Abstract 13826: Lipoprotein (a) Levels Among Children Diagnosed With a Primary Hypercholesterolemia

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Duygu Uzun ◽  
Premchand Anne ◽  
James Maciejko
Keyword(s):  
Risk Factor ◽  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Familial Combined Hyperlipidemia ◽  
Only Children ◽  
Primary Hypercholesterolemia ◽  
Lipoprotein A ◽  
Lipid Clinic ◽  
American Academy Of Pediatrics ◽  
Ascvd Risk

Introduction: The American Academy of Pediatrics (AAP) recommends universal lipid screening in all children beginning at nine years of age. Although not a component of the lipid profile, an elevated lipoprotein (a) (Lp(a)) (≥30 mg/dL) is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) in adults. Plasma Lp(a) levels are a product of the Lp (a) gene, which is fully expressed by 5 years of age, and remains relatively unchanged into adulthood. Limited number of studies have examined Lp(a) levels in children diagnosed with a primary hypercholesterolemia. Hypothesis: To determine the frequency of Lp(a) excess, defined as ≥30 mg/dL, among children diagnosed with a primary hypercholesterolemia (i.e., Familial Hypercholesterolemia (FH), Familial Combined Hyperlipidemia (FCH), Polygenic Hypercholesterolemia (PH). Methods: We reviewed the Ascension St. John Children’s Center Lipid Clinic database between 8/1/2012 and 12/31/2019. Only children diagnosed with a primary hypercholesterolemia and having a baseline Lp(a) assessment were included. FH was diagnosed using the Dutch Lipid Score. PH was diagnosed as an elevated LDL-C level not associated with a monogenic mutation or a secondary cause. FCH was diagnosed as an elevated LDL-C in combination with any triglyceride elevation in the absence of secondary causes. Results: One-hundred and twenty patients were evaluated (mean age: 12.1 ± 2.0 years). Seventy-eight percent (93) of the children were white and 52% (62) were male. The frequency of an Lp(a) excess was 44% (53) in this group. The frequencies of Lp(a) excess by diagnosis, and the median Lp(a) and mean LDL-C levels are displayed in Table 1. Conclusions: Lp(a) excess is relatively frequent among children diagnosed with a primary hypercholesterolemia. Since an Lp(a) excess is an ASCVD risk factor, it should be considered clinically relevant when determining the baseline LDL-C level at which a lipid-lowering agent is initiated in children.

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.

Abstract 14093: High-Sensitivity C-reactive Protein Modifies the Effect of Lipoprotein (a) on Cardiovascular Risk: The Multi-Ethnic Study of Atherosclerosis (MESA)

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Wei Zhang ◽  
Jaime L Speiser ◽  
Miguel Cainzos Achirica ◽  
Khurram Nasir ◽  
Michael Tsai ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Reference Group ◽  
High Sensitivity ◽  
Chinese Americans ◽  
Cox Proportional Hazards ◽  
Atherosclerotic Cardiovascular Disease ◽  
C Reactive Protein ◽  
Lipoprotein A ◽  
Reactive Protein ◽  
Ascvd Risk

Introduction: Lipoprotein (a) (Lp(a)) and inflammation, as represented by elevated high-sensitivity C-reactive protein (hsCRP) concentration, are both considered as risk-enhancers in the 2018 AHA/ACC Cholesterol guidelines. However, little is known as to whether the association of Lp(a) with atherosclerotic cardiovascular disease (ASCVD) risk is modified by inflammation. Objective: We assessed whether hsCRP modifies the association of Lp(a) with ASCVD risk. Methods: MESA participants with baseline hsCRP and Lp(a) levels were included. Incident ASCVD events were ascertained from baseline through 2017. Time to incident ASCVD was analyzed using Kaplan Meir curves. Cox proportional hazards models were used to assess the association between Lp(a), hsCRP, and time to ASCVD events adjusting for covariates. Results: The study included 4,654 participants with mean age of 62 and 52.5% females (1,702 Caucasians, 557 Chinese Americans, 1,336 African Americans and 1,059 Hispanics). With a mean 13.6-year follow-up, 676 ASCVD events occurred among 4,609 participants (Figure 1). In participants with hsCRP <2mg/L, the association of Lp(a) (per 1 Log unit increase) and risk for ASCVD as represented by hazard ratio (HR) and 95%CI was 1.01 (0.79, 1.28). In subjects with hsCRP ≥2mg/L, the risk increased to 1.26 (1.01, 1.58). When compared to the reference group with Lp(a) <50mg/dL and hsCRP <2mg/L, the risk for ASCVD in participants with Lp(a) ≥50mg/dL and hsCRP <2mg/L was 1.13 (0.85, 1.50) and in those with Lp(a) <50mg/dL and hsCRP ≥2mg/L was 1.09 (0.92, 1.31). The risk increased significantly to 1.62 (1.26, 2.07) in participants with Lp(a) ≥50mg/dL and hsCRP ≥2mg/L. Conclusions: Lp(a)-related ASCVD risk is modified by hsCRP levels. The findings of this analysis suggest that Lp(a) may serve as a risk enhancing factor in individuals with hsCRP level ≥2mg/L. Future studies are needed to determine whether Lp(a) is associated with risk of ASCVD in the absence of subclinical inflammation.

