After the report that came out in 2002 from the Women’s Health Initiative (WHI) almost 80% of women who had been on Premarin and Provera stopped taking it. But as more and more women went through the menopausal change, had significant symptoms and the results of the WHI underwent interpretation and reanalysis, women and their physicians sought forms of hormone therapy (HT) that would potentially be safer and “cure” symptoms. In many instances, this involved the use of estradiol instead of Premarin (a type of estrogen that is “conjugated” and made from the urine of pregnant mares). The “new” estrogen that was often preferred was estradiol (the active estrogen that is produced by the ovary and works on the estrogen receptors in our body). It also was more acceptable, especially to vegetarians, because it is manufactured from a vegetable source. Estradiol is currently available as a pill, patch, cream or vaginal ring. And rather than use synthetic Provera, many physicians have switched to a natural progesterone which they prescribe with estrogen in order to protect the lining of the uterus in women who have not undergone hysterectomy. Has this change made a huge difference on the impact of hormone therapy on coronary heart disease mortality?

An attempt to answer this question was addressed in a recent article published in the Journal Obstetrics and Gynecology by the Department of Obstetrics and Gynecology at Helsinki University Hospital in Finland and the Nordic School of Public Health. The risk of coronary heart disease death in hormone therapy users in age-matched women were compared between the pre (1995-2001) and post ( 2002-2009) women’s WHI eras. They used a nationwide register on 290,272 women age 40 years or older who took hormone therapy. (I love the way Scandinavian countries have kept registers and medical data on their population.) The post-WHI group was given estrogen in the form of estradiol and when needed natural progesterone.

The researchers expected to find a higher coronary heart disease death risk in hormone therapy users during the pre-WHI era. But instead, the use of HT was accompanied by significant reductions in the risk of death resulting from coronary heart disease in both groups. They found that exposure to HT for one year or less was accompanied by a 29% reduction and an exposure of 1 to 8 years with the 43% reduction in the risk of coronary heart disease and death in the pre-WHI era. In the post-WHI era HT use of one year or less was associated with an 18% and an exposure of 1 to 8 years with a 54% reduction in coronary heart disease mortality. The differences are not significant. Discontinuation of HT was associated with an increased risk of cardiac death of 42% in the pre-women’s health initiative era and 31% in the post women’s health initiative era during the first post treatment year. This risk apparently vanished in further follow-up during both eras

Their conclusion was that the changes in HT use after the WHI when they were almost exclusively using estradiol and natural progesterone failed to affect coronary heart disease mortality in HT users in their nationwide study. Does this mean all women should consider hormone therapy for prevention of coronary heart disease mortality no matter what? And does the type of hormone make a difference? No … other studies have shown that hormone therapy is helpful in women who are not older than 60 and that estrogen is beneficial if a woman has healthy coronary arteries but it is probably not affective in she has atherosclerotic plaque which is far more likely to be present in the arteries of women older than 60.

So once more decision to use HT is not simple… Should we take hormones for our hearts at least initially and what it does HT do to our risk of breast cancer? (The answer is that long-term use does increase breast cancer risk). And what are the benefits of estradiol and natural progesterone versus previously prescribed forms of HT? Should hormones be taken orally or through patches, creams or vaginal inserts? How long is it safe and have positive impacts? At what age should we stop? There is no question that estrogen it is the out effective therapy for severe menopausal symptoms but it is contraindicated for some women going through the menopausal transition. All this has to be discussed with a physician who has thorough knowledge about the pros and cons of HT. There is now one more study to put into the discussion.

Most of us have heard that men over 50 should consider taking daily aspirin in order to reduce their risk of a heart attack. This recommendation was primarily based on the Physicians Health Study which showed that in the healthy men that were followed, daily aspirin decreased the incidence of first heart attack by as much as 35%. This and other studies have shown, however that “preventative aspirin” has little effect on the risk of stroke in healthy men.

