blood Institute. 2014. http:// http://www.nhlbi.nih.gov/health/health-topics/topics/hdw/signs. Accessed 09 Feb 2016.
Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC), European Association for the Study of Diabetes (EASD). ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD—summary. Diabetes Vasc Dis Res. 2014;11:133–73. CrossRef
Krauss RM, Burke DJ. Identification of multiple subclasses of plasma low density lipoproteins in normal humans. J Lipid Res. 1982;23:97–104. PubMed
Kulkarni KR, Garber DW, Marcovina SM, et al. Quantification of cholesterol in all lipoprotein classes by the VAP-II method. J Lipid Res. 1994;35:159–68. PubMed
Kulkarni KR, Marcovina SM, Krauss RM, et al. Quantification of HDL 2 and HDL 3 cholesterol by the vertical auto profile-II (VAP-II) methodology. J Lipid Res. 1997;38:2353–64. PubMed
Williams PT, Vranizan KM, Krauss RM. Correlations of plasma lipoproteins with LDL subfractions by particle size in men and women. J Lipid Res. 1992;33:765–74. PubMed
Sethi S, Brietzke E. Recent advances in lipidomics: analytical and clinical perspectives. Prostaglandins Other Lipid Mediat. 2016;27(128–129):8–16.
Lőrincz H, Katkó M, Harangi M, et al. Strong correlations between circulating chemerin levels and lipoprotein subfractions in nondiabetic obese and nonobese subjects. Clin Endocrinol. 2014;81:370–7. CrossRef
Sierra-Johnson J, Fisher RM, Romero-Corral A, et al. Concentration of apolipoprotein B is comparable with the apolipoprotein B/apolipoprotein A-I ratio and better than routine clinical lipid measurements in predicting coronary heart disease mortality: findings from a multi-ethnic US population. Eur Heart J. 2009;30:710–7. PubMedCrossRef
Anagnostis P, Stevenson JC, Crook D, et al. Effects of gender, age and menopausal status on serum apolipoprotein concentrations. Clin Endocrinol. 2016;85:733–40. CrossRef
Phan BA, Toth P. Dyslipidemia in women: etiology and management. Int J Women’s Health. 2014;6:185–94.
Campos H, Blijevens E, McNamara JR, et al. LDL particle size distribution. Results from the Framingham Offspring study. Arterioscler Thromb Vasc Biol. 1992;12:1410–9. CrossRef
Forti N, Diament J. High-density lipoproteins: metabolic, clinical, epidemiological and therapeutic intervention aspects. An update for clinicians. Arq Bras Cardiol. 2006;87:672–9. CrossRef
Razay G, Heaton KW, Bolton CH. Coronary heart disease risk factors in relation to the menopause. Q J Med. 1992;85:889–96. PubMed
Walsh BW, Li H, Sacks FM. Effects of postmenopausal hormone replacement with oral and transdermal estrogen on high density lipoprotein metabolism. J Lipid Res. 1994;35:2083–93. PubMed
Griffin B, Farish E, Walsh D, et al. Response of plasma low density lipoprotein subfractions to oestrogen replacement therapy following surgical menopause. Clin Endocrinol. 1993;39:463–8. CrossRef
Vieira JLC, Gomes MEW, Almeida AB, et al. Changes in the profile of lipoprotein subfractions associated with hormone replacement therapy. Arq Bras Cardiol. 2001;76:177–82.
Boardman HM, Hartley L, Eisinga A, et al. Hormone therapy for preventing cardiovascular disease in post-menopausal women. Cochrane Database Syst Rev. 1010;2015:CD002229. doi: 10.1002/14651858.
Vienberg S, Geiger J, Madsen S, et al. MicroRNAs in metabolism. Acta Physiol. 2016. doi: 10.1111/apha.12681 (Epub ahead of print).
Alonso-Magdalena P, Ropero AB, Carrera MP, et al. Pancreatic insulin content regulation by the estrogen receptor ER alpha. PLoS ONE. 2008;30(3):e2069. CrossRef
Farmer JA. Diabetic dyslipidemia and atherosclerosis: evidence from clinical trials. Curr Diabetes Rep. 2008;8:71–7. CrossRef
Haffner SM, American Diabetes Association. Management of dyslipidemia in adults with diabetes. Diabetes Care. 2003;26(S83–6):104.
Hildebrand RB, Lammers B, Meurs I, et al. Restoration of high-density lipoprotein levels by cholesteryl ester transfer protein expression in scavenger receptor class B type I (SR-BI) knockout mice does not normalize pathologies associated with SR-BI deficiency. Arterioscler Thromb Vasc Biol. 2010;30:1439–45. PubMedCrossRef
Kim C. Does menopause increase diabetes risk? Strategies for diabetes prevention in midlife women. Womens Health. 2012;8:155–67.
Russo GT, Giandalia A, Romeo EL, et al. Lipid and non-lipid cardiovascular risk factors in postmenopausal type 2 diabetic women with and without coronary heart disease. J Endocrinol Investig. 2014;37:261–8. CrossRef
Crespo CJ, Smit E, Snelling A, et al. Hormone replacement therapy and its relationship to lipid and glucose metabolism in diabetic and nondiabetic postmenopausal women: results from the Third National Health and Nutrition Examination Survey (NHANES III). Diabetes Care. 2002;25:1675–80. PubMedCrossRef
Lilley SH, Spivey JM, Vadlamudi S, et al. Lipid and lipoprotein responses to oral combined hormone replacement therapy in normolipemic obese women with controlled type 2 diabetes mellitus. J Clin Pharmacol. 1998;38:1107–15. PubMed
Xu Y, Lin J, Wang S, et al. Combined estrogen replacement therapy on metabolic control in postmenopausal women with diabetes mellitus. Kaohsjung J Med Sci. 2014;30:350–61.
- Impact of menopause and diabetes on atherogenic lipid profile: is it worth to analyse lipoprotein subfractions to assess cardiovascular risk in women?
Marília Izar Helfenstein Fonseca
Isis Tande da Silva
Sandra Roberta G. Ferreira
- BioMed Central
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