Screening for Lipid Disorders in Adults
Recommendation StatementDate: June 2008
Screening Women at Increased Risk
Screening Young Men and All Women Not at Increased Risk
Go to the Clinical Considerations section for a discussion of "increased risk."
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Update of Previous USPSTF Recommendation
Recommendations of Others
Members of the USPSTF
|Task Force Grade Definitions|
ImportanceThere is good evidence that high levels of total cholesterol and low density lipoprotein-cholesterol (LDL-C) and low levels of high density lipoprotein-cholesterol (HDL-C) are important risk factors for coronary heart disease. The risk for coronary heart disease is highest in those with a combination of risk factors. The 10-year risk for coronary heart disease is lowest in young men and in women who do not have other risk factors, even in the presence of abnormal lipids.
DetectionThe USPSTF found good evidence that lipid measurement can identify asymptomatic men and women who are eligible for preventive therapy.
Benefits of Detection and Early TreatmentThere is good evidence that lipid-lowering drug therapy substantially decreases the incidence of coronary heart disease in persons with abnormal lipids. The absolute benefits of lipid-lowering treatment depend on a person's underlying risk for coronary heart disease. Men over the age of 35 and women over the age of 45 who are at increased risk will realize a substantial benefit from treatment; younger adults with multiple risk factors for coronary disease, including dyslipidemia, will realize a moderate benefit from treatment; and younger men and women without risk factors for coronary heart disease will realize a small benefit from treatment, as seen inthe risk reduction in 10-year CHD event rate.
Harms of Detection and Early TreatmentThere is good evidence that the harms from screening and treatment are small and include possible labeling and the adverse effects associated with lipid-lowering therapy (e.g., rhabdomyolysis).
USPSTF AssessmentThe USPSTF concludes that the benefits of screening for and treating lipid disorders in all men aged 35 and older and women aged 45 and older at increased risk for coronary heart disease substantially outweigh the potential harms.
The USPSTF concludes that the benefits of screening for and treating lipid disorders in young adults at increased risk for coronary heart disease moderately outweigh the potential harms.
The USPSTF concludes that the net benefits of screening for lipid disorders in young adults not at increased risk for coronary heart disease are not sufficient to make a general recommendation.
- Lipid disorders, also called dyslipidemias, are abnormalities of lipoprotein metabolism and include elevations of total cholesterol, LDL-C, or triglycerides (TG), or deficiencies of HDL-C. These disorders can be acquired or familial (e.g., familial hypercholesterolemia). This recommendation applies to adults aged 20 and older who have not previously been diagnosed with dyslipidemia.
- Increased risk, for the purposes of this recommendation, is defined by the presence of any one of the risk factors listed below. The greatest risk for CHD is conferred by a combination of multiple listed factors. While the USPSTF did not use a specific numerical risk to bound this recommendation, the framework used by the USPSTF in making these recommendations relies on a 10-year risk of cardiovascular events:1
- Previous personal history of CHD or non-coronary atherosclerosis (e.g., abdominal aortic aneurysm, peripheral artery disease, carotid artery stenosis).
- A family history of cardiovascular disease before age 50 in male relatives or age 60 in female relatives.
- Tobacco use.
- Obesity (BMI ≥30).
- The preferred screening tests for dyslipidemia are total cholesterol and HDL-C on non-fasting or fasting samples. There is currently insufficient evidence of the benefit of including TG as a part of the initial tests used to screen routinely for dyslipidemia. Abnormal screening test results should be confirmed by a repeated sample on a separate occasion, and the average of both results should be used for risk assessment.
- Measuring total cholesterol alone is acceptable for screening if available laboratory services cannot provide reliable measurements of HDL-C; measuring both total cholesterol and HDL-C is more sensitive and specific for assessing coronary heart disease risk than measuring total cholesterol alone. In conjunction with HDL-C, the addition of either LDL-C or total cholesterol would provide comparable information, but measuring LDL-C requires a fasting sample and is more expensive. Direct LDL-C testing, which does not require a fasting sample measurement, is now available; however, calculated LDL (total cholesterol minus HDL minus TG/5) is the validated measurement used in trials for risk assessment and treatment decisions. In patients with dyslipidemia identified by screening, complete lipoprotein analysis is useful.
