Cortisol and Cardiovascular Disease

A large and exceedingly important part of the stress response is its direct and rapid effect on the cardiovascular system. As outlined previously, the fight-or-flight response is meant to prepare your body for forceful physical activity. But no matter whether you're saved by your fists (fight) or your feet (flight), your cardiovascular system had better be ready to support whatever vigorous activity you decide to undertake. This means ramping up heart rate, blood pressure, and cardiac output (the amount of blood your heart pumps). It also means shutting down certain nonessential uses of blood, such as digestion, and shunting that blood to more important areas—like the arms and legs, where it can fuel the fighting/fleeing muscles. Shunting blood around the body means coordinating the dilation (relaxation) of some blood vessels and the constriction (narrowing) of others, an effect that results in elevated blood pressure during periods of stress. What a great set of effects! If you were a race car, this stress-induced series of events would be analogous to a supercharger, and—ZOOM!—away you'd dash. The key problem may already be apparent to you: Keep that supercharger opened full throttle for too long, or use it too frequently, and you're likely to blow a gasket, throw a piston, or destroy the entire engine. What this means for your heart and cardiovascular system is clear: Chronic activation of your stress-response system increases your risk of blowing a gasket in your heart—otherwise known as heart disease.

We know that elevated blood pressure can accelerate damage to the interior lining of blood vessels. These small areas of vessel damage become perfect "docking points" for circulating particles of sugar, fat, and cholesterol—so there they stick (and stress has already elevated each of them to serve as fuel for your expected fight/flight). As if that weren't already bad enough, your blood gets thicker because of the tendency of stress hormones to promote blood clotting. Thick blood might be a good thing if you come out on the losing side of a fight, but it's not a good thing if you're simply sitting in a traffic jam with a rapid heart rate, elevated blood pressure, and constricted blood vessels.

A variety of animal studies (in monkeys, rats, mice, and dogs) has supported the concept that stress leads to heart disease. Across these studies, it is clear that the animals subjected to the most social stress are also the ones that develop the most or worst blockages in their blood vessels. High-fat diets appear to compound the problems (duh!). Interestingly, physical stressors do not seem to be quite as bad for the heart, probably because running around, wrestling, or fighting appear to help dissipate stress hormones.

Health professionals have known for decades that blood pressure, cholesterol levels, heart attacks, and strokes are closely related to overall degree of stress. Emotional state has been known to trigger heart attacks in many people, with feelings of sadness, anger, and "control" (that is, how much or how little control people feel they have over their lives and/or destinies) being linked to causation of heart disease. Overall, risk for coronary heart disease is three to five times greater in people with higher levels of anger, anxiety, and worry compared to people who report lower levels.

Researchers from the Mayo Clinic have shown that psychological stress is one of the strongest risk factors for heart attacks. Furthermore, when calculating the economic costs of a high-stress lifestyle, economists have shown that hospital usage costs more than $9,500 per visit in heart-attack patients with high stress, but just over $2,100 in those with low stress.

Most of us understand that heart disease is the leading cause of death in the United States and much of the Western world. Almost all cases of heart attack and stroke are due to atherosclerosis caused by high blood pressure, high cholesterol, diabetes (high blood-sugar and insulin levels), smoking, and physical inactivity. What many people fail to realize, however, is that the cardiovascular aspects of heightened stress may merely be the tip of the iceberg when it comes to the long-term health consequences of elevated cortisol levels.

The good news is that there also appears to be a powerful inverse relationship between stress and the strength of one's social network—meaning that strong social support (from friends, family, and coworkers) can be a key factor in reducing the link between stress and heart disease. Stated another way, those with a stronger social network can withstand more stress before succumbing to disease. More good news is found in reports of the association between stress and hypertension: The dissipation of stress, through either meditation or exercise, helps to bring blood pressure back to normal levels.

