Research Article| Volume 122, ISSUE 7, P1161-1168, October 01, 2018

Serial Studies in Subclinical Atherosclerosis During Menopausal Transition (from the Study of Women's Health Across the Nation)

      Cardiovascular disease risk increases in women after the menopausal transition; why this inflection point occurs remains uncertain. We aimed to characterize the influence of menopause on vascular aging by prospective assessment of change in indexes of subclinical atherosclerosis across the menopausal transition. We evaluated 411 healthy women from SWAN Heart, an ancillary study of SWAN (Study of Women's Health Across the Nation), for subclinical atherosclerosis at baseline and again after an average of 2.3 years. Carotid intima-media thickness and aortic pulse wave velocity were measured by ultrasound. Coronary artery calcium scores were obtained by computed tomography. Women were grouped by menopausal status as premenopausal, postmenopausal, or having undergone the transition during follow-up. Analyses of changes were adjusted for age at baseline and time between scans. Mean age at baseline was 51 ± 3 years; 93 (23%) subjects transitioned to menopause (Pre-Post), 147 (36%) remained premenopausal (Pre-Pre), while 171 (41%) were postmenopausal at baseline (Post-Post). Blood pressure readings did not differ between groups with similar increase noted in carotid intima-media thickness and log coronary artery calcium + 1 from baseline to follow-up. Change in aortic pulse wave velocity from baseline to follow-up was higher in Pre-Post (121 ± 23 cm/s) compared with Pre-Pre (38 ± 250 cm/s, p = 0.029) and Post-Post (41 ± 228 cm/s, p = 0.045). In conclusion, changes in aortic stiffness were more sensitive measures of perimenopausal vascular aging than morphologic indexes of subclinical atherosclerosis in women undergoing the menopausal transition. Serial assessment of such changes could potentially elucidate mechanisms of disease and identify women to target for aggressive lifestyle risk factor modification.
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      1. Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, Ferranti SD De, Floyd J, Fornage M, Gillespie C, Isasi CR, Jim'nez MC, Jordan LC, Judd SE, Lackland D, Lichtman JH, Lisabeth L, Liu S, Longenecker CT, MacKey RH, Matsushita K, Mozaffarian D, Mussolino ME, Nasir K, Neumar RW, Palaniappan L, Pandey DK, Thiagarajan RR, Reeves MJ, Ritchey M, Rodriguez CJ, Roth GA, Rosamond WD, Sasson C, Towfghi A, Tsao CW, Turner MB, Virani SS, Voeks JH, Willey JZ, Wilkins JT, Wu JHY, Alger HM, Wong SS, Muntner P. Heart Disease and Stroke Statistics’2017 Update: A Report from the American Heart Association. 2017.

        • Colditz GA
        • Willett WC
        • Stampfer MJ
        • Rosner B
        • Speizer FE
        • Hennekens CH
        Menopause and the risk of coronary heart disease in women.
        N Engl J Med. 1987; 316: 1105-1110
        • Mondul AM
        • Rodriguez C
        • Jacobs EJ
        • Calle EE
        Age at natural menopause and cause-specific mortality.
        Am J Epidemiol. 2005; 162: 1089-1097
        • Howard B V.
        • Kuller L
        • Langer R
        • Manson JAE
        • Allen C
        • Assaf A
        • Cochrane BB
        • Larson JC
        • Lasser N
        • Rainford M
        • Van HornL
        • Stefanick ML
        • Trevisan M.
        Risk of cardiovascular disease by hysterectomy status, with and without oophorectomy: the women's health initiative observational study.
        Circulation. 2005; 111: 1462-1470
        • Atsma F
        • Bartelink M-LEL
        • Grobbee DE
        • van der Schouw YT
        Postmenopausal status and early menopause as independent risk factors for cardiovascular disease: a meta-analysis.
        Menopause. 2006; 13: 265-279
        • Sowers M
        • Crawford SL
        • Sternfeld B
        • Morganstein D
        • Gold EB
        • Greendale GA
        • Evans D
        • Neer R
        • Matthews K
        • Sherman S
        • Lo A
        • Weiss G
        • Kelsey J
        SWAN: a multicenter, multiethnic, community-based cohort study of women and the menopausal transition.
        Menopause. 2000; (ISBN 0124537901, 9780124537903): 175-188
        • Wildman RP
        • Colvin AB
        • Powell LH
        • a MatthewsK
        • Everson-Rose SA
        • Hollenberg S
        • Johnston JM
        • Sutton-Tyrrell K
        Associations of endogenous sex hormones with the vasculature in menopausal women: the Study of Women's Health Across the Nation (SWAN).
        Menopause. 2008; 15: 414-421
        • El KhoudarySR
        • RP Wildman
        • Matthews K
        • Thurston RC
        • Bromberger JT
        • Sutton-Tyrrell K
        Progression rates of carotid intima-media thickness and adventitial diameter during the menopausal transition.
        Menopause. 2013; 20: 8-14
        • El KhoudarySR
        • KJ Shields
        • Janssen I
        • Budoff MJ
        • Everson-Rose SA
        • Powell LH
        • Matthews KA
        Postmenopausal women with greater paracardial fat have more coronary artery calcification than premenopausal women: the Study of Women's Health Across the Nation (SWAN) cardiovascular fat ancillary study.
        J Am Heart Assoc. 2017; 6: e004545
        • Sutton-Tyrrell K
        • Mackey RH
        • Holubkov R
        • Vaitkevicius P V.
        • Spurgeon HA
        • Lakatta EG
        Measurement variation of aortic pulse wave velocity in the elderly.
        Am J Hypertens. 2001; 14: 463-468
        • Birru MS
        • Matthews KA
        • Thurston RC
        • Brooks MM
        • Ibrahim S
        • Barinas-Mitchell E
        • Janssen I
        • Sutton-Tyrrell K
        African-American ethnicity and cardiovascular risk factors are related to aortic pulse-wave velocity progression.
        Am J Hypertens. 2011; 24: 809-815
        • Janssen I
        • Powell LH
        • Jasielec MS
        • Matthews KA
        • Hollenberg SM
        • Sutton-Tyrrell K
        • Everson-Rose SA
        Progression of coronary artery calcification in black and white women: do the stresses and rewards of multiple roles matter?.
        Ann Behav Med. 2011; 43: 39-49
        • Wang NC
        • Matthews KA
        • Barinas-Mitchell EJM
        • Chang CCH
        • El KhoudarySR
        Inflammatory/hemostatic biomarkers and coronary artery calcification in midlife women of African-American and white race/ethnicity: the Study of Women's Health Across the Nation (SWAN) heart study.
        Menopause. 2016; 23: 653-661
        • Hansen TW
        • Staessen JA
        • Torp-Pedersen C
        • Rasmussen S
        • Thijs L
        • Ibsen H
        • Jeppesen J
        Prognostic value of aortic pulse wave velocity as index of arterial stiffness in the general population.
        Circulation. 2006; 113: 664-670
        • Covic A
        • Siriopol D
        Pulse wave velocity ratio: the new “gold standard” for measuring arterial stiffness.
        Hypertension. 2015; 65: 289-290
        • Suzuki H
        • Kondo K
        Pulse wave velocity in postmenopausal women.
        Pulse (Basel, Switzerland). 2013; 1: 4-13
        • O'Neill SM
        • Liu J
        • O'Rourke MF
        • Khoo SK
        The menopausal transition does not appear to accelerate age-related increases in arterial stiffness.
        Climacteric. 2013; 16: 62-69
        • Zaydun G
        • Tomiyama H
        • Hashimoto H
        • Arai T
        • Koji Y
        • Yambe M
        • Motobe K
        • Hori S
        • Yamashina A
        Menopause is an independent factor augmenting the age-related increase in arterial stiffness in the early postmenopausal phase.
        Atherosclerosis. 2006; 184: 137-142
        • Woodring JH
        • West JW
        Coronary artery calcification identified by CT in patients over forty years of age.
        Australas Radiol. 1989; 33: 79-83
        • Foley PWX
        • Hamaad A
        • El-Gendi H
        • Leyva F
        Incidental cardiac findings on computed tomography imaging of the thorax.
        BMC Res Notes. 2010; 3: 326
      2. Bild DE, Folsom AR, Lowe LP, Sidney S, Kiefe C, Westfall AO, Zheng Z, Rumberger J. Prevalence and Correlates of Coronary Calcification in Black and White Young Adults. 2001.

