A predictor of heart disease?
The Cholesterol Myths
While cardiovascular disease (CVD) is still one of the top health risks in the country, the role cholesterol plays in the disease process is still somewhat controversial. Does a high cholesterol level cause heart disease or is it just a symptom of the disease process? By lowering elevated cholesterol levels are we curing the disease or merely treating a symptom? Does an elevated cholesterol level mean you have heart disease?
Cholesterol is an important substance and the most important compound of those classed as sterols. It is found in practically all animal cells serving as an essential component of the plasma membrane and other membrane structures. In normal human adults it is found in the liver, skin, brain and nervous tissues, intestine and certain endocrine glands, with the adrenal gland containing some 10%. For more information on the synthesis and importance of cholesterol see this article.
The process of plaque formation in the vasculature and what role cholesterol specifically plays in this process is still under debate. Many of the studies performed on the role of cholesterol and CVD have been funded by pharmaceutical companies that have an interest in selling cholesterol lowering medications, so questions have been raised about conflicts of interest.
Homocysteine has also been implicated in the atherosclerotic process. The "father of homocysteine", Kilmer McCully, M.D., gave some general health advice in an interview with the Saturday Evening Post:
Q: In The Heart Revolution, you write at length about the important difference between oxycholesterol and cholesterol in terms of our overall health.
A: This is a tremendously important distinction that many in the general public and in the scientific field do not fully appreciate.
Cholesterol found in whole fresh foods of animal origin--fresh meats, fish, eggs, butter--is highly pure and entirely safe to the arteries. In other words, cholesterol serves as a protective substance the body produces and obtains from the diet. As a matter of fact, this pure cholesterol is a very potent antioxidant, protecting the body against oxidation.
On the other hand, a high homocysteine level promotes the formation of "oxycholesterol" forms that contribute to plaque formation.
Oxycholesterols are also present in certain foods. Some important sources of oxycholesterols in the American diet are powdered eggs and powdered milk that are widely used in manufactured and processed foods, as well as fried foods.
In fast-food restaurants, hot oil is used to fry chicken or fish. Cholesterol from the chicken or fish is oxidized by the oil's high temperature and its exposure to oxygen, creating oxycholesterol. These oxycholesterols dissolve into the oil, so when French fries are cooked in the same oil, they absorb these oxycholesterols. In animal studies, 6 or 12 oxycholesterols have been proven highly damaging to the arteries.
This is an important distinction between the generally safe pure cholesterol and the highly damaging oxycholesterols.
Q: Can you offer our readers some general dietary guidelines?
A: Basically, people should eat fresh, whole, well-prepared foods, including a variety of fruits, vegetables, whole grains, fresh fish, meats, eggs, and other fresh dairy products with a minimum of processing and preservation. Avoid highly processed, preserved, and packaged foods as much as possible, particularly those containing white, wheat, rice, and other highly processed flours, such as cake flour. Avoid foods that contain lots of sugar, such as soft drinks, desserts, or yogurt with added sugars, as well as foods with large quantities of added oils. People should particularly avoid all foods containing hydrogenated oils, including margarine, artificial shortenings, as well as foods containing the partially hydrogenated oils, because these oils contain trans-fatty acids that are very damaging to arteries. Finally, avoid foods containing powdered eggs, powdered milk, and fried foods containing oxycholesterols.
If cholesterol causes heart disease then statistics should show this. On the contrary, half of US heart attack victims have acceptable cholesterol levels. Another study, published in The American Journal of Cardiology, attempted to find a relationship between coronary artery calcium scores identified by electron beam tomography (EBT) and serum lipoprotein levels. The authors concluded that:
There were no significant differences in the calcium scores throughout the entire range of all lipid parameters; calcium percentiles were virtually identical within lipid value subgroups. We conclude that asymptomatic patients with EBT-defined sub-clinical atherosclerosis are not reliably identified by NCEP [National Cholesterol Education Program] guidelines, and TC [Total Cholesterol], LDL-C, HDL-C, TC/HDL-C, and triglyceride levels do not correlate with either the extent or pre-maturity of calcified plaque burden.
There were no significant differences in calcium scores throughout the range of LDL-C except between the highest (≥160 mg/dl) and lowest (<100 mg/dl) groups (p=0.01); the lowest group had the higher score. [i.e. more calcium deposition].
Here are the conclusions of other studies that tried to assess the ability of lipid levels to predict the likelihood of artery plaque:
The comparative effects of more versus less aggressive low-density lipoprotein (LDL) cholesterol lowering (to </=80 vs >80 mg/dl) on calcified coronary plaque progression by electron beam tomography were evaluated in 182 consecutive asymptomatic patients after 1.2 years of treatment with statins alone or in combination with niacin. Despite the greater improvement in lipids in the </=80 versus >80 mg/dl groups, there were no differences in calcified plaque progression (9.3%/year vs 9.1%/year). We conclude that, with respect to LDL cholesterol lowering, "lower is better" is not supported by changes in calcified plaque progression1
In the context of the beneficial effects of statins, irrespective of the low-density lipoprotein cholesterol level (LDL-C) in the Heart Protection Study and the relatively poor event reduction (24%-37%) in the LDL-C reduction trials, electron beam tomography plaque imaging has provided the necessary data to support a reorientation of traditional treatment paradigms. The prognostic superiority of calcified plaque quantitation to conventional risk factor assessment and the poor correlation between pretreatment standard lipid values and amount of plaque in individual patients, as well as between post treatment lipid changes and changes in calcified plaque burden, suggest the following: (1) significant calcified plaque shifts the asymptomatic patient from primary to secondary prevention status; (2) "abnormal" lipid values in individual patients are best defined by the level at which atherosclerosis develops; (3) non LDL-C disorders contribute to CAD and should be identified and treated; (4) plaque burden, rather than plasma lipid values, should be the target of therapy; and (5) adequacy of therapy is best evaluated with serial plaque imaging. Other treatment applications of plaque imaging include triage of patients for stress testing and evaluation of stress test results2.