Your Brain on Cortisol: Anxiety, Depression, and Alzheimer's Disease

Rachel was a single mom with two young children. In addition to her full-time job at her daughter's day care, she also volunteered as a chaperone for her son's Boy Scout troop. As you can imagine, Rachel had more than enough stress in her life in the form of financial constraints, child-care issues, and being a single parent. As a result, she often felt her patience wearing thin, especially when confronted with a dozen screaming Boy Scouts at the end of a stressful day at the day care. Take a look at Chapter 8 to see how Rachel used specific nutritional supplements to deal with heightened anxiety and irritability.

Who among us is not affected to some degree by periods of stress and anxiety? For virtually everybody, modern lifestyles create a fair amount of tension, irritability, worry, and frustration, which can lead to feelings of chronic anxiety and depression. In fact, somewhere between 5 and 20 percent of Americans will experience depression severe enough to warrant medication or other therapy.

In addition to the emotional effects brought on by chronic stress are its direct effects on the brain. Research has shown that stress can increase the incidence of simple forgetfulness and accelerate the development of full-blown memory loss and Alzheimer's disease. Each of these conditions involves a degree of mental deterioration characterized by damage to and death of nerve cells in the brain—and it has been estimated that as many as 30 to 50 percent of adults in industrialized countries suffer from these conditions.

The changes in mood that accompany periods of heightened stress also bring reduced energy levels, feelings of fatigue, irritability, inability to concentrate, and feelings of depression—all of which are related to the same class of brain chemicals, the neurotransmitters. Most notable (and scary), perhaps, are the findings that chronic stress can lead to actual physical changes in the arrangement of the neurons (nerve cells) in the brain. In other words, we're talking now about stress changing both the function and the shape of your brain. No wonder it sometimes doesn't seem to work the way it's supposed to!

Related to depression, but different in a number of ways, is anxiety—that nagging, sometimes overwhelming, sense of disquiet or unease that most of us experience to one degree or another, at least occasionally. Anxiety can get completely out of hand if it takes the form of panic attacks or obsessive-compulsive disorder, both of which appear to be associated with a chronically overactive stress response (and especially with elevated catecholamines; that is, epinephrine and norepinephrine).

Panic disorder occurs in approximately 1 to 2 percent of the population. It typically begins in young adulthood, and women are twice as likely as men to suffer from it. The condition manifests itself in episodes of extreme anxiety and fear. These panic attacks, as they are commonly known, can last from a few seconds to a few hours and may include real physical symptoms such as shortness of breath, sweating, irregular heartbeat, dizziness, and faintness. They can be so severe that the sufferer ends up in the emergency room with fears that she or he is having a heart attack. Compounding the condition is the anticipatory anxiety that plagues the sufferer after experiencing these attacks, leading to a vicious cycle in which more anxiety is caused by worrying about having future panic attacks. It is unclear in these situations whether elevated cortisol levels are the primary causative factor that induces the panic attacks, or whether high cortisol levels result from the initial panic attack and, while remaining elevated, exacerbate the condition and set the stage for another attack. Another variant of anxiety is obsessive-compulsive disorder (OCD), which produces obsessive, almost inescapable thoughts and compulsive behaviors the sufferer cannot help but perform. About 2 percent of the population suffers from OCD. Females are slightly more susceptible than males, and, as with panic disorder, it typically first manifests in young adulthood. People with OCD are in a sense better adapted to anxiety than are individuals with panic disorder, because those with OCD avoid panic attacks via their compulsive behaviors, which may act in a way as "de-stress" exercises. Unfortunately, the behaviors or rituals needed to satisfy the obsession/compulsion often interfere with normal activities and relationships. Most of the compulsions fall into one of four categories: checking, cleaning, counting, and avoidance. In many cases, it is thought that these compulsions act as simple defense mechanisms, whereby the compulsive behavior or obsessive thought patterns help to reduce feelings of anxiety. However, these thoughts and behaviors become ritualized and inescapable, leading to a heightened level of stress and anxiety as they begin to disrupt activities of daily living. Treatment for OCD generally involves both behavioral therapy and drug treatment, but the disorder often persists over time unless the root cause of the stress is fully addressed.

