Update on High Blood Pressure Treatment

When I first began medical school (in the early 1980s), there were only a handful of medications available to treat high blood pressure.  One of the oldest classes of drugs, the diuretics, was a mainstay in the treatment of hypertension at the time.  These drugs reduce blood pressure by stimulating the kidneys to excrete excess body water and salt.  In some patients, diuretics may be contraindicated due to their potential side effects.  Patients with underlying kidney disease, difficulty urinating, gout, severely elevated cholesterol levels, seizure disorders and certain other preexisting conditions may not be ideal candidates for diuretic therapy.  Over the past 20 years, new classes of antihypertensive drugs have been developed.  Alpha-blockers and beta-blockers act by reducing the effects of adrenaline (and related hormones referred collectively to as catecholamines) on the arteries and heart, respectively.  As is the case with diuretics, the catecholamine blocking drugs have been associated with significant side effects of their own.  Another class of drugs, the calcium channel blockers, act to lower blood pressure by causing dilation of the body’s arteries.  More recently, angiotensin converting enzyme inhibitors have become popular for treating high blood pressure and congestive heart failure.  This class of drugs works to relax the body’s blood vessels by blocking the conversion of an enzyme called angiotensin I into angiotensin II.  This, in turn, blocks the formation of aldosterone, a hormone that causes the body’s arteries to constrict. The newest class of antihypertensives includes the so-called angiotensin II type 1 (AT1) receptor blockers.  The AT1 blockers also reduce aldosterone production, although they act at a different point in the aldosterone synthesis pathway than the ACE inhibitors.  Various combinations of different classes of antihypertensive drugs, combined in one pill, have also become quite popular in recent years.

As with many other types of medications, newer (and more costly…) drugs inevitably tend to supplant older and cheaper drugs.  Ostensibly, newer drugs are often regarded as being more effective, and safer, than their predecessors.  It is also a well-known fact that when drug company patents for their top-selling drugs expire, so do their profits as other companies begin to market generic versions of the off-patent medications.  Sometimes, however, a bit of research breathes new commercial and clinical life into “outdated” drugs, and we then learn that the newest—and most expensive—wonder drugs may be no better than their ancestors.  In some cases, research may reveal that the old time-tested drugs may, in fact, even be superior to their designer progeny!

In this week’s Journal of the American Medical Association (JAMA) is a landmark study that compares diuretic therapy against the treatment of hypertension with either calcium channel blocker or ACE inhibitor drugs.  Specifically, the study looked at the impact of each of these three classes of antihypertensive drugs on the incidence of heart attack, need for cardiovascular interventional procedures, heart failure and stroke in patients with chronic high blood pressure.  This study, the grandiloquently titled “Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial,” enrolled 33,357 participants with hypertension and at least one other known risk factor for cardiovascular disease.  More than 600 institutions in North America participated in this huge study.  The study participants were randomized to receive the diuretic chlorthalidone, the calcium channel blocker amlodipine, or the ACE inhibitor lisinopril, and were carefully followed for 4 to 8 years.  After an average of nearly 5 years of follow-up, the study determined that there was no significant difference in the incidence of heart attack among patients taking the three different classes of antihypertensive medications.  Likewise, the risk of death, from any cause, did not significantly differ between the three groups of study patients.  However, the reduction in systolic blood pressure was greater for patients taking the diuretic drug when compared to the other two classes of antihypertensive drugs.  When comparing amlodipine with chlorthalidone, after 6 years, there was a 38% increase in the risk of congestive heart failure among the patients taking amlodipine.  When comparing chlorthalidone with lisinopril, the patients who took lisinopril experienced a slight but significant increase in the risks of developing cardiovascular disease complications after 6 years, including stroke, congestive heart failure, and coronary artery disease occurring in combination with other cardiovascular disease events.  The critical conclusion of this study was that thiazide-type diuretic medications, in addition to being much cheaper than newer classes of antihypertensives, significantly reduced the risk of developing cardiovascular disease complications when compared to calcium channel blockers and ACE inhibitors.  These findings would appear to lay to rest the previous concerns about the potential effects of thiazide diuretics on blood potassium and cholesterol levels, and on insulin metabolism. These concerns, though of theoretical importance, have never before been shown to adversely affect overall health, and cardiovascular health in particular.  However, such hypothetical concerns compelled many physicians to switch their patients from diuretics to newer classes of antihypertensive medications.  The current study, however, makes it clear that these concerns appear to be clinically irrelevant, as the patients assigned to take the diuretic medication in this research study actually experienced a reduction in the risk of serious cardiovascular disease events.

This is a pivotal study on the pharmacologic treatment of hypertension, and closes the many lingering gaps in our knowledge about how best to treat this disease.  Like diabetes, hypertension has been labeled a “silent killer,” and is capable of causing heart dysfunction, stroke and kidney damage if not controlled.  Therefore, in the absence to any preexisting contraindications to diuretic therapy, the study’s authors advise that this class of antihypertensive medication be considered first when prescribing medication to patients newly diagnosed with hypertension.

Echinacea & the Common Cold

The common herbal supplement Echinacea has been touted as both a preventive and therapeutic treatment for upper respiratory infections.  However, there has been little in the way of controlled scientific study to prove such claims.  In the current issue of the Annals of Internal Medicine, dried encapsulated whole-plant Echinacea was evaluated as a treatment for common colds.  A total of 148 student volunteers with recent onset of typical upper respiratory infection symptoms were randomized to receive either Echinacea or a placebo (sugar pill) during the period of symptomatic illness (for up to 10 days).  Severity and duration of symptoms were then recorded for each student volunteer.  No significant difference in the severity or duration of cold symptoms was found among the two groups of students.  The average duration of cold symptoms was 6.01 days among both groups.  The study’s authors conclude that Echinacea does not appear to lessen the severity or duration of common upper respiratory viral illnesses.

Citrus Pectin & Cancer

A great deal of study is being devoted to the search for nontoxic compounds that can prevent or effectively treat cancer.  As our understanding of the molecular mechanisms of cancer development and spread improve, more selective—and less toxic—therapies will be developed.  Of particular interest are substances in foods that might have anticancer properties.  In the current issue of the Journal of the National Cancer Institute, the effects of citrus pectin on mice with breast and colon cancer tumors was studied.  Pectin is a nondigestible fruit-derived dietary fiber that is composed mainly of complex sugar molecules.  It has been previously noted that pectin can be modified by heat and alkaline pH so that it inhibits a protein known as galectin-3.  Galectin-3 has been linked with the development and spread of certain cancers, including cancers of the colon, breast, and thyroid, among other organs. 

In this study, human and colon breast tumors were transplanted into mice.  The modified pectin was then fed to the mice, and its effects on their tumors were then studied.  The study revealed that the mice receiving modified pectin in their diet had smaller tumors than the mice not fed with pectin.  Modified pectin appeared to inhibit tumor growth, and the growth of new blood vessels into the tumors (angiogenesis).  Importantly, modified pectin also reduced the ability of tumor cells to migrate and spread outside of the primary tumor.

This study provides an interesting look at a potential anticancer agent that is derived from common foods, and which appears to have no toxicity or unpleasant side effects.  The next step, of course, will be to try and replicate these results in actual human patients.  As I have often noted before, what works in laboratory mice doesn’t always—and indeed often does not—work in human beings!

Happy holidays to all of my dear readers!  Whatever your faith, may G_d bless you and keep you and your loved ones safe and healthy.

Dr. Robert A. Wascher