Medical science knows much about the mechanical aspects of heart disease and heart attacks. We know a fair amount about cholesterol, triglycerides and fatty acids.
But exactly how the body's vital substances turn against it is somewhat sketchier. In the last two chapters, the material has been mostly scientific fact. This chapter will deal more with hypothesis -- educated theories that are backed up by a body of research, but which have not yet been proven conclusively.
Contrary to popular belief, coronary artery blockages are not simple rubbish heaps of cholesterol. Instead, they are complicated structures composed of connective tissue, cholesterol, muscle cells from the artery wall, and other tissues. In fact, this mass, called an atherosclerotic lesion by physicians, loosely resembles a partially healed wound on other parts of the body.
Medical research shows that coronary arteries undergo characteristic changes in people and other mammals fed a diet high in fat and cholesterol. The first stage, scientists believe, is an injury to the intima, the inner lining of the artery.
The atherosclerotic process begins when white blood cells, known as monocytes, invade the artery wall and embed themselves just inside the first layer of cells.
Monocytes play a role in the body's immune system and can activate other immune defenses when they sense an infection. A monocyte is also capable of transforming itself into an amoeba- like scavenger cell known as a macrophage that attacks bacteria and other foreign objects. Monocytes collect near injuries (such as a cut finger) and are the majority of cells contained in the pus that collects around an infection or injury.
This early involvement of monocytes is one of the strongest clues that atherosclerosis begins with some sort of injury to the artery wall.
Once embedded in the artery wall, the monocytes transform themselves into macrophages which then consume so much cholesterol they resemble fat-filled foam. This early stage of atherosclerosis, present in most people by the end of their 30s, forms fatty streaks in the artery walls which don't appear to be harmful by themselves.
But, as the foamy macrophages gorge on cholesterol, they expand and break through the thin inner layer of artery wall cells and become exposed to the blood. The exposed macrophages attract another part of the blood system -- platelets. The platelets then release a number of proteins, some of which promote the growth of the artery's muscle cells.
The new artery muscle cells synthesize connective tissues (hard, leathery substances which are the main components of ligaments, tendons and scar tissue) that make the lesion more permanent.
The new artery muscle cells absorb LDL cholesterol at much higher rates than normal intima cells. Cellular debris from cells that have died are also embedded in this matrix of new muscle cells, cholesterol particles and connective tissue.
Atherosclerosis is a process of chronic irritation which steadily develops over decades. Unless the substance that triggers the irritation is removed, the lesion grows and grows until it kills.
Unfortunately, there seems to be no shortage of substances that can injure an artery wall. Some of the most important are:
-- high levels of fat and cholesterol,
-- tobacco,
-- high blood pressure,
-- stress,
-- being male or post-menopausal female and
-- glucose intolerance/high insulin levels (diabetes or borderline diabetes).
Fat and cholesterol don't just form part of the atherosclerotic lesion; they may actually help cause the injury that triggered it in the first place.
The LDL, VLDL, and chylomicron molecules themselves may actually irritate artery walls, much like a minor abrasion on the skin. It's not known for sure what causes the irritation, but scientists have hypothesized that it might come from the high chemical reactivity of the double-bonded oxygen atom on the end of every fatty acid. This end of the fatty acid is usually the one exposed since it is the most soluble in the blood. In theory, the active oxygen atom could reach out and steal a hydrogen atom from surrounding tissues, a process known as oxidation. If done millions or billions of times, the damage grows serious.
Oxidation's contribution to atherosclerosis is a subject of much hypothesizing. In addition to the possible involvement of the oxygen on the fatty acid chain, many other chemicals -- known as free radicals -- can cause similar damage. The science of free radicals and their role in human health is still somewhat embryonic. But it's suspected that some may come directly from harmful substances we eat or breath and others may come from the metabolism of fat and other food components.
In addition to a role in atherosclerosis, oxidants/free radicals are suspected of playing a role in cancer and some genetic defects.
Research has shown that the remnants of lipoproteins, left over after the contents have been delivered, may help cause atherosclerosis. Although the exact mechanism is not yet fully known, these fragments may form oxidizing free radicals. In addition, they may contribute to cholesterol deposits in an artery. Even though VLDLs and chylomicrons primarily transport triglycerides, they both contain cholesterol (as much as 45 percent in some VLDLs) which may remain with the remnant and contribute to artery lesions. Other research suggests that free radicals may damage LDL molecules in a way that makes them more likely to be deposited at lesion sites.
The researchers who manage to prove a unified theory on oxidants and heart disease will most likely find themselves on an airplane to Stockholm to pick up their Nobel Prize.
Long recognized as the leading cause of lung cancer, tobacco smoking causes more deaths from heart attack than cancer. Nicotine is a vasoconstrictor which raises blood pressure and decreases the blood supply to the heart and brain. This vasoconstriction alone can precipitate a stroke or heart attack.
