Study looks at hot flushes and heart risk

“Hot flushes may be a blessing,” according to The Daily Telegraph. The newspaper reported that women who experience the menopausal symptom may have a reduced risk of heart attacks and strokes.

The news is based on research that assessed menopausal symptoms, such as hot flushes and night sweats, in 60,027 US women with an average age of 63 years. The researchers followed the women for an average of 9.7 years to assess whether their symptoms were linked to their risk of heart attacks and strokes (cardiovascular events), or death due to any cause. However, the study did not provide conclusive answers, and found that the symptoms assessed were associated with either decreased or increased risk, depending on when they first occurred.

The results also conflict with some previous studies, which means that it is currently not clear whether hot flushes are an indicator of cardiovascular risk. As such, it is inappropriate at the moment to tell women who experience hot flushes that these symptoms are “a blessing” or that they have a “lower risk of heart attacks”.

Where did the story come from?

The study was carried out by researchers from several academic institutions in the US and was funded by the National Heart, Lung, and Blood Institute, the National Institutes of Health and the US Department of Health and Human Services. The study was published in Menopause, the peer-reviewed journal of The North American Menopause Society.

In general, the newspapers over-simplified the findings of this study. The study was not able to conclusively determine the predictive role that hot flushes and other “vasomotor symptoms” may have for cardiovascular disease events. Previous studies have showed them to indicate an increased risk. The current study found them to be associated with either a decreased or increased risk, depending on when the symptoms were experienced. Much further study is needed.

What kind of research was this?

This cohort study investigated the emerging theory that women with menopausal vasomotor symptoms (such as flushing) have increased cardiovascular risk. Previous studies have shown women who experience flushing to have higher blood pressure, cholesterol and body mass index (BMI), all of which are associated with an increased cardiovascular risk. The researchers also say that two major clinical trials - the Women’s Health Initiative (WHI) Hormone Therapy Clinical Trials and the Heart and Estrogen/Progestin Replacement Study – have reported an elevated risk of coronary heart disease among women who experienced hot flushes.

To gain a better understanding of the association, the researchers examined data from the ongoing WHI Observational Study (WHI-OS). This cohort study, they say, includes a larger, more-representative population of women who experience hot flushes than the WHI hormone therapy clinical trials, which excluded women with more significant vasomotor symptoms.

The objective of the current study was to investigate whether vasomotor symptoms predicted the development of cardiovascular disease events (such as a heart attack or stroke), or death from any cause. The researchers also looked at whether there was a difference between women who experienced hot flushes at the start of their menopause and women who developed them later on.

What did the research involve?

From 1994 to 1998, the WHI-OS study enrolled 93,676 women from across 40 US clinical centres. Eligible participants were postmenopausal women aged 50-79 years old, with menopause defined as either no periods for at least 12 months if participants were aged 50-54, or no periods for at least 6 months if they were 55 or over.

At the start of the study, participants completed questionnaires about their lifestyle, demographic details and medical conditions, and had body measurements and blood pressure taken. The questionnaires specifically asked:

whether they had ever been told by a doctor that they had high blood pressure, diabetes or high blood glucose
if they had high cholesterol requiring pills
if they had a family history of heart attack at a young age (over 55 years of age) in a first-degree relative

In addition, women gave details about their use of any hormone therapy (HT), and were classified as never, past or current users of HT.

Women were asked questions to assess if they had ever had vasomotor symptoms and, if so, when they first and last experienced them. They were also asked at the start of the study about the presence of vasomotor symptoms such as hot flushes or night sweats during the four weeks preceding their enrolment in the study. If symptoms were present, they were asked to rate them as mild (symptom did not interfere with usual activities), moderate (some interference with usual activities) or severe (so bothersome that usual activities could not be performed). Women were considered to have had vasomotor symptoms at the onset of menopause if their age when they first had hot flushes or night sweats was less than or equal to their age at menopause.

The study’s outcomes of interest were major coronary heart disease events (fatal or non-fatal heart attacks), any cardiovascular disease events (fatal or non-fatal heart attacks or strokes), and death from any cause. Analyses took into account various potential factors (confounders) that could affect the risk of cardiovascular disease (such as smoking, age and blood pressure).

