Extremely elevated lipoprotein(a) levels are largely undetected but associated with a very high cardiovascular disease risk in a hospital population

2021 ◽  
Vol 331 ◽  
pp. e120
Author(s):  
N.S. Nurmohamed ◽  
Y. Kaiser ◽  
P.C.E. Schuitema ◽  
M. Nierman ◽  
J.C. Fischer ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Lipoprotein A ◽  
Hospital Population ◽  
Very High

scholarly journals Lipoprotein(a): A Genetically Determined, Causal, and Prevalent Risk Factor for Atherosclerotic Cardiovascular Disease: A Scientific Statement From the American Heart Association

2021 ◽  
Author(s):  
Gissette Reyes-Soffer ◽  
Henry N. Ginsberg ◽  
Lars Berglund ◽  
P. Barton Duell ◽  
Sean P. Heffron ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Risk Factor ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Density Lipoprotein ◽  
Major Protein ◽  
Atherosclerotic Cardiovascular Disease ◽  
Lipoprotein A ◽  
Scientific Statement ◽  
Genetically Determined

High levels of lipoprotein(a) [Lp(a)], an apoB100-containing lipoprotein, are an independent and causal risk factor for atherosclerotic cardiovascular diseases through mechanisms associated with increased atherogenesis, inflammation, and thrombosis. Lp(a) is predominantly a monogenic cardiovascular risk determinant, with ≈70% to ≥90% of interindividual heterogeneity in levels being genetically determined. The 2 major protein components of Lp(a) particles are apoB100 and apolipoprotein(a). Lp(a) remains a risk factor for cardiovascular disease development even in the setting of effective reduction of plasma low-density lipoprotein cholesterol and apoB100. Despite its demonstrated contribution to atherosclerotic cardiovascular disease burden, we presently lack standardization and harmonization of assays, universal guidelines for diagnosing and providing risk assessment, and targeted treatments to lower Lp(a). There is a clinical need to understand the genetic and biological basis for variation in Lp(a) levels and its relationship to disease in different ancestry groups. This scientific statement capitalizes on the expertise of a diverse basic science and clinical workgroup to highlight the history, biology, pathophysiology, and emerging clinical evidence in the Lp(a) field. Herein, we address key knowledge gaps and future directions required to mitigate the atherosclerotic cardiovascular disease risk attributable to elevated Lp(a) levels.

scholarly journals Lipoprotein(a) and Family History Predict Cardiovascular Disease Risk

2020 ◽  
Vol 76 (7) ◽  
pp. 781-793 ◽  
Author(s):  
Anurag Mehta ◽  
Salim S. Virani ◽  
Colby R. Ayers ◽  
Wensheng Sun ◽  
Ron C. Hoogeveen ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Family History ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Lipoprotein A

Should we Consider Lipoprotein (a) in Cardiovascular Disease Risk Assessment in Patients with Familial Hypercholesterolaemia?

2019 ◽  
Vol 24 (31) ◽  
pp. 3665-3671 ◽  
Author(s):  
Panagiotis Anagnostis ◽  
Pavlos Siolos ◽  
Dimitrios Krikidis ◽  
Dimitrios G. Goulis ◽  
John C. Stevenson
Keyword(s):  
Cardiovascular Disease ◽  
Familial Hypercholesterolaemia ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Pcsk9 Inhibitors ◽  
Cvd Risk ◽  
Lipoprotein A ◽  
Increased Risk

Background: Familial hypercholesterolaemia (FH) is a genetically determined lipid disorder, affecting 1 per 200-500 individuals in the general population. It is significantly and independently associated with an increased risk of Cardiovascular Disease (CVD), although it remains still an underrecognized and undertreated disease. Lipoprotein (a) [Lp(a)] is a low-density-lipoprotein (LDL)-like molecule, containing an additional protein, apolipoprotein (a). Objective: This review aims to present and discuss available data on the role of Lp(a) in patients with FH, in terms of its potential augmentation of CVD risk. Methods: A comprehensive search of the literature was performed to identify studies evaluating the CV effects of Lp(a) in patients with FH. Results: Lp(a) has been recognised as an independent risk factor for CVD, mainly coronary artery disease (CAD). Most, but not all, studies show increased Lp(a) concentrations in adults and children with FH. There is also evidence of an independent association between Lp(a) and CVD (mainly CAD) risk in these patients. Conclusion: Some therapeutic modalities, such as niacin, oestrogens, tibolone and proprotein convertase subtilisin/ kexin type 9 (PCSK9) inhibitors may effectively reduce Lp(a) concentrations by 25-30%, although their clinical benefit of this effect remains to be established.

scholarly journals Molecular, Population, and Clinical Aspects of Lipoprotein(a): A Bridge Too Far?

