Diabetes Metab J.  2021 Jul;45(4):492-501. 10.4093/dmj.2020.0262.

Management of Cardiovascular Risk in Perimenopausal Women with Diabetes

• Kim C

• KMID: 2518891
• DOI: http://doi.org/10.4093/dmj.2020.0262

Abstract

Cardiovascular disease is the primary cause of mortality in women and men with diabetes. Due to age and worsening of risk factors over the menopausal transition, risk of coronary heart disease events increases in postmenopausal women with diabetes. Randomized studies have conflicted regarding the beneficial impact of estrogen therapy upon intermediate cardiovascular disease markers and events. Therefore, estrogen therapy is not currently recommended for indications other than symptom management. However, for women at low risk of adverse events, estrogen therapy can be used to minimize menopausal symptoms. The risk of adverse events can be estimated using risk engines for the calculation of cardiovascular risk and breast cancer risk in conjunction with screening tools such as mammography. Use of estrogen therapy, statins, and anti-platelet agents can be guided by such calculators particularly for younger women with diabetes. Risk management remains focused upon lifestyle behaviors and achieving optimal levels of cardiovascular risk factors, including lipids, glucose, and blood pressure. Use of pharmacologic therapies to address these risk factors, particularly specific hypoglycemic agents, may provide some additional benefit for risk prevention. The minimal benefit for women with limited life expectancy and risk of complications with intensive therapy should also be considered.

Keyword

Cardiovascular diseases; Coronary diseases; Diabetes mellitus; Heart disease risk factors

Figure

• 

  Fig. 1. Menopausal- and age-related changes in visceral adiposity and endothelial dysfunction, along with increased risk of depression, vasomotor symptoms and sleep disturbances, increase risk of coronary heart disease and stroke in midlife women.

• 

Reference

1. Matthews KA, Gibson CJ, El Khoudary SR, Thurston RC. Changes in cardiovascular risk factors by hysterectomy status with and without oophorectomy: study of Women’s Health Across the Nation. J Am Coll Cardiol. 2013; 62:191–200.

2. Manson JE. The Kronos Early Estrogen Prevention Study by Charlotte Barker. Womens Health (Lond). 2013; 9:9–11.

3. Hodis HN, Mack WJ, Henderson VW, Shoupe D, Budoff MJ, Hwang-Levine J, et al. Vascular effects of early versus late postmenopausal treatment with estradiol. N Engl J Med. 2016; 374:1221–31.

4. de Villiers TJ, Hall JE, Pinkerton JV, Perez SC, Rees M, Yang C, et al. Revised global consensus statement on menopausal hormone therapy. Maturitas. 2016; 91:153–5.

5. Park CY, Lim JY, Park HY. Age at natural menopause in Koreans: secular trends and influences thereon. Menopause. 2018; 25:423–9.

6. Harlow SD, Gass M, Hall JE, Lobo R, Maki P, Rebar RW, et al. Executive summary of the Stages of Reproductive Aging Workshop +10: addressing the unfinished agenda of staging reproductive aging. J Clin Endocrinol Metab. 2012; 97:1159–68.

7. Guthrie JR, Dennerstein L, Dudley EC. Weight gain and the menopause: a 5-year prospective study. Climacteric. 1999; 2:205–11.

8. Tchernof A, Desmeules A, Richard C, Laberge P, Daris M, Mailloux J, et al. Ovarian hormone status and abdominal visceral adipose tissue metabolism. J Clin Endocrinol Metab. 2004; 89:3425–30.

9. Hong SC, Yoo SW, Cho GJ, Kim T, Hur JY, Park YK, et al. Correlation between estrogens and serum adipocytokines in premenopausal and postmenopausal women. Menopause. 2007; 14:835–40.

10. Carr MC. The emergence of the metabolic syndrome with menopause. J Clin Endocrinol Metab. 2003; 88:2404–11.

11. Moreau KL, Hildreth KL, Meditz AL, Deane KD, Kohrt WM. Endothelial function is impaired across the stages of the menopause transition in healthy women. J Clin Endocrinol Metab. 2012; 97:4692–700.

12. Hage FG, Oparil S. Ovarian hormones and vascular disease. Curr Opin Cardiol. 2013; 28:411–6.

13. Bromberger JT, Kravitz HM, Chang YF, Cyranowski JM, Brown C, Matthews KA. Major depression during and after the menopausal transition: Study of Women’s Health Across the Nation (SWAN). Psychol Med. 2011; 41:1879–88.

14. Thurston RC, Joffe H. Vasomotor symptoms and menopause: findings from the Study of Women’s Health across the Nation. Obstet Gynecol Clin North Am. 2011; 38:489–501.

15. Matthews KA, Crawford SL, Chae CU, Everson-Rose SA, Sowers MF, Sternfeld B, et al. Are changes in cardiovascular disease risk factors in midlife women due to chronological aging or to the menopausal transition? J Am Coll Cardiol. 2009; 54:2366–73.

