CORONARY ARTERY NARROWING and RISK of the DISEASE
Abstract: The Artery Blockage Model estimates the degree of coronary artery narrowing at age from estimated rates of atherosclerosis progression and regression during life. Atherosclerosis builds up in and clogs arteries gradually during life from cholesterol levels existing at each prior year. The model recognizes that those that those that have had less favorable cholesterol values in the past than today probably will have more artery narrowing and higher risk of heart disease than those having more usual levels of cholesterol during life. This is recognized as an added risk factor. Life Ahead notes estimated average population values of artery narrowing of 40% or higher as a further caution to those having high risk of heart disease.
The Artery Blockage Model: The general model of Coronary Heart Disease recognizes that coronary arteries gradually build up deposits and plaque that obstruct their cross section and limit blood flow. Heart disease can be diagnosed if this clogging reaches certain levels - as for example if 50% or more of the artery diameter or cross section is blocked. Fatal heart attack often occur when a clot or other debris from a rupture of plaque breaks loose and blocks off a key coronary artery completely.
The italicized cholesterol is used to denote combinations of Total, LDL, and HDL cholesterol. Atherosclerosis produced principally by cholesterol causes artery deposits and narrowing. A general discussion on this is provided separately in the section ‘Atherosclerosis, a BioChemical Process’. The artery blockage model described following provides a rough quantification of the factors that produce this gradual narrowing over time.
It is important to recognize that the Artery Narrowing Model is for an average population only. Rates of narrowing in individuals can vary widely from this average. A coronary artery of an individual can be completely blocked for health factors that will produce less than 40% average narrowing in the population. Also arteries can narrow more than usual at sites of inflammation or other disturbance.
Artery blockage can be described either as artery cross section blocked or artery diameter blocked. The cross section value measures the resistance of fluid flow through the artery, and the diameter value probably best identifies a likelihood of a blockage. Either value can be used, but Life Ahead uses the diameter basis for identification of artery narrowing.
Some Prior Concepts: Researchers were confused for decades about the fact that although cholesterol clearly increased risk of disease by narrowing arteries, attempts to reduce coronary disease risk by modifying cholesterol often were unsuccessful. This is easily explained by the fact that atherosclerosis hardens over time and becomes difficult to remove. For many years some researchers thought that narrowing was essentially permanent. An improvement of cholesterol thus could help only a little to reduce disease by reducing a change in future artery narrowing.
This picture has now changed. First it is now clear that artery deposits and narrowing can regress, but only slowly. Second, the large improvements in cholesterol now achievable from Statin drugs can reduce coronary risk by much more than can be explained by the usual accompanying small reduction in artery narrowing. Some new theories are needed to explain this behavior.
The Development of a Heart Attack: Based on modern research, Life Ahead identifies cholesterol as producing attacks in two different ways. First, it promotes the buildup of atherosclerosis that gradually over decades narrows arteries. This narrowing that can be generalized throughout the length of an artery but invariably will produce differing amounts of narrowing at specific locations. And this process usually proceeds very gradually throughout life.
Second, cholesterol contributes continuously to the formation of soft plaque at specific locations that can develop over a liquid core and that is prone to rupture. High risk cholesterol levels at any time of life will be producing larger amounts of this soft plaque that can rupture within a relatively short time. Thus a level of cholesterol produces both long term artery narrowing and a shorter term increase in risk of disease via its contribution to fresh plaque formation. As mentioned elsewhere, the research of K Lance Gould shows that a majority of heart attacks can occur from plaque rupture before artery narrowing reaches the 50% level.
Yet the amount of artery narrowing must remain as a clear independent factor affecting risk. An individual that develops a high blockage from poor habits for say 50 years can have much narrower arteries than a second similar person having good habits. But by changing habits or use of drugs the previously poor habit person then can obtain a good habit cholesterol level. The cholesterol risk factor suggests they both then will have similar risks. This will not be true. The rate of new plaque formation and risk of rupture may then be similar for each. But the risk of a serious heart attack can be much higher for the individual with seriously narrowed arteries. Clots inevitably will be of varying sizes. And a more narrowed artery can be blocked by smaller clots or debris.
