- Email: [email protected]
A population-based approach to cholesterol control
A Population-Based
Approach
to Cholesterol
Control
Jerome D. Cohen, MD, st. LOU;S,Missouri
The large proportion of the population who have only modest or moderate hypercholesterolemia will experience more coronary events than the smaller percentage of people who are at higher risk from more extreme elevations of serum cholesterol. The high-risk individual strategy for prevention of coronary heart disease (CHD) can result in impressive declines in cholesterol, but the benefits will be concentrated at the upper end of the population distribution. On the other hand, a population strategy for coronary disease prevention will achieve a much more modest reduction of cholesterol, but these changes will be over the entire distribution and will reduce the risk of the much larger proportion of people with average cholesterol levels who otherwise would likely go untreated. In light of the fact that epidemiologic studies and long-term clinical trials predict that a 10% reduction in serum cholesterol will result in a 30% reduction in coronary events, the population strategy has the potential for an enormous impact in reducing CHD, which, despite our great success over the past two decades, still remains the number one killer in the United States. 01997 by Excerpta Medica, Inc. Am J Med. 1997;102(2A):23-25.
From Preventive Cardiology Programs, St. Louis, Missouri. Requests for reprints should be addressed to Jerome D. Cohen, MD, Department of Medicine, Preventive Cardiology Programs, St. Louis Universky Health Sciences Center, 3525 Caroline Avenue, St. Louis, MISsouri 63104.
01997 by Excerpta . .. . . . AlI rlgnrs reservea.
Medica,
Inc.
D
espite impressive gains in reducing death rates over the last 20 years, coronary heart disease (CHD) still remains by far the number one killer in the United States. Furthermore, because of changing demographics and the aging of the population, the actual number of deaths has changed relatively little. Of the nearly 500,000 deaths that occur every yearabout one every minute-many of these deaths are Iii-St-event sudden deaths. About 80% of the coronary deaths among people <65 years of age occur during the initial attack.’ These statistics clearly underscore the importance of a prevention strategy as the principal approach to reducing further this high morbidity and mortality. In fact, the decline in CHD over the past two decades appears to be due primarily to changes in lifestyle and improvement in associated coronary risk factors: i.e., the dietary changes that have led to a reduction in the mean level of serum cholesterol and the impressive decline in cigarette smoking. These two trends alone may account for more than half of the reduction in age-adjusted coronary mortality rates observed over the past two decades.’ In general, there are two basic strategies for prevention. The first is aimed at identification and treatment of the high-risk individual. The second is a population strategy, which encompasses public health interventions, such as dietary recommendations to lower serum cholesterol, on a populationwide basis. The high-risk individual strategy is based on two observations: first, the upper portion of the risk distribution accounts for a disproportionate share of the disease; and second, the relationship between blood cholesterol levels and coronary disease is not linear but exponential, such that the predicted benefits from cholesterol lowering are greater for those who are at the upper end of the distribution. With identification and treatment, the mean reduction of cholesterol among this high-risk group would be relatively large, as would the risk reduction, and the benefits would be limited to this high-risk group. By contrast, the population or mass strategy is based on the achievement of a considerably smaller reduction of mean cholesterol across the entire population. The high-risk individual and population-based strategies are complementary and not mutually exclusive. If successful, the mass strategy would result in a shift of the entire population distribution of serum cholesterol toward the lower end of the spectrum. QOO2-9343/97/$17.00 PII SOOO2-9343(97)00463-9
23
SPECIAL ISSUE ON HYPERCHOLESTEROLEMlA/COHEN
