Arterial hypertension in women: Menopause as a risk window

Abstract

Objectives

Cardiovascular diseases (CVD) exert a heavy toll on health of women, mainly due to hypertension said to cluster around the period of transition to menopause. This makes this period a good window to target for prevention and control. We therefore sought to determine if this period really heralds arterial hypertension and CVD in women in our environment.

Study design

We secondarily analysed our population data on CVD risk factors in free living rural residents.

Main outcome variables

The data considered were blood pressure, anthropometric and biochemical variables in women stratified based on menstruation status.

Results

There were 488 females, with 218 still menstruating. They were younger (p = .000), had lower systolic and diastolic blood pressures (p = .000), lower anthropometric indices attaining significance only with waist circumference (p = .001) and lower total cholesterol (p = .001). Controlling for age, statistically significant differences remained for systolic and diastolic blood pressures, body mass index, waist and hip circumferences, and total cholesterol.

Conclusion

The menopause transition comes with a worse CVD profile. Blood pressure rises and so are the anthropometric variables and some biochemical parameters that fuel CVD. This could be ascribed to age which is higher with those post-menopausal. Controlling for age in this cohort still showed that transiting from pre- to post-menopause still came with CVD burden. Clinicians should take the opportunity presented by menopause transition to screen for CVD risk factors and initiate either preventive or control measures to mitigate morbi-mortality consequences.

Keywords

Hypertension menopuase transition cardiovascular diseases

Introduction

Cardiovascular disease (CVD) is the commonest cause of morbidity and mortality in women; at the centre of most of which is arterial hypertension.¹ Menopause usually brings to an end the ovarian physiology in females, heralding the loss of reproductive capability as a result of cessation of supply of ovarian follicles.² During this period in their lives, women can be particularly at high risk for CVD.³ While this lasts, about 60% of women are said to present to clinicians for consultation regarding symptoms of menopause transition. It therefore makes it an opportune time to intervene in such a manner as to optimise life style measures in minimising their risks for ageing-related diseases.³ These symptoms are broadly classified into psychological, vasomotor and somatic.⁴ Menopause has been identified as a female-specific risk factor contributing significantly to CVD.⁵ To confirm that CVD risk factors really cluster in women around the menopause so that clinicians should be on high alert to screen and manage any CVD perimenopausally, we decided to secondarily analyse data that we generated in a previous rural population study of CVD risk factors. No such study has been reported in our immediate environment, and such confirmation should modify management paradigm when women present with the so-called menopausal symptoms.

Methodology

The methods of data generation in the main study have been previously published.⁶ We secondarily analysed the generated data to be able to answer the research question posed for this communication. The Research Ethics Committee of Jos University Teaching Hospital duly approved the main study before the fieldwork was undertaken in 2008. On each of the fieldwork days, free living individuals 15 years and above were registered on arrival and had personal, social and medical histories recorded before blood was collected, 1 out of 3 in the order of arrival and registration. They all had physical examination, which included anthropometry and blood pressure estimation by standard sphygmomanometry. Blood pressure measurement utilised the ACCOSON brand mercury sphygmomanometer fixed with appropriate adult-size cuff. Field staff who were of the rank of registrars in medical residency training undertook this task after each subject had rested for 3–5 minutes They were seated without tight clothing, feet on the floor, arm resting on a table that ensured the sphygmomanometer was at the same level with the heart. Three readings were taken with about 2 minutes in-between; and the last 2 averaged for use in analysis.

In the study referred to above, we had generated data on the following: (1) whether the women were still or no longer menstruating; (2) systolic and diastolic blood pressures; (3) anthropometric indices – height and weight for body mass index (BMI) determination, waist circumference (WC) and hip circumference (HC); (4) and biochemical indices – blood glucose (BG), total cholesterol (TC) and high-density lipid cholesterol (HDL)

STATISTICS: Relevant data were analysed in the Research Support Unit of the University of Jos Computer Centre using SPSS Version 17 software. Continuous variables were expressed as mean ± SD. ANOVA tests were used to assess the association between continuous variables and menstruation status. Data were also subjected to post-hoc multiple comparison to assess the association between menstruation status and continuous variables, controlling for age. Statistical significance was set at p < .05.

Results

The study included 448 females with 218 (48.7%) still menstruating, while 230 (51.3%) were no longer menstruating. Expectedly, the mean age of those who had stopped menstruating was higher than that for those still menstruating (56.33 ± 15.91 SD vs 33.84 ± 10.43 SD). All blood pressure indices systolic (SBP) and diastolic (DBP) were significantly higher in the post-menopausal group. The other indices that were higher in the post-menopausal group were WC and TC. These are highlighted in Table 1.

Table 1.

Differences in data between menstruating and non-menstruating (menopausal) women in the studied population.

Index	Menstruating	Menopausal	p
Age (yrs)	33.84 (10.43)	56.33 (15.91)	0
SBP (mmHg)	119.40 (20.47)	141.48 (29.97)	0
DBP (mmHg)	76.14 (11.21)	83.60 (13.74)	0
BMI (kg/m²)	23.98 (5.05)	24.09 (5.02)	.814
WC (cm)	82.99 (11.47)	86.83 (11.96)	.001
HC (cm)	95.98 (10.51)	96.67 (10.52)	.483
TC (mmol/l)	4.14 (0.95)	4.68 (1.12)	.001
HDL (mmol/l)	1.32 (0.32)	1.40 (0.35)	.124
BG (mmol/l)	4.30 (0.89)	4.48 (1.09)	.237

The data in Table 1 clearly show that those who had stopped menstruating and hence post-menopausal were older, had higher abdominal fat and total cholesterol, and higher blood pressures to a statistically significant level. As is common knowledge, hypertension increases as individuals age. To control for age, we decided to divide the subjects into 3 groups along the lines recommended by Manson⁷: < 40 years (pre-menopausal), 40–45 years (peri-menopausal) and > 45 years (menopausal); making age the independent variable leaving the other indices as dependent. The following indices showed between-group differences to a statistically significant extent: SBP (0.000), DBP (0.000), BMI (0.013), WC (0.000), HC (0.001) and TC (0.004). HDL and BG did not show any between group differences (see Table 2).

