Lipid Update: Risk Stratification in Primary Prevention

Joette C. Hughes, MSN, CRNP
Cardiovascular Nurse Practitioner, Penn Medicine: The Heart Group of LG Health, Lancaster, PA

The 2018 Guideline on the Management of Blood Cholesterol is the most recent iteration of the guidelines. The guidelines still rely heavily on the use of statin therapy for those with atherosclerotic cardiovascular disease (ASCVD) or ischemic cardiomyopathy. In addition, a history of heart failure when coupled with one major ASCVD event, places an individual at very high risk of future ASCVD events¹. Statins are indicated for those with diabetes aged 40 to 75, and those with LDL-c ≥190 md/dL. However, there is a gray area for those who are non-ischemic. In the absence of atherosclerosis, we need further risk stratification.

Primary prevention is more complex. Clinicians should start with calculating the patient’s ASCVD Risk with the ASCVD Risk Estimator Plus available at http://tools.acc.org/ASCVD-Risk-Estimator-Plus/#!/calculate/estimate/. Note there is no one risk score that is appropriate for all, as risk may be underestimated in certain populations². While the low and high-risk categories are clear, those in the borderline or intermediate risk categories may need additional stratification. The guidelines offer ASCVD Risk Enhancers, biomarkers, and other measurements that can help to delineate risk.

One biomarker to consider is lipoprotein(a), a genetic LDL like particle. Lipoprotein(a) contributes to both atherosclerosis and thrombosis. It is also proinflammatory and is implicated in calcific aortic valve pathology. There is a 50% chance of inheritance, existing in 1 in 5 people, and levels are fully established by age 5. Furthermore, levels are not affected by lifestyle. High levels of lipoprotein(a) can lead to skewed measurement of LDL-c due to the presence of its LDL-like particle. Evidence suggests that elevated levels >125nMol/L are an independent risk factor for ASCVD³. Statin therapy is the mainstay of treatment, with add-on therapy to further lower LDL-c. Niacin is no longer recommended due to lack of evidenced based data. See the 2019 National Lipid Association clinical statement on use of lipoprotein(a) in clinical practice for full details⁴. Clinicians should investigate for the presence of lipoprotein(a) in those where LDL-c appears not to be responding to therapy. Measurement is excellent in delineating risk and treatment.

When risk decision is still uncertain, consider a coronary artery calcium (CAC) score. Those in the 5% to 20% risk category on the ASCVD risk calculator may be reclassified given calcium score data⁵. While calcification is a pathogenic process, and not the result of aging, it is an independent predictor for developing cardiovascular disease⁶. Performed by non-contrast CT scan, detection of calcium is graded by age and gender. A score of zero is the strongest negative predictive risk factor for ASCVD. Conversely, detection of any coronary calcium remains an independent predictor for developing CV events. For those with coronary calcium, statin therapy is indicated. The absolute risk reduction with statin therapy is proportional to the calcium score. After initiating statin treatment, expect a rise in coronary calcium due to delipidization of soft cholesterol plaque. Therefore, it is not recommended to follow serial calcium scores. A score of 1-100, especially if in a high percentile with respect to age and gender (>75th), would put patient at risk. Any adult under 55 with a non-zero score has a significant 10 year and lifetime risk. Generally speaking, there is no evidence to support ischemic evaluation in asymptomatic patients with elevated CAC scores<sup>7</. Aspirin should be considered in those with CAC scores greater than 100. At the time of this writing, the National Lipid Association announced their 2020 Scientific Statement on Coronary Calcium Scoring.

Risk stratification in the primary prevention population can be complex, but consideration of the guidelines, risk enhancers, biomarkers and concomitant conditions can help further distinguish when therapy is indicated. Always remember to start the risk and benefit discussion, and to include the patient in the decision-making process.

References

Grundy, S.M. et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. JACC. 2019; 73(24): e285-e350.
Arnett, D.K. et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019; 140(11): e596-e646 .
Moriarty, P.M. et al. Lipoprotein(a) – Fast Facts and Clinical Perspectives. Lipid Spin. 2018; 16(3): 7-10.
Wilson, D.P. et al. Use of lipoprotein(a) in clinical practice: A biomarker whose time has come – A scientific statement from the Nation Lipid Association. Journal of Clinical Lipidology. 2019; 13: 374-392.
Mintz, G.L. & Tummala, R. Borderline Risk is Immediate Risk. Lipid Spin. 2019; 17(4): 17-20.
Jacoby, D. & Ayers, M. New Cholesterol Guidelines – Coronary Artery Calcium Scores a Win. Lipid Spin. 2019; 17(4): 21-23.
Orringer CE, Blaha MJ, Blankstein R, Budoff MJ, Goldberg RB, Gill EA, Maki KC, Mehta L, Jacobson TA, The National Lipid Association Scientific Statement on Coronary Artery Calcium Scoring to Guide Preventive Strategies for ASCVD Risk Reduction, Journal of Clinical Lipidology (2021), doi: https://doi.org/10.1016/j.jacl.2020.12.005.