The effect of this strategy would be to reduce minimally the risk of CHD in people who are at high risk based on their higher serum cholesterol levels, but also, and even more importantly, it would reduce the risk of the large portion of the population who are lower in the cholesterol distribution, having “average” serum cholesterol levels. Many of these people, indeed perhaps most of them, would otherwise be untreated because their cholesterol levels are “average,” We have known for many decades now that population groups with higher levels of serum cholesterol have a higher risk for future coronary events. Data from both the Framingham Study and the Multiple Risk Factor Intervention Trial (MRFIT) screening study’ clearly demonstrate and confIrm this relationship. When discussing the risk of disease, it is important to recognize the distinction between absolute and relative risk. Absolute risk is the observed rate of an event in a given population over time. It is expressed in units such as per 1,000 persons per year and gives information about the frequency of the disease (i.e., incidence). Relative risk is a ratio of incidence rates, a numerical value without units, used to express the risk of an event, e.g., heart attack in subgroups with higher or lower cholesterol levels. This value is usually compared with the risk of the entire population, which is assigned an arbitrary value of 1.0. Relative risk is useful in evaluating the strength of the association between the risk factor and the disease but gives no information regarding the magnitude and overall importance of the risk factor in the population. The relative risk of various levels of cholesterol for coronary mortality from the MRFIT is shown in Figure 1 .4,5 To appreciate the potential impact of a populationbased approach, it is important to examine the concept of population attributable risk. This is the excess risk of disease associated with the presence of a risk factor in the population when compared with the risk of that portion of the population in whom the risk factor is absent. In this way, the proportion of the disease attributable to various levels or cutpoints of a risk factor, e.g., serum cholesterol in the population, can be examined, and an estimate can be made of the overall disease impact of that factor. Data from MRFIT have been analyzed to study the relationship between coronary death rates and the distribution of cholesterol levels in the population6 Considering serum cholesterol levels < 180 mg/dL as baseline risk, about 20% of the population were in this low-risk group. About half of all coronary deaths could be prevented by lowering the cholesterol level of the other 80% of the population to achieve a total cholesterol level of 180 mg/dL. The majority of the excess or potentially preventable deaths in MRFIT 24
FEBRUARY
17,
1997
The Amencan
Journal
of Medlclne@
Volume
Risk ratio
01 100 (2.59)
I
/
I
I
150 (3.88)
200 (5.17)
250 (6.47)
300 (7.76)
Plasma cholesterol
mg/dL (mmol/L)
Figure 1. Plasma cholesterol
mortality by risk ratios in the Multiple Risk Factor lntervenbon Trial (MRFIT). A continuous relationship between cholesterol level and cardiovascular mortality exists beginning at a cholesterol level of 150-l 60 mg/dL. (Adapted with permission from Grundy SM.5)
were among those with a serum cholesterol level >180 mg/dL and ~250 mg/dL. This demonstrates a basic principle in the population strategy of disease prevention-a large percentage of people exposed to a moderate risk, such as modestly elevated levels of serum cholesterol, will give rise to more cases than the smaller percentage of people who have a more extreme elevation of risk.7 In the high-risk individual prevention strategy, those persons who are at the upper end of the distribution are identified and appropriate care provided. While this is beneficial for those high-risk individuals so identified and treated, the fact that there is a relatively small number in this group means that the ultimate impact on CHD deaths in the overall population, even with a very successful screening and treatment program, will not be large. When examining strategies that will yield the greatest impact on the prevention of CHD, population-based approaches, e.g., dietary changes designed to shift the whole cholesterol distribution toward the lower end of the scale, will have a larger effect. This has been pointed out by Rose, who said that a mass approach is “inherently the only ultimate answer to the problem of a mass disease.‘17Rose also recognized that individual changes may be so subtle as to be considered clinically insignificant, even though the impact of such small changes across the entire population would be considerable. He coined the term “prevention paradox,” to acknowledge that a measure that brings large benefits to the community as a whole may offer little perceptible change to each individual.7 In addition to considering the cholesterol level, the impact of the presence of other risk factors must be considered. It is clear, when looking at the data from both the Framingham study and the MRFIT 10'2
