From time to time, Cecilia, our resident science journalist and poet, will contribute reviews of her various readings and occasional attendance at conferences. Tom will add his comments regarding various aspects of the subject matter where he considers amplification, correction, or modification is warranted.
Well-known risk factors for atherosclerosis such as diabetes, hyperlipidemia, hypertension, and smoking, account for only about 50% of clinically diagnosed cases. Below is a brief review of theories that try to take a different and/or broader view of the causes of atherosclerosis.
The foremost of the contending theories is the inflammation theory, championed by Paul Ridker, MD, a Harvard cardiologist. Ridker argues that atherosclerosis cannot be regarded as a lipid-accumulation disease. The "cholesterol hypothesis" of heart disease can't explain why heart attacks occur in people with perfectly normal-range or even low cholesterol, or the fact that autopsies show clogged arteries in one individual, and clean arteries in someone else with very similar cholesterol readings. Neither total nor LDL cholesterol has much predictive power, according to Ridker. Clinicians who look only at serum lipids miss 65% of cardiovascular disease.
A particularly interesting and unexpected argument against the cholesterol hypothesis of atherosclerosis is the now well established finding about the benefits of statins. Patients on statin drugs have a lower incidence of heart attacks than patients in the same cholesterol range who are not taking statins. Ridker points out that statins reduce inflammation, as reflected in much lower levels of C-reactive protein. Statins also reduce the risk of stroke, even though high cholesterol is not a risk factor for stroke.
Actually, it is enough to look at the fact that aspirin reduces the risk of a heart attack. Aspirin does not lower cholesterol. It lowers inflammation, as reflected in the levels of C-reactive protein.
Ridker maintains that what matters is the stability or instability of atherosclerotic plaque. Inflammation destabilizes the plaque, making a heart attack more likely. Even low cholesterol does not protect against heart attack in the presence of high degree of inflammation. Conversely, some people with high cholesterol never develop heart disease.
{Inflammation is also involved in the initial buildup of atherosclerotic plaque as well as its stabilization. Thus, anti-inflammatories such as aspirin prevent heart attack by at least two modalities. --Tom}
Nevertheless, high serum lipids are a contributing factor: patients with high C-reactive protein and high lipids are at the highest risk. The typical signs of an imminent heart attack are as follows: high triglycerides, low HDL cholesterol, and high markers of inflammation such as C-reactive protein and interleukin-6. (Ridker discovered that high interleukin-6 (IL-6), a pro-inflammatory cytokine that recruits macrophages to migrate into the atherosclerotic plaque, is also a good predictor of a heart attack.)
In Ridker's view, atherosclerosis is first and foremost an inflammatory disease. In order for atherosclerosis to develop, inflammation and thus the immune system have to be involved. If we can prevent inflammation, we can presumably prevent heart disease (and Alzheimer's disease and cancer, in the view of some alternative physicians).
{Note that this does not imply that all inflammation is inherently bad and should be abolished if possible. Most of the body's inflammatory responses are healthy and beneficial. What needs to be reduced is excessive or inappropriate inflammation which can be harmful. The difference between these two is not always clear, but it is important to not throw out the good with the bad. --Tom}
The inflammatory theory of heart disease is also called the immunological hypothesis. "The genesis of an atherosclerotic plaque depends on interplay of cellular components of the immune system such as monocytes, cytokines, and cell adhesion molecules with lipids, platelets, and endothelial cells," Ridker concludes R.
What causes the inflammation that leads to full-blown atherosclerosis? There is no single cause, but rather several possible factors. One such factor is toxins, such as those found in cigarettes. Another factor is infections. Yet another is emotional stress (some would argue that chronic emotional stress is as disastrous to cardiovascular health as smoking, if not more so). Finally, obesity too increases the inflammatory state. This may have to do with the ability of fat cells to produce IL-6.
The preventive implication of the inflammatory theory of atherosclerosis is obvious: reduce your inflammatory burden. Stress reduction, avoidance of toxins and exposure to infection, and the right diet and exercise for the prevention of obesity are all important. Modern life makes these measures difficult, however. In addition, we know that the amount of inflammation increases with age. We must seriously consider using non-toxic anti-inflammatories such as fish oil and flavonoids; in some cases, aspirin, ibuprofen, and/or COX-2 inhibitors would be beneficial. All known antioxidants also act to reduce inflammation.
{While the selective COX-2 inhibitors are important new drugs, their history of therapeutic usage is too short as yet to recommend them for chronic anti-inflammatory purposes except where clear underlying pathologies exist. In this regard, one should even be cautious with chronic use of aspirin and ibuprofen, unless taken at low dosages. --Tom}
Yet another view holds that the most important factor in preventing heart disease is the right diet. Richard Fleming, MD, also regards cholesterol as basically irrelevant; he sees excess calories as the prime cause of atherosclerosis. The answer is calorie restriction. Ideally, we should eat only 70% of what we are used to eating. The diet should emphasize natural unprocessed plant food. Animal studies provide abundant evidence for the cardioprotective benefits of lowering calorie intake.
Fleming also points out that there is a correlation between heart disease and breast cancer. One can predict both based on the levels of calcium deposits in the arteries and other soft tissue. We know that high dietary calcium intake helps prevent obesity, and is needed to keep calcium in the bones (although calcium is not the only factor; several hormones are also involved). This area needs much more research.
{Research makes it clear that levels of calcium in arteries and soft tissue are not much related to dietary calcium. Thus, it would not be wise to lower dietary calcium in an attempt to reduce risk of arterial and soft tissue accumulation or remove calcium from such tissues. --Tom}
Finally, some alternative clinicians have concluded that the most important risk factor for heart disease, as well as cancer, is emotional stress. The biochemistry of chronic stress is highly toxic and pro-inflammatory. Stress management, various relaxation practices, learning to live in the moment, and deliberate induction of positive emotions are important preventive and therapeutic tools.
While these theories differ in emphasis, they are not mutually exclusive. It is important to bear in mind that cardiovascular disease is multifactorial. Prevention needs to be multifactorial also.