Cardiovascular disease risk associated with elevated lipoprotein(a) attenuates at low low-density lipoprotein cholesterol levels in a primary prevention setting

Verbeek, Rutger; Hoogeveen, Renate M.; Langsted, Anne; Stiekema, Lotte C.A.; Verweij, Simone L.; Hovingh, G. Kees; Wareham, Nicholas J.; Khaw, Kay‐Tee; Boekholdt, S. Matthijs; Nordestgaard, Børge G.; Stroes, Erik S.G.

doi:10.1093/eurheartj/ehy334

Cited by 116 publications

(78 citation statements)

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“…An increased Lp(a) concentration is a causal, independent risk factor for ASCVD and a predictor of incident or recurrent cardiovascular events. At low Lp(a) concentrations (up to 30 mg/dL) and in the “gray” zone (>30‐50 mg/dL), Lp(a)‐mediated risk is clinically less important, because LDL‐C‐mediated risk, caused by the far more numerous regular LDL particles, prevails . Patients with raised concentrations of Lp(a) (ie, >50 mg/dL), even while taking statins, are at a significantly higher risk of ASCVD .…”

Section: Introductionmentioning

confidence: 99%

“…At low Lp(a) concentrations (up to 30 mg/dL) and in the "gray" zone (>30-50 mg/dL), Lp(a)-mediated risk is clinically less important, because LDL-C-mediated risk, caused by the far more numerous regular LDL particles, prevails. 13 Patients with raised concentrations of Lp(a) (ie, >50 mg/dL), even while taking statins, are at a significantly higher risk of ASCVD. 14 Despite the lack of controlled intervention studies, the European Atherosclerosis Consensus Panel formulated a desirable range below the 80th percentile (ie, <50 mg/dL).…”

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confidence: 99%

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Real‐world study: Escalating targeted lipid‐lowering treatment with PCSK9‐inhibitors and lipoprotein apheresis

Spitthöver

Röseler²,

Julius

et al. 2019

J of Clinical Apheresis

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Introduction Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition with monoclonal antibodies has complemented the armamentarium of lipid‐lowering therapy (LLT) before the final step of commencing chronic lipoprotein apheresis (LA). Data are scarce on patients who, after escalation of LLT with PCSK9 antibodies, have commenced chronic LA or PCSK9 antibody treatment during ongoing long‐term LA. Patients and Methods In this study, a cohort of 110 patients with established atherosclerotic cardiovascular disease (ASCVD) due to hypercholesterolemia or concomitant lipoprotein(a)‐hyperlipoproteinemia, who received PCSK9 antibodies for the first time during routine care, were consecutively identified. Results Mean LDL‐C concentration prior to initiation of LA or PCSK9 antibody treatment was 5.3 ± 2.6 mmol/L (205 ± 102 mg/dL). Due to established ASCVD, the risk‐adjusted LDL‐C target value was <1.8 mmol/L (<70 mg/dL) in all patients. Use of PCSK9 antibodies increased the proportion of patients attaining the LDL‐C target concentration by 41.8% overall. Treatment emergent adverse events (TEAE) associated with PCSK9 antibody medication were reported in 35 patients (31.8%). Discontinuation of PCSK9 antibody therapy due to TEAEs occurred in 25 patients (22.7%). Conclusion Finally, 55.5% of patients received a combination of PCSK9 antibody therapy and LA at individually optimized treatment frequencies resulting in an increase of target attainment in 54.1% of patients. About 18.1% of chronic LA patients terminated LA treatment in this real‐world study. The termination of long‐term LA therapy, which has hitherto prevented the progression of ASCVD, requires careful individual risk assessment and cannot be recommended by the general criteria of LDL‐C reduction.

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Real‐world study: Escalating targeted lipid‐lowering treatment with PCSK9‐inhibitors and lipoprotein apheresis

Spitthöver

Röseler²,

Julius

et al. 2019

J of Clinical Apheresis

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“…The physiological function of Lp(a) is still poorly understood. Although the hazard ratios in the Copenhagen City Heart Study showed an invariable relative risk increase when comparing Lp(a) ≥80 th cohort percentile with Lp(a) <80th cohort percentile, the absolute risk characterizing a patient with elevated Lp(a) depended on the LDL-C level of that subject [6]. Given levels of Lp(a) combined with different decreasing corrected LDL-C resulted in corresponding decreased Lp(a) associated relative risk.…”

Section: Ldl and Lp(a) Particles Exhibit Mutual Ascvd Risk Effect Modmentioning

confidence: 92%

“…Given levels of Lp(a) combined with different decreasing corrected LDL-C resulted in corresponding decreased Lp(a) associated relative risk. In view of the overwhelming evidence on LDL-C lowering therapies and decrease in ASCVD risk independent from treatment modality, these observational data imply that aggressive lowering of LDL-C in individuals with high Lp(a) could divert a substantial part of the adverse effects of Lp(a), thereby markedly reducing the absolute ASCVD risk at least in a primary prevention setting [6]. Intervention studies for primary as well as secondary prevention showed that Lp(a) retains its character as a risk factor, even when the target range of LDL-C < 70 mg/dl has been achieved in manifested ASCVD.…”

Section: Ldl and Lp(a) Particles Exhibit Mutual Ascvd Risk Effect Modmentioning

confidence: 95%

“…Above 50 mg/dl the curve of Lp(a) and ASCVD risk association follows an almost linear fashion. At low Lp(a) concentrations, up to 30 mg/dl and the grey zone between concentrations of 30 to 50 mg/dl, Lp(a)-mediated risk seems to be clinically less important, putatively because low-density lipoprotein cholesterol (LDL-C) mediated risk, caused by the far more numerous regular LDL particles prevails [6]. As a result of this relationship and despite the lack of controlled intervention studies, the European Atherosclerosis Consensus Panel formulated a desirable range for Lp(a) below <50 mg/dl [7].…”

