Unmet need in the hyperlipidaemia population with high risk of cardiovascular disease: a targeted literature review of observational studies

Mitchell, Sarah; Roso, S.; Samuel, Moody; Pladevall-Vila, Manel

doi:10.1186/s12872-016-0241-3

Cited by 33 publications

(28 citation statements)

References 43 publications

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“…Previous studies showed that an achievement of recommended LDL-C goal is associated with decreased risk of future CV events among patients with established CVD [7,8]. Despite the benefit of LDL-C goal achievement, the current management of LDL-C in actual clinical settings is suboptimal, leading to the elevated risk of CV events among patients with dyslipidemia [9,10]. Unfortunately, there is a paucity of evidence for current status of LDL-C goal achievement among broad population with various CV risk levels in South Korea.…”

Section: Introductionmentioning

confidence: 99%

Achievement of the low-density lipoprotein cholesterol goal among patients with dyslipidemia in South Korea

et al. 2020

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BackgroundIt is important to achieve the low-density lipoprotein cholesterol (LDL-C) goal recommended by clinical guidelines in managing the risk of cardiovascular (CV) events, however, the current management of LDL-C in actual clinical settings is suboptimal. We examined the LDL-C level among patients with dyslipidemia against the 2015 Korean guidelines, the crude rates of CV events based on LDL-C goal achievement, and the factors associated with LDL-C goal achievement. MethodsThis was a retrospective cohort study using the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) database from 2006 to 2013. Patients who had a health examination with LDL-C measurement between January 1, 2007, and December 31, 2011 were identified. Patients were required to have at least one diagnosis of dyslipidemia during the 1 year before the index date, defined as the first date of LDL-C measurement. The 2015 Korean guidelines were used to measure LDL-C goal achievement based on the CV risk level. Crude CV event rates were calculated for total and individual CV events as the number of events divided by person-years (PYs) during the follow-up period. CV events included acute coronary syndrome, ischemic stroke, peripheral artery disease, CV death, and all-cause death. Factors associated with LDL-C goal achievement were assessed using logistic regression. ResultsIn the NHIS-HEALS database, 69,942 patients met the eligibility criteria: 36.7%, 22.5%, 20.1%, and 20.6% were among the very high-, high-, moderate-, and low-risk groups for the CV events, respectively, as defined by the 2015 Korean guidelines. Approximately half of the patients with dyslipidemia (47.6%) achieved their recommended LDL-C goal, but the achievement rates were substantially different across CV risk levels (17.6%, 47.2%, 66.9%, and 82.4% for very high-, high-, moderate-, and low-risk groups, respectively; P<0.0001).

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Section: Introductionmentioning

confidence: 99%

Achievement of the low-density lipoprotein cholesterol goal among patients with dyslipidemia in South Korea

et al. 2020

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“…Se define como un aumento de la concentración de lípidos en sangre [1]. Estos lípidos circulan unidos a proteínas, denominándose lipoproteínas, entre las que encontramos las lipoproteínas de baja densidad (LDL), las cuales son susceptibles de sufrir modificaciones como la oxidación dando lugar a las LDL oxidadas (OxLDL) [2,3]. Estas OxLDL están implicadas en procesos inflamatorios, disfunción endotelial y remodelación de la matriz extracelular (MEC) [4].…”

Section: Introductionunclassified

Análisis molecular de las relaciones entre hiperlipidemia y fibrosis vascular

Serrano-García¹,

Asenjo-Bueno²,

Henández-López³

et al. 2019

DIANAS

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Palabras clave: Hiperlipidemia; OxLDL; fibrosis vascular; NFkB; ET-1; ROS ResumenLa hiperlipidemia es uno de los desórdenes metabólicos más implicados en enfermedades cardiovasculares como la aterosclerosis que cursa con un aumento de LDL oxidadas (OxLDL) en sangre. El objetivo del estudio fue establecer la relación entre hiperlipidemia y fibrosis vascular, evaluando los mecanismos implicados. Para ello, se incubaron células endoteliales con OxLDL encontrando un aumento tanto en la expresión de fibronectina como en la producción de radicales libres. Las OxLDL revelaron la activación del factor de transcripción NFkB vía producción de radicales libres. Además, experimentos con EMSA confirman que el factor NFkB está implicado directamente en el aumento de la expresión de fibronectina estimulado por las OxLDL en células endoteliales. Por otro lado, las OxLDL son capaces de inducir la expresión del enzima conversor de endotelina-1 y la producción de endotelina-1 (ET-1). La ET-1 sintetizada en células endoteliales se libera y llega a otros tipos celulares. Por tanto, se analizó el efecto directo de la ET-1 en células musculares lisas (CML). La ET-1 también estimula fibrosis en CML medida como expresión de la proteína pro-fibrótica CTGF y las proteínas de MEC, fibronectina y colágeno I. La ET-1 también favorece la producción de radicales libres. El efecto de la ET-1 sobre la fibrosis fue específico de su unión al receptor ETA presente en CML, porque el antagonista específico BQ123 bloqueó completamente el efecto de la ET-1. En conclusión, durante la aterosclerosis se favorecerían los procesos de fibrosis tanto a nivel endotelial por las OxLDL como a nivel muscular por la ET-1 generada por ellas, que podría ser la causa de la disfunción vascular presente en la aterosclerosis.