(2A)
SPECIAL ISSUE ON HYPERCHOLESTEROLEMlA/COHEN
(Figure 1),4,5that the influence of the presence of other risk factors is important in determining overall risk factor status and the absolute risk of any given individual.8~gConsideration of this fact also serves to point out that the most prevalent high-risk profile encompasses only modest elevations of blood pressure and cholesterol, particularly in the presence of other risk factors, such as cigarette smoking. The level of a single risk factor when considered alone might not reach the therapeutic threshold for intervention by a clinician. However, when considering overall risk, those patients who have multiple risk factors are, in fact, at high absolute risk and must be identified and treated aggressively. Since the prevalence of these multiple risk factors in the U.S. population is so high, and since they tend to cluster, a population-based cholesterol-lowering strategy would have a considerable impact on these high-risk multiple-risk-factor patients, many of whom would be otherwise untreated. Another indication of the potential impact and value of a population-based strategy is to examine the predicted effects of population-based interventions such as diet. It has been estimated that there are 52 million U.S. citizens who are candidates for dietary therapy to lower cholesterol in accordance with the National Cholesterol Education Program guidelines. lo If a 10% reduction in low-density lipoprotein (LDL) cholesterol could be achieved, the vast majority of these 52 million U.S. citizens (75%) would reach their LDL goals and no pharmacotherapy would be indicated. Thus, only 12.7 million would remain above their LDL goal and be potential candidates for pharmacotherapy. It has been estimated that a 10%reduction in cholesterol will result in a 30% reduction in CHD.” The impact of such a population-based LDL change on CHD would be enormous and would far outstrip the change that could be achieved by the high-risk individual strategy for treatment of all individuals at the highest end of the cholesterol distribution. The magnitude of the
effect of a successful population-based strategy on reducing the coronary burden would be large by any measure. As healthcare providers, we have an obligation to our individual patients, but we also have an obligation to society as a whole. To continue the impressive reduction in CHD mortality rates, we must redouble our efforts to promote the concept of prevention based on both the individual high-risk strategy and population-based programs.
REFERENCES 1. American Heart Associatron. Heart plement. Dallas, TX: AHA, 1995.
and Stroke
Facts:
1996
2. Goldman L, Cook EF. The decline in ischemrc heart disease an analysis of the comparatrve effects of medrcal interventions lifestyle. Ann Intern Med. 1984;101:825-836. 3. Kannel WB, Castelk WP, Gordon sclerotic disease: new perspectives
Statistical
Sup-
mortality rates: and changes in
T. Cholesterol In the prediction of athero based on the Framrngham Study. Ann Intern
Med. 1979;90:85-91. 4. Stamler J, Wentworth D, Neaton JD. Is the relationshrp between lesterol and risk of premature death from coronary heart disease and graded? JAMA. 1986;256:2823-2828. 5. Grundy SM. Cholesterol and coronary
heart
disease:
serum chocontinuous
a new era. JAMA.
1986;256:2849-2858. 6. Martin
MJ, Hulley
SB, Browner
WS, et al. Serum cholesterol,
and mortality: rmplrcations from 1986;ir:933-936. 7. Rose G. Strategy of preventron: Med J. 1981;282:1847-1851. 8. Kannel WB, Wolf PA, Garrrson
a cohort lessons RJ, eds.
of
361
662
blood
from cardiovascular The Framrngham
pressure,
men.
Lancet.
disease. Study:
Br
an epide
miologrcal invesbgation of cardiovascular disease: section 30. Some characteristrcs related to the incidence of cardiovascular drsease and death: Framingham study, l&year follow-up. US Dept of Health, Education, and Welfare; 1974. Publication (NIH) 74-599. 9. Neaton JD, Wentworth D, for the Multiple Rusk Factor Intervention Trial Research Group. Serum cholesterol, blood pressure, cigarette smoking, and death from coronary heart drsease. Overall findrngs and differences by age for 316 099 white men. Arch Intern Med. 1992;152:56-64. 10. Sempos CT, Cleeman JI, Carroll MD, et al. Prevalence of high blood cho lesterol among US adults. An update based report of the Natronal Cholesterol Education JAMA. 1993;269:3009-3014.
on guidelines from the second Program Adult Treatment Panel.
11. Law MR, Wald NJ, Thompson SG. By how much and how quickly does reduction in serum cholesterol concentrahon lower risk of rschaemic heart disease? Br Med J. 1994;308:367-372.