- The optimal interval for screening is uncertain. On the basis of other guidelines and expert opinion, reasonable options include every 5 years, shorter intervals for people who have lipid levels close to those warranting therapy, and longer intervals for those not at increased risk who have had repeatedly normal lipid levels.
- An age to stop screening has not been established. Screening may be appropriate in older people who have never been screened; repeated screening is less important in older people because lipid levels are less likely to increase after age 65. However, because older adults have an increased baseline risk for coronary heart disease, they stand to gain greater absolute benefit from the treatment of dyslipidemia, compared with younger adults.
- Treatment decisions should take into account a person's overall risk of heart disease rather than lipid levels alone. Overall risk assessment should include the presence and severity of the following risk factors: age, gender, diabetes, elevated blood pressure, family history (in younger adults), and smoking. Risk calculators that incorporate specific information on multiple risk factors provide a more accurate estimation of cardiovascular risk than tools that simply count numbers of risk factors.1
- Drug therapy is usually more effective than diet alone in improving lipid profiles, but choice of treatment should consider overall risk, costs of treatment, and patient preferences. Guidelines for treating lipid disorders are available from the National Cholesterol Education Program of the National Institutes of Health (http://www.nhlbi.nih.gov/about/ncep/).
- Although lifestyle modifications (diet and physical activity) are appropriate initial therapies for most patients, a minority achieves substantial reductions in lipid levels from changes in diet alone; drugs are frequently needed to achieve therapeutic goals, especially for those at increased risk for coronary heart disease. Lipid-lowering treatments should be accompanied by interventions addressing all modifiable risk factors for heart disease, including smoking cessation, treatment of blood pressure, diabetes, and obesity, as well as promotion of a healthy diet and regular physical activity. Long-term adherence to therapies should be emphasized.
Burden of DiseaseCardiovascular disease, including coronary heart disease, accounts for nearly half of all deaths in the United States. Over the past 50 years, there has been a long-term downward trend in cardiovascular mortality associated with improved risk factor management and access to early detection and new treatments. The 2002 age-adjusted death rate for heart disease was 59% lower than the rate in 1950.2
The lifetime risk of having a coronary heart disease event, calculated at age 40, is estimated to be 49% for men and 32% for women in the United States; nearly one third of coronary heart disease events are attributable to total cholesterol levels above 200 mg/dL. Consistent, good-quality evidence from long-term prospective studies has shown that high levels of total cholesterol and LDL-C and low levels of HDL-C are important risk factors for coronary heart disease. The risk for coronary heart disease events and mortality increases with increasing levels of total cholesterol and LDL-C and declining levels of HDL-C, in a continuous and graded fashion, with no clear threshold. Coronary heart disease mortality is associated with several risk factors, including dyslipidemia, high blood pressure, tobacco use, diabetes, a family history of premature coronary heart disease, older age, male gender, and diet; other risk factors for coronary heart disease include socioeconomic status, obesity, and physical inactivity. Consideration of lipid levels along with other risk factors allows for an accurate estimation of coronary heart disease risk.3
Scope of ReviewThe USPSTF reviewed the literature on the accuracy of screening tests, the efficacy of treatment, and the harms of screening and treatment for dyslipidemia.
Accuracy of Screening TestsSerum lipid screening is an accurate measure of serum lipids. Good-quality evidence shows that total cholesterol, LDL-C, and HDL-C are independent predictors of coronary heart disease risk, and ratios of total cholesterol to HDL-C (total cholesterol/HDL-C) or LDL-C to HDL-C (LDL-C/HDL-C) classify risk better than total cholesterol alone. Although the triglyceride level is a strong univariate predictor of coronary events, its association with coronary heart disease events is reduced substantially by adjustment for other risk factors. At least two serum lipid measurements are necessary to ensure that true values are within 10% of the mean of the measurements.4
Effectiveness of TreatmentThe USPSTF examined the evidence for the efficacy of various treatments for dyslipidemia, including diet, exercise, and lipid-lowering drug therapy. Lipid screening does not clearly improve the effectiveness of routine diet interventions.
