Why do 40-year-old men die of heart attacks, but 40-year-old women don’t?

Although cardiovascular disease is the overall leading cause of death in women, it rarely occurs before menopause in women who don’t take birth control pills or smoke cigarettes. But despite the now-proven protection that higher levels of testosterone gives men against cardiovascular disease, men in their 40s still die of heart attacks. Yet pre-menopausal women of the same ages have significantly less illness such as heart attack, stroke and death from cardiovascular diseases.1

For years the focus has been on the much lower oestrogen levels that are seen after the menopause. But there’s another obvious difference between menstruating women and post-menopausal women that appears to have even more impact on cardiovascular disease risk in women: not having menstrual periods! Yes, not having monthly blood loss is actually a very real health hazard for older women. (It’s a hazard for men, too, but that’s not the main point here.) I’ll get to the ‘hows’ and ‘whys’ of why this is the case shortly, after a brief review of the extent of the problem.

One death per minute due to heart disease

In 2008 (the latest year for which complete statistics are available), more women died from cardiovascular disease than from cancer, chronic lower respiratory diseases, and Alzheimer’s disease combined. But close to 100% of these women were either post-menopausal, pre-menopausal women taking birth control pills, or smokers.  A report on heart disease and stroke statistics from the American Heart Association cited that cardiovascular disease caused about one death per minute among American women in 2008.2 As a general trend, the incidence of cardiovascular disease (CVD) and coronary heart disease (CHD) is significantly lower in women than men of similar ages.  This incidence in women lags behind men by about 10 years and the gap narrows with age.3 Differences in the incidence of cardiovascular disease between men and women have been assumed to be age related, with the loss of the hormones of the menstrual cycle long believed to be the major key turning point for women. Reduced nitric oxide-mediated vasodilation and increasingly adverse lipid profiles have also been cited as contributing factors.4,5

However, there’s more than just oestrogen and progesterone behind the differences we see in the incidence of heart disease among pre- and post-menopausal women. Thirty-two years ago, researchers reported that after hysterectomy, the risk of heart disease increased at a similar rate whether or not the ovaries (and their hormone production) had also been removed.6 This fact suggests that – independently of the ovaries and their hormonal contribution – a functioning uterus reduces women’s cardiovascular disease. And as everyone knows, the two major functions of the uterus are having babies and monthly menstrual bleeding.

Delving into data from the Framingham Study

In a 1978 publication reporting on 2,873 pre-menopausal women whose health was tracked for up to 24 years (one small part of the famous ‘Framingham Study’), it was reported that not a single one of the pre-menopausal nonsmoking women who weren’t taking patented pseudo-oestrogen and pseudo-progesterone oral contraceptives (‘birth control pills’) had a heart attack or had died or had any form of coronary heart disease.7 That’s none, 0-for-2,873, a finding never duplicated with the same number of men of the same ages.

The authors of this report wrote that changes in traditional cardiovascular risk factors could not explain the increased incidence of cardiovascular disease after menopause. Could the cessation of menstrual periods themselves, rather than hormone levels, contribute causatively to increased risk of CHD in adult women?  Another report from the Framingham Study found that women who had a hysterectomy prior to menopause had a 2.7 times higher risk (for the technically inclined, p<0.01) of new-onset coronary heart disease than pre-menopausal women of the same age, regardless of ovary removal.8

Some researchers hypothesised that decreased body iron secondary to menopause might explain these findings. But a review of research (for the technically inclined, a ‘meta analysis’) found that while seven epidemiological studies associated indicators of body iron with increased coronary heart disease risk, 18 other epidemiological studies found either a negative association or no association at all.9

Losing blood leads to better blood flow

How could monthly pre-menopausal blood loss result in lower risk for cardiovascular diseases? A report, written by a research team, led by biophysicist Marina Kameneva of the University of Pittsburgh, that focused on the differences in red blood cells in pre-menopausal women and men of the same ages, gives us a clue.10 The women’s red blood cells were a smaller proportion of total blood volume (for the technically inclined, women’s ‘haematocrits’ were lower). The women’s blood was less thick or ‘viscous’. A marker of inflammation (‘sedimentation rate’ or ‘sed rate’) was lower in the women’s blood, and the women’s blood cells were more flexible than the men’s.