FEBRUARY
17,
1997
The American
Journal
of Medicrnee
Volume
102
(2A)
25
Approach
to Cholesterol
Control
Jerome D. Cohen, MD, st. LOU;S,Missouri
The large proportion of the population who have only modest or moderate hypercholesterolemia will experience more coronary events than the smaller percentage of people who are at higher risk from more extreme elevations of serum cholesterol. The high-risk individual strategy for prevention of coronary heart disease (CHD) can result in impressive declines in cholesterol, but the benefits will be concentrated at the upper end of the population distribution. On the other hand, a population strategy for coronary disease prevention will achieve a much more modest reduction of cholesterol, but these changes will be over the entire distribution and will reduce the risk of the much larger proportion of people with average cholesterol levels who otherwise would likely go untreated. In light of the fact that epidemiologic studies and long-term clinical trials predict that a 10% reduction in serum cholesterol will result in a 30% reduction in coronary events, the population strategy has the potential for an enormous impact in reducing CHD, which, despite our great success over the past two decades, still remains the number one killer in the United States. 01997 by Excerpta Medica, Inc. Am J Med. 1997;102(2A):23-25.
From Preventive Cardiology Programs, St. Louis, Missouri. Requests for reprints should be addressed to Jerome D. Cohen, MD, Department of Medicine, Preventive Cardiology Programs, St. Louis Universky Health Sciences Center, 3525 Caroline Avenue, St. Louis, MISsouri 63104.
01997 by Excerpta . .. . . . AlI rlgnrs reservea.
Medica,
Inc.
D
espite impressive gains in reducing death rates over the last 20 years, coronary heart disease (CHD) still remains by far the number one killer in the United States. Furthermore, because of changing demographics and the aging of the population, the actual number of deaths has changed relatively little. Of the nearly 500,000 deaths that occur every yearabout one every minute-many of these deaths are Iii-St-event sudden deaths. About 80% of the coronary deaths among people <65 years of age occur during the initial attack.’ These statistics clearly underscore the importance of a prevention strategy as the principal approach to reducing further this high morbidity and mortality. In fact, the decline in CHD over the past two decades appears to be due primarily to changes in lifestyle and improvement in associated coronary risk factors: i.e., the dietary changes that have led to a reduction in the mean level of serum cholesterol and the impressive decline in cigarette smoking. These two trends alone may account for more than half of the reduction in age-adjusted coronary mortality rates observed over the past two decades.’ In general, there are two basic strategies for prevention. The first is aimed at identification and treatment of the high-risk individual. The second is a population strategy, which encompasses public health interventions, such as dietary recommendations to lower serum cholesterol, on a populationwide basis. The high-risk individual strategy is based on two observations: first, the upper portion of the risk distribution accounts for a disproportionate share of the disease; and second, the relationship between blood cholesterol levels and coronary disease is not linear but exponential, such that the predicted benefits from cholesterol lowering are greater for those who are at the upper end of the distribution. With identification and treatment, the mean reduction of cholesterol among this high-risk group would be relatively large, as would the risk reduction, and the benefits would be limited to this high-risk group. By contrast, the population or mass strategy is based on the achievement of a considerably smaller reduction of mean cholesterol across the entire population. The high-risk individual and population-based strategies are complementary and not mutually exclusive. If successful, the mass strategy would result in a shift of the entire population distribution of serum cholesterol toward the lower end of the spectrum. QOO2-9343/97/$17.00 PII SOOO2-9343(97)00463-9
23
SPECIAL ISSUE ON HYPERCHOLESTEROLEMlA/COHEN