Do these studies apply to women. ..can we be considered “little men”? The answer of course is no… In order to make a gender appropriate recommendation, there must be gender appropriate studies! Only male physicians were included in the Physicians Health Study. But wait, we do have a large study that examined whether aspirin afforded heart attack prevention for healthy women: The Women’s Health Study (WHS) which was reported in 2005. A recent article in the North American Menopause Society Journal reminded physicians of the results of this study and was published under the headline “Practice Pearl”. I thought it would be helpful to review this “pearl” on this week’s website.

The WHS evaluated the benefits and risks of low-dose aspirin (100 mg on alternative days) for the prevention of heart attack, stroke and cardiovascular death among 39,876 initially healthy women age 45 and older who were followed for 10 years. The study demonstrated that aspirin significantly lowered the risk of stroke by 17% and the risk of ischemic stroke (caused by a clot in a cerebral artery which shuts off blood flow to a region of the brain) by 24% in these women. But aspirin DID NOT lower the risk of heart attack or cardiovascular death in healthy women under the age of 65. Moreover, aspirin increased bleeding risks. Gastrointestinal hemorrhage requiring transfusions were 40% more common with aspirin use and there was a 24% increase in the risk of hemorrhagic stroke. The study did show heart benefits for women, but only among those who were age 65 and older. Regular aspirin use was associated with a 26% reduction in the risk of major cardiovascular events, ischemic stroke (risk reduction, 30%) and heart attack (risk reduction, 34%).

These and other studies have definitely shown that aspirin prevents further adverse cardiac events in men and women who have coronary vascular disease, especially if they have had a heart attack. But for primary prevention of heart attack i.e. use of aspirin if you are heart healthy, the study we rely on indicates that women who are under 65 should not routinely take aspirin. Older women are likely to experience a net benefit from daily low dose aspirin unless they have bleeding or allergy contraindications. Most experts would recommended doses between 81-100 mg daily.

Bottom line: Do not routinely take aspirin if you are younger than 65 for coronary protection unless you have an elevated coronary risk, have been diagnosed with coronary artery disease, or have had a heart attack or ischemic stroke. Assess your risk with your physician…diabetes, a strong family history of heart disease, smoking, hypertension and obesity may all contribute to risk.

Every once in a while I find an article in one of my journals that has information that I was not aware of and which would, most probably, also be news to my patients. Such an article appeared in the July 24 issue of JAMA. I put it aside to report at a later date, and this is that later date. (Also, I didn’t find any other great articles this week, although I must admit I spent last week in New York for a Save the Children board meeting and caught up with journal reading later than usual.) The article basically suggests that there is an increased risk of coronary heart disease (manifested by heart attack) in women who have been diagnosed with kidney stones.

The authors examined the histories of a total of 242,105 participants of whom close to 20,000 reported a history of kidney stones. The men in the study were followed for 24 years and the women for 18 years. (The former consisted of men in the Health Professionals Follow-up Study and the latter, The Nurses’ Health Study, was made up of women…I won’t deal with the gender separations in these long term studies.) The researchers found that among women with a reported history of kidney stones the risk of coronary heart disease compared to those without a history of renal stones increased by up to 48%. There was no similar increase in men.

The prevalence of kidney stones is huge, occurring in 10.6% of men and 7.1% of women. And the number of “stone sufferers” has increased since 1980. (The authors didn’t state why, but I would suggest that this may have to do with diet, weight and a change in our environment…but then we can blame so many medical problems on these factors. It’s too early to blame the government shut down!) Previous studies have found that there is an association between kidney stones and other systemic diseases such as atherosclerosis, hypertension, diabetes as well as cardiovascular disease. It’s postulated that abnormalities of calcium metabolism or it’s breakdown is partly responsible for some of these disorders. Another theory is that the initial cause for development of the stones is an injury that occurs in the small bloods vessels of the kidney which then gives rise to calcification and this in turn becomes the center for stone formation. Vascular damage also occurs in the other chronic diseases and hence the possible correlation.

