Elevated Lp(a) in the setting of strongly positive FHx and high coronary artery calcium score for the patient’s age
C. Address all modifiable cardiovascular risk factors, initiate cascade screening, and start high-intensity statin therapy and aspirin, 81 mg, daily
Lp(a) is proatherogenic, prothrombotic, and proinflammatory1,2 and has an estimated global prevalence of around 20%.1 While the upper Lp(a) threshold that indicates an elevated ASCVD risk does vary, values above the 80th (100 nmol/L) or 85th (125 nmol/L) are clinically accepted.1,3 Although Lp(a)-lowering therapies are currently under investigation, elevated Lp(a) is actionable. This patient’s elevated Lp(a) level is concerning due to his FHx of premature ASCVD and South Asian ancestry. Despite being at low 10-year ASCVD risk by the PCEs, he was noted to have 3 risk-enhancing factors (REFs). The presence of 3 or more REFs may incrementally increase ASCVD risk beyond the PCE estimates.4 In individuals with a FHx of premature ASCVD, risk stratification using the PCEs may not be high enough to merit consideration and points to a unique use of the REFs. This patient’s clinical management can be improved by (1) counseling, (2) coronary artery calcium (CAC) scoring to guide medical therapy, and (3) cascade screening of family members. Counseling patients about the association between elevated Lp(a) and ASCVD should underscore the need for comprehensively treating all modifiable ASCVD risk factors. While treating risk factors does not lower Lp(a) levels, it can reduce overall ASCVD risk. Lifestyle modifications outlined in the American Heart Association’s Life’s Essential 8 can significantly reduce ASCVD risk.1,2 CAC scoring is recommended when a risk decision for statin therapy is uncertain. Indeed, with this patient’s FHx and elevated Lp(a) level, risk information to support statin therapy is already available. However, a significantly elevated CAC score could support more intensive lipid-lowering and aspirin therapy. A CAC score and Lp(a) level add independently to risk stratification in these individuals.1,2 While PCSK9 inhibitors can lower Lp(a) by 15% to 25%, therapy should focus on lowering low-density lipoprotein cholesterol (LDL-C), which has greater ASCVD risk reduction per mmol/L.1,2 Given that approximately 80% to 90% of an individual’s Lp(a) level is genetically determined in an autosomal codominant inheritance pattern,1 cascade screening, a high-yield method of screening first-degree relatives who have a much higher likelihood of having the abnormal trait, may be warranted (Figure 2).