To read all the articles in the series, you can go to the mini-site: "Aging of Your Heart and Blood Vessels is Risky" by clicking here.

Introduction

Health care consumers, and physicians too, have been accustomed to the idea that "hardening of the arteries" occurs as one gets older. Until recently, it has been erroneously believed that this arterial stiffening is an inevitable component of "normal" aging and beyond an individual's control. It is now apparent that vascular aging, of which hardening or stiffening of the arteries is just one component, occurs at different rates and to varying degrees in different individuals within a given society, as well as differing among races/societies. Vascular stiffening has also been proven to be risky with respect to incurring major cardiovascular diseases, rather than just an accomplice to aging. However, the good news is that there is increasing evidence that aging of the vascular system can be slowed down by interventions such as exercise, optimal nutrition and novel drugs.

Understanding Large Artery Structure and Function

In order to understand how large blood vessels, like the coronary arteries, change with aging we need to learn a little about arterial vessel anatomy and function.

ANATOMY
The arterial wall has three components: the intima, the media and the adventitia. The intima, or inner coat of the vessel, is that part which is closest to the blood flowing within the artery. It consists of a single layer of cells, called endothelial cells. The media, or middle layer, is made up of vascular smooth muscle cells, which are surrounded by a network of collagenous and elastic fibers. Collagen and elastin are proteins, which together form the nest or matrix in the vessel's middle layer wherein the smooth muscle cells reside. The elastin forms concentric rings within the vessel wall. The outermost covering of the arterial wall is called the adventitia, which is basically connective tissue. The opening through which the blood flows is called the lumen.

Arteries contract and relax

When the heart contracts (systole), blood is pumped into the large arteries, such as the aorta and the carotid arteries which then expand (like a spandex garment). As blood flows out of these arteries into smaller ones throughout your body the large blood vessels then recoil back to the size they were prior to the heartbeat. As the arteries relax your heart also relaxes and fills with blood in preparation for the next heartbeat (diastole). (See Article "What Was Once Believed to Be Normal Aging Is Now Considered To Be Dangerous".)

Thus, the large blood vessels (e.g. aorta and carotid arteries), which supply blood to your head and body, expand when your heart contracts and recoil when your heart is filling with blood for the next heartbeat

How is contraction and expansion of the arteries affected by their stiffness ?

The extent and rate of expansion and contraction of the arterial vessel wall, which occurs during and after each heartbeat, depends in large measure upon the stiffness of the arteries. Consider this! Your grandchild is having a birthday party. You need to blow up both the balloons and the tires for her little red fire engine. Try blowing the same volume of air into one of the birthday balloons and then into one of the small rubber tires, which is approximately the same size as the balloon. The balloon, due to its softness and flexibility, will expand easily. The rubber tire will resist expansion due to its increased thickness and stiffness. You would probably rather blow up the balloon!

Within the arteries, it is the also the flexibility or stiffness which determines the ease of expansion. Just as the relative ease of expansion of the balloon and tire are dependent on their material composition, expansion in arteries is determined by their individual composition. Returning to anatomy, we know that the composition of the artery is largely matrix proteins (elastin and collagen), and smooth muscle cells. A young person's arteries are similar to soft latex birthday balloons. But, for many older persons, the arteries have become more like rubber tires. This stiffness, which is determined by the status of both the smooth muscle cells and matrix proteins of the arteries, affects both the systolic pressure and the pulse pressure when blood is pumped into the arterial tree. (See Article "What Was Once Believed to Be Normal Aging Is Now Considered To Be Dangerous".)

Calcium takes a supporting role

If you have been following this Series of articles you know that calcium plays a major, or starring, role in the ability of heart cells to contract in unison to produce a heartbeat. (See Article "The Essence of the Heartbeat Changes with Aging".) With regard to the regulation of stiffness in the arteries calcium again plays a part. However, this time calcium plays a supporting role.

