Systolic blood pressure as the mediator of the effect of early menarche on the risk of coronary artery disease: A Mendelian randomization study

Hsien-Yu Fan; Yen-Tsung Huang; Yun-Yu Chen; Justin BoKai Hsu; Hung-Yuan Li; Ta-Chen Su; Hung-Ju Lin; Kuo-Liong Chien; Yang-Ching Chen

doi:10.3389/fcvm.2022.1023355

Systolic blood pressure as the mediator of the effect of early menarche on the risk of coronary artery disease: A Mendelian randomization study

Front Cardiovasc Med. 2023 Jan 9:9:1023355. doi: 10.3389/fcvm.2022.1023355. eCollection 2022.

Authors

Hsien-Yu Fan^{1

2}, Yen-Tsung Huang^{1

3

4}, Yun-Yu Chen^{1

5

6

7

8}, Justin BoKai Hsu⁹, Hung-Yuan Li¹⁰, Ta-Chen Su¹⁰, Hung-Ju Lin¹⁰, Kuo-Liong Chien^{1

10}, Yang-Ching Chen^{2

11

12

13}

Affiliations

¹ Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan.
² Department of Family Medicine, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
³ Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
⁴ Department of Mathematics, National Taiwan University, Taipei, Taiwan.
⁵ Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
⁶ Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan.
⁷ Heart Rhythm Center, Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
⁸ Cardiovascular Research Center, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁹ Department of Computer Science and Engineering, Yuan Ze University, Taoyuan, Taiwan.
¹⁰ Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
¹¹ Department of Family Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
¹² School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan.
¹³ Graduate Institute of Metabolism and Obesity Sciences, Taipei Medical University, Taipei, Taiwan.

Abstract

Background: Menarche timing may not be directly associated with the risk of coronary artery disease (CAD). Therefore, we investigated the roles of metabolic factors in explaining the effect of age at menarche on CAD risk.

Methods: We identified women with age at menarche and CAD by using three analytical methods: Mendelian randomization (MR), logistic regression analysis, and Cox proportional hazard regression. The first two analyses were performed in the Taiwan Biobank (N = 71,923) study, and the last analysis was performed in the Chin-Shan Community Cardiovascular Cohort study (N = 1,598). We further investigated the role of metabolic factors in mediating the effect of age at menarche on CAD risk by using three complementary methods with mediation analyses.

Results: One standard deviation of earlier age at menarche was associated with a 2% higher CAD risk [odds ratio = 1.02, 95% confidence interval (CI) = 1.001-1.03] in the MR analysis, an 11% higher risk (odds ratio = 1.11, 95% CI = 1.02-1.21) in the logistic regression analysis, and a 57% higher risk (hazard ratio = 1.57, 95% CI = 1.12-2.19) in the Cox proportional hazard regression. All the analyses consistently supported the role of systolic blood pressure in mediating this effect. The MR results indicated that 29% (95% CI = 26%-32%) of the effect of genetically predicted earlier age at menarche on CAD risk was mediated by genetically predicted systolic blood pressure.

Conclusion: The results obtained using different analytical methods suggest that interventions aimed at lowering systolic blood pressure can reduce the cases of CAD attributable to earlier age at menarche.

Keywords: Mendelian randomization; cardiovascular disease; mediator; menarche age; metabolic factor.

Grants and funding

This work was supported by the Taipei Medical University Hospital (111TMUH-MOST-05) and the Ministry of Science and Technology of Taiwan (MOST 110-2628-B-038-014 and MOST 111-2628-B-038-022). The study was also supported by Taipei Medical University TMU108-AE1-B34 (PI. Yang Ching Chen).