JACC
HOME SUBSCRIPTIONS CURRENT ISSUE PAST ISSUES CARDIOSOURCE SEARCH HELP FEEDBACK
QUICK SEARCH:   [advanced]


     

J Am Coll Cardiol, 1999; 34:768-776
© 1999 by the American College of Cardiology Foundation
This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Goldman, L.
Right arrow Articles by Weinstein, M. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Goldman, L.
Right arrow Articles by Weinstein, M. C.

CLINICAL STUDIES

The relative influence of secondary versus primary prevention using the National Cholesterol Education Program Adult Treatment Panel II guidelines

Lee Goldman, MD, MPH, FACC*, Pamela Coxson, PhD*, Maria G. M. Hunink, MD, PhD{dagger}, Paula A. Goldman, MPH{ddagger}, Anna N. A. Tosteson, ScD§, Murray Mittleman, DrPh, MDCM||, Lawrence Williams, MS and Milton C. Weinstein, PhD{ddagger}

* Department of Medicine, University of California, San Francisco, School of Medicine, San Francisco, California, USA
{dagger} Department of Health Sciences, University of Groningen, Groningen, the Netherlands
{ddagger} Department of Health Policy and Management, Harvard School of Public Health, Boston, Massachusetts, USA
§ Department of Clinical Research, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire, USA
|| Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA
Brigham and Women’s Hospital, Boston, Massachusetts, USA

Manuscript received October 6, 1998; revised manuscript received April 2, 1999, accepted May 14, 1999.

Reprint requests and correspondence: Dr. Lee Goldman, Department of Medicine, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, California 94143-0120
goldman{at}medicine.ucsf.edu


   Abstract
Top
 Abstract
Methods
 Results
 Discussion
 References
 
OBJECTIVES

This study was undertaken to project the population-wide effect of full implementation of the Adult Treatment Panel (ATP) II guidelines of the National Cholesterol Education Program (NCEP).

BACKGROUND

The ATP II has proposed guidelines for cholesterol reduction, but the long-term epidemiologic influence of its components has not been fully examined.

METHODS

We used a calibrated, validated simulation of the U.S. population, aged 35 to 84 years to estimate the potential for the NCEP guidelines, under varying assumptions, to reduce coronary heart disease morbidity and mortality and overall mortality from the years 2000 to 2020.

RESULTS

Primary prevention would yield only about half of the benefits of secondary prevention despite requiring nearly twice as many person-years of treatment. The projected increase in quality-adjusted years of life per year of treatment for secondary prevention was 3- to 12-fold higher than for primary prevention. To yield population-wide epidemiologic benefits equivalent to NCEP recommendations for secondary prevention, primary prevention would require a nearly sixfold increase in the number of persons treated compared with NCEP recommendations. All benefits of universal success of the NCEP primary prevention "screen and treat" guidelines could be achieved by a 11 mg/dl (8%) population-wide reduction in low-density lipoprotein cholesterol levels among persons without preexisting coronary heart disease.

CONCLUSIONS

The NCEP guidelines for targeted primary prevention can be a useful component of a rational public health strategy, but only as a complement to the more appealing strategies of secondary prevention and "across-the-board" programs to lower all cholesterol levels.

Abbreviations and Acronyms
  ATP = Adult Treatment Plan
  HDL = high-density lipoprotein
  LDL = low-density lipoprotein
  NCEP = National Cholesterol Education Program
  NHANES = National Health and Nutrition Examination Survey

The National Cholesterol Education Program (NCEP) (1,2) clinical strategy guidelines for screening and treating elevated cholesterol levels are rapidly becoming the standard of care in the U.S. We and others (3–8) have previously presented cost-effectiveness analyses indicating that cholesterol reduction using medications becomes progressively more attractive as the overall risk of coronary heart disease events increases, and that secondary prevention is nearly always more attractive than primary prevention from a cost-effectiveness perspective. However, little attention has been paid to the population-wide epidemiologic considerations. Because many more people would be potentially eligible for primary prevention of a first coronary heart disease diagnosis than for secondary prevention after their initial diagnosis, we analyzed the epidemiologic effect of the three different components of the NCEP guidelines: secondary prevention, primary prevention in higher-risk persons and primary prevention in moderate-risk persons. We also analyzed the potential incremental benefit of extending "diet-only" interventions to more individuals, and our analyses considered alternative scenarios.


   Methods
Top
 Abstract
 Methods
Results
 Discussion
 References
 
The Coronary Heart Disease Policy Model (3,9–11) is a Markov state-transition, computer-based model with three integrated submodels: Demographic–Epidemiologic, Bridge and Disease History. The model is based on the assumption that categorized data from observational cohort studies (12) are consistent with experimental clinical trials (13–17) and can estimate the risk of coronary heart disease events, and that ultimately such events influence mortality (18).