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Lipoprotein(a) and mortality—a high risk relationship

Klingel

Heibges

Fassbender

2019

Clin Res Cardiol Suppl

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Lipoprotein(a) (Lp(a)) is an independent cardiovascular risk factor playing a causal role for atherosclerotic cardiovascular disease (ASCVD). Early or progressive ASCVD or a familial predisposition are key findings which can be associated with Lp(a)-hyperlipoproteinemia (Lp(a)-HLP). The German guideline for the indication of lipoprotein apheresis in patients with Lp(a)-HLP has proved to be of value to identify patients at highest risk, using the composite of a Lp(a) threshold >60 mg/dl (>120 nmol/l) and clinical ASCVD progression despite effective LDL-C lowering therapy. In particular for such patients it appears to be plausible that Lp(a)-associated risk would increase cardiovascular mortality as the most important part of total mortality in Western populations. By the majority of existing investigations an association of Lp(a) concentration on total or cardiovascular mortality was demonstrated. However, inconsistency in the findings between studies exists without a clear trend for any study feature to explain this. Genetic homogeneity of the population, long-term follow-up, and clinically guided selection of patients might be important to further clarify the impact of Lp(a) concentration on progression of ASCVD, and finally total or cardiovascular mortality. LDL and Lp(a) particles exhibit a mutual effect modification on related ASCVD risk. Therefore, LDL-C levels and concomitant LDL-C lowering treatment must be considered in this context. Prospective evaluation is needed to document that specific Lp(a)-lowering additional to targeted LDL-C lowering will in fact reduce cardiovascular or total mortality. BackgroundAtherosclerotic cardiovascular diseases (ASCVD) are recognized as the leading causes of death in Western countries and increasingly worldwide. The majority of these ASCVD deaths are attributable to either coronary heart disease (CHD) or cerebrovascular disease. It was demonstrated already in 1981 that Lipoprotein(a) (Lp(a)) concentrations above 30 mg/dl are associated with an increasing risk for myocardial infarction (MI) in genetically homogeneous Caucasian populations [1,2]. The Copenhagen City Heart Study was ground-breaking in retrieving attention to the clinical relevance of Lp(a) for ASCVD especially MI in the general population [3][4][5]. Above the 90th percentile (in this study >85 mg/dl), relative risk was about 3-fold higher.

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LDL‐C and hs‐CRP Jointly Modify the Effect of Lp(a) on 5‐Year Death in Patients With Percutaneous Coronary Intervention

Li,

Yan,

Zhu

et al. 2024

Clinical Cardiology

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BackgroundRecent studies have suggested that adverse events associated with lipoprotein(a) [Lp(a)] might be modified by low‐density lipoprotein cholesterol (LDL‐C) or high‐sensitivity C‐reactive protein (hs‐CRP) levels, but whether LDL‐C and hs‐CRP jointly mediate the outcome of Lp(a) remains unknown in patients with coronary artery disease.Methods and ResultsA prospective study was conducted, enrolling consecutive 10 724 patients with percutaneous coronary intervention (PCI) in 2013. The endpoint event was all‐cause death. A total of 10 000 patients with complete baseline data were finally included. During a median follow‐up of 5.1 years, Lp(a) ≥ 30 mg/dL was an independent risk factor of all‐cause death in the overall population, LDL‐C ≥ 70 mg/dL, and hs‐CRP ≥ 2 mg/L population, respectively. According to concurrent LDL‐C (70 mg/dL) and hs‐CRP (2 mg/L) levels, further analysis revealed that when LDL‐C < 70 mg/dL regardless of hs‐CRP levels, Lp(a) ≥ 30 mg/dL was not an independent predictor of all‐cause death. However, when LDL‐C ≥ 70 mg/dL, Lp(a) ≥ 30 mg/dL was independently associated with a higher risk of all‐cause death in hs‐CRP ≥ 2 mg/L (HR: 1.488, 95% CI: 1.059‒2.092), but not in hs‐CRP < 2 mg/L (HR: 1.303, 95% CI: 0.914‒1.856).ConclusionAmong PCI patients, Lp(a)‐associated outcome was jointly affected by LDL‐C and hs‐CRP. As long as LDL‐C is well controlled, the adverse effects of increased Lp(a) on cardiovascular risk seem to be weakened, and only when LDL‐C and hs‐CRP increase at the same time, elevated Lp(a) is associated with poorer long‐term outcome.

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Cardiovascular disease risk associated with elevated lipoprotein(a) attenuates at low low-density lipoprotein cholesterol levels in a primary prevention setting

Abstract: Lipoprotein(a) and LDL-C are independently associated with CVD risk. At LDL-C levels below <2.5 mmol/L, the risk associated with elevated Lp(a) attenuates in a primary prevention setting.

Cited by 116 publications

References 35 publications

Real‐world study: Escalating targeted lipid‐lowering treatment with PCSK9‐inhibitors and lipoprotein apheresis

Real‐world study: Escalating targeted lipid‐lowering treatment with PCSK9‐inhibitors and lipoprotein apheresis

Lipoprotein(a) and mortality—a high risk relationship

LDL‐C and hs‐CRP Jointly Modify the Effect of Lp(a) on 5‐Year Death in Patients With Percutaneous Coronary Intervention

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