I know that the minute you see this you’re going to think that you should stop your calcium intake and that this will help protect you from renal stones and from coronary vascular disease. I want to remind everyone however, that there is a certain amount of calcium that’s needed for bone formation and maintenance of bone density. In general it’s 1000 to 1200 mg a day and this amount should be either part of your diet or if necessary taken as a supplement. The calcium supplement calcium citrate has not been found to increase stone formation. As a matter of fact, in this study the researchers looked at the mean intake of calcium in women who had no kidney stones and those who had kidney stones. Those with no kidney stones had an average of between 800 and 879 mg of calcium daily whereas those who developed kidney stones ingested a lower amount, between 751 and 821 mg of calcium.

Bottom line, if you have been diagnosed with kidney stones in the past make sure you let your current physician know and get appropriate screening for coronary heart disease. (I’m going to add this, and I don’t mean for it to be totally frivolous, but couldn’t help it…” None of us want to be a stone’s throw away from a heart attack.”)

Now that I’ve reported on the article I just want to remind all my patients that the flu season is coming and we should all be getting our flu shots. We have them in the office and when you come in for a check up or a problem my nurse will be happy to give you your shot. If you are not coming in, get the flu shot at the pharmacy. This is one of the most important things you can do to insure your health over the next year.

I know this is the Fourth of July weekend and many of my patients and readers will be busy with family, barbecues and hopefully celebrating the independence of the fabulous country we live in. (And, of course, there are those wonderful sales!). But if you happen to be glancing at this website, I want to take this opportunity to indulge in a modicum of self-congratulation; a committee opinion from the American College of Obstetricians and Gynecologists was just released and it supports what I’ve been telling my patients for years; that hormone therapy does not increase coronary heart disease risk for healthy women who have recently become menopausal. What also makes this committee opinion novel is that it states that if a woman’s quality of life is diminished by menopausal symptoms past the age of 65, extended therapy may be considered. Let me repeat: The American College of Obstetricians and Gynecologists now recommends against routine discontinuation of systemic estrogen at age 65 for women who need HT to manage their vasomotor symptoms (hot flashes and night sweats).

So that’s the summary. And you can go back to your holiday celebrations. But if you want to read further here are some of the studies and facts that the committee used in its announcement:

Much of the controversy about the impact of hormone therapy (HT) on cardiovascular disease came out of the Women’ Health Initiative (WHI) and the Heart and Estrogen/progestin Study (HERS) which seemed to show an increase in heart attack and stroke in women who took hormone therapy. But more recent studies have cast doubt on some of the methodologies used. Many of the women who were in the those two studies were over the age of 63 when they started hormone therapy and already had underlying coronary heart disease, hence they had an underlying increased risk for developing heart attack and stroke, which perhaps was augmented by hormone therapy. But newer studies indicate that when hormone therapy is started at a younger age, in women aged 50 to 59, the opposite occurs. An important study used CT scans to examine the distribution of calcification (plaque) in the coronary arteries in 1064 women who were in that 50 to 59 year range. Those who took estrogen had calcium scores that were lower than women who took a placebo, moreover, those who stayed on estrogen for more than five years had a significant reduction of 40% in their calcification scores.

The committee also looked at other variables of hormone therapy that could affect cardiovascular disease. They stated that synthetic medroxyprogesterone acetate (Provera) causes constriction of blood vessels whereas natural progesterone causes the vessels to relax and therefore may have a positive effect on blood pressure. In addition, unlike synthetic progestins, natural progesterone causes little or no reduction in high density lipoprotein. (Remember, high density lipoprotein is the good cholesterol and works like a rotor router to protect vessels from plaque formation). The committee doesn’t go so far as to state that ET or HT improve cardiovascular outcomes, they simply state that the evidence is as yet insufficient. But they do say that recent evidence suggests that women in early menopause who are in good cardiovascular health are at low risk of adverse cardiovascular outcomes and should be considered candidates for estrogen therapy or combined estrogen and progesterone therapy for relief of their menopausal symptoms. And women over 65 should talk to their doctor. If their symptoms are persistent, it’s OK to consider continuing their hormone therapy.