        • McClelland RL
        • Chung H
        • Detrano R
        • Post W
        • Kronmal RA
        Distribution of coronary artery calcium by race, gender, and age: results from the Multi-Ethnic Study of Atherosclerosis (MESA).
        Circulation. 2006; 113: 30-37
        • Kral BG
        • Becker LC
        • Vaidya D
        • Yanek LR
        • Qayyum R
        • Zimmerman SL
        • Dey D
        • Berman DS
        • Moy TF
        • Fishman EK
        • Becker DM
        Noncalcified coronary plaque volumes in healthy people with a family history of early onset coronary artery disease.
        Circ Cardiovasc Imaging. 2014; 7: 446-453
        • Rodriguez K
        • Kwan AC
        • Lai S
        • Lima JAC
        • Vigneault D
        • Sandfort V
        • Pattanayak P
        • Ahlman MA
        • Mallek M
        • Sibley CT
        • Bluemke DA
        Coronary plaque burden at coronary CT angiography in asymptomatic men and women.
        Radiology. 2015; 277: 73-80
        • Johnson BD
        • Dwyer KM
        • Stanczyk FZ
        • Bittner V
        • Berga SL
        • Braunstein GD
        • Azziz R
        • Yang YC
        • Hale GE
        • Bairey Merz CN
        The relationship of menopausal status and rapid menopausal transition with carotid intima-media thickness progression in women: a report from the Los Angeles atherosclerosis study.
        J Clin Endocrinol Metab. 2010; 95: 4432-4440
        • Folsom AR
        • Kronmal RA
        • Detrano RC
        • O'Leary DH
        • Bild DE
        • Bluemke DA
        • Budoff MJ
        • Liu K
        • Shea S
        • Szklo M
        • Tracy RP
        • Watson KE
        • Burke GL
        Coronary artery calcification compared with carotid intima-media thickness in the prediction of cardiovascular disease incidence: the Multi-Ethnic Study of Atherosclerosis (MESA).
        Arch Intern Med. 2008; 168: 1333-1339
        • Gepner AD
        • Young R
        • Delaney JA
        • Tattersall MC
        • Blaha MJ
        • Post WS
        • Gottesman RF
        • Kronmal R
        • Budoff MJ
        • Burke GL
        • Folsom AR
        • Liu K
        • Kaufman J
        • Stein JH
        Comparison of coronary artery calcium presence, carotid plaque presence, and carotid intima-media thickness for cardiovascular disease prediction in the Multi-Ethnic Study of Atherosclerosis.
        Circ Cardiovasc Imaging. 2015; 8e002262
        • Jensen J
        • Nilas L
        • Christiansen C
        Influence of menopause on serum lipids and lipoproteins.
        Maturitas. 1990; 12: 321-331
        • Matthews KA
        • Crawford SL
        • Chae CU
        • Everson-Rose SA
        • Sowers MF
        • Sternfeld B
        • Sutton-Tyrrell K
        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: 2366-2373