The Demographic–Epidemiologic submodel applies to the U.S. population aged 35 to 84 years without coronary heart disease. Each year, a new cohort of 35-year-old individuals (19,20) enters, and persons turning age 85 exit. To exit before age 85, persons must die or develop coronary heart disease, at which time they enter the Bridge submodel.

The Demographic–Epidemiologic submodel assesses each individual’s risk of developing coronary heart disease and death from all causes based on risk strata defined by age (35 to 84 years in annual intervals), gender, smoking status (yes or no), diastolic blood pressure (≤94, 95–104 or ≥105 mm Hg), serum cholesterol (≤240 mg/dl [6.21 mmol/L], 240–299 mg/dl [6.21–7.75 mmol/L] or >299 mg/dl [7.75 mmol/L]), high-density lipoprotein (HDL) cholesterol (<35 mg/dl [0.91 mmol/L], 35–49 mg/dl [0.91–1.27 mmol/L] or >49 mg/dl [1.27 mmol/L]) and low-density lipoprotein (LDL) cholesterol (<160 mg/dl [4.16 mmol/L], 160–189 mg/dl [4.16–4.91 mmol/L] or >189 mg/dl [4.9 mmol/L]). The initial multivariate distributions of risk factors, conditional on age and gender, and transitions with aging were modeled using data from the Second National Health and Nutrition Examination Survey (NHANES II) (21) and updated to reflect 1986 population averages based on observed trends (22,23) and data from NHANES III (24).

To predict the annual probability of a coronary heart disease event or noncoronary heart disease death on the basis of risk factors, multiple logistic risk functions that controlled for all risk factors in the model simultaneously and that allowed for interaction terms between risk factors and age were estimated using 36-year follow-up data from the Framingham Heart Study (25). The analysis assumed that serum cholesterol did not affect noncoronary mortality (13,14), but we also considered possible adverse effects in sensitivity analyses. We assumed that the effect of risk factor reduction on coronary mortality was mediated by its influence on coronary events (13–17). Coronary mortality and overall mortality were derived from U.S. vital statistics (26).

The Bridge submodel characterizes participants as having angina, myocardial infarction or cardiac arrest during the first 30 days after they develop coronary heart disease, and applies mortality probabilities and 30-day resource costs to persons in each group (9). The Disease History submodel tracks subsequent coronary heart disease events (myocardial infarction, coronary revascularization and cardiac arrest), case-fatality rates and resource costs in persons with prevalent coronary heart disease who survive the Bridge submodel or who enter the model at age 35 with preexisting coronary heart disease.

Implementation of NCEP guidelines.   The guidelines of the Adult Treatment Panel II of the NCEP for dietary and drug treatment of LDL cholesterol call for secondary prevention to reduce LDL to 100 mg/dl, aggressive primary prevention with a goal of 130 mg/dl for some patients ("goal 130") and less demanding primary prevention with a goal of 160 mg/dl for other patients. We assumed all persons would meet the stated goals either with diet or medications as needed beginning at age 35 and continuing to age 84. The target population for secondary prevention includes all persons with clinical evidence of coronary heart disease, with subjective guidelines for including persons with coronary heart disease and low LDL levels (100 to 129 mg/dl). The more aggressive primary prevention (which we term "high-risk") targets the population free of coronary heart disease but with medium (160–189 mg/dl) or high (>189 mg/dl) LDL and a net of two or more additional coronary heart disease risk factors, where age (≥45 for men and ≥55 for women), smoking, hypertension, low HDL (<35 mg/dl), family history of premature coronary heart disease and diabetes mellitus are each positive risk factors, and high HDL (>60 mg/dl) is a negative (protective) factor. The less demanding primary prevention (which we term "medium-risk") targets persons with high LDL and at most one additional risk factor. Additional categories of persons are identified as candidates for "diet-only" intervention.

In our simulations, the target population for secondary prevention was assumed to be all persons with coronary heart disease. For primary prevention, simulations included all NCEP risk factors, except that we could not specifically identify persons with a family history of premature coronary heart disease or diabetes mellitus. The NCEP guidelines were simulated by decreasing the mean LDL level for each cell in the model that corresponded to the target population to the specified goal for that population.

Outcome measures included myocardial infarction, coronary heart disease death, years of life and quality-adjusted years of life. Quality of life adjustments using time trade-off utility weights were calculated for persons with a history of coronary heart disease (10,27). All simulations were for the 21-year period from 2000 to 2020.