My final summation: If you develop symptoms that make you miserable – start hormone therapy in the early years of menopause, there is no increased risk of CHD if you are healthy… and continuation beyond age 65 may be an appropriate option if your quality of life is significantly reduced by these symptoms. We still have to discuss risk- benefits (most specifically breast cancer risk…) There is no free lunch or hormone!

As I read the current medical journals, I have to make use of a new “library” of terms that refer to our bodies’ genes, RNA messengers, proteins and enzymes, not to mention the generic names of the drugs meant to impact the molecular basis of disease. But as medical knowledge becomes more “micro,” we can’t discount the macro…the need for individuals to get basic screening, diagnosis and therapy of common disorders. There is no requirement for medical ten-dollar words to understand the recent “Vital Signs” article in JAMA. It was a report by the National Center for Health Statistics at the CDC, documenting the prevalence, treatment and control of hypertension in the United States.  Here are some of the stats that they reported, which could on their own make ones blood pressure go up by at least a few points. (I’m talking systolic here…)

  • Every year, hypertension contributes to one out of seven deaths in the U.S. and tonearly half of all cardiovascular disease-related deaths (heart attack and stroke).Hypertension affects an estimated 68 million U.S. adults.
  • If all individuals received adequate treatment for their hypertension, 46,000 deaths might be averted each year.
  • Direct and indirect costs of hypertension are more than $93.5 billion per year
  • Cardiovascular disease and stroke account for 17% of total health expenditures in the US annually
  • Overall U.S prevalence of hypertension among adults after the age of 18 between 2005 and 2008 was 30.9% (and highest among persons at or older than 65). This prevalence has remained unchanged during the past 10 years.
  • 30% of patients with hypertension are not being treated pharmacologically.
  • Only 45.8% of those with hypertension have their blood pressure adequately controlled.

There are, of course, recommendations as to what should be done to deal with this pervasive disorder and the resultant disease. Blood pressure readings should be taken seriously (and regularly). Anyone who has a blood pressure that is 140/90 needs to consider medication and lifestyle changes. Physicians now think that blood pressure reductions below the threshold for clinical hypertension (115/75) can have health benefits over time. An analysis of over 61 prospective observational studies of blood pressure and mortality (you know the ones that follow large groups of individuals for years) have shown that for each 20 mmHG increase in usual systolic blood pressure (This is the top number in blood pressure readings and represents the pressure that your heart is exerting to get the blood to flow through your arteries) or 10mmHG increase in usual diastolic blood pressure (which represents the pressure of the vessels between heart beats) above 115/75 mmHG was associated with a doubling in stroke mortality and death from heart attack at ages 40 to 69.

Before I sound the “get thee medicated” alarm, let’s go over the behavioral changes that can impact blood pressure. They should be adopted by all of us. (I’m sure we all know them, but since the American Heart Association has made them official here they are: (1) achieving and maintaining a healthy body weight; (2) participating in regular leisure-time physical activity (and I don’t think shopping counts, unless you have to walk rapidly for a total of 30 minutes from store to store to car.) (3) adoption of a healthy diet, including reducing salt intake and increasing potassium intake; (4) smoking cessation; and (5) stress management) Note, the AHA gave no indication in this report as to how to do this and I’m not going to begin to tackle stress reduction  in this “brief” newsletter. It would require a treatise in philosophy, psychology, economics and the 24-hour news cycle!

There are, of course, multiple pharmacologic therapies and frequently more than one is needed to achieve adequate blood pressure control. That’s where a physician’s knowledge and choices of medication are needed (as well as health insurance to help pay for access to the physician, appropriate follow-up and purchase of the medications… According to this CDC report, one of the groups with the lowest prevalence of blood pressure control consists of individuals without health insurance.)

Molecular biology may help us understand the whys, wherefores and potential treatments of disease. But unless we self-maintain our own health by eating right, moving our derrieres off the chair (I guess you should get off your computer, iPad or Blackberry where you are currently reading this admonition), adhere to prescribed medication and improve access to care, that “one in seven” (deaths due to hypertension) will continue.