Clearly, various treatments exist for people suffering from anxiety. Aside from behavioral therapy, which is often all that is needed (especially for simple phobias), several medicinal treatments exist that vary according to the type of anxiety and whether or not the anxiety is combined with other problems. Traditional tranquilizers, such as Valium, are often the first medications that come to mind. However, anxiety frequently goes hand in hand with depression, and antidepressants such as Prozac, Zoloft, and Wellbutrin are often prescribed to treat the combination of problems. For individuals who prefer a more "natural" approach to treatment, there are many alternatives in the form of supplements, herbs, and combination products that may help alleviate anxiety, reduce stress, and control cortisol levels. These are covered in detail in upcoming chapters.

The ultimate cause of depression is exceedingly complex—and well beyond the scope of this book. From our perspective relating to the association of stress with depression, however, it is known that cortisol levels tend to be higher in people suffering from depression, while levels of brain neurotransmitters such as dopamine, norepinephrine, and serotonin are lower. Does this mean that cortisol lowers brain neurotransmitters or causes depression? Not necessarily, but we know quite clearly that the people who are under the highest levels of stress also tend to be the ones who succumb to periods of moderate depression. Part of the reason may be that during periods of heightened stress, the brain becomes accustomed to high cortisol levels, and when the stressor is removed (or reduced) the brain is unable to function effectively. We know from animal studies, for example, that the brains of rats exposed to repeated stresses eventually become resistant to specific pleasure pathways; therefore, higher and higher levels of the brain's "feel-good" chemicals (dopamine, serotonin, and endorphins) are needed to induce a response. It has also been known for more than twenty years that patients given high doses of cortisol-like drugs (such as corticosteroids to treat autoimmune diseases) also tend to develop memory problems and signs of clinical depression.

So, in asking ourselves the question "Does cortisol cause depression?," the answer is definitely, probably "maybe." It certainly appears that having elevated cortisol levels raises one's risk of developing depression. It also appears that cortisol does a pretty good job of gumming up the works when it comes to the synthesis, transport, breakdown, and overall activity of the neurotransmitters in the brain. Finally, we also know that using specialized drugs to "shut off" the production of cortisol can reduce the symptoms of depression—but these drugs, known as adrenal steroidogenesis inhibitors, have a list of nasty side effects as long as your arm.

Again, however, if we look at the relationship between stress and brain function, we see a two-phase effect, wherein short-term stress appears to enhance cognitive function, while chronic stress disrupts many aspects of brain neurochemistry. Researchers theorize that it works something like this: Acute stress causes an increase in blood flow, oxygen, and glucose to the muscles (for fight/flight), and also to the brain. We know that hypoglycemia (low blood sugar) can impair concentration and ability to think, so the increased supply of glucose should, at least transiently, increase brainpower. And it does; studies of people exposed to short-term stressors show that they have an enhanced memory capacity and ability for problem solving. Unfortunately, the brain-boosting effects of stress are short-lived (lasting less than thirty minutes), because wthen the body is fully awash in cortisol, which causes blood flow and glucose delivery to the brain begin to fall. Prolonged exposure of brain cells (neurons) to cortisol reduces their ability to take up glucose (their only fuel source) and—here's the really scary part—causes them to shrink in size! So there you have it. Repeated stress and prolonged exposure to cortisol—once again, the Type C condition—actually lead to a progressive destruction of the neurons in the brain. Not good.

The connection between adult-onset (type-2) diabetes and depression has been known since the late 1600s, when British physicians noted that diabetes was more common in people who suffered long-term sorrow. The link between stress/depression and diabetes/obesity (now often referred to as "diabesity") has also been known for many years, but it is just within the past decade or so that cortisol has emerged as the linchpin between the conditions. Cortisol builds up during depression, which could directly trigger a tendency toward "diabesity." Indeed, researchers from the University of Michigan have shown that reducing the conversion of inactive cortisol into active cortisol in fat cells (using flavonoids, as described in Chapter 4) results in a drop in cortisol levels of 45 to 73 percent and a reduction in abdominal fat of 10 to 13 percent within twelve weeks. Another group of Dutch researchers has found that being depressed increases a person's risk of developing diabetes by 37 percent—about equal to the risk posed by smoking or lack of exercise.