Variations on model assumptions.   In alternative simulations, an association between cholesterol and noncoronary heart disease death was estimated based on the natural logarithm of serum cholesterol using pooled data from several studies (28,29). We also implemented a modified version of the NCEP guidelines in which high-risk and medium-risk persons free of coronary heart disease were treated with as aggressive an LDL goal as the population with coronary heart disease.

In other analyses, we assumed that the NCEP guidelines for dietary intervention alone, i.e., without follow-up drug intervention, would be implemented for: 1) persons with medium LDL (160–190 mg/dl) and at most one additional coronary heart disease risk factor; and 2) persons with low LDL (130–160 mg/dl) and at least two additional coronary heart disease risk factors, and that a 10% reduction in LDL could be realized. Our model does not have a separate subcategory for LDL between 130 and 160 mg/dl, but we estimated from NHANES data that the population with two coronary heart disease risk factors and LDL in this range is roughly half (41% for men, 52% for women) of the population of persons with LDL less than 160 mg/dl, and made our estimates accordingly.


   Results
Top
 Abstract
 Methods
 Results
Discussion
 References
 
If the Adult Treatment Panel II (ATP) recommendations of the NCEP were followed to achieve the desired cholesterol goals over the 21-year period from the year 2000 to 2020 in adults 35 to 84-years-old, there would be about 500 million person-years of treatment, with an average of about 11.5 million (48%) women and 12.5 million (52%) men treated each year. About two-thirds of the years of treatment are estimated to be for primary prevention, while secondary prevention would be projected to account for only about one-third of the overall person-years of treatment.

Impact of treatment.   In women, the 26% of treatment years for secondary prevention are projected to yield 59% of the overall decrease in myocardial infarctions, 78% of the decrease in coronary heart disease deaths, 80% of the increase in years of life and 77% of the increase in quality-adjusted years of life (Table 1). The projected increase in quality-adjusted years of life per year of treatment was more than 5.5-fold higher for secondary prevention than for high-risk primary prevention and nearly 12-fold higher for secondary prevention compared with medium-risk primary prevention.


View this table:
[in this window]
[in a new window]
  		Table 1 Impact of NCEP Guidelines on Women (2000–2020)

 
In men, the 42% of the person-years of treatment allocated toward secondary prevention was estimated to yield 60% of the decrease in myocardial infarctions, 76% of the decrease in coronary heart disease deaths, 78% of the increase in years of life and 75% of the increase in quality-adjusted years of life (Table 2). Overall, secondary prevention yielded projected increases in quality-adjusted years of life per person-year of treatment that were more than threefold higher than for high-risk primary prevention and nearly sixfold higher than for medium-risk primary prevention.


View this table:
[in this window]
[in a new window]
  		Table 2 Impact of NCEP Guidelines on Men (2000–2020)

 
Age considerations.   Across all ages among both men and women, secondary prevention provided about 60% to 80% of the additional years of life and quality-adjusted years of life after the institution of treatment estimated to be obtained from following the ATP II guidelines (Fig. 1). For the population as a whole, however, the projected percent increase in expected quality-adjusted years of life after the institution of treatment was generally small, and was more than 4% only among men over age 65 and women over age 75 (Fig. 2).



View larger version (28K):
[in this window]
[in a new window]
  		Figure 1 Additional quality-adjusted years of life (2000–2020). The shaded bar is for secondary intervention, the white bar is for secondary plus high-risk primary interventions and the black bar is for secondary and high-risk primary plus medium-risk primary intervention. The added years in each age range reflect the effects of the intervention in this age range as well as the delayed effects of intervention in earlier ages.

 


View larger version (25K):
[in this window]
[in a new window]
  		Figure 2 Additional quality-adjusted years of life as a percent of person-years of treatment (2000–2020). The added quality-adjusted years of life (from Fig. 1) are displayed here as a percent of person-years of treatment.

 
The percent change in years of life increases for age ranges 45 to 54 and older due to the cumulative effect of lives saved by intervention in younger ages. For example, by 2020, 75- to 84-year-old men and women have estimated increases in years of life of 3.3% and 2.3%, respectively. By 2020, 65- to 74-year-old men have a projected 1.6% additional years of life. All other age ranges have less than a 1% increase. In contrast, for the absolute number of myocardial infarctions and coronary heart disease deaths, the cumulative effect is in the reverse direction, because persons who would now survive to an older age are at risk for myocardial infarctions and coronary heart disease death, even if at a reduced rate. Thus, although all age ranges have a projected decrease in rates of myocardial infarction and coronary heart disease death, the absolute number of these events is projected to increase in ages 55 to 64 and 65 to 74.