The smooth muscle control of vascular wall stiffness, called "tone", is regulated, in part, by the contractile properties of vascular smooth muscle cells. These properties result from calcium within cells interacting with the contractile machinery (myofilaments). This resembles, in some ways, the calcium regulation of the heart's contraction. Receptors on the vascular smooth muscle cell surface receive neurotransmitters and other types of signals that regulate their contractile status. In particular, the receptors receive signals from endothelial cells that line the blood vessel lumen. (See Article "Messages Transmitted From the Brain Fine Tune The Heart".) Changes in the contractile status (tone) of vascular smooth muscle cells can occur acutely, and impact acute changes in stiffness within the arterial wall. This differs from the gradual regulation of arterial stiffness by matrix proteins (discussed in the next section, "The Role of Collagen and Elastin".

Due to cell death associated with the aging process itself the number of vascular smooth muscle cells in the arteries decline. The remaining cells work harder. When smooth muscle cells work harder it causes them to get larger. This is similar to what's going on in the heart. This will be the topic of a future article.

The role of collagen and elastin

From time to time some vascular smooth muscle cells change their character, or nature, much like great supporting actors. They give up their contractile machinery (their customary role) and instead of contracting as usual, they produce matrix proteins i.e. elastin, collagen and other matrix substances. You could say, they improvise! The balance of production and destruction activity of these proteins regulates their level. The destruction process involves their being chewed up, or disintegrated, by enzymes. We can, perhaps, equate these enzymes to sports or movie-going fans who determine who is in or out of popularity at any given moment. Vascular wall stiffness, in addition to being determined by the amount of collagen and elastin, is also regulated by how these are linked to each other (or "what union they belong to") and by how much they are stretched (or "asked to work").

With aging the amount of vascular collagen increases, causing an imbalance of collagen and elastin to occur, and abnormal cross-links form between the collagen strands as a result. These cross-links are the result of what are called advanced glycation end products (AGES).

This same process is what makes a turkey skin become brown during roasting. Also with aging the elastin membranes become stretched and laden with calcium and they rupture. The elasticity of the vessel becomes like the spandex of an old girdle. The net result is that the arterial lumen enlarges, and the artery walls thicken. With each heartbeat the expansion of the artery, due to blood pumped from the heart, is lessened, as is the subsequent recoil contraction. In essence, the artery has now become "hardened" or stiffened.

Vascular aging is risky !

The age-associated changes in vascular structure that we have discussed have been found to be risk factors for strokes and heart attacks. The greater the stiffening and thicken of the arteries, the greater is your risk. While we can't yet stop the aging process, we can make use of the new technologies that are becoming available to make the human lifespan enjoyable to its endpoint. Modern cardiologists now have access to a myriad of these new technologies, such as doppler/ultrasound, so that they can non-invasively acquire precise information regarding the structure and stiffness of human arteries from youth to old age. But, unless you have occasion to visit a cardiologist due to cardiovascular disease, or by request, these technologies will not be readily available to you. Therefore, you won't know if your arteries put you at risk for stroke, heart attack or cardiovascular disease. However, there is a way you might get some idea as to how you compare to others whose arteries have been studied to determine their risk for these diseases.

How you can assess your arterial stiffness

Because stiffening of the large arteries causes changes in blood pressure to occur, you can get a rough idea about the stiffness of your large arteries from your blood pressure numbers, which are measured routinely by physicians and other allied health personnel, and which can also be self measured. In particular, the difference between the systolic (top) number and the diastolic (bottom number), called the pulse pressure, is a rough index of vessel stiffening. You can get some idea as to whether your arteries are stiffening at a greater or lesser rate as you age and thus estimate your "risk", by comparing your pulse pressure to other persons pulse pressures that have been studied by researchers in this field.

Medical trials have recently confirmed that high values of pulse pressure, i.e., the systolic minus the diastolic pressure, that commonly occur in older persons can be an independent risk factor for future strokes, heart attacks or cardiovascular deaths. More specifically, a pulse pressure greater than 70mmHg at any age should cause some concern.

Dr. Ed is a physician/scientist, who is internationally recognized for studies that range from humans to molecules on how the heart and blood vessels work in health and disease as the body ages.