scholarly journals Lipoprotein(a) Is an Independent Risk Factor for Cardiovascular Disease in Heterozygous Familial Hypercholesterolemia

2005 ◽  
Vol 51 (11) ◽  
pp. 2067-2073 ◽  
Author(s):  
Daniel T Holmes ◽  
Brian A Schick ◽  
Karin H Humphries ◽  
Jiri Frohlich
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Risk Factor ◽  
Familial Hypercholesterolemia ◽  
Independent Risk Factor ◽  
Independent Predictor ◽  
Cvd Risk ◽  
Lipoprotein A ◽  
Heterozygous Familial Hypercholesterolemia ◽  
Lipid Clinic

Abstract Background: The role of lipoprotein(a) [Lp(a)] as a predictor of cardiovascular disease (CVD) in patients with heterozygous familial hypercholesterolemia (HFH) is unclear. We sought to examine the utility of this lipoprotein as a predictor of CVD outcomes in the HFH population at our lipid clinic. Methods: This was a retrospective analysis of clinical and laboratory data from a large multiethnic cohort of HFH patients at a single, large lipid clinic in Vancouver, Canada. Three hundred and eighty-eight patients were diagnosed with possible, probable, or definite HFH by strict clinical diagnostic criteria. Multivariate Cox regression analysis was used to study the relationship between several established CVD risk factors, Lp(a), and the age of first hard CVD event. Results: An Lp(a) concentration of 800 units/L (560 mg/L) or higher was a significant independent risk factor for CVD outcomes [hazard ratio (HR) = 2.59; 95% confidence interval (CI), 1.53–4.39; P &lt;0.001]. Other significant risk factors were male sex [HR = 3.19 (1.79–5.69); P &lt;0.001] and ratio of total to HDL-cholesterol [1.18 (1.07–1.30); P = 0.001]. A previous history of smoking or hypertension each produced HRs consistent with increased CVD risk [HR = 1.55 (0.92–2.61) and 1.57 (0.90–2.74), respectively], but neither reached statistical significance (both P = 0.10). LDL-cholesterol was not an independent predictor of CVD risk [HR = 0.85 (0.0.71–1.01); P = 0.07], nor was survival affected by the subcategory of HFH diagnosis (i.e., possible vs probable vs definite HFH). Conclusion: Lp(a) is an independent predictor of CVD risk in a multiethnic HFH population.

Prognostic impact of cascade screening for familial hypercholesterolemia on cardiovascular events

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Tada ◽  
H Okada ◽  
A Nomura ◽  
A Nohara ◽  
M Yamagishi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Familial Hypercholesterolemia ◽  
Cardiovascular Events ◽  
Lipid Lowering ◽  
Funding Source ◽  
Atherosclerotic Cardiovascular Disease ◽  
Prognostic Impact ◽  
Cascade Screening ◽  
Ascvd Risk ◽  
The Impact