Absolute benefit of treatment.   In the secondary treatment of women, the projected additional quality-adjusted years of life per person-year of treatment ranged from 8 per 1,000 for women ages 35 to 44 to nearly 140 per 1,000 for women ages 75 to 84 (Table 3). In comparison, for medium-risk primary prevention, the estimated yield was about 2 quality-adjusted years of life per 1,000 years of treatment for women ages 35 to 44, rising to 28 per 1,000 years of treatment for women ages 75 to 84. Trends in men were analogous but less dramatic (Table 3).


View this table:
[in this window]
[in a new window]
  		Table 3 Incremental Quality-adjusted Years of Life per 1,000 Person-Years of Treatment (2000–2020)

 
These estimates of differential effects are not surprising given the very different baseline risks. The annualized risk of coronary heart disease death in women who already have coronary heart disease is 10% to 130% higher than those of high-risk and medium-risk women without coronary heart disease who are 30 years older (Fig. 3). Similarly, men who already have coronary heart disease also have risks that are 15% to 50% higher than those of high-risk men without coronary heart disease who are 30 years older (Fig. 4). Annualized risks for myocardial infarction follow similar patterns.



View larger version (18K):
[in this window]
[in a new window]
  		Figure 3 Annualized risk per 1,000 of coronary heart disease (CHD) death for women (2000–2020). Baseline values represent the risk to the population in the category if no intervention is implemented for that group. Postintervention values give the risk if NCEP guidelines are implemented as described in the text.

 


View larger version (20K):
[in this window]
[in a new window]
  		Figure 4 Annualized risk per 1,000 of coronary heart disease (CHD) death for men (2000–2020). Baseline values represent the risk to the population in the category if no intervention is implemented for that group. Postintervention values give the risk if NCEP guidelines are implemented as described in the text.

 
Aggressiveness of treatment.   The greater influence of secondary prevention is related in part to the more aggressive goal of LDL cholesterol reduction for secondary prevention (100 mg/dl) than for high-risk primary prevention (130 mg/dl) or medium-risk primary prevention (160 mg/dl). However, even if all three groups were treated to reduce their LDL cholesterol levels to 100 mg/dl, about 50% of the reduction in coronary heart disease deaths in both women and men would be due to secondary prevention, although only about 4% of the years of treatment of women and 7% of the years of treatment in men would be for secondary prevention. To achieve the aggressive goals, about 68 million medium-risk women and 47 million medium-risk men would need to be treated annually, and the estimated total number of treated persons would be increased by nearly sixfold compared with NCEP recommendations.

Alternative primary prevention strategies.   The influence of the Adult Treatment Panel II recommendations for primary prevention of coronary heart disease would be the equivalent of the results achieved by an 8% (11 mg/dl) reduction in LDL cholesterol in persons without coronary heart disease. Alternatively, an 8-mm Hg decrease in diastolic blood pressure or an 18% decrease in smoking rates in persons without coronary heart disease would save about the same number of quality-adjusted years of life.

Influence of including "diet-only" subjects.   If "diet-only" individuals are included in primary prevention, the number of person-years of treatment roughly doubles. Even in the unlikely event that dietary interventions would reduce LDL cholesterol by 10%, at least half of the decrease in myocardial infarctions as well as two-thirds of the decrease in coronary heart disease deaths and the increases in years of life and quality-adjusted years of life would be attributable to secondary prevention, although only 15% of the person-years of treatment would be for secondary prevention.

Possible noncoronary heart disease effects of cholesterol reduction.   If the noncoronary heart disease death rate increased because of adverse effects of cholesterol lowering, the benefits of cholesterol reduction would be blunted by an average of about 11,000 more noncoronary deaths per year. Nevertheless, years of life and quality-adjusted years of life were still estimated to increase in every age range for both men and women by about 80% to 90% of what would be predicted without adverse effects on noncoronary mortality. The incremental years of life gained by cholesterol reduction would be less blunted in secondary prevention than in primary prevention, and estimates of the relative benefit of interventions would be even more in favor of secondary prevention.

Altering HDL criteria.   Of persons with HDL >50 mg/dl, about 60% of men and 45% of women have HDL levels <60 mg/dl, and hence do not meet NCEP ATP II criteria for a protective HDL level. However, even if we assumed that all people with HDL >50 mg/dl would be eligible for treatment under the NCEP ATP II guidelines, the proportion of population-wide benefit attributable to primary prevention would increase by only about one percentage point in men and two percentage points in women, and conclusions regarding the relative influence of primary versus secondary prevention were not appreciably affected by our use of an HDL cutoff of 50 mg/dl.


