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Screening and Treatment for Lipid Disorders in Children and Adolescents

Systematic Evidence Review

Figure 2. Analytic Framework and Key Questions (Text Description)

This figure displays graphically the logical progression of the systematic evidence review on Screening for Lipid Disorders in Children and Adolescents. A series of arrows represents key questions which, if answered with evidence from systematic reviews, may form an indirect chain of evidence linking screening for lipid disorders with improved health outcomes.

The figure proceeds from left to right, with two downward side-tracks for key questions 3 and 9, which relate to the adverse effects of screening and detection of the disease, respectively.

The key questions are listed at the bottom of the figure. Key question 2 includes 6 individual questions, numbered 2a through 2f.

Key question 1 is indicated by the topmost arrow. It relates the over-arching question: "Is screening for dyslipidemia in children/adolescents effective in delaying the onset and reducing the incidence of coronary heart disease (CHD) events. "Risk assessment and testing," indicated by a bold heading on the upper left of the figure, is linked to the ultimate desired outcome, "delayed onset and reduced incidence of CHD-related events," indicated in the rectangle on the extreme right side of the figure.

Key question 2 is indicated by an arrow connecting the population under investigation, "children and adolescents in the general population," to the information to be gained by answering the question, indicated in the rectangular lozenge-shaped box labeled "detection of children and adolescents with dyslipidemia." The sub-questions 2a through 2f are not displayed graphically. (Dyslipidemia is a technical term for "lipid disorders.")

Key question 3 is indicated by the downward-curving arrow linked to the oval labeled "adverse effects."

Key question 4 is indicated by an arrow just under the arrow for key question 1, in the right-hand half of the figure. It connects the section of the figure labeled by the bold header "treatment," consisting of a list of treatments: diet, exercise, drug [treatments], and combination [treatments], to a lozenge-shaped box labeled "reduced incidence of adult dyslipidemia" and to the rectangle at the extreme right side of the figure indicating the ultimate desired outcome of treatment, "delayed onset and reduced incidence of CHD-related events."

An arrow connects the lozenge "detection of children and adolescents with dyslipidemia" to a series of branching arrows for key questions 5, 6, 7, and 8. These key questions attempt to relate each specific treatment (diet, exercise, drug, and combination) to an intermediate outcome in children—reduced total cholesterol. This intermediate outcome is displayed in a lozenge-shaped box containing total cholesterol and its 4 sub-elements, with short arrows to the left of each element and sub-element to indicate the direction of desirable change. Only one arrow, the bottom one, points upward; this is because an increase in HDL-C levels is protective against CHD events.

Key question 9 is indicated by a downward-curving arrow beginning before the arrow on treatment branches off into key questions 5 through 8, and connecting with a second oval labeled "adverse effects." It refers to the adverse effects of the treatments, taken together, which are investigated individually key questions 5 through 8.

Key question 10 is indicated by an arrow connecting the lozenge containing the intermediate outcomes of treatment in children with a lozenge containing a desired outcome in adults, "reduced incidence of adult dyslipidemia." This lozenge includes the 5 elements of reduced total cholesterol and its sub-elements, with arrows indicating the direction of desired change, as in the lozenge to the left describing reduced total cholesterol in children.

A broken arrow connects this last lozenge with the rectangle on the extreme right side of the figure. This indicates either that there is an already-established evidence-based link between the intermediate outcomes of reduced cholesterol in adults and the ultimate desired outcome, "delayed onset and reduced incidence of CHD-related events," or that no key question has been framed which can establish this connection.

Key Questions

  1. Is screening for dyslipidemia in children/adolescents effective in delaying the onset and reducing the incidence of CHD-related events?
  2. What is the accuracy of screening for dyslipidemia in identifying children/adolescents at increased risk of CHD-related events?
    2a. What are abnormal lipid values in children/adolescents?
    2b. What are appropriate tests? How well do screening tests (non-fasting total cholesterol, fasting total cholesterol, fasting lipoprotein analysis) identify individuals with dyslipidemia?
    2c. How well do lipid levels track from childhood to adulthood?
    2d. What is the accuracy of family history in determining risk?
    2e. What are other important risk factors?
    2f. What are effective screening strategies for children/adolescents (including frequency of testing, optimal age for testing)?
  3. What are the adverse effects of screening (including false positives, false negatives, labeling)?
  4. In children/adolescents, what is the effectiveness of drug, diet, exercise, and combination therapy in reducing the incidence of adult dyslipidemia and delaying the onset and reducing the incidence of CHD-related events (including optimal age for initiation of treatment)?
  5. 6, 7, 8. What is the effectiveness of drug, diet, exercise, and combination therapy for treating dyslipidemia in children/adolescents?
  6. What are the adverse effects of drug, diet, exercise, and combination therapy in children/adolescents?
  7. Does improving dyslipidemia in childhood reduce the risk of dyslipidemia in adulthood?

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