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Screening for lipid disorders in adults

Screening for lipid disorders in adults
Author:
Sandeep Vijan, MD
Section Editors:
Mason W Freeman, MD
Joann G Elmore, MD, MPH
Deputy Editor:
Jane Givens, MD, MSCE
Literature review current through: Sep 2022. | This topic last updated: Aug 02, 2021.

INTRODUCTION — This topic addresses issues surrounding screening for lipid disorders in an adult primary prevention setting. The lipid profile and its components (total cholesterol, low-density lipoprotein [LDL] cholesterol, high-density lipoprotein [HDL] cholesterol, and triglycerides) are some of the most commonly ordered laboratory tests in clinical practice. The most common indication for this test (or its components) is for aiding the process of determining cardiovascular disease (CVD) event risk. Other indications for these tests include the following:

Identifying patients who are at high risk for a lipid abnormality due to a family history of genetic disorder, such as familial hypercholesterolemia. This has been referred to as "reverse cascade screening." (See "Inherited disorders of LDL-cholesterol metabolism other than familial hypercholesterolemia".)

Identifying the cause of another clinical problem such as pancreatitis.

Managing patients with established atherosclerotic CVD.

Evaluating the efficacy of and/or adherence with lipid-lowering therapy and lifestyle modification.

Screening for lipid disorders in children and young adults is discussed elsewhere, as is screening for familial syndromes of severe lipid abnormalities such as familial hypercholesterolemia. (See "Dyslipidemia in children and adolescents: Definition, screening, and diagnosis", section on 'Rationale for lipid screening' and "Inherited disorders of LDL-cholesterol metabolism other than familial hypercholesterolemia".)

The recommendations in this topic apply to patients screened for primary prevention. Testing for lipid abnormalities is indicated for patients with diabetes mellitus and for those with a history of familial disorders of lipid metabolism. (See "Overview of general medical care in nonpregnant adults with diabetes mellitus", section on 'Dyslipidemia' and "Familial hypercholesterolemia in adults: Overview" and "Inherited disorders of LDL-cholesterol metabolism other than familial hypercholesterolemia".)

TERMINOLOGY — Blood lipids, such as cholesterol and triglyceride, are insoluble in plasma. They are made soluble by inclusion into circulating lipoproteins. The lipoprotein consists of esterified and unesterified cholesterol, triglycerides, phospholipids, and protein. There are five major lipoproteins in blood: chylomicrons, very low-density lipoprotein (VLDL), intermediate-density lipoprotein, low-density lipoprotein (LDL), and high-density lipoprotein (HDL). Each of these classes of lipoproteins carries cholesterol and triglyceride in varying amounts, with LDL carrying the majority of cholesterol and VLDL carrying the majority of triglyceride in most individuals. (See "Lipoprotein classification, metabolism, and role in atherosclerosis".)

The terms dyslipidemia, lipid disorder, lipoprotein disorder, hyperlipidemia, and hypercholesterolemia are sometimes used interchangeably. However, they have different meanings:

Lipid disorders – Includes disorders of lipoprotein metabolism but also lipodystrophies and some lipid storage disorders. In many clinical discussions, this term has been used to mean clinical disorders associated with abnormal levels of total, HDL, and LDL cholesterol, as well as triglycerides.

Lipoprotein disorder – Specifically refers to clinical disorders of the lipoproteins that carry cholesterol and triglyceride.

Dyslipidemia – Used for lipid values that are associated with disease or increased risk of disease and for which lipid-altering therapy might be of value.

Hyperlipidemia – Elevation of serum total or LDL cholesterol or triglyceride.

Terminology is further complicated by the presence of lipid subfractions. As an example, LDL cholesterol is heterogeneous and can vary between small, dense particles (thought to be particularly atherogenic) and larger, low-density particles. These have been subdivided into four or even eight categories [1], and the efficacy (in coronary heart disease reduction) of treatment targeted at these various subfractions has not been firmly established. A review of lipoprotein metabolism and the function of the different apolipoproteins is presented elsewhere. (See "Lipoprotein classification, metabolism, and role in atherosclerosis".)

RATIONALE FOR SCREENING — Despite the evidence presented below of a potential benefit(s) to widespread (population) screening of a young adult population, there is no evidence that it leads to improved patient outcomes [2]. We believe that the results of screening for lipid disorders are important, primarily when used in combination with assessment of other factors that contribute to disease propensity, to enable the clinician to obtain the most reliable estimate of future cardiovascular disease (CVD) risk. (See "Atherosclerotic cardiovascular disease risk assessment for primary prevention in adults: Our approach".)