Needs for a BioChemical Engineering Model: A casually based model of coronary risk thus requires some measure of artery narrowing for an assessment of risk. Artery narrowing will be due mostly to factors that occurred in the past. Thus present cholesterol level, diet, smoking or other factors that exists at present can be largely irrelevant to an existing extent of artery narrowing. Life Ahead as a life cycle model is designed to develop effects of factors such as this that occur gradually over life.
LDL cholesterol is now recognized as the key factor that produces atherosclerosis. The rate of atherosclerosis buildup in any time period as for example one year will depend in part of the level of LDL cholesterol in that year. Life ahead first estimates deposit formation as related to the sum of the LDL-cholesterol years in each year to a present age or age of interest. A first estimate of probable artery narrowing is guided by the work of Strong as described in the separate discussion of Atherosclerosis.
Other health factors affect the rate at which LDL cholesterol produces atherosclerosis and heart disease. These include HDL cholesterol, smoking, exercise, antioxidants and fats in diet, and the other factors known to affect risk of heart disease. We do not have specific data on the contribution to artery narrowing of each of these factors. But their effects on atherosclerosis can be inferred from their well identified effects on heart disease.
Further, atherosclerotic deposits do regress. Any quantified generalized model of artery narrowing must recognize and quantify this. Preliminary attempts to build a useful mathematical model of artery narrowing showed that without regression most arteries would clog completely at some age and nearly everyone would suffer heart disease. This is not true.
Rates of Atherosclerosis Formation and its Regression: Various options for quantifying atherosclerosis development and regression were considered in developing the Life Ahead Model of coronary artery narrowing. The only scenario found that fit the available known facts derives from the assumption that the body is always attempting to repair itself via the immune system. This process of repair results in a general reduction in overall atherosclerosis deposits at a rate now estimated at about 4% per year. The higher the total amount of deposits, the greater is the amount removed each year via this process. This model mechanism can explain how atherosclerosis in response to a lowering of cholesterol either can continue to increase but at a slower rate, or actually start to diminish in its extent. No other model tested could accomplish this requirement for a useful representation of known facts.
Opposing this rate of repair is a continuing formation of atherosclerosis from LDL cholesterol and its many modifying factors. If this formation rate is higher than the repair rate, arteries will continue to narrow. If the formation rate drops below the repair rate, narrowing can actually diminish. But as the deposits build to certain levels a balance can be obtained at which narrowing reaches a given plateau.
Estimating Artery Narrowing: The Life Ahead Artery Blockage model first simulates the formation of deposits as percentage of artery surface area as found by the Strong research. The function (LDL Cholesterol – 50) is used to represent s key or starting cause of deposit buildup. This function is needed because at a LDL cholesterol of 50 no atherosclerosis appears to form. Thus only the elevation of cholesterol above this null-effect value is pertinent. Deposits accumulate each year as a further function of the LDL that is present during this specific year. Deposits are considered to initiate at year 1 of age. But because cholesterol usually is low during childhood the amounts of deposits accumulating then usually are small.
The rate of this deposit formation is then modified directly by risk factors such as HDL cholesterol, family risk, diabetes, blood pressure, antioxidants, body weight and cigarette smoking. The adjustment for cardiofitness assumes that average artery diameter will increase somewhat with increase in cardiofitness levels as per the discussion of the role of exercise and fitness. For each year of deposit formation 4% of the atherosclerosis total surface area value is subtracted to account for regression. A relationship between artery surface area coverage and probable average artery diameter blockage derived from various data sources then produces an estimate of artery narrowing at each age of life.
The values of artery narrowing produced by the blockage model are consistent with the measurements taken in Viet Nam and Minnesota mentioned in the accompanying discussion for the usual values of total cholesterol and amounts of cigarette smoking in male populations at that time. They are consistent with limited other data found on amounts of artery narrowing. Average population coronary artery narrowing and rates of coronary disease probably are lower today than 2-3 decades ago because of lesser population smoking and lower levels of total cholesterol. .