Regular menstruation in pre-menopausal women can account for all these differences. During menstruation, typically between 50-100 millilitres (approximately two to four ounces) of blood or more is lost, enough to account for significantly reduced haematocrit.  While blood volume is typically 15-20% lower in women than men during their reproductive years, renewal of red blood cells after monthly blood loss results in about 80% more young red blood cells and 85% fewer old red blood cells than blood in males. These newer blood cells are more flexible and less likely to aggregate and impede blood flow, resulting in decreased blood viscosity, while older red blood cells are less flexible, more rigid, and more likely to ‘stick’ (aggregate) and clot. Increased red blood cell (RBC) aggregation and rigidity are well-documented risk factors for heart disease.11

Because men don’t naturally undergo periodic blood loss, their old red blood cells are destroyed by the body in the spleen after 100 to 120 days. This releases free haemoglobin which inhibits the blood vessel dilating effects of nitric oxide, resulting in blood vessel constriction and therefore less blood flow.12,13 Decreased nitric oxide levels are linked to hypertension and atherosclerosis.14

After menopause, when women stop menstruation their red blood cell parameters start to change, ultimately becoming virtually the same as men’s after several years. A study of 821 women ages 25 to 74 found that post-menopausal women have significantly higher haematocrit (percent of blood cells in total blood volume), significantly higher plasma and blood viscosity (thickness), as well as higher fibrinogen levels (‘fibrinogen’ is the precursor of ‘fibrin’, a major protein in blood clots) than pre-menopausal women.15

Monthly blood loss and the resulting renewal of RBCs have been shown to significantly reduce blood viscosity. Both systolic blood viscosity and diastolic viscosity (thickness of blood at highest and lowest points of blood pressure) are reduced and improved as a result of blood volume declines as well as the improved deformability of newer, younger red blood cells.  Menses in pre-menopausal women literally ‘rejuvenates’ the blood, reducing blood viscosity and improving blood flow and tissue perfusion, bringing in nutrients and removing cellular waste. The monthly rejuvenation of the blood causes formation, release and circulation of a greater proportion of younger, more deformable red blood cells. This monthly blood rejuvenation appears to be a major factor – if not the major factor – in preventing cardiovascular disease in pre-menopausal women.

Isn’t nature and creation marvellous? The same organ – the uterus – that enables a woman to bear children also protects her, with monthly menstrual periods, from dying of a heart attack or stroke until her children are grown, or almost grown!

Lower your risk of heart attack: copy nature!

This effect needn’t be limited to younger women. Even though men don’t have menstrual periods, men can donate blood. A large prospective clinical study of 2,682 middle-aged men followed for a mean of five years, showed that heart attack risk was reduced by 86% for blood donors.16 Perhaps more surprising, another large study of about 4,000 people found nonsmoking men who had given blood in the previous three years showed about half the risk of myocardial infarction or stroke as those men who had never given blood.17

Blood donation or therapeutic phlebotomy (deliberate withdrawal of a safe but significant amount of blood) will likely do the same thing as monthly menstrual periods do for younger women. New blood cells can be made ‘on demand’ at any age by both men and women, and blood withdrawal creates that demand. Since, these newer blood cells will be more flexible and less likely to clump and impede blood flow. The combination of a smaller (but still within normal) total number  of blood cells with a higher percentage of more flexible younger blood cells decreases blood viscosity significantly, considerably decreasing physical injury to blood vessel walls, one of the basic – if not the most basic – initiators of the entire atherosclerotic process.

In addition to lowering blood viscosity, periodic blood donation or therapeutic phlebotomy results in wider, more dilated blood vessels as there is less nitric-oxide-inhibiting ‘free haemoglobin’ released from the smaller population of older blood cells. Blood that flows more easily in blood vessels that are more dilated results in significantly less hypertension and atherosclerosis, as well as a significantly lower risk of death from cardiovascular disease.

Wishing you the best of health,

Dr. Jonathan V. Wright
Editor
Nutrition & Healing

Volume 7, Issue 4 – April 2013


Full references and citations for this article are available in the downloadable PDF version of the monthly Nutrition and Healing issue in which this article appears.

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