Beyond Bad Cholesterol
ALTHOUGH LDL frequently sparks the sequence of events I have outlined, scientists have identified several other factors that unequivocally increase a person’s risk for atherosclerosis or its complications. Many of these risk factors, and a few still under study, exhibit intriguing inflammatory properties. Before I describe some of those features, I must first point out that LDL probably plays an even larger role in initiating and perpetuating atherosclerosis than is generally recognized.
A much repeated statistic says that half of all patients who have angina or have had a heart attack do not have above-average LDL levels—a finding frequently interpreted to mean that in such individuals, LDL exerts no influence on the atherosclerosis at the root of those disorders. But typical LDL levels in Western society exceed by far the body’s needs and can actually promote arterial disease.
Indeed, in response to new data correlating heart health with lipoprotein levels, public health experts have progressively refined the definition of “healthy” LDL levels. Guidelines released last year by an expert panel convened in cooperation with the National Institutes of Health now explicitly label LDL-cholesterol levels below 100 milligrams per deciliter of blood (mg/dL) as optimal. They also suggest considering drug treatment earlier than before—at 130 mg/dL instead of 160—for certain people with multiple risk factors. For adults with a relatively low risk of heart disease, the guidelines recommend (as before) initiating “lifestyle changes”—diet and exercise— at 160 mg/dL and considering drug treatment at 190 mg/dL.
Investigators have yet to explore the connections between other risk factors and inflammation with the intensity accorded to LDL, but they have uncovered suggestive links. Diabetes, for instance, elevates glucose levels in the blood; this sugar can enhance the glycation, and thus the inflammatory properties, of LDL. Smoking causes oxidants to form and might hasten the oxidation of LDL’s constituents, thereby fostering arterial inflammation even in individuals with average LDL levels. Obesity contributes to diabetes and vascular inflammation. High blood pressure may not exert direct inflammatory effects, but a hormone partly responsible for much human hypertension—angiotensin II—appears to incite inflammation as well; elevated levels of this hormone, then, might give rise to hypertension and atherosclerosis simultaneously.
Conversely, high-density lipoprotein (HDL) seems beneficial; as levels of this “good cholesterol” decline, the likelihood of suffering a heart attack goes up. Accordingly, to fine-tune estimates of cardiovascular risk, many physicians today measure not only levels of LDL in the blood but also the level of HDL and the ratio of LDL (or LDL plus its various relatives) to HDL. HDL may achieve its beneficial effects in part by reducing inflammation: along with cholesterol, it can transport antioxidant enzymes able to break down oxidized lipids.
Given inflammation’s usual responsibility in the body—blocking and eliminating infectious agents—biologists have naturally looked at whether arterial infections might contribute to inflammation in the arteries. Recent work suggests that atherosclerosis can develop in the absence of infection. Nevertheless, circumstantial evidence suggests that certain microorganisms, such as herpesviruses or the bacterium Chlamydia pneumonia (a frequent cause of respiratory infections), could well induce or aggravate atherosclerosis at times. C. pneumonia, for instance, appears in many atherosclerotic plaques, and its constituents can evoke inflammatory responses by macrophages and by vascular endothelial and smooth muscle cells.
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Add CommentLinus Pauling wrote in 1986 that vitamin C decreases LDL and increases HDL in the blood. C binds to cholesterol and transports it to the liver, where it is converted to bile and excreted. Vitamin C is a component of collagen, an essential structural component of arteries. Dr. Pauling wrote that atherosclerotic plaque is an evolutionary adaptation to the chronically low levels of vitamin C in humans, one of the few species who do not synthesize vitamin C internally. The medical-pharmaceutical establishment does not advocate vitamin C to prevent heart disease because there is far greater profit in treating heart disease, by means of medical procedures and drugs.
Reply | Report Abuse | Link to thisAlthough most people don’t realize it, atherosclerosis is a disease which, in addition to being a lipid storage disorder, also has components of inflammatory and immunologic disease. Thanks to television commercials, the cartoon image of cholesterol plaques that most people have in their head is if a yellow cholesterol plaque stuck to a red arterial wall. The truth is that most of that yellow plaque is not make up of cholesterol; it is made up of the body’s own cells responding to an endothelial disturbance, in addition to cellular markers of inflammation such as TNF-a, IL-6, hsCRP, foam cells, among many others. One of the main differences in the effectiveness of HMG CoA reductase inhibitors or “statins” in addition to their ability to increase the metabolism of cholesterol, is their ability to decrease inflammation. The two drugs that are best at decreasing inflammation cholesterol metabolism are Lipitor (atorvastatin) and Crestor (rosuvasatin). No currently marked drug exists which can affect the immunologic or cell migration effect in atherosclerotic plaques.
Reply | Report Abuse | Link to thisI suggest a new round of actualization now in 2010. Influenza would sure receive more consideration today regarding myocardial infarction triggering. But I continue to insist that triggering not its sole contribution.
Reply | Report Abuse | Link to thisMaria Ines Azambuja, MD
see Connections Braz J Med Biol Res January 2008, Volume 41(1) 1-4
I came to this article to see what a respected institution had to say about the causes of Atherosclerosis. The lipid theory has been significantly discredited by most research untouched by big pharma. This piece while not directly advocating it is pointing to statin therapy, and relating Atherosclerosis to LDL levels. When research said that there is no difference amongst patients who have had a heart attack in terms of their cholesterol levels - the proponents say we need to lower the LDL threshold, despite the almost total lack of evidence that LDL serum levels have anything to do with MI. What is disappointing is that there is NO discussion about what causes the inflammation in the first place. The levels of MI in our society have increased steadily in the past 100 years or so. These breakthroughs (in statin therapy) have not provided any solution to this health issue. The key is understanding lies in what causes the inflammation that leads to Atherosclerosis and modifying our lifestyle and diet to suit. The information must be there somewhere - there is somehting that has changed in the past 100 yrs that have made this MI epidemic, but maybe its not in the interest of some stakeholders for us to find out. Unfortunately SA have added more fuel to the old song about cholesterol myth and I await patiently when this Stalin billion dollar scam blows open.
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