Lipoprotein(a) as a cardiovascular risk factor: current status

By B. Nordestgaard, M. Chapman, K. Ray, Jan Boren, F. Andreotti, G. Watts, H. Ginsberg, P. Amarenco, Alberico L. Catapano, O. Descamps and 9 more. European Heart Journal, 2010

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Aims The aims of the study were, first, to critically evaluate lipoprotein(a) [Lp(a)] as a cardiovascular risk factor and, second, to advise on screening for elevated plasma Lp(a), on desirable levels, and on therapeutic strategies. Methods and results The robust and specific association between elevated Lp(a) levels and increased cardiovascular disease (CVD)/coronary heart disease (CHD) risk, together with recent genetic findings, indicates that elevated Lp(a), like elevated LDL-cholesterol, is causally related to premature CVD/CHD. The association is continuous without a threshold or dependence on LDL- or non-HDL-cholesterol levels. Mechanistically, elevated Lp(a) levels may either induce a prothrombotic/anti-fibrinolytic effect as apolipoprotein(a) resembles both plasminogen and plasmin but has no fibrinolytic activity, or may accelerate atherosclerosis because, like LDL, the Lp(a) particle is cholesterol-rich, or both. We advise that Lp(a) be measured once, using an isoform-insensitive assay, in subjects at intermediate or high CVD/CHD risk with premature CVD, familial hypercholesterolaemia, a family history of premature CVD and/or elevated Lp(a), recurrent CVD despite statin treatment, ≥3% 10-year risk of fatal CVD according to European guidelines, and/or ≥10% 10-year risk of fatal + non-fatal CHD according to US guidelines. As a secondary priority after LDL-cholesterol reduction, we recommend a desirable level for Lp(a) <80th percentile (less than ∼50 mg/dL). Treatment should primarily be niacin 1–3 g/day, as a meta-analysis of randomized, controlled intervention trials demonstrates reduced CVD by niacin treatment. In extreme cases, LDL-apheresis is efficacious in removing Lp(a). Conclusion We recommend screening for elevated Lp(a) in those at intermediate or high CVD/CHD risk, a desirable level <50 mg/dL as a function of global cardiovascular risk, and use of niacin for Lp(a) and CVD/CHD risk reduction.

Subfields: Emergency Medicine, Immunology, Surgery

View Paper: https://www.semanticscholar.org/paper/696debc961236c391ab92d3525f7b8b370ae6e5f

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Citations in the corpus

Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel (2020, background): “and Lp(a) are directly causal in ASCVD, independent of LDL-C levels.(6,7,9,11) Indeed, the hazard ratios for myocardial infarction for a”
Triglyceride-rich lipoproteins and their remnants: metabolic insights, role in atherosclerotic cardiovascular disease, and emerging therapeutic strategies—a consensus statement from the European Atherosclerosis Society (2021, background): “nants will be synergistic to those of other apoB-containing lipoproteins, particularly LDL and lipoprotein(a).(17,25,93,104,206)”
Guidelines on the Use of Therapeutic Apheresis in Clinical Practice – Evidence‐Based Approach from the Writing Committee of the American Society for Apheresis: The Eighth Special Issue (2019, neutral): “References [788–801]”
Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease (2013, background): “a well-established causal risk factor for cardiovascular disease irrespective of LDL cholesterol concentration.(29,30) Elevated Lp(a) is Figure 6 Overlap of clinical and mutation diagnosis of heterozygous familial hypercholesterolaemia.”
Familial hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients: clinical guidance from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. (2011, background): “Affected subjects are at increased risk for all forms of atherosclerotic disease and premature death secondary to lifelong pathogenic elevations in serum LDL cholesterol.(18) National Lipid Association Expert Panel on Familial Hypercholesterolemia: Anne C.”
2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. (2016, background): “Plasma Lp(a) is not recommended for risk screening in the general population; however, Lp(a) measurement should be systematically considered in people with high CVD risk or a strong family history of premature atherothrombotic disease (Box 7).(109) The risk is regarded as significant when Lp(a) is a”
ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). (2011, background): “Plasma Lp(a) is not recommended for risk screening in the general population; however, Lp(a) measurement should be considered in people with high CVD risk or a strong family history of premature atherothrombotic disease.(51)”
2016 European Guidelines on cardiovascular disease prevention in clinical practice (2017, positive): “There is no randomized intervention study showing that reducing Lp(a) decreases CVD risk [362].”
National lipid association recommendations for patient-centered management of dyslipidemia: part 1--full report. (2015, background): “An Lp (a) concentration of $50 mg/L represents approximately the 80th percentile of the general population.(161,252) C-reactive protein, which generally reflects the level of inflammation, is also a marker of risk for ASCVD events.”
2016 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult. (2016, background): “A continuous increase in CVD risk is evident in 30% of the population with Lp(a) levels > 30 mg/dL.(55)”
A Test in Context: Lipoprotein(a): Diagnosis, Prognosis, Controversies, and Emerging Therapies. (2017, background): “5 mg/dl, and niacin reduced Lp(a) 19% to w11 mg/dl (43), changes which would be unlikely to result in clinical benefit.”
Hyperlipidemia as a Risk Factor for Cardiovascular Disease (2012, background): “Elevated Plasma Lipoprotein(a) Relationship to CVD unclear, studies contradictory (48; 49)”