16. Kim C, Harlow SD, Zheng H, McConnell DS, Randolph JF Jr. Changes in androstenedione, dehydroepiandrosterone, testosterone, estradiol, and estrone over the menopausal transition. Womens Midlife Health. 2017; 3:9.

17. Zhou H, Zhang C, Ni J, Han X. Prevalence of cardiovascular risk factors in non-menopausal and postmenopausal inpatients with type 2 diabetes mellitus in China. BMC Endocr Disord. 2019; 19:98.

18. Emerging Risk Factors Collaboration, Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet. 2010; 375:2215–22.

19. Adler AI, Stratton IM, Neil HA, Yudkin JS, Matthews DR, Cull CA, et al. Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study. BMJ. 2000; 321:412–9.

20. Turner RC, Millns H, Neil HA, Stratton IM, Manley SE, Matthews DR, et al. Risk factors for coronary artery disease in noninsulin dependent diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS: 23). BMJ. 1998; 316:823–8.

21. Cowie CC, Casagrande SS, Menke A, Cissell MA, Eberhardt MS, Meigs JB, et al. Diabetes in America. 3rd ed. Bethesda: National Institutes of Health;2018. . Chapter 18, Heart disease and diabetes. Available from: https://www.ncbi.nlm.nih.gov/books/NBK568001.

22. The NAMS 2017 Hormone Therapy Position Statement Advisory Panel. The 2017 hormone therapy position statement of The North American Menopause Society. Menopause. 2017; 24:728–53.

23. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA. 2002; 288:321–33.

24. Sprague BL, Trentham-Dietz A, Cronin KA. A sustained decline in postmenopausal hormone use: results from the National Health and Nutrition Examination Survey, 1999-2010. Obstet Gynecol. 2012; 120:595–603.

25. Marjoribanks J, Farquhar C, Roberts H, Lethaby A, Lee J. Longterm hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev. 2017; 1:CD004143.

26. Margolis KL, Bonds DE, Rodabough RJ, Tinker L, Phillips LS, Allen C, et al. Effect of oestrogen plus progestin on the incidence of diabetes in postmenopausal women: results from the Women’s Health Initiative Hormone Trial. Diabetologia. 2004; 47:1175–87.

27. Howard BV, Hsia J, Ouyang P, Van Voorhees L, Lindsay J, Silverman A, et al. Postmenopausal hormone therapy is associated with atherosclerosis progression in women with abnormal glucose tolerance. Circulation. 2004; 110:201–6.

28. Ferrara A, Quesenberry CP, Karter AJ, Njoroge CW, Jacobson AS, Selby JV, et al. Current use of unopposed estrogen and estrogen plus progestin and the risk of acute myocardial infarction among women with diabetes: the Northern California Kaiser Permanente Diabetes Registry, 1995-1998. Circulation. 2003; 107:43–8.

29. Grodstein F, Clarkson TB, Manson JE. Understanding the divergent data on postmenopausal hormone therapy. N Engl J Med. 2003; 348:645–50.

30. Manson JE, Chlebowski RT, Stefanick ML, Aragaki AK, Rossouw JE, Prentice RL, et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women’s Health Initiative randomized trials. JAMA. 2013; 310:1353–68.

31. Harman SM, Black DM, Naftolin F, Brinton EA, Budoff MJ, Cedars MI, et al. Arterial imaging outcomes and cardiovascular risk factors in recently menopausal women: a randomized trial. Ann Intern Med. 2014; 161:249–60.

32. Schierbeck LL, Rejnmark L, Tofteng CL, Stilgren L, Eiken P, Mosekilde L, et al. Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial. BMJ. 2012; 345:e6409.

33. Tepper PG, Randolph JF Jr, McConnell DS, Crawford SL, El Khoudary SR, Joffe H, et al. Trajectory clustering of estradiol and follicle-stimulating hormone during the menopausal transition among women in the Study of Women’s Health across the Nation (SWAN). J Clin Endocrinol Metab. 2012; 97:2872–80.

34. Jung KJ, Jang Y, Oh DJ, Oh BH, Lee SH, Park SW, et al. The ACC/AHA 2013 pooled cohort equations compared to a Korean Risk Prediction Model for atherosclerotic cardiovascular disease. Atherosclerosis. 2015; 242:367–75.

35. Coleman RL, Stevens RJ, Retnakaran R, Holman RR. Framingham, SCORE, and DECODE risk equations do not provide reliable cardiovascular risk estimates in type 2 diabetes. Diabetes Care. 2007; 30:1292–3.

36. Goff DC Jr, Lloyd-Jones DM, Bennett G, Coady S, D’Agostino RB, Gibbons R, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association task force on practice guidelines. Circulation. 2014; 129(25 Suppl 2):S49–73.