But cigarettes may also injure arteries. In addition to nicotine, cigarette smoke is a potent stew of toxic chemicals ranging from formaldehyde to cyanide. These poisons can kill cells in the artery walls and pave the way for atherosclerosis. In addition, components of cigarette smoking:
-- accelerate the clotting process;
-- may cause cardiac rhythm problems (arrythmias) and
-- are allergenic to many people.
Water pipes crack and burst under too much pressure. High blood pressure, in most cases, has a far less dramatic effect, but there are indications that raising blood pressure may cause minute fissures in the artery wall, providing a site for a lesion to begin. Other research indicates that the injuries from high blood pressure may also come from turbulence in specific areas of an artery.
High blood pressure (above 160/95) can increase risks dramatically. For example, an otherwise healthy 35-year-old man with a blood pressure of 142/90 has twice the chance of dying from a heart attack within 20 years than if his blood pressure were 120/80. A level of 152/95 increases the chance to 2.5 times.
Stress can raise blood pressure by constricting arteries; it also makes blood more likely to clot. In addition, the adrenalin produced while people are under stress mobilizes the body's fat stores and raises the blood levels of free fatty acids (FFAs) to provide muscle energy. If, as some hypothesize, the oxygen molecule is an oxidant, chronic high levels of stress-induced FFAs may contribute to the formation of atherosclerotic lesions.
Finally, stress actually raises LDL cholesterol levels. Studies of tax accountants found steady increases in LDL leading up to and peaking around April 15. Levels steadily eased off afterwards.
While pre-menopausal heart disease in women has increased in the past 20 years (due primarily to increases in cigarette smoking and job stress), women under 60 still have less than one-third the risk (one woman in 10) of having a heart attack as men of the same age (one man in three).
Estrogen, it seems, increases HDLs while testosterone reduces it. From adolescence on, men have a 10 to 20 percent lower HDL than women and about 10 percent higher LDL.
Moderate consumption of alcohol plays a role in this sex-related mechanism. A 1992 study at the University of Pittsburgh found that post-menopausal women who were moderate alcohol consumers had a lower coronary death rate than abstainers or heavy drinkers, primarily because of increased levels of estradiol (one of the female sex hormones). The research indicated that alcohol may contribute by helping to change androgen (male sex hormones) into estradiol. It's known that female hormones are found in very low levels in men and male hormones in women. While no research yet exists on the effect of alcohol on male estrogen levels, this might offer one possible mechanism for alcohol's cardio-protective effect.
Physicians have known for decades that people suffering from diabetes have astronomically high risks of heart disease; uncontrolled diabetes almost always leads to blood vessel damage and heart disease.
Diabetes works its evil because another vital substance, glucose, becomes damaging once its concentration in the blood rises too high. Glucose is a simple sugar which is used for energy by most body cells. But when concentrations remain high (150 mg/dl) for long periods, they damage the tiniest of arteries, arterioles, which supply blood directly to the tissues. This causes the poor circulation which many diabetics first experience in their hands and feet; it also scars and blocks coronary arterioles.
Diabetes is characterized primarily by the body's inability to produce enough insulin which helps the body metabolize glucose and also affects the storage and metabolism of fatty acids.
While low insulin levels allow glucose to build up in the blood, high levels can be equally detrimental. Insulin stimulates the production of fatty acids (from glucose and similar compounds) which then increases blood triglyceride levels as VLDL molecules transport the new fat to storage in adipose cells. While the fat deposited under your waist is no longer circulating in the blood, the remnants of the VLDLs continue along, contributing their atherosclerotic damage.
The January 1992 issue of the British Medical Journal confirmed that women who drink alcohol moderately have the same reduced heart disease risks as men. But the study also found that while these women had elevated HDLs and lower levels of triglycerides and LDLs, they also had lower insulin levels (without suffering from the glucose intolerance found in diabetics).
This research supports the hypothesis that alcohol, particularly when consumed moderately with meals, tends to moderate insulin levels. It keeps them from hitting harmful peaks but without impairing the body's ability to handle glucose.
In addition, soluble fiber, found in fresh fruits and vegetables as well as in beans and oat bran, seems to help diabetics maintain stable glucose levels. This may also contribute to heart health in non-diabetics as well.
The role of obesity is somewhat confused. While most obese people have elevated fat and cholesterol levels, high-blood pressure and an increased incidence of diabetes, research shows that when these factors are removed, excess weight by itself has little relationship to increased risk of heart disease. (Textbook of Medicine, Beeson, McDermott & Wyngaarden, 15th edition, p.1221). Studies have shown that weight loss in people with high cholesterol levels can reduce overall cholesterol and increase HDLs.