Neither cholesterol values, body mass index, gender, age nor presence of individual risk factors predicted progression of coronary calcium. CONCLUSION: Presence of elevated homocysteine (>12mumol/L) strongly and independently predicts progression of coronary plaque burden3.
There was no correlation between either calcium percentile or score and any lipid measurement. CONCLUSIONS: This study demonstrates the shortcomings of employing NCEP guidelines to identify asymptomatic women with subclinical CAD, particularly women >55 years, and suggests increased utilization of EBT for primary prevention in the female population4.
We investigated whether coronary artery calcium (CAC) progression and low-density lipoprotein (LDL) reduction have a complementary prognostic impact.....CONCLUSIONS: Progression of CAC was significantly greater in patients receiving statins who had an MI compared with event-free subjects despite similar LDL control. Continued expansion of CAC may indicate failure of some patients to benefit from statin therapy and an increased risk of having cardiovascular events5.
Calcified plaque progression by electron beam tomography was evaluated in 176 aggressively treated asymptomatic patients. Similar plaque progression was noted irrespective of baseline low-density lipoprotein cholesterol levels, including those with low-density lipoprotein cholesterol <100 mg/dl.6
Tracking of coronary artery calcium (CAC) has been suggested for monitoring the effects of lipid control, but it is not known whether lipid control decreases progression of CAC. Seven hundred sixty-one subjects (mean age 64.5 +/- 7.3 years; 91% men; 69% positive for CAC) in an ongoing cohort study underwent baseline and follow-up (after 7.0 +/- 0.5 years) computed tomography for CAC. Subjects were stratified into low-risk (<2 risk factors), intermediate-risk (> or =2 risk factors but <20% risk of coronary heart disease over 10 years), or high-risk (> or =2 risk factors and >20% risk of coronary heart disease in 10 years or diabetes) groups. Lipid control was defined according to criteria of the National Cholesterol Education Program. Two-way analysis of covariance was used to examine the relation of low-density lipoprotein (LDL) cholesterol and risk group to change in CAC volume score. Control of levels of high-density lipoprotein (HDL) cholesterol and triglycerides was also examined in relation to progression of CAC. After adjustment for other risk factors and baseline CAC volume, CAC progression was similar between those with adequate and those with inadequate control of LDL cholesterol and across categories of optimal, intermediate, and higher risk LDL cholesterol.7
TABLE 1. Univariable and Multivariable Association Between Risk Factors, CAC, and Cardiac Events in Men8
|The 6-predictor Cox proportional hazards regression models included simultaneously all variables listed in the table.|
As you can see from Table 1, hypercholestrolemia was by far the weakest predictor of cardiac events out of all the risk factors studied. On the other hand, presence of CAC was strongly associated with all cardiac events.
It is obvious from recent studies, only some of which have been quoted in this article, that EBT is by far the best tool for detecting CAD. Electron-beam tomography (EBT) plaque imaging has the potential to fundamentally change the practice of prevention, through application of the following principles: (1) Asymptomatic patients with significant calcified plaque should be considered to have a clinical coronary artery disease risk equivalent. (2) Measurement of nontraditional parameters should be incorporated into the evaluation of patients with calcified plaque. (3) Drug treatment should focus on the asymptomatic patient with sub-clinical atherosclerosis. (4) Change in plaque rather than change in lipid values should guide treatment9.
1 Hecht HS, Harman SM., Relation of aggressiveness of lipid-lowering treatment to changes in calcified plaque burden by electron beam tomography, Am J Cardiol. 2003 Aug 1;92(3):334-6.
2 Hecht HS, Translating tomographic plaque imaging into treatment: interventional lipidology, Prog Cardiovasc Dis. 2003 Sep-Oct;46(2):149-70.
3 Rasouli ML, Nasir K, Blumenthal RS, Park R, Aziz DC, Budoff MJ, Plasma homocysteine predicts progression of atherosclerosis, Atherosclerosis, 2005 Jul;181(1):159-65.
4 Hecht HS, Superko HR., Electron beam tomography and National Cholesterol Education Program guidelines in asymptomatic women., J Am Coll Cardiol. 2001 May;37(6):1506-11.
5 Raggi P, Callister TQ, Shaw LJ, Progression of coronary artery calcium and risk of first myocardial infarction in patients receiving cholesterol-lowering therapy., Arterioscler Thromb Vasc Biol. 2004 Jul;24(7):1272-7. Epub 2004 Apr 1.
6 Hecht HS, Harman SM., Relation of response of subclinical atherosclerosis detected by electron beam tomography to baseline low-density lipoprotein cholesterol levels., Am J Cardiol. 2004 Jan 1;93(1):101-3.
7 Wong ND, Kawakubo M, LaBree L, Azen SP, Xiang M, Detrano R., Relation of coronary calcium progression and control of lipids according to National Cholesterol Education Program guidelines., Am J Cardiol. 2004 Aug 15;94(4):431-6.
9 Hecht HS., Lipid disorders and plaque imaging., Am J Cardiol. 2001 Jul 19;88(2A):56E-58E.
The Cholesterol Myths
Cycles of Precession