Of the 93,676 postmenopausal women initially enrolled, 78,249 had no prior history of cardiovascular disease or cancer. Of these, 77,631 (99.2%) reported information on vasomotor symptoms at the start of the study and 60,773 (77.7%) reported information on vasomotor symptoms at the onset of menopause. The study’s analysis only included the 60,027 women who fulfilled all of these criteria.

What were the basic results?

The average age of women in this study was 63.3 years old, and they had gone through the menopause an average of 14.4 before enrolment in the study. The average (median) follow-up time of these women was 9.7 years. Of the women included, 4.3% withdrew before the end of follow-up and 6.7% died.

Of the 60,027 women analysed:

31.3% (18,799) had never experienced vasomotor symptoms
41.2% (24,753) had experienced them at the start of their menopause but they were gone by study enrolment (referred to as early symptoms)
25.1% (15,084) had had vasomotor symptoms persistently since menopause, both at the start of the menopause and at enrolment (referred to as persistent symptoms)
2.3% (1,391) did not have symptoms at start of menopause but had them at the time of enrolment (referred to as late symptoms)

Overall, the researchers reported that there was no association between having experienced vasomotor symptoms and the risk of any cardiovascular outcomes or death from any cause. However, results of these overall statistical analyses were not shown in the paper.

The researchers then separately analysed the three different groups who had vasomotor symptoms at different times. They found that, compared to women who had never experienced these symptoms:

Women who experienced early symptoms had a significantly reduced risk of any cardiovascular disease event (fatal or non-fatal heart attack or stroke, hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.81 to 0.97), stroke (HR 0.83, 95% CI 0.72 to 0.96), or death from any cause (HR 0.92, 95% CI 0.85 to 0.99). There was no significant association with major coronary heart disease events.
For women with persistent vasomotor symptoms, there was no significant association with any of the outcomes.
Women who experienced late symptoms had an increased risk of major coronary heart disease events (HR 1.32, 95% CI 1.01 to 1.71), a borderline increased risk of any cardiovascular disease event (HR 1.23, 95% CI 1.00 to 1.52), and an increased risk of death from any cause (HR 1.29, 95% CI 1.08 to 1.54). There was no significant association with stroke.

How did the researchers interpret the results?

The researchers concluded that early vasomotor symptoms were not associated with increased cardiovascular risk, but with decreased risk of stroke, total cardiovascular events, and death from any cause. However, late vasomotor symptoms were associated with increased coronary heart disease risk and death from any cause.

As such, they say that the value of vasomotor symptoms for predicting cardiovascular disease events may vary depending on the stage of menopause at which they first occurred. They say there is a need for further research to examine the mechanisms underlying these associations.

Conclusion

This research has attempted to determine whether menopausal symptoms, such as hot flushing and sweats, can predict heart attacks and strokes (cardiovascular events) and death. However, the research does not provide conclusive answers.

Previous studies have shown hot flushes to indicate increased risk of cardiovascular disease, but the current study found these symptoms to be associated with either a decreased or increased risk, depending on when they were experienced. However, when the research considered the experience of hot flushes at any time during menopause, it found no association with the risk of cardiovascular disease events. How this seemingly complex relationship works was not examined by this research and, as the authors say, much further study is required.

This study had strengths in that it included a large sample of women who did not have cardiovascular disease at start of the study. It followed them for almost 10 years. The study had a low drop-out rate, it objectively assessed a large amount of health and lifestyle data, and accounted for a large number of potential confounders.

Among the study’s limitations are its retrospective assessment of symptoms that occurred before enrolment in the study, which may potentially have been inaccurately recalled by the participants. Another limitation, acknowledged by the authors, is the difficulty in picking apart the relationship between vasomotor symptoms and use of hormone therapy, although they attempted to do this by adjusting for hormone therapy use in their analyses.

In isolation, the findings of this research suggest a potentially complex relationship between vasomotor symptoms and risk of cardiovascular disease. The results also seem to differ from other studies in this area. As such, the link between vasomotor symptoms and cardiovascular risk are unclear and still require further research. Therefore, it is inappropriate at the current time to tell women who experience hot flushes that they are "a blessing" or that they have a "lower risk of heart attacks", as some newspapers have done.

Not smoking and maintaining a healthy weight through a balanced diet and regular exercise are the best ways to maintain good cardiovascular health.