Estimates of average population values of artery narrowing are approximate only. The amounts of narrowing for individuals will vary considerably from these averages. And the maximum areas of narrowing at specific locations in arteries that provide the major risk will be higher than these average values. Thus values of percent narrowing provide only a general guide. The specific Life Ahead valuations of actual risk of and death from disease shown in all Life Ahead results will be more accurate and meaningful than are estimates of artery narrowing.
Use of the Artery Narrowing Model in Life Ahead: It is useful to first define a 'Usual Effect' of Cholesterol as that related to risk of disease defined in the accompanying article on Cholesterol. This 'Usual Effect' on risk of coronary disease that from the large MRFIT study is related to levels of Total, LDL, and HDL cholesterol maintained for long periods during life. This relationship should be quite accurate. But this overall effect includes both the long term results of artery narrowing AND the short term direct effect of cholesterol in producing plaque formation. Research on the benefits of cholesterol lowering noted in this article show that short term reduction in risk for a given change in Total and HDL cholesterol is a bit more than half of cholesterol's 'Usual Effect.' This suggests that the short term effect of Cholesterol on plaque formation accounts for about 55% and long term narrowing explains about 45% of the overall 'Usual Effect' of cholesterol in producing heart disease.
Why is this of interest? The problem requiring solution is that of evaluating the risk of persons having the same cholesterol today but who had far different past habits and cholesterol levels. Their artery narrowing and true risks will be quite different. Life Ahead develops a separate risk factor to represent any deviation in likely present artery narrowing vs. average. Any Life Ahead user that enters only a single or very few recent cholesterol values will have a unity blockage factor because past habits either were similar to average or they were unknown.
But consider a man of say age 50 that had quite high cholesterol and then achieved normal cholesterol with drugs. His risk will be helped significantly by the drugs. But his arteries almost certainly are narrowed by previous unfavorable cholesterol. And by no means will his risk revert immediately to the much lower 'Usual Effect' risk of a person that had lifetime normal cholesterol. For this user Life Ahead will compute artery narrowing and an artery narrowing risk from the cholesterol values prior to drug use. This will recognize that the results of prior risks simply do not disappear immediately. A similar scenario will be true for a person of very poor health habits that accomplishes a large improvement in cholesterol from good habits.
But although cholesterol improvement may achieve only 55% of 'Usual Effect' benefit immediately, a continued improved cholesterol usually will reduce artery narrowing for each future year it is maintained. Thus over the longer term artery narrowing risk usually will decline. Eventually the benefit of the lower cholesterol should approach the 'Usual Effect' risk benefit of cholesterol.
The Life Ahead computer program identifies values of artery narrowing at the heart disease option on the main result display. Changing factors such as diet and exercise starting say at middle age usually will not produce a large difference in artery narrowing during the next 10-20 years. Rather, the narrowing factor will be revealed most importantly for factors maintained throughout life and prior to present age such as smoking starting at say age 17, and diets starting say at age 20-30. Thus its effect cannot be identified completely using the Demo program that initiates changes in habits starting at age 50. The purpose of the narrowing factor is to reflect a modest recognition of the effect of habits prior to present age that will not be reflected by present health risks or cholesterol levels. To access the free Life Ahead program, download it from Download Life Ahead
Future Improvements: Artery narrowing values produced now in Life Ahead for average populations rarely go above 60% even for very high combination risks. In the real world many individuals having heart attacks will have one or more coronary arteries 100% obstructed. Concise forecasts of such narrowing are beyond the capability of the present method. But a more sophisticated BioChemical model of the process of atherosclerosis and of the formation of vulnerable plaques than that now is provided by the very elementary model included here could make a very useful contribution to the further reduction of heart disease of our population.
Yet artery narrowing values provided by the program can give some added insight about risk of heart disease, and are provided by Life Ahead. Computed values of artery narrowing above 40% identify significant risk. Narrowing values above 50% suggest possible presence of actual heart disease, substantial risk, and a need for visiting a doctor.