   Discussion
Top
 Abstract
 Methods
 Results
 Discussion
References
 
We do not dispute the role of LDL cholesterol as a risk factor, HDL cholesterol as a protective factor, or the benefits of medications for improving lipid levels and reducing coronary heart disease events, coronary heart disease mortality or overall mortality (1,13–18,30). Of note is that the CHD Policy Model has been accurate in previous predictions (31,32), but we cannot guarantee future predictions. Our model could not include diabetes or a positive family history of premature coronary heart disease, and its specifications required that we model an HDL threshold of >50 mg/dl, rather than >60 mg/dl, as a protective factor. These limitations led to some underestimation of the number of persons eligible for primary prevention, but a sensitivity analysis suggests that any effect on our estimates of the population-wide influence of primary prevention is very minor. Furthermore, our estimate of the number of Americans eligible for secondary prevention is also on the lower side of the various estimates (33), and any increase in persons eligible for secondary prevention would only reinforce our conclusions.

Our analyses emphasize that under a wide variety of assumptions, 60% to 75% of the population-wide epidemiologic benefit of cholesterol reduction potentially achievable from the ATP II guidelines would be in secondary prevention. These analyses demonstrate that the segment of the population for which cholesterol reduction is the most cost-effective on a per-person basis (3–8) is also the segment that is likely to realize about two-thirds of overall benefits.

Our estimates were remarkably consistent, were similar for women and men, and were of reasonably similar relative effect across various age groups. Even much more aggressive treatment goals or the inclusion of a "diet-only" intervention in a much larger number of persons would have only a small effect on the relative epidemiologic importance of secondary as compared with primary prevention despite the inclusion of far greater numbers of persons in a primary prevention intervention.

The guidelines of the ATP of the NCEP (1) emphasize a case-finding strategy, sometimes called "screen and treat," analogous to the very successful approach to diagnosing and treating hypertension (34). This approach to hypertension is widely credited with achieving substantial populationwide reductions in blood pressure and stroke (35) and is clearly worth the cost (36), mostly because screening can be performed inexpensively during routine health visits.

For population-wide "screen and treat" programs for cholesterol reduction, however, the challenge is more complicated. Effective classification may require multiple blood tests, and these tests must be repeated to assess treatment efficacy. Furthermore, current medications are generally more costly on an annual basis than medications to control hypertension, and it is not surprising that cost-effectiveness estimates for primary prevention have generally been far less favorable for hypercholesterolemia than for hypertension.

Prior concerns regarding the ATP II guidelines have focused on the potential adverse effects of lowering cholesterol (37), the current cost of medications (38) and the practicality of screening, classifying and appropriately treating the entire population (39), but we are less concerned with these three issues. First, recent data suggest that fears regarding the adverse effects of lowering cholesterol were at least exaggerated if not unfounded (13–18,30). Second, concerns about cost-effectiveness can be addressed by lowering the cost of medications, which represent most of the costs of implementing the ATP II guidelines. Third, although recent surveys estimate that only 1 in 12 adults is being screened annually (39) and that more than 50% of hypercholesterolemic U.S. citizens remain unaware of their elevated cholesterol levels (40), such logistic hurdles could be overcome if the recommended strategy is truly the most appropriate route to solving a major public health problem. In addition, cholesterol reduction likely reduces stroke (41), a noncoronary heart disease benefit that is often overlooked in economic analyses.

However, even if the ATP II guidelines were followed perfectly nationwide, about two-thirds of the influence would come from secondary prevention, where costs per benefit are lower (41) and the likelihood of implementation by physicians and compliance by patients is far higher. Although not directly modeled, the stroke benefit of cholesterol reduction would also likely be largest in persons with more advanced atherosclerosis and other evidence for coronary heart disease, thereby being consistent with our estimate of the relatively greater influence of secondary as compared with primary prevention. Second, the population-wide influence of perfect implementation of the ATP II guidelines for primary prevention in persons without coronary heart disease would be roughly equivalent to an 8% (11 mg/dl) reduction in LDL cholesterol in these same persons. Reductions of this magnitude (about 13–14 mg/dl in total cholesterol) have been achieved over the last decade or so (42–44), without an appreciable reliance on medications or systematic changes in the food supply. Of course, it is unlikely that any "screen and treat" strategy will ever be successful to its full potential epidemiologic influence (45,46). Interventions across the population, such as immunization, fluoridation or even dietary changes (2,46), as suggested by the Population Strategy Panel of the NCEP (47) and by others, are as or are more likely to succeed compared with more complicated approaches that require targeted screening, treatment and compliance.

A successful public health program for the prevention of coronary heart disease via lipid lowering should emphasize secondary prevention with diet and medications. Primary prevention with approaches such as dietary changes that do not require individual measurement of cholesterol levels (2,48) are also extremely appealing. Targeted "screen and treat" primary prevention based on the ATP II guidelines can also be very useful and can be cost-effective for especially high-risk patients without clinical coronary heart disease, but should not be misinterpreted as the principal strategy for maximizing public health effects (49,50). Because a substantial proportion of coronary heart disease deaths occur in previously asymptomatic persons, the development of cost-effective primary prevention strategies must remain a high public health priority.