2019 ◽  
Vol 8 (12) ◽  
pp. 2073 ◽  
Author(s):  
Natalie C. Ward ◽  
Karam M. Kostner ◽  
David R. Sullivan ◽  
Paul Nestel ◽  
Gerald F. Watts
Keyword(s):  
Cardiovascular Disease ◽  
Risk Factor ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Outcome Data ◽  
Clinical Aspects ◽  
Cardiovascular Disease Risk Factor ◽  
Atherosclerotic Cardiovascular Disease ◽  
Lipoprotein A ◽  
Risk Reclassification

There is now significant evidence to support an independent causal role for lipoprotein(a) (Lp(a)) as a risk factor for atherosclerotic cardiovascular disease. Plasma Lp(a) concentrations are predominantly determined by genetic factors. However, research into Lp(a) has been hampered by incomplete understanding of its metabolism and proatherogeneic properties and by a lack of suitable animal models. Furthermore, a lack of standardized assays to measure Lp(a) and no universal consensus on optimal plasma levels remain significant obstacles. In addition, there are currently no approved specific therapies that target and lower elevated plasma Lp(a), although there are recent but limited clinical outcome data suggesting benefits of such reduction. Despite this, international guidelines now recognize elevated Lp(a) as a risk enhancing factor for risk reclassification. This review summarises the current literature on Lp(a), including its discovery and recognition as an atherosclerotic cardiovascular disease risk factor, attempts to standardise analytical measurement, interpopulation studies, and emerging therapies for lowering elevated Lp(a) levels.

Utility of Genetically Predicted Lp(a) (Lipoprotein [a]) and ApoB Levels for Cardiovascular Risk Assessment

2021 ◽  
Author(s):  
Haoyu Wu ◽  
Jian’an Luan ◽  
Vincenzo Forgetta ◽  
James C. Engert ◽  
George Thanassoulis ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Risk Assessment ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Atherosclerotic Cardiovascular Disease ◽  
Uk Biobank ◽  
Lipoprotein A ◽  
Lipid Guidelines ◽  
Atherosclerotic Cardiovascular Disease Risk ◽  
Prospective Investigation

Background: Current lipid guidelines suggest measurement of Lp(a) (lipoprotein[a]) and ApoB (apolipoprotein B) for atherosclerotic cardiovascular disease risk assessment. Polygenic risk scores (PRSs) for Lp(a) and ApoB may identify individuals unlikely to have elevated Lp(a) or ApoB and thus reduce such suggested testing. Methods: PRSs were developed using LASSO regression among 273 222 and 356 958 UK Biobank participants of white British ancestry for Lp(a) and ApoB, respectively, and validated in separate sets of 60 771 UK Biobank and 15 050 European Prospective Investigation into Cancer and Nutrition-Norfolk participants. We then assessed the proportion of participants who, based on these PRSs, were unlikely to benefit from Lp(a) or ApoB measurements, according to current lipid guidelines. Results: In the UK Biobank and European Prospective Investigation into Cancer and Nutrition-Norfolk cohorts, the area under the receiver operating curve for the PRS-predicted Lp(a) and ApoB to identify individuals with elevated Lp(a) and ApoB was at least 0.91 (95% CI, 0.90–0.92) and 0.74 (95% CI, 0.73–0.75), respectively. The Lp(a) PRS and measured Lp(a) showed comparable association with atherosclerotic cardiovascular disease incidence, whereas the ApoB PRS was in general less predictive of atherosclerotic cardiovascular disease risk than measured ApoB. In the context of the ESC/EAS lipid guidelines, at a 95% sensitivity to identify individuals with elevated Lp(a) and ApoB levels, at least 54% of Lp(a) and 24% of ApoB testing could be reduced by prescreening with a PRS while maintaining a low false-negative rate. Conclusions: A substantial proportion of suggested testing for elevated Lp(a) and a modest proportion of testing for elevated ApoB could potentially be reduced by prescreening individuals with PRSs.

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