Bottom line: Make sure your blood pressure is checked regularly and if elevated, even “a bit” (over 115/75) work on your lifestyle. If 140/90 or over, check with your physician as to your need for medication and adhere to whatever is prescribed. The pressures of life (and death) start with your own!

In the midst of our horror about the earthquake, tsunami and nuclear reactor disasters in Japan and concerns about the latter’s impact on the air, ocean and life forms, I thought that the timing of the article in the March issue of The New England Journal of Medicine was intriguing. It brought up another less immediate but valid concern, that of the effect of coal on our food and risk of disease.  (I hope that those of you reading this article acknowledge coal’s impact on climate change and the ecologic repercussions that are, in themselves, a disaster). The NEJM article was titled “Mercury Exposure and Risk of Cardiovascular Disease in Two U.S. Cohorts.”

A quick review: as we use coal for power, we contaminate our atmosphere with mercury. This then returns to the oceans of the earth and is incorporated into plankton where it is converted into organic methylmercury. The latter is stored in the fat of fish. As larger fish eat smaller fish, their levels of methylmercury go up. We then eat the fish and the methylmercury gets into our bodies (and is also stored in our fat). Chronic, low-level methylmercury exposure can cause neurodevelopment delay in infants. It’s currently recommended that women of childbearing age, pregnant or nursing mothers, and infants and young children eat no more than 2 servings of fish per week and also limit their intake of certain species of fish that are especially high in mercury. The worst culprits are the ones on the top of the fish eating food chain: shark, swordfish, king mackerel, and tilefish. Then to complicate matters, fish from streams and rivers in areas that have high mercury pollution may also be less than safe, especially if consumed regularly. (For information on mercury pollution check

For adults, the main health concern regarding chronic low levels of methylmercury (not high, toxic ones) is the risk for cardiovascular damage and disease. Government agencies, the Institute of Medicine and (I assume) the rest of us want to know if mercury exposure is correlated with cardiovascular disease.

There has been robust research that shows that fish consumption is heart healthy; indeed, fish intake has been shown to be inversely associated with the risk of coronary heart disease, especially fatal heart attack and stroke. So what is a fish eating person (like myself, who does not eat meat) to do?

Researchers from Harvard, the University of Washington, and the University of Missouri studied mercury exposure in 2 large groups of individuals. The first was comprised of male physicians followed from 1986 in the Health Professionals Follow-up Study (don’t get me started on my gender protests regarding this study) and the second was through the Nurses Health Study (as you may guess, all female) in which the nurses were followed from 1976. The two studies totaled 51,529 men and 121,700 women.
And here is where it gets really interesting… Their toenail clippings were stored! (I read this, believe it or not, while getting a pedicure and wondered if I should save my own toe nail clippings for research.) Apparently concentrations of mercury and selenium in toenails have been found to be excellent biomarkers of usual methylmercury and selenium exposure. The researchers wanted to check selenium (which we get from consuming plants grown on selenium –rich soil) because this trace element provides protection against mercury toxicity in some experimental studies.

They identified 3427 participants with cardiovascular disease and matched them to controls who were the same age, sex, race and smoking status. They also had information on their fish consumption and lifestyle habits. Their toenail mercury and selenium concentrations were assessed by (and I’m sure you will get this) the use of neutron-activation analysis. The usual complicated statistical analysis (actually called a multivariate analysis) was done and demonstrated that participants with higher mercury exposures did not have a higher risk of cardiovascular disease nor did selenium concentrations make a difference in the results.
The authors concluded that their findings “provide no support for clinically relevant adverse affects of typical levels of dietary methylmercury exposure on cardiovascular disease in U.S. adults”. They went on to state that the absence of an association “should not alter ongoing public health and policy efforts to reduce mercury contamination in fish and the environment.”

Bottom line: Most of us can continue to eat the “right” fish for our heart’s sake, but women who are pregnant or may become pregnant, or who are breast feeding should limit their fish consumption. Now, we can start worrying about the impact of radiation on those fish…