   Footnotes
 
Supported by Grant RO1 H5-06258 from the Agency for Health Care Policy and Research, Rockville, MD.


   References
Top
 Abstract
 Methods
 Results
 Discussion
 References
 

  1. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). JAMA. 1993;269:3015–3023[CrossRef][Medline]
  2. National Cholesterol Education Program. Report of the Expert Panel on Population Strategies for Blood Cholesterol Reduction: executive summary. Arch Intern Med. 1991;151:1071–1084[CrossRef][Medline]
  3. Goldman L, Weinstein MC, Goldman PA, Williams LW. Cost-effectiveness of HMG-CoA reductase inhibition for primary and secondary prevention of coronary heart disease. JAMA. 1991;265:1145–1151[Abstract]
  4. Goldman L, Gordon DJ, Rifkind BM, et al. Cost and health implications of cholesterol lowering. Circulation. 1992;85:1960–1968[Abstract]
  5. Hamilton VH, Racicot FE, Zowall H, et al. The cost-effectiveness of HMG-CoA reductase inhibitors to prevent coronary heart disease: estimating the benefits of increasing HDL-C. JAMA. 1995;273:1032–1038[Abstract]
  6. Pedersen TR, Kjekshus J, Berg K, et al. Cholesterol lowering and the use of healthcare resources: results of the Scandinavian Simvastatin Survival Study. Circulation. 1996;93:1796–1802[Abstract/Free Full Text]
  7. Johannesson M, Borgquist L, Jonsson B, Lindholm LH. The cost effectiveness of lipid lowering in Swedish primary health care. The CELL Study Group. J Intern Med. 1996;240:23–29[CrossRef][Medline]
  8. Pharoah PD, Hollingworth W. Cost effectiveness of lowering cholesterol concentration with statins in patients with and without pre-existing coronary heart disease: life table method applied to health authority population. Br Med J (Clin Res Ed). 1996;312:1443–1448
  9. Weinstein MC, Coxson PG, Williams LW, et al. Forecasting coronary heart disease incidence, mortality and cost: the Coronary Heart Disease Policy Model. Am J Public Health. 1987;77:1417–1426[Abstract/Free Full Text]
  10. Stinnett AA, Mittleman MA, Weinstein MC, et al. The cost-effectiveness of dietary and pharmacologic therapy for cholesterol reduction in adults. Gold MR, Siegel JE, Russell LB, Weinstein MC. Cost-Effectiveness in Health and Medicine. Oxford, U.K: Oxford University Press; 1996. p. 349–391
  11. Hunink MGM, Goldman L, Tosteson ANA, et al. The recent decline in mortality from coronary heart disease, 1980–1990: the effect of secular trends in risk factors and treatment. JAMA. 1997;277:535–542[Abstract]
  12. Wilson PWF, D’Agostino RB, Levy D, et al. Prediction of coronary heart disease using risk factor categories. Circulation. 1998;97:1837–1847[Abstract/Free Full Text]
  13. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4,444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344:1383–1389[CrossRef][Medline]
  14. Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med. 1995;333:1301–1307[Abstract/Free Full Text]
  15. Sacks FM, Pfeffer MA, Moye LA, et al. The effects of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med. 1996;335:1001–1009[Abstract/Free Full Text]
  16. Downs JR, Clearfield M, Weis S, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels. JAMA. 1998;279:1615–1622[Abstract/Free Full Text]
  17. Long-Term Intervention with with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad reange of initial cholesterol levels. N Engl J Med. 1998;229:1349–1357
  18. Gould AL, Rossouw JE, Santanella NC, Heyse JF, Furburg CD. Cholesterol reduction yields clinical benefit. Circulation. 1998;97:946–952[Abstract/Free Full Text]
  19. U.S. Bureau of the Census. Projections of the Population of the United States by Age, Sex, and Race: 1982–2050. Current Population Reports. Population Estimates and Projections. Washington, DC: U.S. Government Printing Office; Series P-25. No. 922, 1982.
  20. U.S. Bureau of the Census. U.S. Population Estimates by Age, Sex, Race and Hispanic Origin: 1989. Current Population Reports, Population Estimates and Projections. Washington, DC: U.S. Department of Commerce, Bureau of the Census; Series P-25, No. 1057, 1990.
  21. National Center for Health Statistics. National Health and Nutrition Examination Survey, 1976–1980 [public use data tapes]. Hyattsville, MD: U.S. Department of Health and Human Services; 1990. Tape Nos. 5305 and 5301 and catalog No. 5411.
  22. National Center for Health Statistics. Vital and Health Statistics. Smoking and Other Tobacco Use: United States, 1987. Hyattsville, MD: U.S. Department of Health and Human Services, Public Health Service, National Center for Health Statistics; National Health Survey Series 10, No. 169, PHS 89-1597, 1989.
  23. National Health Interview Survey, United States, 1986. Hyattsville, MD: U.S. Department of Health and Human Services, Public Health Service, National Center for Health Statistics; Maryland National Health Survey Series 10, No. 164, PHS 87-1592, 1987.
  24. Johnson CL, Rifkind BM, Sempos CT, et al. Declining serum total cholesterol levels among US adults: the National Health and Nutrition Examination Surveys. JAMA. 1993;269:3002–3008[Abstract]
