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 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.

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 Associations Between High-Density Lipoprotein Particles and Ischemic Events by Vascular Domain, Sex, and Ethnicity

Circulation ◽  
2020 ◽  
Vol 142 (7) ◽  
pp. 657-669 ◽  
Author(s):  
Kavisha Singh ◽  
Alvin Chandra ◽  
Thomas Sperry ◽  
Parag H. Joshi ◽  
Amit Khera ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Ischemic Stroke ◽  
High Density Lipoprotein ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Large Population ◽  
Density Lipoprotein ◽  
High Density ◽  
Cholesterol Concentration ◽  
Atherosclerotic Cardiovascular Disease

Background: High-density lipoprotein (HDL) cholesterol concentration (HDL-C) is an established atheroprotective marker, in particular for coronary artery disease; however, HDL particle concentration (HDL-P) may better predict risk. The associations of HDL-C and HDL-P with ischemic stroke and myocardial infarction (MI) among women and Blacks have not been well studied. We hypothesized that HDL-P would consistently be associated with MI and stroke among women and Blacks compared with HDL-C. Methods: We analyzed individual-level participant data in a pooled cohort of 4 large population studies without baseline atherosclerotic cardiovascular disease: DHS (Dallas Heart Study; n=2535), ARIC (Atherosclerosis Risk in Communities; n=1595), MESA (Multi-Ethnic Study of Atherosclerosis; n=6632), and PREVEND (Prevention of Renal and Vascular Endstage Disease; n=5022). HDL markers were analyzed in adjusted Cox proportional hazard models for MI and ischemic stroke. Results: In the overall population (n=15 784), HDL-P was inversely associated with the combined outcome of MI and ischemic stroke, adjusted for cardiometabolic risk factors (hazard ratio [HR] for quartile 4 [Q4] versus quartile 1 [Q1], 0.64 [95% CI, 0.52–0.78]), as was HDL-C (HR for Q4 versus Q1, 0.76 [95% CI, 0.61–0.94]). Adjustment for HDL-C did not attenuate the inverse relationship between HDL-P and atherosclerotic cardiovascular disease, whereas adjustment for HDL-P attenuated all associations between HDL-C and events. HDL-P was inversely associated with the individual end points of MI and ischemic stroke in the overall population, including in women. HDL-P was inversely associated with MI among White participants but not among Black participants (HR for Q4 versus Q1 for Whites, 0.49 [95% CI, 0.35–0.69]; for Blacks, 1.22 [95% CI, 0.76–1.98]; P interaction =0.001). Similarly, HDL-C was inversely associated with MI among White participants (HR for Q4 versus Q1, 0.53 [95% CI, 0.36–0.78]) but had a weak direct association with MI among Black participants (HR for Q4 versus Q1, 1.75 [95% CI, 1.08–2.83]; P interaction <0.0001). Conclusions: Compared with HDL-C, HDL-P was consistently associated with MI and ischemic stroke in the overall population. Differential associations of both HDL-C and HDL-P for MI by Black ethnicity suggest that atherosclerotic cardiovascular disease risk may differ by vascular domain and ethnicity. Future studies should examine individual outcomes separately.

scholarly journals Association of Fitness and Fatness with Clustered Cardiovascular Disease Risk Factors in Nigerian Adolescents

2020 ◽  
Vol 17 (16) ◽  
pp. 5861
Author(s):  
Danladi I. Musa ◽  
Abel L. Toriola ◽  
Daniel T. Goon ◽  
Sunday U. Jonathan
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Risk Factor ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Cvd Risk ◽  
Standardized Residuals

Purpose: This study examinedthe independent and joint association of fitness and fatness with clustered cardiovascular disease risk (CVDrs) in 11–18 year-old Nigerian adolescents. Methods: A hundred and ninety seven adolescents (100 girls and 97 boys) were evaluated forfitness, fatness and CVDrs. Fitness was evaluated with the progressive aerobic cardiovascular endurance run test while fatness was assessed using body mass index. A clustered CVDrs was computed from the standardized residuals of total cholesterol, high density lipoprotein cholesterol, Low density lipoprotein cholesterol, triglycerides, plasma glucose, systolic blood pressure, and diastolic blood pressure. Regression models controlling for waist circumference assessed the association of fitness and fatness with CVDrs. Results: Prevalence of clustered CVD risk was 7.1% (girls = 3.0%; boys = 4.1%). Based on risk factor abnormalities, 52.8% of participants had one or more CVD risk factor abnormalities with more boys (27.4%) affected. Low fitness was associated with clustered CVDrs in both girls (R2 = 9.8%, β = −0.287, p = 0.05) and boys (R2 = 17%, β = −0.406, p < 0.0005). Fatness was not associated with the CVDrs in both sexes. After controlling for all the variables in the model, only fitness (R2 = 10.4%) and abdominal fat (R2 = 19.5%) were associated with CVDrs respectively. Unfit girls were 3.2 (95% CI = 1.31–7.91, p = 0.011) times likely to develop CVD risk abnormality compared to their fit counterparts. The likelihood of unfit boys developing CVD risk abnormality was 3.9 (95% CI = 1.15–10.08, p = 0.005) times compared to their fit peers. Conclusions: Fitness but not fatness was a better predictor of CVDrs in Nigerian boys and girls. The result of this study suggests that any public health strategies aimed at preventing or reversing the increasing trends of CVD risk in adolescents should emphasize promotion of aerobic fitness.

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.

scholarly journals Lp(A): When and how to measure it

2020 ◽  
pp. 000456322096847
Author(s):  
Jaimini Cegla ◽  
Michael France ◽  
Santica M Marcovina ◽  
R Dermot G Neely
Keyword(s):  
Cardiovascular Disease ◽  
Risk Factor ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Lipoprotein A ◽  
Clinical Laboratories ◽  
Considerable Work ◽  
The Uk ◽  
Size Heterogeneity ◽  
Eqa Schemes

Lipoprotein(a) has long been regarded as a risk factor for cardiovascular disease; however, its routine use in clinical practice has been hampered by difficulties inherent in the measurement of this complex lipoprotein. The major challenges relate to its size heterogeneity and related issues including (1) use of appropriate calibrators (2) standardization of calibration protocols (3) traceability and (4) reporting units. In the UK, results from the current EQA schemes for lipoprotein(a) suggest that there is considerable work required to standardize lipoprotein(a) measurement. This is becoming increasingly pertinent with the increasing recognition of lipoprotein(a) as an independent risk factor for cardiovascular disease in international guidelines and the emergence of novel antisense therapies to effectively reduce lipoprotein(a). This article raises awareness of the importance of measurement of lipoprotein(a) for the assessment of cardiovascular disease risk and gives guidance to clinical laboratories regarding choice of appropriate assays.

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