The only trials examining diet and its association with coronary heart disease outcomes have used modified diet in conjunction with interventions for other risk factors, modified diet in patients with heart disease, or modified diet using atypical institutional diets. Reduction in dietary saturated fat and weight loss have been shown to lower total cholesterol and LDL-C as much as 10% to 20% in some individuals, but the average effect of diet interventions in outpatients is relatively modest (2% to 6% reduction in total cholesterol). A meta-analysis of 95 studies found that subjects assigned to exercise had post-intervention cholesterol levels that were 7 to 13 mg/dL lower than controls; interventions associated with weight loss have resulted in greater reductions in lipid levels.5
A meta-analysis of 4 fair- to good-quality primary prevention trials conducted mainly among middle-aged men of European descent (Lipid Research Clinical Trial [LRC], using a bile-acid binding resin; Helsinki Heart Study [HHS], using a fibric acid derivative; and the West of Scotland Coronary Prevention Study [WOSCOPS] and the Air Force/Texas Coronary Atherosclerosis Prevention Study [AFCAPS-TexCAPS], both using HMG Co-A reductase inhibitors) found that cholesterol-lowering drug treatment for 5 to 7 years decreased the risk of coronary heart disease events (defined as the sum of nonfatal myocardial infarctions and deaths from coronary heart disease) by approximately 30% in people with high total cholesterol or average cholesterol and low HDL-C.6 According to this meta-analysis, drug therapy reduced the relative risk of coronary heart disease death by 26%, with a 95% CI from 2% to 43%, but had little overall effect on total mortality for the 5 to 7 years over which these trials were conducted (OR, 0.91; 95% CI, 0.78, 1.07). Longer-term follow-up recently available from WOSCOPS demonstrated enduring significant decreases in both cardiovascular mortality and all cause mortality over the trial period and the 10 years following.7
Subsequent to this meta-analysis, 5 fair- to good-quality trials addressed the efficacy of HMG CoA reductase inhibitors in patients at increased risk for coronary heart disease (e.g., those who had a history of coronary heart disease, diabetes, hypertension, and other coronary heart disease risk factors).8-12 Four of these trials showed a 15% to 37% reduction in coronary heart disease events in those treated for 3.2 to 5.5 years with statins, compared with those in the placebo group. One trial, ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack—Lipid-lowering Arm), a fair-quality, open-label randomized trial comparing a group treated with statins with a group receiving usual care, found no statistically significant reduction in coronary heart disease events; however, nearly 30% of the usual-care group had received statins by the 6th year of the trial, thereby confounding results.7
Primary prevention trials examining the efficacy of lipid-lowering agents in asymptomatic women have yielded conflicting results, with some studies showing no benefit and others showing some coronary heart disease event benefit.13 In the secondary prevention studies, women with diabetes, coronary heart disease, or coronary heart disease-equivalent conditions had statistically significant reductions in coronary heart disease mortality, coronary heart disease events, nonfatal myocardial infarctions, and revascularization; the magnitude of benefit was similar to those for men. The risk for total mortality was not lower in women treated with lipid-lowering drugs, regardless of whether or not they had prior coronary heart disease.
There is limited evidence about primary prevention of coronary heart disease using drugs in older populations; however, several secondary prevention trials that included individuals aged 65 and older showed a reduction in coronary heart disease events in the group receiving statins compared with the group receiving placebo.5,14 In the Heart Protection Study, for example, HMG Co-A reductase inhibitors reduced major vascular events compared with placebo (28.7% vs. 23.6%) in subjects 70 years and older; and, in subjects aged 75 to 80 at study entry, the reduction in coronary heart disease was even greater compared with placebo (32.3% vs. 23.1%). In one meta-analysis of the 6 secondary prevention trials reporting results for subjects 65 and older, statins reduced all-cause mortality by 15% compared with placebo (RR, 0.85; 95% CI, 0.73-0.99; ARR, 1.8%; n=4941).11
Potential Harms of Screening and TreatmentScreening for and identifying lipid disorders in adults do not appear to have important psychological sequelae or produce important changes in indices of mental health. The research to date has not been sufficient, however, to rule out important changes in small subsets of patients or to detect subtle changes in anxiety.