Table 2.

Analysis of variance comparing indices between age groups.

Index	F	p
SBP (mmHg)	77.99	0
DBP (mmHg)	42.52	.000
BMI (kg/m²)	4.40	.013
WC (cm)	27.23	.000
HC (cm)	6.87	.001
TC (mmol/l)	5.80	.004
HDL (mmol/l)	0.16	.852
BG (mmol/l)	1.14	.323

When subjected to post multiple comparison tests, the pre-menopausal group had consistently significant lower values than those in the peri-menopausal and post-menopausal groups regarding SBP (p = .000), DBP (p = .000), BMI (p = .010), WC (p = .000) and HC p = .001). For TC, statistically significant difference was only attained when comparing the pre-menopausal (< 40 years) with post-menopausal (> 45 years) group; p = .001. HDL and BG did not show any statistically significant difference.

Discussion

The result of this study has shown that the post-menopausal women had significantly higher blood pressure indices as well as WC and TC. This would explain why they are at a particularly high risk for CVD.³ This has been shown in a few studies coming from sub-Saharan Africa.^8–10

In our study, the menopausal segment of the population was expectedly older. The corresponding variables of SBP, DBP, WC and TC were also significantly higher. These variables are known to increase with age; and age has actually been touted as the explanation of CVD burden in post-menopausal women.¹¹ However, that would be rather simplistic as menopause is known to come with several other issues capable of initiating CVD. These include hormonal perturbation of ovarian senescence.¹² Transition to menopause irrespective of age has been shown to be associated with perturbations of lipid profile, overweight/obesity and the metabolic syndrome.¹³ As posited by Coylewright et al.,¹¹ genegender and geneenvironment interactions are critical for development of hypertension in women. Menopause irrespective of age may be that environmental trigger activating genetic influences modulating hypertension in women. Menopause also comes with changes in self-esteem, body image perception and sexuality which have been correlated with psychosomatic stress of menopause.⁴ The sympathetic overdrive of this state irrespective of age can initiate the process of developing hypertension

Our study found that independent of age, the menopausal groups differed from the pre-menopausal group in all indices of blood pressure, SBP and DBP, BMI, WC, HC and TC. This implies that notwithstanding the age at which menopausal transition occurs, blood pressure starts to rise. As the oestrogen level declines with depletion of ovarian follicle supply, its associated vasodilatory effect also declines.¹⁴

Anthropometric indices of BMI, WC and HC irrespective of age also were significantly higher in the menopausal groups. Although these components of the metabolic syndrome are higher with ageing, obesity has also been shown to rise after surgical menopause.¹⁵ Even in instances where women do not gain weight post-menopausally, there is a fat re-distribution in favour of the mid-section.¹⁶ This may explain why the p value was higher for WC than HC in our study. WC measures more of visceral fat which is more atherogenic than HC; the latter of which includes sub-cutaneous fat, known to be a metabolic sink.

Menopause is known to be associated with more atherogenic shifts¹⁷ with post-menopausal women having higher TC and lower HDL.¹⁸ In our study, TC was higher in menopausal than pre-menopausal women, but there was no statistically significant difference in the levels of the protective HDL. This results in atherosclerosis which leads to increased arterial stiffness, explaining why SBP would be higher in the post-menopausal women.¹⁹ The role of hyperglycaemia in the hypertension of post-menopausal women is said to be controversial.²⁰ In our study, there was no statistically significant difference between the groups as regards blood glucose.

Our study is limited by being a one-centre study including only rural residents. This limits its external validity. Though reasonable, the number included is also a weakness. Another weakness was that we did not request if they were on concomitant medications as such was bound to affect blood pressure readings of those with a history of hypertension. This is however due to it being a secondary analysis of data generated not purposively for this interrogation. Its strength however is in including free living women not encumbered by any gynaecological pathology, as well as related menopausal status additionally to anthropometric and biochemical variables.

Conclusion

Notwithstanding that menopause is age related, age does not appear to be the only explanation for the increased CVD morbidity and mortality seen in women at menopausal transition. Multiple aetiology and contributing factors are likely to be in operation²⁰; and in the opinion of Prabakaran et al.,¹³ it is likely to be a combination of ageing and menopausal transition. This transition presents a risk window when primary and primordial prevention strategies should be put in place to mitigate the gloomy morbi-mortality statistics of women in relation to CVD.

Footnotes

Acknowledgements

The authors acknowledge the contribution of research assistants and field staff who worked very hard in the field while data were being collected. The assistance of Chief Toro of the Research Support Unit of the Computer Centre University of Jos is lavishly acknowledged.

Contributionship

All authors are in agreement with the contents of the manuscript. BNO developed the concept, data acquisition and analysis, and write up. HAA developed data acquisition and analysis. EKC developed data acquisition and analysis. IOI developed laboratory analysis of samples and data generation.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The work which data are being secondarily analysed was supported by a grant awarded by the Senate Central Research Grant Committee of University of Jos (RGC/2008/01). We are all employees of University of Jos and Jos University Teaching Hospital. BNO and HAA have received grants from Fogarty International Centre (D43TW010130) for a study unrelated to this survey and publication.

Ethical approval

The Ethics and Research Committee of Jos University Teaching Hospital approved the study.

Guarantor

The Principal Investigator, BNO, is the guarantor for this publication.

ORCID iD

Basil N Okeahialam

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