Abstract Background Early diagnosis and timely treatment for the patients with familial hypercholesterolemia (FH) can substantially lower the risk of atherosclerotic cardiovascular disease (ASCVD). In this sense, cascade screening could be one of the most useful options. However, few data exist regarding the impact of cascade screening for FH on the reduction of risk of ASCVD events. Objectives We aimed to evaluate the prognostic impact of cascade screening for FH. Methods We retrospectively investigated the health records of 1,050 patients with clinically diagnosed FH, including probands and their relatives who were cascade-screened. We used Cox models that were adjusted for established ASCVD risk factors to assess the association between cascade screening and major adverse cardiovascular events (MACE). The median period of follow-up was 12.3 years (interquartile range [IQR] = 9.1–17.5 years), and MACE included death from any causes or hospitalization due to ASCVD events. Results During the observation period, 246 participants experienced MACE. The mean age of patients identified through cascade screening was 18-years younger than that of the probands (38.7 yr vs. 57.0 yr, P&lt;0.001), with a lower proportion of ASCVD risk factors. Interestingly, patients identified through cascade screening under milder lipid-lowering therapies were at reduced risk for MACE (hazard ratio [HR] = 0.36; 95% CI = 0.22 to 0.60; P&lt;0.001) when compared with the probands, even after adjusting for those known risk factors. Conclusions The identification of patients with FH via cascade screening appeared to result in better prognoses. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Scientific research grants from the Ministry of Education, Science and Culture of Japan (no. 16K19394, 18K08064, and 19K08575)

Prospective Study of Lipoprotein(a) as a Risk Factor for Atherosclerotic Cardiovascular Disease in Patients With Diabetes

Diabetes Care ◽  
1995 ◽  
Vol 18 (2) ◽  
pp. 241-244 ◽  
Author(s):  
T. Hiraga ◽  
T. Kobayashi ◽  
M. Okubo ◽  
K. Nakanishi ◽  
T. Sugimoto ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Risk Factor ◽  
Prospective Study ◽  
Atherosclerotic Cardiovascular Disease ◽  
Lipoprotein A ◽  
Patients With Diabetes

scholarly journals Factors Associated with Disparities in Appropriate Statin Therapy in an Outpatient Inner City Population

2020 ◽  
Author(s):  
Giselle Alexandra Suero Abreu ◽  
Aris Karatasakis ◽  
Sana Rashid ◽  
Maciej Tysarowski ◽  
Analise Y Douglas ◽  
...  
Keyword(s):  
Statin Therapy ◽  
Statin Treatment ◽  
Blood Cholesterol ◽  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Care Clinic ◽  
Black Race ◽  
Black Patients ◽  
Hispanic Patients ◽  
Ascvd Risk

Introduction: Appropriate lipid-lowering therapies are essential for the primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD). The aim of this study is to identify discrepancies between cholesterol management guidelines and current practice in an underserved population, with a focus on statin treatment. Methods: We reviewed the records of 1,042 consecutive patients seen between August 2018 and August 2019 in an outpatient academic primary care clinic. Eligibility for statin and other lipid-lowering therapies was determined based on the 2018 American Heart Association and American College of Cardiology (AHA/ACC) guideline on the management of blood cholesterol. Results: Among 464 statin-eligible patients, age was 61.1 +/- 10.4 years and 53.9% were female. Most patients were Black (47.2%), followed by Hispanic (45.7%), and White (5.0%). Overall, 82.1% of patients were prescribed a statin. Statin-eligible patients who qualified based only on a 10-year ASCVD risk > 7.5% were less likely to be prescribed a statin (32.8%, p<0.001). After adjustment for gender and health insurance status, appropriate statin treatment was independently associated with age > 55 years (OR = 4.59 [95% CI 1.09 - 16.66], p = 0.026), hypertension (OR = 2.38 [95% CI 1.29 - 4.38], p = 0.005) and chronic kidney disease (OR = 3.95 [95% CI 1.42 - 14.30], p = 0.017). Factors independently associated with statin undertreatment were Black race (OR = 0.42 [95% CI 0.23 - 0.77], p = 0.005), and statin-eligibility based solely on an elevated 10-year ASCVD risk (OR = 0.14 [95% CI 0.07 - 0.25], p < 0.001). Hispanic patients were more likely to be on appropriate statin therapy when compared to Black patients (86.8% vs 77.2%). Conclusion: Statin underprescription is seen in approximately one out of five eligible patients, and is independently associated with Black race, younger age, fewer comorbidities, and eligibility via 10-year ASCVD risk only. Hispanic patients are more likely to be on appropriate statin therapy compared to Black patients.

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.