There is good quality evidence on the harms of drug therapy. Statins can cause muscle damage (ranging from mild elevations in creatine phosphokinase [CPK] levels to muscle weakness related to rhabdomyolysis); the incidence of fatal rhabdomyolysis associated with statins is estimated at 0.15 per million prescriptions. Observational studies suggest that older age, hypothyroidism, surgery or trauma, heavy exercise, excessive alcohol intake, and renal or liver impairment can increase the risk of myopathy with statins. Combinations of statins with some fibrates may increase the risk of rhabdomyolysis. Increased liver transaminases (prevalence 2% to 5%) is a common side effect of statins and is more prevalent in those with underlying liver disease. In addition, neuropathy, pancreatitis, and memory loss may be rare complications of statin use.2
Update of Previous USPSTF RecommendationThis recommendation updates the prior recommendation released in 2001. The major change in the current recommendation is that adult women at any age should be screened only if other risk factors for cardiovascular disease are present; the 2001 version recommended screening for younger higher risk women (20-45 years) and all women over 45 years of age.
Recommendations of OthersA fasting lipoprotein profile (total cholesterol, LDL-C, HDL-C, and TG) in all adults over the age of 20 once every 5 years is recommended by the National Cholesterol Education Program's Adult Treatment Panel III (ATP III), sponsored by the National Institutes of Health, and endorsed by the American Heart Association.15 The American Academy of Family Physicians strongly recommends periodic cholesterol measurement in men aged 35 to 65 and in women aged 45 to 65.16 The American College of Obstetricians and Gynecologists recommends screening women every 5 years beginning at age 45; screening is recommended for women aged 19-44 based on risk factors.17
References1. Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation 1998;97:1837-1847.
2. National Center for Health Statistics, US, 2004 with Chartbook on Trends in the Health of Americans. Hyattsville, Maryland, 2004.
3. Helfand M, Carson S. Screening for lipid disorders in adults: Selective update of 2001 U.S. Preventive Services Task Force review. Prepared for the Agency for Healthcare Research and Quality; by the Oregon Evidence-based Practice Center at the Oregon Health and Science University, Portland, Oregon, under Contract Number 290-02-0024. April 2008. Evidence Synthesis No. 49. AHRQ Publication No. 08-05114-EF-1.
4. Pignone MP, Philllips CJ, Lannon CM et al. Screening for Lipid Disorders. Rockville, Maryland: Agency for Healthcare Research and Quality; April 2001. AHRQ Publication No. 01-S004.
5. Tran ZV, Weltman A. Differential effects of exercise on serum lipid and lipoprotein levels seen with changes in body weight: A meta-analysis JAMA 1985;254:919-924.
6. Pignone M, Philllips C, Mulrow C. Use of lipid lowering drugs for primary prevention of coronary heart disease: meta-analysis of randomized trials. BMJ 2000;321:983-986.
7. Ford I, Murray H, Packard CJ et al. Long-term follow-up of the West of Scotland Coronary Prevention Study Group. New Engl J Med 2007;357(15):1477-1486.
8. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7-22.
9. Sever PA, Dahlof B, Poulter NR et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA,): a multicentre randomised controlled trial. Lancet 2003;361:1149-1158.
10. ALLHAT Investigators. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomised to pravastatin versus usual care. JAMA 2002;288:2998-3007.
11. Sheperd J, Blauw GJ, Murphy MB, et al, Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002;360:1623-1630.
12. Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): Multicenntre randomised placebo-controlled trial. Lancet 2004;364:685-696.