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“…[2][3][4] Despite the widespread availability of effective lipid-lowering agents, such as statins, a significant proportion of patients at high risk of ASCVD continue to be managed suboptimally due to insufficient therapeutic efficacy, safety concerns regarding higher doses of statins, and poor compliance. 5,6 Therefore, there is a medical need for additional lipid-lowering options capable of minimizing the residual cardiovascular risk of patients who display a suboptimal response and/or intolerance to current first-line agents. 7 Bococizumab is a humanized monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9), [8][9][10][11][12][13][14][15][16][17] which is a protein that regulates the availability of the LDL receptor (LDLR) expressed predominantly on hepatocytes.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics, pharmacodynamics, and safety of bococizumab, a monoclonal antibody against proprotein convertase subtilisin/kexin type 9, in healthy subjects when administered in co‐mixture with recombinant human hyaluronidase: A phase 1 randomized trial

Bass

Plotka

Mridha³

et al. 2018

Health Science Reports

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AimPrior to the discontinuation of bococizumab's clinical development, it was considered advantageous to develop an infrequent dosing regimen (eg, monthly). Therefore, we conducted a phase 1 study to evaluate the pharmacokinetics, pharmacodynamics, and safety of bococizumab when administered in co‐mixture with recombinant human hyaluronidase (rHuPH20).MethodHealthy subjects (N = 60) were randomized equally among 4 groups that received a single subcutaneous dose of either bococizumab 150, 300, or 450 mg co‐mixed with rHuPH20 or bococizumab 300 mg alone. Bioavailability and lipid‐lowering effect of bococizumab were evaluated by using ANCOVA models.ResultsIn the groups administered bococizumab co‐mixed with rHuPH20, dose‐normalized Cmax and AUCinf were 26.6 to 39.1% and 18.3 to 36.6% greater, respectively, compared with bococizumab 300 mg alone. Despite these increases, mean percent reductions from baseline in low‐density lipoprotein cholesterol were smaller in the bococizumab 300 mg + rHuPH20 group than in the bococizumab 300‐mg group at Day 21 (52.2% and 59.5%, respectively) and were similar at Day 29 (51.7% and 49.6%, respectively). Compared with the group administered bococizumab 300 mg alone, the bococizumab 300 mg + rHuPH20 group did not show a significantly altered AUEC85 (ratio of adjusted means: 102.5%, 90% confidence interval: 96.1‐109.3%) but did show a higher MaxELDL‐C (ratio of adjusted means: 125.4%, 90% confidence interval: 103.3‐152.2%), indicating diminution of efficacy. The most frequent adverse events were injection‐site erythema, injection‐site bruising, and nasopharyngitis; all injection‐site adverse events were mild.ConclusionCo‐mixture with rHuPH20 increased the bioavailability of bococizumab without proportional increase in pharmacodynamic effect.Trial RegistrationClinicalTrials.gov, NCT02667223.

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Unmet need in the hyperlipidaemia population with high risk of cardiovascular disease: a targeted literature review of observational studies

Cited by 33 publications

References 43 publications

Achievement of the low-density lipoprotein cholesterol goal among patients with dyslipidemia in South Korea

Achievement of the low-density lipoprotein cholesterol goal among patients with dyslipidemia in South Korea

Análisis molecular de las relaciones entre hiperlipidemia y fibrosis vascular

Pharmacokinetics, pharmacodynamics, and safety of bococizumab, a monoclonal antibody against proprotein convertase subtilisin/kexin type 9, in healthy subjects when administered in co‐mixture with recombinant human hyaluronidase: A phase 1 randomized trial

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