An ACE-I in the Hole

Sometimes in the course of medical progress, we find new uses for old drugs. A five year trial named HOPE (Heart Outcomes Prevention Evaluation) enrolled 9297 men and women over the age of 55 to see if a class of drugs called ACE Inhibitors might decrease incidence of heart attacks, strokes, or heart-related deaths. You may know some of these drugs: Capoten, Vasotec, Zestril, Prinivil, Accupril, Altace, Monopril, Lotensin, Aceon. . .the list continues to grow. Most people think of these drugs as blood pressure medicines. . .and traditionally, they have been. They can also ‘boost the pump’ when the heart is weakened by congestive heart failure. But, the HOPE trial has demonstrated significant benefit of several specific drugs in this class in reducing not only heart-related adverse events, but also decreasing the incidence of new diabetes. Let’s explore the exciting benefit of an “ACE I” in the hole this week.

All of the blood vessels in our bodies are lined with an efficient, healthy lining called the endothelium. There is a basic homeostasis that allows optimal transfer of oxygen, relaxed, optimal flow of blood through the vessels, and optimal elasticity to accommodate the ebb and flow of pressures generated by the hemodynamic pump–the heart. A healthy endothelium is able to prevent the adherence of ‘sticky’ platelets and blood clots on its surface. Also, in its pristine state, endothelium has mechanisms to minimize inflammation–which, in turn, decrease unhealthy scarring of this smooth, efficient lining. Unfortunately, through disease and/or various abuses of our bodies because of lifestyles that foster hypertension, diabetes, roughened blood vessel walls, and the steady building of plaque which narrows the channels through which our blood flows. . .we disrupt and damage this perfect lining. It’s functions are jeopardized in proportion to the degree of injuries. However, research has demonstrated significant benefit of angiotensin converting enzyme inhibitors in blocking some of the injury and preserving function.

The importance of decreasing cardiovascular disease is obvious. It’s the number one cause of death worldwide, the number two cause of death in developing nations, and the leading cause of disability worldwide. There’s a timeline for development of atherosclerosis (hardening of the arteries) that leads to progressive blockage of healthy blood vessels and decreases the normal function of the endothelium progressively along the way. The earliest lesions occur primarily because thin layers of fat deposit along the blood vessel walls. However, in the later stages, clots, and layers of thickened fibrous tissue are added to progressively jeopardize blood flow.

In the HOPE Trials, patients benefited from ACE inhibitors irrespective of their histories of cardiovascular disease, diabetes, hypertension, heart attacks, strokes, or peripheral vascular disease. Moreover, both men and women alike derived significant benefits, as did patients at least 65 years old, as well as the younger individuals. Surprisingly, patients who were treated with an ACE inhibitor in the study had a 34% reduction in the incidence of new-onset diabetes. It was already known that ACE Inhibitors improve insulin sensitivity in patients, but it was amazing how significantly this effect translated into delayed onset of diabetes as a disease. If your brain is hurting from all this complicated information, hang in there! It’s gonna be worth it.

So what tears up blood vessels? Well, the BIG FOUR are: Hypertension, Hyperlipidemia (Hi levels of unhealthy Cholesterol and Triglycerides), Smoking, and Diabetes. Both Smoking and Diabetes damage the blood vessel walls over time and thereby accelerate inflammatory changes and scarring. As the endothelium becomes progressively dysfunctional, one’s risks of heart attack, stroke, and death from other circulatory illnesses rise proportionately. So, obviously, it behooves us to take good care of the channels that contain and transport our life-sustaining blood to all areas of our bodies.

When blood vessel walls are repeatedly subjected to the stress generated by the above problems, they spasm, become pitted, become inflamed, and try mightily to repair and correct all of these phenomena. In that process of trying to escape from the insults and also correct the damage they’re causing,the endothelium induces the production of a substance called angiotensin II. Unfortunately, this substance causes blood pressure to increase and increases vascular ‘injury’ in its own right. Ultimately, unopposed levels of angiotensin II lead to blood vessel scarring. But, when an ACE Inhibitor is added to the mix, it blocks the conversion of a harmless precursor into the destructive angiotensin II.

Additionally, it prevents the degradation of a substance called bradykinin. By preserving bradykinin levels, the blood vessel walls remain relaxed, less likely to spasm/contract, and more capable of delivering larger volumes of blood to the target tissues and organs. If you feel overwhelmed by this complicated lesson in biochemistry and physiology, just imagine how a first year medical student feels when bombarded with such facts day after day for a whole year! I’m subjecting you to this complicated subject so you’ll understand the important role of ACE Inhibitors in keeping the blood vessels healthy. We haven’t known this information for that long. And, if you fall into any of the above risk categories, your progression to frank heart disease could be dramatically decreased by adding an ACE inhibitor to your medication mix. Of course, healthy lifestyles with no smoking, healthy,low-fat eating patterns, adequate exercise, and mindful, joyful living will always be the mainstays of good self-care.

Not all of the ACE Inhibitors have been shown to be equally effective in preserving endothelium function. And dosage does seem to be important. A few specific contraindications to ACE inhibitor use do exist. Additionally, there’s another closely related class of drugs that may have similar beneficial effects in minimizing endothelial dysfunction–but the data in such trials are still premature. Check with your doctor about the specifics on these points. In any case, now you’re aware of the significant benefits of having an ACE I in the blood vessel ‘hole’…and your body as a whole.

Stephen L. Hines, M.D.
November 2001