The Great Blood Pressure Medication Debate

Recently, I reported on a large-scale study that compared several different classes of medications commonly used to treat high blood pressure.  The study concluded that the inexpensive and venerable diuretic medications were actually superior in preventing the potentially life-threatening complications of high blood pressure when compared to their more recent—and far more expensive—pharmacological brethren.  However, a study just published in the current issue of the New England Journal of Medicine has apparently come to a different conclusion.  This new study compared the effects of long-term treatment with diuretics versus treatment with the so-called angiotensin converting enzyme (ACE) inhibitors.  The diuretics work by stimulating the kidneys to excrete excess water and salt from the body.  The ACE inhibitors work primarily by blocking the formation of enzymes that constrict the body’s blood vessels, thus causing a relaxation of these vessels.

This prospective randomized study evaluated over 6,000 patients with hypertension over an average period of 4 years.  The incidence of heart attacks and death due to heart attack occurring among patients receiving either a diuretic drug or an ACE inhibitor were then studied.  Elevated blood pressure was effectively and comparably reduced by both diuretics and ACE inhibitors.  However, in contrast to the previous study that found a significantly lower risk of cardiovascular events among patients taking diuretics, this new study identified a slight increase in the risk of cardiovascular events among patients taking diuretics when compared to the patients taking ACE inhibitors (59.8 vs. 56.1 per 1000 patient-years, respectively).  The rather modest reduction in cardiovascular events among patients taking ACE inhibitors appeared to apply primarily to men with hypertension, while no significant treatment-based difference in the risk of cardiovascular morbidity was seen among women with hypertension.

The authors conclude that, at least for men, ACE inhibitors appear to reduce the risk of heart attack and death due to heart attack when compared to diuretics.  However, I would caution patients who are currently receiving diuretics to abruptly change their medication if their blood pressure is currently well-controlled on such medications.  Although ACE inhibitors may bring added health benefits to hypertensive patients with diabetes or congestive heart failure, hypertensive patients without these added health problems are not likely to experience any additional health benefits by switching from diuretics to ACE inhibitors (as long as their hypertension is well-controlled by their diuretics), as the cardiovascular benefits associated with the use of ACE inhibitors over diuretics in this study were very modest.  To further muddy the waters, many patients with significant hypertension will eventually require the use of more than one single anti-hypertensive medication to effectively control their blood pressure.  Stay tuned for additional developments in this area!

Premature babies weighing 1,250 grams or less at birth are at particularly high risk of developing brain hemorrhages and long-term developmental delays.  These babies may experience substantial neurocognitive problems later in life.  This week’s Journal of the American Medical Association contains a study of 296 infants weighing 600 to 1250 grams at birth.  The babies were followed by this study from 1989 to 1992.  The babies were evaluated at birth, and then again at 36, 54, 72 and 96 months of age (adjusted for their original due date).  The babies were all assessed with several standardized tests for cognitive function and IQ at each of these intervals. 

The study determined that very low birth-rate babies, overall, made substantial gains in cognitive function and IQ during the course of the study.  The three factors that were associated with the greatest gains in the babies’ cognitive function were: increasing age of the baby, living in a household with 2 parents, and higher levels of maternal education.  Among babies with moms having less than a high school education, the most significant gains occurred when professional intervention was available to such babies.  Unfortunately, babies experiencing brain hemorrhage following birth had the greatest cognitive difficulties early on, and these cognitive handicaps generally became more severe with the passage of time.

Three interesting Alzheimer’s disease (AD) studies are presented in the current issue of the Archives of Neurology.  The first study sought to evaluate the fat content of the diet as a risk factor for developing AD.  A total of 815 clinically healthy volunteers aged 65 years and older completed dietary surveys at the beginning of the study.  Total fat intake, and the type of fats consumed, were carefully assessed by the study’s survey.  At a mean follow-up of just over 3 years, 131 of the study volunteers had developed AD.  After analyzing their data, the study’s researchers determined that a diet high in saturated fats, and the so-called “trans-fatty acids” (most prevalent in solid fats like margarine and solid vegetable shortenings), were associated with more than twice the risk of AD when compared to diets low in these types of fats.   On the other hand, diets low in saturated fats but rich in polyunsaturated vegetable oils appeared to be associated with a significantly lower risk of AD.  Although the mechanism behind these findings is not clear at the moment, these findings are consistent with numerous other studies linking a diet low in saturated fat with improved health and longevity.  Now, it appears, we may be able to add a reduced risk of AD to the list of potential benefits deriving from a healthy diet.

A second study in the Archives of Neurology looked at the effect of antioxidant vitamins on the risk of developing AD.  Previous studies have implicated free radical damage to brain cells as at least one possible mechanism behind the development of AD.  Therefore, one might expect that vitamins capable of reducing the generation of free radicals might, in theory, reduce the risk of AD. 

The study included 980 elderly volunteers who were assessed for their dietary levels of the antioxidant vitamins beta carotene, vitamin C and vitamin E over an average period of 4 years.  The incidence of subsequent AD in these volunteers was then assessed during the course of the study.  Essentially, no significant difference was found in the incidence of AD between volunteers with the highest and lowest levels of dietary antioxidant vitamins.  It remains to be seen, however, whether very high dietary levels of these supplements might reduce the risk of AD, or if longer periods of observation might identify a trend towards lower rates of AD among people with high antioxidant vitamin intake.  However, based upon this study’s results, no AD-reducing benefits can yet be claimed for antioxidant vitamins.

Finally, there has been an enormous debate over the effects, both good and bad, of postmenopausal hormone replacement therapy (HRT) over the past year.  Previous claims that HRT reduced the risk of cardiovascular disease and stroke, and minimally increased the risk of breast cancer, have been called into question by recent large-scale research studies.  One ray of light that has continued to shine on HRT, however, has been the observation of an apparent reduction in the risk of AD in postmenopausal women taking HRT when compared to those who do not use HRT.  Indeed, the presence of premenopausal levels of estrogen in the blood of postmenopausal women has been associated with improved cognitive brain function by several studies to date.  A new study in the current issue of the Archives of Neurology calls this observation into question, however. 

The study evaluated 120 postmenopausal women with AD.  All of the women were placed on Premarin (Wyeth-Ayerst, Philadelphia, PA) for a period of 1 year, and their blood levels of estrogen hormones were measured throughout the duration of the study.  At the beginning of the study, blood levels of estrogens were, as expected, quite low.  Treatment with 0.625 mg per day of Premarin was associated with a 4-fold increase in estradiol and estrone levels in the blood.  A daily Premarin dose of 1.25 mg per day increased blood levels of these hormones about 8-fold.  Standardized neuropsychological testing was conducted at the beginning of the study, 2 months into the study, and again at the conclusion of the 1-year study.  Unfortunately, no noticeable improvement in cognitive function was noted during the course of the study, and no relative improvement was seen between the two groups of women with respect to their blood levels of estradiol and estrone.  As with the antioxidant vitamin study, it is unclear if longer periods—or earlier initiation—of HRT might have some beneficial effect on cognitive brain function in patients with AD.  However, this study further chips away at the 50-plus year image of HRT as a near-miraculous and complication-free elixir of youth and vitality.

Dr. Robert A. Wascher