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. 2023 Aug 1;30(8):956-978.
doi: 10.5551/jat.63592. Epub 2022 Oct 5.

Female Reproductive Events and Subclinical Atherosclerosis of the Brain and Carotid Arteriopathy: the Ohasama Study

Wakana Sato  1 , Kyoko Nomura  2   3 , Michihiro Satoh  4   5 , Azusa Hara  6 , Megumi Tsubota-Utsugi  3 , Takahisa Murakami  4   5   7 , Kei Asayama  3   8 , Yukako Tatsumi  3 , Yuki Kobayashi  2 , Takuo Hirose  9 , Ryusuke Inoue  10 , Tomoko Totsune  11 , Masahiro Kikuya  3   8 , Atsushi Hozawa  5 , Hirohito Metoki  4   5   8 , Yutaka Imai  8 , Hiroyuki Watanabe  1 , Takayoshi Ohkubo  3   8
Affiliations

Female Reproductive Events and Subclinical Atherosclerosis of the Brain and Carotid Arteriopathy: the Ohasama Study

Wakana Sato et al. J Atheroscler Thromb. .

Abstract

Aims: Few studies have investigated the subclinical atherosclerotic changes in the brain and carotid artery, and in East Asian populations. We sought to investigate whether gravidity, delivery, the age at menarche and menopause and estrogen exposure period are associated with subclinical atherosclerosis of the brain and carotid arteriopathy.

Methods: This cross-sectional study formed part of a cohort study of Ohasama residents initiated in 1986. Brain atherosclerosis and carotid arteriopathy were diagnosed as white matter hyperintensity (WMH) and lacunae evident on brain magnetic resonance imaging (MRI) and carotid intimal media thickness (IMT) or plaque revealed by ultrasound, respectively. The effect of the reproductive events on brain atherosclerosis and carotid arteriopathy was investigated using logistic regression and general linear regression models after adjusting for covariates.

Results: Among 966 women aged ≥ 55 years in 1998, we identified 622 and 711 women (mean age: 69.2 and 69.7 years, respectively) who underwent either MRI or carotid ultrasound between 1992-2008 or 1993-2018, respectively. The highest quartile of gravidity (≥ 5 vs. 3) and delivery (≥ 4 vs. 2), and the highest and second highest (3 vs. 2) quartiles of delivery were associated with an increased risk of WMH and carotid artery plaque, respectively. Neither of age at menarche, menopause, and estrogen exposure period estimated by subtracting age at menarche from age at menopause was associated with atherosclerotic changes of brain and carotid arteries.

Conclusions: Higher gravidity and delivery are associated with subclinical atherosclerosis of the brain and carotid plaque.

Keywords: Carotid plaque; Delivery; Gravidity; Lacunar; Menarche; Menopause; Plaque; Reproductive events; White matter hyperintensity.

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Conflict of interest statement

H.M., K.A., Y.I., and T.O. concurrently held the position of director of the Tohoku Institute for Management of Blood Pressure and were supported by Omron Healthcare Co., Ltd. K.A. and T.O. received a joint research grant from Omron Healthcare Co., Ltd.

Figures

Fig.1. Unadjusted measures of brain atherosclerosis and carotid arteriopathy across the five reproductive events
Fig.1. Unadjusted measures of brain atherosclerosis and carotid arteriopathy across the five reproductive events
The quartiles of gravidity appeared to linearly increase with the proportions of WMH and plaque lesions, and mean IMT. The quartiles of delivery appeared to linearly increase with the proportions of lacunar, WMH, and plaque lesions. The quartiles of age at menarche appeared to linearly increase with the proportions of WMH and plaque lesions, and mean IMT.
Fig.2. Adjusted odds ratios and 95% confidence intervals of the effects of gravidity, delivery, and age at menarche and menopause on brain and carotid arteriopathy
Fig.2. Adjusted odds ratios and 95% confidence intervals of the effects of gravidity, delivery, and age at menarche and menopause on brain and carotid arteriopathy
The highest quartiles of gravidity and delivery were associated with an increased risk of WMH (B). The highest quartiles of gravidity and delivery and the second highest quartile of delivery were associated with an increased risk of plaque lesions (C).
See this image and copyright information in PMC

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