Comparison of cardiovascular disease risk assessment tools in primary prevention patients with raised lipoprotein(a)

Abstract Background Genetically inherited lipoprotein (a) (lp(a)) is an independent cardiac risk factor. The approach to cardiovascular disease (CVD) risk modification is, however, uncertain. Current CVD risk calculators do not take lp(a) into account and guidance suggests binary treatment decisions based on presentation of lp(a) without considering other risk factors. A new CVD risk assessment tool has been developed which includes lp(a) concentration, Lp(a) Clinical Guidance (lpaclinicalguidance.com). Purpose The aim was to compare the CVD risk estimations and management impact, over both 10 years and lifetime, using the HEART UK consensus statement, QRISK3, Lp(a) Score, Score-2, Score-2 OP, and LIFE-CVD assessment tools in 20 primary prevention patients with raised lp(a). Methods This was a retrospective analysis from an existing database, recruited through lipid and cardiology outpatient services, with raised lp(a), and no history of CVD. A random selection with a broad range of lp(a) concentrations were chosen. The 10-year risk threshold to treat was based on current NICE guidance at 10% and, in the absence of consensus, a lifetime risk threshold of 25%. Lp(a) was measured by a reference clinical laboratory using a Roche platform (Denka Seiken reagent, isoform insensitive). Results The subset (n=20) included patients with lp(a) ranging from 64 nmol/L to >720 nmol/L, aged 20 to 78 (12 females). Risk assessment tool age restrictions prohibited risk estimation in all patients (explaining the variation in denominator below). Figure 1 shows a comparison of 10-year risk assessment tools, figure 2 lifetime risk. HEART UK guidance would indicate 90% of patients (18/20) were eligible to commence lipid lowering therapy, however, all patients would have treatment indicated based on Lp(a) Score (16/16). Using Score-2, no patients would have treatment indicated (0/6). Only 25% of patients (1/4) would have treatment indicated using Score-2 OP despite a minimum age criterion that alone introduces a major CVD risk factor. Of the remaining risk estimation tools: LIFE-CVD, QRISK3 lifetime risk, and QRISK3 10-year risk indicated 85% (11/13), 50% (8/16), and 38% (6/16) of patients, respectively, would have treatment indicated. Conclusions In primary prevention patients with raised lp(a), CVD risk estimation and decision-making is impaired by discrepancies in risk assessment tools. There may be underestimation in CVD risk, and subsequently under-treatment, with principal use of QRISK3 10-year risk to guide lipid lowering therapy. Lifetime CVD risk may be underestimated by QRISK and LIFE-CVD proportionally to the degree of elevation of lp(a). Risk assessment is imperfect; population data can only provide limited information when applied to an individual and the wide discrepancy found here calls into question the validity of risk estimation formulae in this population, or alternatively provides a range of tools for clinicians to select to suit the question asked.