Screening of asymptomatic patients with elevated lipoprotein(a) levels by coronary computed tomography angiography

The management of asymptomatic patients at risk for atherosclerotic cardiovascular disease (ASCVD) depends on their estimated risk category based on clinical scores, such as the European SCORE2 for fatal cardiovascular events or the ASCVD score. However, a limitation of such clinical risk models is that they do not take into account cardiovascular risk factors other than the traditional ones.¹

Lipoprotein (a) [Lp(a)] is a molecule similar to low-density lipoprotein (LDL) with an apolipoprotein(a) attached to apolipoprotein B-100 via a disulfide bridge. Lipoprotein (a) shares similarities to LDL moiety and plasminogen and thus it is considered an independent risk factor for atherosclerotic vascular disease due to its pro-atherosclerotic and prothrombotic properties.² The increase in cardiovascular risk conferred by Lp(a) seems to be dose-dependent.³ For patients with high Lp(a) levels, the actual risk may be much higher than that predicted by clinical models.⁴

In their article, Nurmohamed et al.⁵ present interesting data on the association between Lp(a) levels and cardiovascular outcomes. Specifically, a group with Lp(a) concentrations >99th percentile had a ∼2.6-fold higher risk for ASCVD and a ∼3.4-fold higher risk for myocardial infarction when compared with a group with Lp(a) levels ≤20th percentile. Lp(a) levels over the 99th percentile when added to risk scores led to reclassification of about one-third of this population into a higher cardiovascular disease risk category. Therefore, Lp(a)-related cardiovascular risk should be more closely monitored in primary prevention.

Screening by coronary computed tomography angiography (CCTA) for coronary atherosclerosis has a class IIb recommendation in asymptomatic patients,⁶ reserved mainly for diabetic patients at very high cardiovascular risk.⁷ However, CCTA screening in certain patient subgroups may be reasonable to rule-in the presence of coronary atherosclerosis that mandates more aggressive preventive measures (including aggressive lipid-lowering treatment and/or antiplatelets).

In our centre, we may proceed to asymptomatic screening by CCTA of patients in the presence of strong non-traditional cardiovascular risk factors, such as very high Lp(a) levels (i.e. >99th percentile) to detect the presence of coronary plaques. For example, Figure 1 shows the CCTA findings from the asymptomatic screening of a 62-year-old non-smoker female patient with extremely high Lp(a) values (>250 mg/dL), dyslipidaemia under rosuvastatin treatment (LDL-cholesterol 109 mg/dL) and prediabetes. Coronary calcium score offers limited prognostic information in such cases, as it is known that statins increase coronary calcium deposition.⁸ Therefore, a CCTA scan was ordered, which unexpectedly, demonstrated a 60% luminal stenosis in the proximal left anterior descending due to a mixed-calcified plaque (without high-risk plaque features) extending into the left main and the left circumflex artery (Figure 1). Given the linear risk-reduction associated with LDL-cholesterol lowering,⁹ intensification of lipid-lowering therapy with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (alirocumab 75 mg once every 2 weeks) as well as low-dose aspirin (100 mg/day) was prescribed.

Figure 1

Coronary computed tomography angiography images of a mixed (calcified and non-calcified) obstructive lesion in the proximal left anterior descending artery causing 60% luminal stenosis; curved multiplanar reformatted images of left anterior descending (A and B, arrows indicate the lesion) and focused cross-sectional (C and D) and longitudinal (along the vessel axis (E) of the left anterior descending lesion.

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Coronary computed tomography angiography enhances risk prognostication,¹⁰ and its use in large clinical trials is associated with reduced risk for myocardial infarction thanks to the early intensification of medical treatment and improved patient adherence. Moreover, accumulating data^11,12 have solidified the concept that total plaque burden rather than luminal stenosis is the predictor of coronary events since acute coronary syndromes are caused predominantly by minor plaques that rupture, while functionally significant anatomical stenoses lead to ischaemia and symptoms. Enhanced cardiovascular risk prognostication by CCTA¹⁰ can be also gained by detection of anatomical high-risk plaque features or even coronary inflammation detection by newer metrics such as perivascular fat imaging.^10,13

Therefore, compelling emerging evidence prompts for a paradigm shift in the risk stratification of asymptomatic patients. Screening of asymptomatic patients with non-traditional risk factors such as high Lp(a) levels (which are not captured by clinical scores) seems a rational approach to detect subclinical coronary atherosclerosis, optimize medical treatment and lower the risk for future coronary events. However, further clinical evidence is required to demonstrate the net benefit and cost-effectiveness of this approach in everyday clinical practice.

References

Author notes