The rationale for screening is based on the following evidence:

Epidemiological studies have consistently demonstrated a log-linear relationship between total and low-density lipoprotein (LDL) cholesterol levels and coronary heart disease (CHD) risk (figure 1). This is a continuous, graded relationship without clear thresholds below which CHD risk is zero. (See "Overview of established risk factors for cardiovascular disease".)

Treatment of lipid disorders in patients at high risk of (or with established) CHD decreases the risk of cardiovascular events [3].

Abnormal values for one or more tests of blood lipids are highly prevalent. By World Health Organization (WHO) definitions, about 40 percent of people globally have elevated total cholesterol levels, while about 50 percent have elevated levels in Europe and the Americas [4].

Lipid testing is relatively quick, easy, and inexpensive. The tests are generally reliable.

Thus, the identification of patients at risk and the initiation of treatment will improve cardiovascular outcomes in many individuals. Some experts have argued that screening adults without other risk factors for CVD should not be performed until age 40 or 50 years since the absolute risk reduction in CVD events by such therapy will be small. Others argue that knowledge of the presence of a lipid disorder may become an opportunity for the clinician to motivate some patients to adopt healthier lifestyles. Judging these claims is difficult as there are no studies showing a positive effect of screening (compared with not screening) younger (eg, ages 18 to 35) adults, and there are potentially substantial costs in screening the entire population, including the use of unnecessary medication in lower-risk individuals. Screening in younger adults is therefore an area of significant uncertainty.

WHO SHOULD BE SCREENED — There is controversy regarding which adults (eg, what age or with what other risk factors) should be screened for a lipid disorder. This controversy stems from the absence of evidence that demonstrates benefit from screening in younger adults. This issue is further complicated by recommendations from some organizations to perform screening for dyslipidemia in all children before puberty (age 9 to 11) and after puberty (age 17 to 21). (See "Dyslipidemia in children and adolescents: Definition, screening, and diagnosis", section on 'Rationale for lipid screening'.)

For young adults who have not been screened as children, we obtain a baseline lipid profile at the time of initiation of care with an adult primary care practitioner to screen for familial hyperlipidemia and to assess cardiovascular disease (CVD) risk. If the results are normal, the timing and frequency of future screening should be guided by the patient’s risk of CVD and potential for interventions to improve patient outcomes. (See "Atherosclerotic cardiovascular disease risk assessment for primary prevention in adults: Our approach".)

CVD risk is influenced by age (increases as patients get older), sex (more common in men than women), hypertension, diabetes mellitus, cigarette smoking, obesity, sedentary lifestyle, and family history of premature coronary heart disease (CHD; first-degree male relative with CHD before age 55; first-degree female relative with CHD before age 65). (See "Cardiovascular disease risk assessment for primary prevention: Risk calculators" and "Atherosclerotic cardiovascular disease risk assessment for primary prevention in adults: Our approach".)

For patients at higher cardiovascular risk (hypertension, diabetes mellitus, cigarette smoking, family history of premature CHD), we suggest follow-up lipid screening be performed in males between the ages of 25 to 30 and in females between the ages of 30 to 35.

For patients at lower cardiovascular risk (none of the above factors), we suggest follow-up lipid screening be performed in males at age 35 and in females at age 45.

Screening earlier or later may be appropriate for patients based on their individual willingness to participate in a lifestyle modification program or to initiate treatment with statins.

CHOICE OF TESTS — As discussed below, only the total cholesterol and high-density lipoprotein (HDL) cholesterol are technically needed for screening, since most lipid screening is performed to help in cardiovascular risk assessment. However, as costs are generally similar and triglycerides can add useful information in specific patient populations, we screen with the full lipid profile (that includes total cholesterol, low-density lipoprotein [LDL] cholesterol, HDL cholesterol, and triglycerides) in most patients. (See 'Using the results of screening' below.)

Screening for lipid disorders will most often be performed by a primary care clinician. In some settings, it is practical for the patient to be fasting at the time of the screen. Ordering a fasting test may prevent the patient for having to return for a second test if a non-fasting test raises the possibility of high triglyceride level. If a fasting test is not practical, we order non-fasting total cholesterol and an HDL cholesterol. (See "Measurement of blood lipids and lipoproteins", section on 'Fasting versus non-fasting tests'.)

