Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement

Abstract

This 2022 European Atherosclerosis Society lipoprotein(a) [Lp(a)] consensus statement updates evidence for the role of Lp(a) in atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis, provides clinical guidance for testing and treating elevated Lp(a) levels, and considers its inclusion in global risk estimation. Epidemiologic and genetic studies involving hundreds of thousands of individuals strongly support a causal and continuous association between Lp(a) concentration and cardiovascular outcomes in different ethnicities; elevated Lp(a) is a risk factor even at very low levels of low-density lipoprotein cholesterol. High Lp(a) is associated with both microcalcification and macrocalcification of the aortic valve. Current findings do not support Lp(a) as a risk factor for venous thrombotic events and impaired fibrinolysis. Very low Lp(a) levels may associate with increased risk of diabetes mellitus meriting further study. Lp(a) has pro-inflammatory and pro-atherosclerotic properties, which may partly relate to the oxidized phospholipids carried by Lp(a). This panel recommends testing Lp(a) concentration at least once in adults; cascade testing has potential value in familial hypercholesterolaemia, or with family or personal history of (very) high Lp(a) or premature ASCVD. Without specific Lp(a)-lowering therapies, early intensive risk factor management is recommended, targeted according to global cardiovascular risk and Lp(a) level. Lipoprotein apheresis is an option for very high Lp(a) with progressive cardiovascular disease despite optimal management of risk factors. In conclusion, this statement reinforces evidence for Lp(a) as a causal risk factor for cardiovascular outcomes. Trials of specific Lp(a)-lowering treatments are critical to confirm clinical benefit for cardiovascular disease and aortic valve stenosis.

Acute impact of the early application of alirocumab on lipoprotein (a) and interleukin-6 in patients with unstable angina pectoris: a retrospective before-after study

“…Based on the level of Lp(a) (cutoff value was 50 mg/dL) at baseline, patients were divided into 2 subgroups: high-Lp(a) subgroup (n = 11) and low-Lp(a) subgroup mg/dL (n = 42). The levels of Lp(a) in high-Lp(a) subgroup (95.10 ± 29.85 mg/dL) were similar to the distribution of Lp(a) found in other Eastern Asian population studies [10,11], which suggested that patients in high-Lp(a) subgroup exposed to higher residual cardiovascular risk. The details for subgroups were presented in Table 2.…”

“…Elevated concentrations of lipoprotein (a) [Lp(a)] and associated in ammation disorder sharply increase the risk of atherosclerotic cardiovascular disease (CVD)-related events [1,2] and impair the medical efforts in improving CVD prognosis [3] based on the multidimensional ndings in pathophysiology [4], epidemiology [5], Mendelian randomization [6], genome-wide analysis [7], post hoc analysis of randomized controlled clinical trials [8]and meta-analysis [9]. Meanwhile, the available evidence strongly suggests that the pathogenicity of Lp(a) is widespread across ethnic groups [3], owing to its proin ammatory and pro-atherosclerotic properties [10]. Moreover, Lp(a), independent of low-density lipoprotein cholesterol (LDL-C), is signi cantly associated with residual cardiovascular risk in patients with unstable angina (UA) [11][12][13], especially in certain Chinese populations with high Lp(a) levels [14].…”

World Heart Federation Cholesterol Roadmap 2022

“…As lipoprotein(a) cannot be estimated from other lipid measures it has to be measured directly, preferably using an isoform independent assay reporting values in terms of concentration (e.g., nmol/L) rather than mass (e.g., mg/dL). As levels do not change much over a lifetime, except in women where values further increase after menopause, or in acute inflammatory states, a single measurement once in a lifetime in adults is useful to reliably exclude significant elevations [18].…”

Consensus and guidelines on lipoprotein(a) – seeing the forest through the trees

“…This, however, does not exclude a potential impact of Lp(a) on arterial thrombogenic potential, as attested by the observation that (very) high Lp(a) associates with early arterial stroke in children [7–9]. A meta-analysis included in the recent European Atherosclerosis Society (EAS) Lp(a) consensus paper supported that lifelong very low Lp(a) concentrations may associate with future risk of diabetes; the mechanism behind is currently not well understood [1 ▪ ].…”