Cardiovascular Risk — Identifying Outliers to the Guideline

Watson, Karol E., MD, PhD
Professor of Medicine/Cardiology
Co-director, UCLA Program in Preventive Cardiology
Director, UCLA Barbra Streisand Women’s Heart Health Program
Also by this Author 

The 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol provides a basis for assessing and reducing the risk of atherosclerotic cardiovascular disease (ASCVD) events in adults.1

The guideline identifies groups of patients most likely to benefit from statin therapy, based on the new Pooled Cohort Risk Assessment Equations,to estimate 10-year ASCVD risk.1 Dr. Karol Watson, Professor of Medicine/Division of Cardiology, Co-director, UCLA Program in Preventive Cardiology, explains why certain patients may not be covered by the guideline and discusses approaches for identifying and assessing risk in these “outliers” to the guideline.

Guideline Parameters

“The guideline is a great start for assessing risk and will capture most people by using the pooled cohort risk calculator,”2, 3 notes Dr. Watson. The guideline recommends use of the new Pooled Cohort Equations to estimate 10-year ASCVD risk as a basis for identifying higher risk individuals for statin therapy. Using extensive data from randomized clinical trials (RCTs) the guideline indicates four statin benefit groups for targeting efforts to reduce ASCVD risk through secondary and primary prevention.1

These four groups are:

  1. Individuals with clinical ASCVD
  2. Individuals with primary elevations of LDL-C ≥190 mg/dL
  3. Individuals 40 to 75 years of age with diabetes and LDL-C 70 to 189 mg/dL without clinical ASCVD
  4. Individuals without clinical ASCVD or diabetes who are 40 to 75 years of age and have LDL-C 70 to 189 mg/dL and an estimated 10-year ASCVD risk of ≥7.5%. This requires a clinician-patient discussion.1

The guideline also stresses that lifestyle modification (adhering to a heart-healthy diet, regular exercise habits, avoidance of tobacco products, and maintenance of a healthy weight) remains an important aspect of ASCVD risk reduction, both before, and in combination with, the use of cholesterol-lowering drug therapies.1

Guideline Limitations

“While the guideline captures most people at-risk, physicians see patients every day who appear to be at risk from a clinical assessment but whose risk is very low when calculated by the risk calculator. This gnaws at you, as you believe this is really a higher risk patient. The reason for the discrepancy is that there are other factors which contribute to risk which are not captured by the risk calculator.”

The guideline recognizes that there are patients who may fall outside its parameters: “The evidence-based recommendations in this guideline focus on patient groups who are well represented in randomized controlled trials (RCTs) and/or are highly likely to have high-risk genetic conditions, so the recommendations are designed to inform clinical judgment, not to replace it. However, there are other patient groups in whom a robust evidence base is lacking, but which may nevertheless include some persons in whom statin treatment should be considered …These patient groups include:

  • younger adults (<40yrs) with low 10 year ASCVD risk but high lifetime risk
  • those with serious comorbidities and increased ASCVD risk (e.g., individuals with HIV, rheumatologic or inflammatory diseases, or who have undergone a solid organ transplant).”1

Strategies for Identifying Outliers to the Guideline

“To help refine a decision about risk,” says Dr. Watson, “physicians should carefully review family history, and take into account additional measures such as coronary calcium score, ankle-brachial index and high LDL. In patients in whom the risk decision is certain, there is no need to look further.  In patients who we believe may have some hidden risk either due to family or other co-morbidity it may be wise to look further. In assessing a patient who we believe has some hidden risk we may also perform advanced lipid testing. This consists of looking at other lipid or lipid-related parameters, which we know confer risk but wouldn’t be captured in a standard lipid panel. These include lipoprotein(a) [Lp(a)] and LDL particle number (LDL-P).  Results from these tests help you tailor your estimation of risk and determine whether or not to initiate statin treatment.”

In summarizing her approach to applying the guideline, Dr. Watson emphasizes the importance of individual patient assessment. “The guideline provides an excellent basis for assessing risk,” she says, “and will help identify a large number of at-risk patients for treatment. However, we understand that every patient is an individual and that risk can be driven by a variety of factors. Some patients, identified as intermediate or low risk by the risk calculator, will fall outside of the guideline parameters but would still benefit from statin therapy. So we need to take the right steps to capture the patients we believe are at risk but don’t quite meet the guideline criteria, by looking at other parameters with the aid of advanced lipid testing to refine their risk.”


  1. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults. Circulation.2014; 129: S1-S45
  2. 2013 Prevention Guidelines Tools CV Risk Calculator
  3. 2013 Prevention Guidelines ASCVD Risk Estimator