13. Grady D, Chaput L, Kristof M. Systematic Review of Lipid Lowering Treatment to Reduce Risk of Coronary Heart Disease in Women. Rockville, Maryland: Agency for Healthcare Research and Quality; 2003.
14. Wilt TJ, Bloomfield HE, MacDonald R et al. Effectiveness of statin therapy in adults with coronary heart disease. Archives of Internal Medicine 2004;164:1427-1436.
15. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III). JAMA 2001;285:2486-2497.
16. American Academy of Family Physicians.summary of policy recommendations for periodic health examinations. Revision 5.4, August 2003. Available at: http://www.aafp.org/PreBuilt/PHErev54.pdf. Accessed April 2, 2008.
17. Primary and preventive care: periodic assessments. ACOG Committee Opinion No. 292. American College of Obstetricians and Gynecologists. Obstet Gynecol 2003;102:1117-24.
Members of the U.S. Preventive Services Task ForceCorresponding Author: Ned Calonge, MD, MPH, Chair, U.S. Preventive Services Task Force, c/o Program Director, 540 Gaither Road, Rockville, MD 20850.
Members of the U.S. Preventive Services Task Force* are Ned Calonge, MD, MPH, Chair, USPSTF (Chief Medical Officer and State Epidemiologist, Colorado Department of Public Health and Environment, Denver, CO); Diana B. Petitti, MD, MPH , Vice-chair, USPSTF (Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Sierra Madre, CA); Thomas G. DeWitt, MD (Carl Weihl Professor of Pediatrics and Director of the Division of General and Community Pediatrics, Department of Pediatrics, Children's Hospital Medical Center, Cincinnati, OH); Leon Gordis, MD, MPH, DrPH (Professor, Epidemiology Department, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD); Kimberly D. Gregory, MD, MPH (Director, Women's Health Services Research and Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA); Russell Harris, MD, MPH (Professor of Medicine, Sheps Center for Health Services Research, University of North Carolina School of Medicine, Chapel Hill, NC); Kenneth W. Kizer, MD, MPH (President and CEO, National Quality Forum, Washington, DC); Michael L. LeFevre, MD, MSPH (Professor, Department of Family and Community Medicine, University of Missouri School of Medicine, Columbia, MO); Carol Loveland-Cherry, PhD, RN (Executive Associate Dean, Office of Academic Affairs, University of Michigan School of Nursing, Ann Arbor, MI); Lucy N. Marion, PhD, RN (Dean and Professor, School of Nursing, Medical College of Georgia, Augusta, GA); Virginia A. Moyer, MD, MPH (Professor, Department of Pediatrics, University of Texas Health Science Center, Houston, TX); Judith K. Ockene, PhD (Professor of Medicine and Chief of Division of Preventive and Behavioral Medicine, University of Massachusetts Medical School, Worcester, MA); George F. Sawaya, MD (Associate Professor, Department of Obstetrics, Gynecology, and Reproductive Sciences and Department of Epidemiology and Biostatistics, University of California, San Francisco, CA); Albert L. Siu, MD, MSPH (Professor and Chairman, Brookdale Department of Geriatrics and Adult Development, Mount Sinai Medical Center, New York, NY); Steven M. Teutsch, MD, MPH (Executive Director, Outcomes Research and Management, Merck & Company, Inc., West Point, PA)**; and Barbara P. Yawn, MD, MSPH, MSc (Department of Research, Olmsted Medical Center, Rochester, MN).
*Members of the Task Force at the time this recommendation was finalized. For a list of current Task Force members, go to http://www.uspreventiveservicestaskforce.org/about.htm.Disclaimer: Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
**Steven Teutsch, MD, MPH, was recused from voting on this topic.
**Steven Teutsch, MD, MPH, was recused from voting on this topic.
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AHRQ Publication No. 08-05114-EF-2
Current as of June 2008
Current as of June 2008
U.S. Preventive Services Task Force. Screening for Lipid Disorders in Adults: U.S. Preventive Services Task Force Recommendation Statement. June 2008. http://www.uspreventiveservicestaskforce.org/uspstf08/lipid/lipidrs.htm