Clinical Review

Hyperlipidemia management: A calibrated approach

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Gauge the level of LDL cholesterol and assess risk-enhancing factors for ASCVD—thus setting the table for primary and secondary prevention with medical therapy



An elevated serum level of cholesterol has been recognized as a risk factor for atherosclerotic cardiovascular disease (ASCVD) since the publication of the Framingham Study in 1961.1 Although clinical outcomes related to ASCVD have improved in recent decades, ASCVD remains the leading cause of morbidity and mortality across the globe and remains, in the United States, the leading cause of death among most racial and ethnic groups. Much of this persistent disease burden can be attributed to inadequate control of ASCVD risk factors and suboptimal implementation of prevention strategies in the general population.2

The most recent (2019) iteration of the American College of Cardiology/American Heart Association (ACC/AHA) Guideline on the Primary Prevention of Cardiovascular Disease emphasizes a comprehensive, patient-centered, team-based approach to the management of ASCVD risk factors.2 In this article, I review how, first, medication to reduce ASCVD risk should be considered only when a patient’s risk is sufficiently high and, second, shared decision-making and social determinants of health should, in all cases, guide and inform optimal implementation of treatment.2

  • Use an alternative to the Friedewald equation, such as the Martin–Hopkins equation, to estimate the low-density lipoprotein cholesterol (LDL-C) value; order direct measurement of LDL-C; or calculate non–high-density lipoprotein cholesterol to assess the risk for atherosclerotic cardiovascular disease (ASCVD) in patients who have a low LDL-C or a high triglycerides level. C
  • Consider the impact of ASCVD riskenhancing factors and coronary artery calcium scoring in making a recommendation to begin lipid-lowering therapy in intermediate-risk patients. C
  • Add ezetimibe if a statin does not sufficiently lower LDL-C or if a patient cannot tolerate an adequate dosage of the statin. C

Strength of recommendation (SOR)

A. Good-quality patient-oriented evidence

B. Inconsistent or limited-quality patientoriented evidence

C. Consensus, usual practice, opinion, disease-oriented evidence, case series

Estimating risk for ASCVD by ascertaining LDL-C

  • The Friedewald equation. Traditionally, low-density lipoprotein cholesterol (LDL-C) is estimated using the Friedewald equationa applied to a fasting lipid profile. In patients who have a low level of LDL-C (< 70 mg/dL), however, the Friedewald equation becomes less accurate; in patients with hypertriglyceridemia (TG ≥ 400 mg/dL),estimation of LDL-C is invalid.
  • The Martin–Hopkins equation offers a validated estimation of LDL-C when the LDL-C value is < 70 mg/dL.3 This equation—in which the fixed factor of 5 used in the Friedewald equation to estimate very low-density lipoprotein cholesterol is replaced by an adjustable factor that is based on the patient’s non-HDL-C (ie, TC–HDL-C) and TG values—is preferred by the ACC/AHA Task Force on Clinical Practice Guidelines in this clinical circumstance.4
  • National Institutes of Health equation. This newer equation provides an accurate estimate of the LDL-C level in patients whose TG value is ≤ 800 mg/dL. The equation has not been fully validated for clinical use, however.5
  • Direct measurement obviates the need for an equation to estimate LDL-C, but the test is not available in all health care settings.

For adults ≥ 20 years of age who are not receiving lipid-lowering therapy, a nonfasting lipid profile can be used to estimate ASCVD risk and document the baseline LDL-C level. If the TG level is ≥ 400 mg/dL, the test should be administered in the fasting state.4

  • Apolipoprotein B. Alternatively, apolipoprotein B (apoB) can be measured. Because each LDL-C particle contains 1 apoB molecule, the apoB level describes the LDL-C level more accurately than a calculation of LDL-C. Many patients with type 2 diabetes and metabolic syndrome have a relatively low calculated LDL-C (thereby falsely reassuring the testing clinician) but have an elevated apoB level. An apoB level ≥ 130 mg/dL corresponds to an LDL-C level >160 mg/dL.4
  • Calculation of non-HDL-C. Because the nonfasting state does not have a significant impact on a patient’s TC and HDL-C levels, the non-HDL-C level also can be calculated from the results of a nonfasting lipid profile.

Non-HDL-C and apoB are equivalent predictors of ASCVD risk. These 2 assessments might offer better risk estimation than other available tools in patients who have type 2 diabetes and metabolic syndrome.6

Continue to: Applying the estimate of 10-year ASCVD risk...


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