Statins and increases in Lp(a): an inconvenient truth that needs attention

Tsimikas, Sotirios; Gordts, Philip L.S.M.; Nora, Chelsea; Yeang, Calvin; Witztum, Joseph L.

doi:10.1093/eurheartj/ehz776

Cited by 21 publications

(13 citation statements)

References 5 publications

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“…There are exceptions to generally stable levels, including a stressful environment such as sepsis, in which Lp(a) levels are acutely elevated [18,19]. Normal lifestyle activities such as diet, exercise, and weight loss have limited effect on Lp(a), and lipid medications, such as statins, may modestly raise Lp(a) levels [20,21]. Lp(a) may act as an acute phase reactant and has been noted to be increased in acute cardiovascular events [22][23][24][25][26].…”

Section: Lp(a) and Antifibrinolytic Effectsmentioning

confidence: 99%

Lipoprotein(a) and Its Potential Association with Thrombosis and Inflammation in COVID-19: a Testable Hypothesis

Moriarty

Gorby

Stroes

et al. 2020

Curr Atheroscler Rep

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Purpose of Review The COVID-19 pandemic has infected over > 11 million as of today people worldwide and is associated with significant cardiovascular manifestations, particularly in subjects with preexisting comorbidities and cardiovascular risk factors. Recently, a predisposition for arterial and venous thromboses has been reported in COVID-19 infection. We hypothesize that besides conventional risk factors, subjects with elevated lipoprotein(a) (Lp(a)) may have a particularly high risk of developing cardiovascular complications. Recent Findings The Lp(a) molecule has the propensity for inhibiting endogenous fibrinolysis through its apolipoprotein(a) component and for enhancing proinflammatory effects such as through its content of oxidized phospholipids. The LPA gene contains an interleukin-6 (IL-6) response element that may induce an acute phase-type increase in Lp(a) levels following a cytokine storm from COVID-19. Summary Thus, subjects with either baseline elevated Lp(a) or those who have an increase following COVID-19 infection, or both, may be at very high risk of developing thromboses. Elevated Lp(a) may also lead to acute destabilization of preexisting but quiescent atherosclerotic plaques, which might induce acute myocardial infarction and stroke. Ongoing studies with IL-6 antagonists may be informative in understanding this relationship, and registries are being initiated to measure Lp(a) in subjects infected with COVID-19. If indeed an association is suggestive of being causal, consideration can be given to systematic testing of Lp(a) and prophylactic systemic anticoagulation in infected inpatients. Therapeutic lipid apheresis and pharmacotherapy for the reduction of Lp(a) levels may minimize thrombogenic potential and proinflammatory effects. We propose studies to test the hypothesis that Lp(a) may contribute to cardiovascular complications of COVID-19.

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Section: Lp(a) and Antifibrinolytic Effectsmentioning

confidence: 99%

Lipoprotein(a) and Its Potential Association with Thrombosis and Inflammation in COVID-19: a Testable Hypothesis

Moriarty

Gorby

Stroes

et al. 2020

Curr Atheroscler Rep

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“…In a follow-up comment, Banach and Penson [ 51 ] noted that most of the listed trials had mean Lp(a) < 30 mg/dL, and thus, although some of the reported rises were up to 101 mg/dL, in most cases these changes may not have been clinically relevant. Specifically, in subjects with Lp(a) ≥ 30–50 mg/dL in the statin group, the mean absolute Lp(a) change was 18.1 mg/dL, whereas in those with Lp(a) ≥ 50 mg/dL, the mean absolute change was 10.3 mg/dL [ 52 ].…”

Section: Statinsmentioning

confidence: 99%

Lipoprotein(a) Lowering—From Lipoprotein Apheresis to Antisense Oligonucleotide Approach

Greco

Sirtori

Corsini

et al. 2020

JCM

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It is well-known that elevated lipoprotein(a)—Lp(a)—levels are associated with a higher risk of cardiovascular (CV) mortality and all-cause mortality, although a standard pharmacotherapeutic approach is still undefined for patients with high CV risk dependent on hyperlipoproteinemia(a). Combined with high Lp(a) levels, familial hypercholesterolemia (FH) leads to a greater CVD risk. In suspected FH patients, the proportion of cases explained by a rise of Lp(a) levels ranges between 5% and 20%. In the absence of a specific pharmacological approach able to lower Lp(a) to the extent required to achieve CV benefits, the most effective strategy today is lipoprotein apheresis (LA). Although limited, a clear effect on Lp(a) is exerted by PCSK9 antagonists, with apparently different mechanisms when given with statins (raised catabolism) or as monotherapy (reduced production). In the era of RNA-based therapies, a new dawn is represented by the use of antisense oligonucleotides APO(a)Lrx, able to reduce Lp(a) from 35% to over 80%, with generally modest injection site reactions. The improved knowledge of Lp(a) atherogenicity and possible prevention will be of benefit for patients with residual CV risk remaining after the most effective available lipid-lowering agents.

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“…5 However, statins, which also enhance LDL receptor function, may actually increase circulating Lp(a) levels in humans. 6 To explain this discrepancy, we can speculate that Lp(a) uptake is modulated by other means than the LDL hepatic receptors. These could bind to apo(a), apoB, apoE or even oxidised phospholipids of Lp(a) and may include various lipoprotein receptors, lectins, annexin A2, toll-like and scavenger receptors as well as plasminogen receptors.…”

Section: Evangelos Liberopoulosmentioning

confidence: 99%

Lipoprotein(a) reduction with proprotein convertase subtilisin/kexin type 9 inhibitors: An unsolved mystery

Liberopoulos

2020

European Journal of Preventive Cardiology

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Statins and increases in Lp(a): an inconvenient truth that needs attention

Cited by 21 publications

References 5 publications

Lipoprotein(a) and Its Potential Association with Thrombosis and Inflammation in COVID-19: a Testable Hypothesis

Lipoprotein(a) and Its Potential Association with Thrombosis and Inflammation in COVID-19: a Testable Hypothesis

Lipoprotein(a) Lowering—From Lipoprotein Apheresis to Antisense Oligonucleotide Approach

Lipoprotein(a) reduction with proprotein convertase subtilisin/kexin type 9 inhibitors: An unsolved mystery

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