A fasting lipid profile may be useful if the screening total cholesterol is greater than 250 mg/dL since it could be elevated due to high triglycerides, or if the HDL cholesterol is lower than 40 mg/dL since low HDL cholesterol is often associated with hypertriglyceridemia. In addition, as LDL cholesterol is the focal point of treatment, the LDL cholesterol must be calculated in some cases and the triglyceride level is needed for this calculation (see "Measurement of blood lipids and lipoproteins"). Many labs can measure LDL cholesterol directly, which may also allow patients to undergo a non-fasting lipid test and still have an accurate assessment of LDL cholesterol.

When screening patients with a family history of genetic hyperlipidemia or when evaluating patients for possible hypertriglyceridemia, we ask the patient to fast. This issue is discussed in detail separately. (See "Measurement of blood lipids and lipoproteins", section on 'Fasting versus non-fasting tests'.)

Other patients for whom a fasting lipid profile should be considered as the better approach include those who are overweight, have diabetes, or are taking medications that are known to raise triglyceride values such as steroids.

Triglyceride levels are important for the following additional reasons: virtually all outcome studies have used the calculated LDL cholesterol value as the target of treatment and that value requires a serum triglyceride measurement; triglyceride levels can help identify patients with secondary metabolic abnormalities that may require specific treatment interventions such as diabetes, steatosis, or non-alcoholic fatty liver disease; and very high triglyceride levels are a risk factor for the development of pancreatitis. The entire lipid profile is typically only slightly more in cost than an HDL cholesterol and total cholesterol, although costs vary dramatically across sites and payers.

Several studies using only univariate approaches have suggested that triglycerides are predictors of coronary heart disease (CHD) risk [5]. However, they appear to have relatively smaller predictive power once HDL cholesterol is considered, perhaps because of a strong inverse relationship with HDL levels. As a result, triglycerides are not a major component of most risk stratification models [6]. Treatment of hypertriglyceridemia to lower CHD risk is discussed elsewhere. (See "Hypertriglyceridemia in adults: Management" and "Hypertriglyceridemia in adults: Management", section on 'Treatment goals'.)

Specific lipid subfractions contribute differently to predictions of overall CHD risk (see "Lipoprotein classification, metabolism, and role in atherosclerosis"). Lipid subfractions are generally classified by relative density, with LDL and HDL most commonly measured. Many additional measurements are available, including further subfractions of LDL based on density [1] and measurement of various apolipoproteins (apo) A-1 and B.

There are numerous studies examining the power of each of these various lipoproteins in predicting CHD risk. There is generally a consensus that non-HDL cholesterol (total cholesterol minus HDL cholesterol) or the total cholesterol to HDL cholesterol ratio is a better predictor of CHD risk than LDL cholesterol alone [7,8]. The literature is largely consistent on this matter:

In an analysis of data from the Framingham study, the ratio of total cholesterol to HDL cholesterol significantly affected the risk for CHD events (hazard ratio [HR] 1.39, 95% CI 1.22-1.58), while LDL cholesterol was not a significant predictor of such events (HR 1.11, CI 0.97-1.27) [9].

In an individual patient meta-analysis of 302,430 people, the ratio of non-HDL cholesterol to HDL cholesterol was a better predictor of CHD risk than LDL cholesterol (HR 1.49 versus 1.38) [10].

In a study examining the predictive power of lipid levels on CHD events in patients on statins, the predictive power of non-HDL cholesterol was superior to that of LDL cholesterol (p = 0.002) [11].

In a cohort study of close to 400,000 adults from 19 countries, the 30-year cardiovascular disease (CVD) event rates were approximately three to four times higher among those in the highest (≥5.7 mmol/L) non-HDL cholesterol category compared with those in the lowest (<2.6 mmol/L) category (33.7 versus 7.7 percent in women, and 43.6 versus 12.8 percent in men) [12]. A continuous and linear association between higher levels of non-HDL cholesterol and greater CVD risk remained after multivariable adjustment.

USING THE INFORMATION FROM LIPID SCREENING — As discussed above, the most frequent application of the results of lipid screening is to input the data into a cardiovascular disease (CVD) risk calculator. Some calculators use only total cholesterol and high-density lipoprotein (HDL), while some also incorporate low-density lipoprotein (LDL). The choice of risk estimator/calculator is discussed separately. (See "Cardiovascular disease risk assessment for primary prevention: Risk calculators".)