The effect of this strategy would be to reduce minimally the risk of CHD in people who are at high risk based on their higher serum cholesterol levels, but also, and even more importantly, it would reduce the risk of the large portion of the population who are lower in the cholesterol distribution, having “average” serum cholesterol levels. Many of these people, indeed perhaps most of them, would otherwise be untreated because their cholesterol levels are “average,” We have known for many decades now that population groups with higher levels of serum cholesterol have a higher risk for future coronary events. Data from both the Framingham Study and the Multiple Risk Factor Intervention Trial (MRFIT) screening study’ clearly demonstrate and confIrm this relationship. When discussing the risk of disease, it is important to recognize the distinction between absolute and relative risk. Absolute risk is the observed rate of an event in a given population over time. It is expressed in units such as per 1,000 persons per year and gives information about the frequency of the disease (i.e., incidence). Relative risk is a ratio of incidence rates, a numerical value without units, used to express the risk of an event, e.g., heart attack in subgroups with higher or lower cholesterol levels. This value is usually compared with the risk of the entire population, which is assigned an arbitrary value of 1.0. Relative risk is useful in evaluating the strength of the association between the risk factor and the disease but gives no information regarding the magnitude and overall importance of the risk factor in the population. The relative risk of various levels of cholesterol for coronary mortality from the MRFIT is shown in Figure 1 .4,5 To appreciate the potential impact of a populationbased approach, it is important to examine the concept of population attributable risk. This is the excess risk of disease associated with the presence of a risk factor in the population when compared with the risk of that portion of the population in whom the risk factor is absent. In this way, the proportion of the disease attributable to various levels or cutpoints of a risk factor, e.g., serum cholesterol in the population, can be examined, and an estimate can be made of the overall disease impact of that factor. Data from MRFIT have been analyzed to study the relationship between coronary death rates and the distribution of cholesterol levels in the population6 Considering serum cholesterol levels < 180 mg/dL as baseline risk, about 20% of the population were in this low-risk group. About half of all coronary deaths could be prevented by lowering the cholesterol level of the other 80% of the population to achieve a total cholesterol level of 180 mg/dL. The majority of the excess or potentially preventable deaths in MRFIT 24
FEBRUARY
17,
1997
The Amencan
Journal
of Medlclne@
Volume
Risk ratio
01 100 (2.59)
I
/
I
I
150 (3.88)
200 (5.17)
250 (6.47)
300 (7.76)
Plasma cholesterol
mg/dL (mmol/L)
Figure 1. Plasma cholesterol
mortality by risk ratios in the Multiple Risk Factor lntervenbon Trial (MRFIT). A continuous relationship between cholesterol level and cardiovascular mortality exists beginning at a cholesterol level of 150-l 60 mg/dL. (Adapted with permission from Grundy SM.5)
were among those with a serum cholesterol level >180 mg/dL and ~250 mg/dL. This demonstrates a basic principle in the population strategy of disease prevention-a large percentage of people exposed to a moderate risk, such as modestly elevated levels of serum cholesterol, will give rise to more cases than the smaller percentage of people who have a more extreme elevation of risk.7 In the high-risk individual prevention strategy, those persons who are at the upper end of the distribution are identified and appropriate care provided. While this is beneficial for those high-risk individuals so identified and treated, the fact that there is a relatively small number in this group means that the ultimate impact on CHD deaths in the overall population, even with a very successful screening and treatment program, will not be large. When examining strategies that will yield the greatest impact on the prevention of CHD, population-based approaches, e.g., dietary changes designed to shift the whole cholesterol distribution toward the lower end of the scale, will have a larger effect. This has been pointed out by Rose, who said that a mass approach is “inherently the only ultimate answer to the problem of a mass disease.‘17Rose also recognized that individual changes may be so subtle as to be considered clinically insignificant, even though the impact of such small changes across the entire population would be considerable. He coined the term “prevention paradox,” to acknowledge that a measure that brings large benefits to the community as a whole may offer little perceptible change to each individual.7 In addition to considering the cholesterol level, the impact of the presence of other risk factors must be considered. It is clear, when looking at the data from both the Framingham study and the MRFIT 10'2
(2A)