  25. Department of Health and Human Services, 1987. The Framingham Study: an epidemiological investigation of cardiovascular disease. Some risk factors related to the annual incidence of cardiovascular disease and death using pooled repeated biennial measurements: Framingham Heart Study, 30-year follow-up. Section 34, NIH Publication 87-2703. Bethesda, MD: National Heart, Lung, and Blood Institute.
  26. National Center for Health Statistics. Vital Statistics of the United States 1986: Volume II: Mortality, Part A. Hyattsville, MD: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention; 1989.
  27. Fryback DG, Dasbach EJ, Klein R, et al. The Beaver Dam Health Outcomes Study: initial catalog of health-state quality factors. Med Decis Making. 1993;13:89–102[Abstract/Free Full Text]
  28. Jacobs D, Blackburn H, Higgins M, et al. Report on the Conference on Low Cholesterol: mortality associations. Circulation. 1992;86:1046–1060[Abstract/Free Full Text]
  29. Neaton JD, Blackburn H, Jacobs D, et al. Serum cholesterol level and mortality findings for men screened in the Multiple Risk Factor Intervention Trial. Arch Intern Med. 1992;152:1490–1500[Abstract]
  30. Hebert PR, Gaziano JM, Chan KS, Hennekens CH. Cholesterol lowering with statin drugs, risk of stroke, and total mortality. An overview of randomized trials. JAMA. 1997;278:313–321[Abstract]
  31. Russell L. Prevention and Medicare costs. N Engl J Med. 1998;339:1158–1160[Free Full Text]
  32. Morris C. A comparison of economic modelling and clinical trials in the economic evaluation of cholesterol-modifying pharmacotherapy. Health Economics. 1997;6:589–601[CrossRef][Medline]
  33. Sempos CT, Cleeman JI, Carroll MD, et al. Prevalence of high blood cholesterol among US adults: an update based on guidelines from the second report of the National Cholesterol Education Program Adult Treatment Panel. JAMA. 1993;269:3009–3014[Abstract]
  34. The fifth report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V). Arch Intern Med. 1993;153:154–183[CrossRef][Medline]
  35. Sytkowski PA, D’Agostino RB, Belandger AJ, Kannel WB. Secular trends in long-term sustained hypertension, long-term treatment, and cardiovascular mortality. Circulation. 1996;93:697–703[Abstract/Free Full Text]
  36. Edelson JT, Weinstein MC, Tosteson ANA, et al. Long-term cost-effectiveness of various initial mono-therapies for mild to moderate hypertension. JAMA. 1990;263:408–413
  37. Hulley SB, Walsh JM, Newman TB. Health policy on blood cholesterol. Time to change directions. [Editorial].Circulation. 1992;86:1026–1029[Free Full Text]
  38. Garber AM, Browner WS. American College of Physicians guidelines for using serum cholesterol, high-density lipoprotein cholesterol, and triglyceride levels as screening tests for preventing coronary heart disease in adults. Ann Intern Med. 1996;124:515–517[Abstract/Free Full Text]
  39. Stafford RS, Blumenthal D, Pasternak RC. Variations in cholesterol management practices of U.S. physicians. J Am Coll Cardiol. 1997;29:139–146[Abstract]
  40. Luepker RV. Current status of cholesterol treatment in the community: the Minnesota heart survey. Am J Med. 1997;102:37–42[Medline]
  41. Goldman L, Weinstein MC, Williams LW. Relative impact of targeted versus populationwide cholesterol interventions on the incidence of coronary heart disease. Circulation. 1989;80:254–260[Abstract/Free Full Text]
  42. Burke GL, Sprafka JM, Folsom AR, et al. Trends in serum cholesterol levels from 1980 to 1987: the Minnesota Heart Study. N Engl J Med. 1991;324:941–946[Abstract]
  43. McGovern PG, Pankow JS, Shahar E, et al. Recent trends in acute coronary heart disease: mortality, morbidity, medical care, and risk factors. N Engl J Med. 1996;334:884–890[Abstract/Free Full Text]
  44. Johnson CL, Rifkind BM, Sempos CT, et al. Declining serum total cholesterol levels among U.S. adults; the national health and nutrition examination surveys. JAMA. 1993;269:3002–3008[Abstract]
  45. Schectman G, Hiatt J. Drug therapy for hypercholesterolemia in patients with cardiovascular disease: factors limiting achievement of lipid goals. Am J Med. 1996;100:197–204[CrossRef][Medline]
  46. Schrott HG, Bittner V, Vittinghoff E, et al. Adherence to national cholesterol education program treatment goals in postmenopausal women with heart disease. JAMA. 1997;277:1281–1286[Abstract]
  47. Expert Panel on Population Strategies for Blood Cholesterol Reduction. Report of the Expert Panel on Population Strategies for Blood Cholesterol Reduction: a statement from the National Cholesterol Education Program. Circulation. 1991;83:2154–2232[Free Full Text]
  48. Tosteson ANA, Weinstein MC, Hunink MGM, et al. Cost-effectiveness of population-wide educational approaches to reduce serum cholesterol levels. Circulation. 1997;95:24–30[Abstract/Free Full Text]
  49. West of Scotland Coronary Prevention Study. Identification of high-risk groups and comparison with other cardiovascular intervention trials. Lancet. 1996;348:1339–1342[CrossRef][Medline]
  50. Durrington PN, Prais H, Bhatnagar D, et al. Indications for cholesterol-lowering medication: comparison of risk-assessment methods. Lancet. 1999;353:278–281[CrossRef][Medline]



