Practical Pearls: A Personalized Approach to Risk Stratification

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Clinical practice guidelines are integral to daily management of cardiovascular diseases, including hyperlipidemia. The most recent 2018 Multisociety Cholesterol Guidelines advocate for a more personalized approach to risk assessment. Consider the following vignette: A 50-year-old man of South Asian descent with hypertension, 20-plus years of tobacco use – he quit 10 years ago – and premature coronary artery disease (CAD) in both his father and brother presents for risk stratification of atherosclerotic cardiovascular disease (ASCVD). His blood pressure is 132/85 on lisinopril 20mg daily, body mass index (BMI) 27 kg/m2 , total cholesterol 220 mg/dL, high-density lipoprotein cholesterol (HDL-C) 45 mg/dL, low-density lipoprotein cholesterol (LDL-C) 115mg/dL and hemoglobin A1c (HbA1c) 6%. Using the pooled cohort equation (PCE), his estimated 10-year ASCVD risk is 5.5%, putting him at borderline risk, but this may not adequately describe his condition. Given our patient’s riskenhancing factors (ethnicity, strong family history of CAD and metabolic syndrome), a coronary artery calcium (CAC) score was obtained. The CAC score was 120 Agatston units (AU), enabling us to recalculate his 10-year risk at 13.6% using the MultiEthnic Study of Atherosclerosis (MESA) risk-scoring system, which incorporates both CAC score and family history. Based on the risk-assessment calculations and after thorough shared decision-making with the patient, statin therapy is initiated along with optimizing risk-factor modifications.

Risk calculators estimate risk based on population-based studies; however, individual patients often may possess factors not included in the risk calculator. PCE may overestimate risk in groups with a higher socioeconomic status or those receiving consistent screening and preventive care. It also may underestimate risk in patients from certain racial/ethnic groups (e.g. South Asian) and those with chronic kidney disease, chronic inflammatory diseases and a family history of premature cardiovascular disease.(1) The latest guidelines highlight the importance of clinician-patient risk discussion involving risk-enhancing factors such as family history, race/ethnicity and certain biomarkers (e.g. lipoprotein A  [Lp(a)].(1) If the decision regarding statin therapy for primary prevention for a patient at borderline or intermediate risk (10-year ASCVD risk estimates between 5% and 20%) remains uncertain after risk calculation and discussion, the guidelines support using the CAC score to help restratify risk in borderline or intermediaterisk patients. A CAC score of >100 AU (or 75th percentile for age/sex/race/ethnicity) would highly favor initiation of statin therapy, as it did in our patient above. A score of 0 would predict a low event rate and suggest withholding or delaying drug therapy may be appropriate. In our patient above, if he had a CAC score of 0, his MESA risk score would have been 3.9%, putting him in the low-risk stratum.

It is important to realize that, while these risk-enhancing factors and CAC score add incremental value to risk stratification in borderline or intermediate risk patients, their utility is limited in very low-risk (<2.5%) or high-risk (>20%) patients because the addition of these variables does not reclassify the patient into a different risk stratum. In addition, it is worthwhile to note that statins actually may increase the CAC score through “de-lipidation” and stabilization of soft, cholesterol-laden plaques, leading to a rise in calcium density. Therefore, serial CAC scores should not be used to determine the efficacy of statin therapy. While the latest guidelines and risk assessment tools such as the PCE provide a framework for risk stratification, they have limitations and should not replace clinical judgement based on an individual patient’s unique circumstances and preferences. Ultimately, there is no perfect risk calculator that can substitute for individualized and patientspecific clinical decisionmaking, and it is up to the health care provider to integrate all of the available information to arrive at a joint decision with the patient regarding management. As we usher in the era of “precision medicine,” a personalized approach to cardiovascular prevention that incorporates the socioeconomic, racial and behavioral determinants of health will help physicians provide better care for patients.(1) (figure 1).

Disclosure statement: Dr. Goldenberg received honoraria from Amarin, Regeneron, and Amgen. Dr. Meng has no financial disclosures to report. Dr. Milea has no financial disclosures to report. Dr. Chawla has no financial disclosures to report.