SPECIAL ISSUE ON HYPERCHOLESTEROLEMlA/COHEN
(Figure 1),4,5that the influence of the presence of other risk factors is important in determining overall risk factor status and the absolute risk of any given individual.8~gConsideration of this fact also serves to point out that the most prevalent high-risk profile encompasses only modest elevations of blood pressure and cholesterol, particularly in the presence of other risk factors, such as cigarette smoking. The level of a single risk factor when considered alone might not reach the therapeutic threshold for intervention by a clinician. However, when considering overall risk, those patients who have multiple risk factors are, in fact, at high absolute risk and must be identified and treated aggressively. Since the prevalence of these multiple risk factors in the U.S. population is so high, and since they tend to cluster, a population-based cholesterol-lowering strategy would have a considerable impact on these high-risk multiple-risk-factor patients, many of whom would be otherwise untreated. Another indication of the potential impact and value of a population-based strategy is to examine the predicted effects of population-based interventions such as diet. It has been estimated that there are 52 million U.S. citizens who are candidates for dietary therapy to lower cholesterol in accordance with the National Cholesterol Education Program guidelines. lo If a 10% reduction in low-density lipoprotein (LDL) cholesterol could be achieved, the vast majority of these 52 million U.S. citizens (75%) would reach their LDL goals and no pharmacotherapy would be indicated. Thus, only 12.7 million would remain above their LDL goal and be potential candidates for pharmacotherapy. It has been estimated that a 10%reduction in cholesterol will result in a 30% reduction in CHD.” The impact of such a population-based LDL change on CHD would be enormous and would far outstrip the change that could be achieved by the high-risk individual strategy for treatment of all individuals at the highest end of the cholesterol distribution. The magnitude of the
effect of a successful population-based strategy on reducing the coronary burden would be large by any measure. As healthcare providers, we have an obligation to our individual patients, but we also have an obligation to society as a whole. To continue the impressive reduction in CHD mortality rates, we must redouble our efforts to promote the concept of prevention based on both the individual high-risk strategy and population-based programs.
REFERENCES 1. American Heart Associatron. Heart plement. Dallas, TX: AHA, 1995.
and Stroke
Facts:
1996
2. Goldman L, Cook EF. The decline in ischemrc heart disease an analysis of the comparatrve effects of medrcal interventions lifestyle. Ann Intern Med. 1984;101:825-836. 3. Kannel WB, Castelk WP, Gordon sclerotic disease: new perspectives
Statistical
Sup-
mortality rates: and changes in
T. Cholesterol In the prediction of athero based on the Framrngham Study. Ann Intern
Med. 1979;90:85-91. 4. Stamler J, Wentworth D, Neaton JD. Is the relationshrp between lesterol and risk of premature death from coronary heart disease and graded? JAMA. 1986;256:2823-2828. 5. Grundy SM. Cholesterol and coronary
heart
disease:
serum chocontinuous
a new era. JAMA.
1986;256:2849-2858. 6. Martin
MJ, Hulley
SB, Browner
WS, et al. Serum cholesterol,
and mortality: rmplrcations from 1986;ir:933-936. 7. Rose G. Strategy of preventron: Med J. 1981;282:1847-1851. 8. Kannel WB, Wolf PA, Garrrson
a cohort lessons RJ, eds.
of
361
662
blood
from cardiovascular The Framrngham
pressure,
men.
Lancet.
disease. Study:
Br
an epide
miologrcal invesbgation of cardiovascular disease: section 30. Some characteristrcs related to the incidence of cardiovascular drsease and death: Framingham study, l&year follow-up. US Dept of Health, Education, and Welfare; 1974. Publication (NIH) 74-599. 9. Neaton JD, Wentworth D, for the Multiple Rusk Factor Intervention Trial Research Group. Serum cholesterol, blood pressure, cigarette smoking, and death from coronary heart drsease. Overall findrngs and differences by age for 316 099 white men. Arch Intern Med. 1992;152:56-64. 10. Sempos CT, Cleeman JI, Carroll MD, et al. Prevalence of high blood cho lesterol among US adults. An update based report of the Natronal Cholesterol Education JAMA. 1993;269:3009-3014.
on guidelines from the second Program Adult Treatment Panel.
11. Law MR, Wald NJ, Thompson SG. By how much and how quickly does reduction in serum cholesterol concentrahon lower risk of rschaemic heart disease? Br Med J. 1994;308:367-372.
FEBRUARY
17,
1997
The American
Journal
of Medicrnee
Volume
102
(2A)
25