37. Yang X, Li J, Hu D, Chen J, Li Y, Huang J, et al. Predicting the 10-year risks of atherosclerotic cardiovascular disease in Chinese population: the China-PAR project (Prediction for ASCVD Risk in China). Circulation. 2016; 134:1430–40.

38. Bae JH, Moon MK, Oh S, Koo BK, Cho NH, Lee MK. Validation of risk prediction models for atherosclerotic cardiovascular disease in a prospective Korean community-based cohort. Diabetes Metab J. 2020; 44:458–69.

39. Rossouw JE, Prentice RL, Manson JE, Wu L, Barad D, Barnabei VM, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA. 2007; 297:1465–77.

40. Kim DY, Park HL. Breast cancer risk prediction in Korean women: review and perspectives on personalized breast cancer screening. J Breast Cancer. 2020; 23:331–42.

41. Gail MH, Brinton LA, Byar DP, Corle DK, Green SB, Schairer C, et al. Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst. 1989; 81:1879–86.

42. Min JW, Chang MC, Lee HK, Hur MH, Noh DY, Yoon JH, et al. Validation of risk assessment models for predicting the incidence of breast cancer in Korean women. J Breast Cancer. 2014; 17:226–35.

43. Park B, Ma SH, Shin A, Chang MC, Choi JY, Kim S, et al. Korean risk assessment model for breast cancer risk prediction. PLoS One. 2013; 8:e76736.

44. Salpeter SR, Walsh JM, Ormiston TM, Greyber E, Buckley NS, Salpeter EE. Meta-analysis: effect of hormone-replacement therapy on components of the metabolic syndrome in postmenopausal women. Diabetes Obes Metab. 2006; 8:538–54.

45. Al-Delaimy WK, Manson JE, Solomon CG, Kawachi I, Stampfer MJ, Willett WC, et al. Smoking and risk of coronary heart disease among women with type 2 diabetes mellitus. Arch Intern Med. 2002; 162:273–9.

46. Clair C, Rigotti NA, Porneala B, Fox CS, D’Agostino RB, Pencina MJ, et al. Association of smoking cessation and weight change with cardiovascular disease among adults with and without diabetes. JAMA. 2013; 309:1014–21.

47. Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray GA, Harsha D, et al. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. N Engl J Med. 2001; 344:3–10.

48. Hu FB, Stampfer MJ, Solomon C, Liu S, Colditz GA, Speizer FE, et al. Physical activity and risk for cardiovascular events in diabetic women. Ann Intern Med. 2001; 134:96–105.

49. Hu G, Jousilahti P, Barengo NC, Qiao Q, Lakka TA, Tuomilehto J. Physical activity, cardiovascular risk factors, and mortality among Finnish adults with diabetes. Diabetes Care. 2005; 28:799–805.

50. Look AHEAD Research Group, Wing RR, Bolin P, Brancati FL, Bray GA, Clark JM, et al. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med. 2013; 369:145–54.

51. American Diabetes Association. 10. Cardiovascular disease and risk management: standards of medical care in diabetes-2020. Diabetes Care. Diabetes Care. 2020; 43(Suppl 1):S111–34.

52. Kunutsor SK, Seidu S, Khunti K. Aspirin for primary prevention of cardiovascular and all-cause mortality events in diabetes: updated meta-analysis of randomized controlled trials. Diabet Med. 2017; 34:316–27.

53. Hemmingsen B, Lund SS, Gluud C, Vaag A, Almdal TP, Hemmingsen C, et al. Targeting intensive glycaemic control versus targeting conventional glycaemic control for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2013; (11):CD008143.

54. Riddle MC, Gerstein HC, Holman RR, Inzucchi SE, Zinman B, Zoungas S, et al. A1C targets should be personalized to maximize benefits while limiting risks. Diabetes Care. 2018; 41:1121–4.

55. Zelniker TA, Wiviott SD, Raz I, Im K, Goodrich EL, Furtado RH, et al. Comparison of the effects of glucagon-like peptide receptor agonists and sodium-glucose cotransporter 2 inhibitors for prevention of major adverse cardiovascular and renal outcomes in type 2 diabetes mellitus. Circulation. 2019; 139:2022–31.

56. Brunstrom M, Carlberg B. Effect of antihypertensive treatment at different blood pressure levels in patients with diabetes mellitus: systematic review and meta-analyses. BMJ. 2016; 352:i717.

57. Ettehad D, Emdin CA, Kiran A, Anderson SG, Callender T, Emberson J, et al. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet. 2016; 387:957–67.

58. >Heart Outcomes Prevention Evaluation Study Investigators. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Lancet. 2000; 355:253–9.

59. Emdin CA, Rahimi K, Neal B, Callender T, Perkovic V, Patel A. Blood pressure lowering in type 2 diabetes: a systematic review and meta-analysis. JAMA. 2015; 313:603–15.