REPEAT SCREENING — Many patients will undergo screening for a lipid disorder but not have preventive therapies started due to having a CVD risk below some threshold. We suggest assessing CVD risk and repeating measurements every five years. In patients near a threshold for treatment (whether based on total CVD risk or an LDL cholesterol goal), we suggest repeating measurements every three years. We also repeat measurements at least every three years in those found to be at increased CVD risk based on their lipid measurements.

STOPPING SCREENING — There are no studies that allow us to definitively determine an appropriate age to stop lipid screening. It is reasonable to continue screening patients without known cardiovascular disease (CVD) who are in generally good health through age 79. However, in patients who have had more than one prior normal lipid profile, we suggest stopping screening at age 65.

Although the clinical benefit from statin therapy may take years when used for primary prevention (it is as short as one to two years or sooner when used for secondary prevention) (see "Mechanisms of benefit of lipid-lowering drugs in patients with coronary heart disease", section on 'Timing and mechanisms of benefit'), we consider performing an initial screen for lipid abnormalities in patients above age 65.

Coronary heart disease (CHD) risk clearly increases with age, which is the dominant factor in most risk models; this suggests that ongoing monitoring of overall CHD risk is important. However, lipid levels tend to decrease in older adults. As an example, in a national sample of United States adults done from 1999 to 2002, average total cholesterol was 207 mg/dL among men ages 60 to 69 but 196 in men 70 and older; similarly, in women ages 60 to 69, total cholesterol was 223 mg/dL, while it was 220 mg/dL in those 70 and older [13]. Additionally, there are few data on treatment in the very old (age >75). (See "Management of elevated low density lipoprotein-cholesterol (LDL-C) in primary prevention of cardiovascular disease".)

USING THE RESULTS OF SCREENING — Once the decision to screen has been made, and lipid levels have been obtained, risk calculators can be used to estimate the 10-year risk of cardiovascular events. (See "Atherosclerotic cardiovascular disease risk assessment for primary prevention in adults: Our approach".)

Patients with a 10-year risk of a cardiovascular event >10 percent are generally considered for statin therapy (as well as daily aspirin), and many patients with a risk between 7.5 and 10 percent are also good candidates. Statin therapy will reduce the relative risk of cardiovascular events by 20 to 25 percent when used for primary prevention; thus, those with the highest baseline risk are likely to receive the greatest absolute improvement in risk with treatment. (See "Management of elevated low density lipoprotein-cholesterol (LDL-C) in primary prevention of cardiovascular disease".)

However, as there is no definitive treatment benefit that would be acceptable to all patients, a choice of threshold for treatment, particularly in the intermediate-risk group (7.5 to 20 percent risk), should be based on discussion with patients.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Lipid disorders in adults".)

SUMMARY AND RECOMMENDATIONS

Goal of screening – Screening for lipid abnormalities is widely recommended and practiced in industrialized nations, with a goal not only of identifying those who are candidates for lipid-lowering therapy but of more broadly identifying those at increased risk for cardiovascular disease (CVD) who could benefit from various interventions aimed at reducing CVD risk. (See "Overview of primary prevention of cardiovascular disease" and 'Introduction' above.)

Who should be screened

For young adults who have not been screened as children, we suggest obtaining a lipid profile at the time of initiation of care with an adult primary care practitioner (Grade 2C). (See 'Who should be screened' above.)

Our advice for repeat testing for lipid disorders in adults is as follows:

-For patients at higher cardiovascular risk (hypertension, diabetes mellitus, cigarette smoking, family history of premature coronary heart disease [CHD]), we suggest that follow-up lipid screening be performed in males between the ages of 25 to 30 and in females between the ages of 30 to 35 (Grade 2C).

-For patients at lower cardiovascular risk (none of the above), we suggest that follow-up lipid screening be performed in males at age 35 and in females at age 45 (Grade 2C).

Screening earlier or later may be appropriate for patients based on their individual willingness to initiate treatment with statins given a particular absolute reduction that can be achieved in CVD risk. (See 'Who should be screened' above.)

Choice of tests – When a decision is made to screen lipids to assess CVD risk, we prefer a full fasting lipid profile. However, in patients for whom fasting is not practical, initial screening can be performed with a non-fasting lipid panel or a non-fasting total cholesterol and a high-density lipoprotein (HDL) cholesterol. (See 'Choice of tests' above.)

Frequency of repeat screening – In patients whose prior lipid measurement places them clearly below an appropriate threshold for treatment, we suggest repeating measurements every five years (Grade 2C). In patients near a threshold for treatment based on total CVD risk and in patients above a threshold for treatment, we suggest repeating measurements every three years (Grade 2C). (See 'Repeat screening' above.)

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