Abstract 16936: Implications of the 2013 ACC/AHA Cholesterol Guidelines for Adults in Contemporary Cardiovascular Practice: Insights from the NCDR® PINNACLE Registry®

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Thomas Maddox ◽  
William Borden ◽  
Fengming Tang ◽  
Salim Virani ◽  
William Oetgen ◽  
...  
Keyword(s):  
Statin Therapy ◽  
Current Practice ◽  
Risk Group ◽  
National Registry ◽  
Lipid Lowering ◽  
Fixed Dose ◽  
Atherosclerotic Cardiovascular Disease ◽  
Ascvd Risk ◽  
Cholesterol Guidelines ◽  
Testing Patterns

Background: In a significant update, the 2013 ACC/AHA cholesterol guidelines recommend fixed-dose statin therapy for those at risk and do not recommend non-statin therapies or treatment to target LDL-C levels, limiting the need for repeated LDL-C testing. We examined the implications of these updated guidelines on current lipid treatment and testing patterns in a national registry of cardiology practices. Methods: Using NCDR® PINNACLE Registry® data from 2008 to 2012, we assessed current practice patterns as a function of the 2013 cholesterol guidelines. Lipid-lowering therapies and LDL-C testing patterns by patient risk group (atherosclerotic cardiovascular disease (ASCVD), diabetes, off-treatment LDL-C ≥190mg/dL, or an estimated 10-year ASCVD risk ≥7.5%) were described. Results: Among a cohort of 1,174,545 patients, 1,129,205 (96.1%) were statin-eligible (91.2% ASCVD, 6.6% diabetes, 0.3% off-treatment LDL-C ≥190mg/dL, 1.9% estimated 10-year ASCVD risk ≥7.5%). 377,311 (32.4%) patients were not receiving statin therapy and 259,143 (22.6%) were receiving non-statin therapies. 20.8% patients had 2 or more LDL-C assessments during the study period, and 7.0% had more than 4 assessments. Conclusions: In U.S. cardiovascular practices, 32.4% of statin-eligible patients, as defined by the 2013 ACC/AHA cholesterol guidelines, were not currently receiving them. In addition, 22.6% were receiving non-statin lipid-lowering therapies and 20.8% had repeated LDL-C testing. Achieving concordance with the new cholesterol guidelines would result in significant increases in statin use, as well as significant reductions in non-statin therapies and laboratory testing.

scholarly journals Plasma Lipoprotein(a) Indicates Risk for 4 Distinct Forms of Vascular Disease

2007 ◽  
Vol 53 (4) ◽  
pp. 679-685 ◽  
Author(s):  
Gregory T Jones ◽  
Andre M van Rij ◽  
Jennifer Cole ◽  
Michael JA Williams ◽  
Emma H Bateman ◽  
...  
Keyword(s):  
Risk Factor ◽  
Vascular Disease ◽  
Plasma Lipids ◽  
Association Studies ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Odds Ratios ◽  
Lipoprotein A ◽  
History Of ◽  
Artery Disease

Abstract Background: Increased lipoprotein(a) [Lp(a)] concentrations are predictive for coronary artery disease (CAD). The risk conferred by Lp(a) for other types of vascular disease compared with CAD has not been investigated within a single population. This study aimed to investigate Lp(a) risk association for 4 different types of vascular disease (including CAD) within a predominantly white population. Methods: We used an Lp(a) ELISA that measures Lp(a) independently of apolipoprotein(a) size to measure plasma Lp(a) in patients [384 CAD, 262 peripheral vascular disease, 184 ischemic stroke (stroke), 425 abdominal aortic aneurysm] and 230 disease-free controls. We then conducted association studies with logistic regression, integrating the potential confounding effects of age, sex, diabetes, plasma lipids, and a history of previous hypertension, hypercholesterolemia, and smoking. Results: Multivariate analyses with Lp(a) concentrations of &gt;45 nmol/L (the 75th percentile value for controls) as the clinical cutoff showed increased Lp(a) concentrations to be a risk factor for all disease groups, with adjusted odds ratios ranging from 1.96 [95% confidence interval (CI) 1.24–3.08] for CAD to 2.33 (95% CI 1.39–3.89) for PVD. The risk conferred by Lp(a) appeared to be independent of other confounders, including exposure to statin/fibrate therapies. Similar odds ratios and CIs between disease groups indicated that increased Lp(a) conferred a similar risk for all groups studied. Conclusions: Lp(a) constitutes a stable risk factor of similar magnitude for 4 major forms of vascular disease. This association was not altered by exposure to standard lipid-lowering therapy.

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