A group of researchers from the National Institute of Occupational Health, in Copenhagen, Denmark, have recently shown that "bullying" at work increases stress levels and is associated with adverse health outcomes. Workers who indicated having been bullied on the job reported more symptoms of depression, anxiety, and overall stress, accompanied by elevated cortisol levels. It was interesting to note in these studies that while daytime levels of cortisol were elevated in the bullied workers (indicating high stress levels at work), their "waking" cortisol levels were suppressed (indicating a high risk of developing stress disorders such as chronic fatigue and fibromyalgia). A similar series of studies by German researchers at the University of Trier found that higher measures of cortisol at work were associated with workers feeling more tense, unhappy, and angry.

Mental health researchers from the University of Michigan have recently calculated that approximately 90 percent of episodes of depression are due directly to stressful life events. It also appears that lower levels of sex hormones (estrogen and testosterone in women and testosterone in men) can exacerbate the depressive effects of cortisol during middle age. Researchers in Sweden have further shown that women with stress-related depression have increased levels of cortisol and IL-6 (a marker of inflammation from immune cells), suggesting that depression might also affect immune function.

It is interesting (and confusing) to note that a number of studies have shown cortisol levels to be low in people suffering from posttraumatic stress disorder (PTSD), while an equal number of studies have shown high cortisol levels in PTSD. Still other studies show no difference in cortisol levels between PTSD sufferers and "normal" individuals. Whether cortisol levels are high or low, it is clear that people with PTSD have many of the same day-to-day complaints as people suffering from "everyday" stress, including sleep disturbances, memory problems, daytime fatigue, and abdominal weight gain. Dutch researchers studying the similarities between PTSD and burnout have found many of the same levels of exhaustion, cynicism, feelings of reduced competence, and reduced cortisol levels—but they have also found that psychotherapeutic intervention (such as stress-management therapy) leads to a significant reduction in complaints and to an increase in cortisol levels back toward normal values (from suppressed levels). Neurobiology researchers in California have shown that cortisol is both good and bad for memory and overall brain function. At low levels, cortisol actually helps with memory formation and with retrieval of stored memories, but at very low levels (as in some cases of PTSD), or at high levels (as in cases of extreme or chronic stress), cortisol has been shown to interfere with the brain's ability to store new memories and recall old ones.

When it comes to extending what we know about cortisol's effects on the brain in terms of mood, anxiety, and depression to other brain abnormalities, it is tempting to speculate about the role of stress in Alzheimer's disease. It is important to note, however, that while there may be some superficial associations between high stress levels and Alzheimer's disease, we simply have no direct evidence that cortisol causes Alzheimer's disease, although chronic stress and elevated cortisol levels certainly appear able to make the situation much worse. It is true that most of us past the age of forty will begin to experience some degree of "normal" age-related memory loss (often called age-related cognitive decline or ARCD), but this is a far cry from the severe mental deterioration (senile dementia) usually seen with Alzheimer's disease. Although Alzheimer's disease may affect as many as 50 percent of people over age eighty-five to a certain degree, the condition involves a whole lot more than simple forgetfulness. Studies of the brain neurons from Alzheimer's patients show a clear pattern of death and destruction of cells in the parts of the brain involved in memory and higher thoughts.

It is also interesting, in light of our discussions of depression and anxiety, to note that Alzheimer's disease often begins with damage to the brain cells that produce a neurotransmitter called acetylcholine. The loss of acetylcholine causes symptoms ranging from the subtle, such as trouble remembering names or dates, to the more noticeable behavioral problems, such as depression and anxiety, and eventually to extreme disorientation and a loss of ability care for oneself. Drug treatment with Cognex or Aricept, which increase acetylcholine action, can produce a modest improvement in mild cases of Alzheimer's disease, but no existing drugs are able to restore normal function to the damaged regions of the brain. So, stress and cortisol are erasing your memory, dashing your emotions, causing you anxiety, and killing your brain cells. Yikes! But you can do something about it. There are lots of steps you can take to make positive impacts on your stress response, on your cortisol levels, and on your feelings of depression and anxiety. That's what the next several chapters are about.


Shawn Talbott

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