This article has been cited by other articles:


Home page
 J Am Coll CardiolHome page
R. M. Califf, T. Ryan, P. Douglas, and P. J. Goldschmidt-Clermont
A time of accelerated change in academic cardiovascular medicine: Implications for academic divisions of cardiology and their training programs
J. Am. Coll. Cardiol., November 16, 2004; 44(10): 1957 - 1965.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
J. A. Spertus, M. J. Radford, N. R. Every, E. F. Ellerbeck, E. D. Peterson, and H. M. Krumholz
Challenges and opportunities in quantifying the quality of care for acute myocardial infarction: Summary from the acute myocardial infarction working group of the American heart association/American college of cardiology first scientific forum on quality of care and outcomes research in cardiovascular disease and stroke
J. Am. Coll. Cardiol., May 7, 2003; 41(9): 1653 - 1663.
[Full Text] [PDF]

Home page
 CirculationHome page
J. A. Spertus, M. J. Radford, N. R. Every, E. F. Ellerbeck, E. D. Peterson, and H. M. Krumholz
Challenges and Opportunities in Quantifying the Quality of Care for Acute Myocardial Infarction: Summary From the Acute Myocardial Infarction Working Group of the American Heart Association/American College of Cardiology First Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke
Circulation, April 1, 2003; 107(12): 1681 - 1691.
[Full Text] [PDF]

Home page
 CirculationHome page
References
Circulation, December 17, 2002; 106(25): 3373 - 3421.
[Full Text]

Home page
 J Am Coll CardiolHome page
L. Goldman, K. A. Phillips, P. Coxson, P. A. Goldman, L. Williams, M. G. M. Hunink, and M. C. Weinstein
The effect of risk factor reductions between 1981 and 1990 on coronary heart disease incidence, prevalence, mortality and cost
J. Am. Coll. Cardiol., October 1, 2001; 38(4): 1012 - 1017.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart JHome page
M Higgins
Patients, families and populations at high risk for coronary heart disease
Eur. Heart J., September 2, 2001; 22(18): 1682 - 1690.
[PDF]

Home page
 JAMAHome page
K. A. Phillips, M. G. Shlipak, P. Coxson, P. A. Heidenreich, M. G. M. Hunink, P. A. Goldman, L. W. Williams, M. C. Weinstein, and L. Goldman
Health and Economic Benefits of Increased {beta}-Blocker Use Following Myocardial Infarction
JAMA, December 6, 2000; 284(21): 2748 - 2754.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart JHome page
J. Muntwyler and T.F. Luscher
Assessment of cardiovascular risk: time to apply genetic risk factors?
Eur. Heart J., April 2, 2000; 21(8): 611 - 613.
[PDF]

This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Goldman, L.
Right arrow Articles by Weinstein, M. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Goldman, L.
Right arrow Articles by Weinstein, M. C.

HOME SUBSCRIPTIONS CURRENT ISSUE PAST ISSUES CARDIOSOURCE SEARCH HELP FEEDBACK