Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 175
Filtrar
1.
Expert Rev Cardiovasc Ther ; 17(4): 241-250, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30916582

RESUMO

INTRODUCTION: Lipoprotein(a) [Lp(a)] is a potent, highly heritable and common risk factor for atherosclerotic cardiovascular disease (ASCVD). Evidence for a causal association between elevated Lp(a) and ASCVD has been provided by large epidemiological investigations that have demonstrated a curvilinear association with increased risk, as well as from genetic examinations and cellular and transgenic animal studies. Although there are several therapies available for lowering Lp(a), none are selective for Lp(a) and there is no clinical trial data that has specifically shown that lowering Lp(a) reduces the risk of ASCVD. Hence, screening for elevated Lp(a) is not routinely incorporated into clinical practice. Areas covered: This paper reviews the current evidence supporting the causal role of Lp(a) in the primary and secondary prevention of ASCVD, screening approaches for high Lp(a), current guidelines on testing Lp(a), and barriers to the routine screening of elevated Lp(a) in clinical practice. Expert opinion: At present, there is a moderate level of evidence supporting the routine screening of elevated Lp(a). Current guidelines recommend testing for elevated Lp(a) in individuals at intermediate or high risk of ASCVD.


Assuntos
Doenças Cardiovasculares/sangue , Lipoproteína(a)/sangue , Animais , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/prevenção & controle , Humanos , Lipoproteína(a)/fisiologia , Programas de Rastreamento , Fatores de Risco
2.
Vnitr Lek ; 64(12): 1160-1168, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30704252

RESUMO

About 20 % of the population has raised Lp(a) concentrations and evidence suggests that high levels of Lp(a) are an independent cardiovascular risk factor. Both the European Society of Cardiology and the European Atherosclerosis Society recommend measuring Lp(a) values in intermediate to high-risk patients for risk stratification, as well as in patients already under statin treatment and with recurrent clinical events as a residual risk factor that calls for lipid-lowering therapy intensification. Strategies used to lower Lp(a) concentrations have either been partially disappointing in the past or lack cardiovascular outcome data. Therefore, Lp(a) has often been considered as a nonmodifiable cardiovascular risk factor. New and consistent data retrieved from the PCSK9 inhibitor trials now suggest that Lp(a) can be decreased effectively by roughly 30 %, while emerging data from apo(a) antisense therapy trials suggest that selective and potent Lp(a) reduction is a feasible treatment approach in the future. The impact of such decreases on the occurrence of cardiovascular outcomes, independent from LDL-C, could, if established, herald Lp(a) in the treatment of atherosclerosis. Key words: alirocumab - atherosclerosis - cardiovascular disease - evolocumab - hypercholesterolaemia - lipoprotein(a) - lipoprotein apheresis.


Assuntos
Doenças Cardiovasculares , Lipoproteína(a) , Doenças Cardiovasculares/etiologia , Humanos , Lipoproteína(a)/fisiologia , Pró-Proteína Convertase 9 , Fatores de Risco
4.
Artigo em Russo | MEDLINE | ID: mdl-30251983

RESUMO

AIM: To evaluate the role of lipoprotein (a) in an atherosclerotic lesion of precerebral arteries and stroke development. MATERIAL AND METHODS: Thirty-eight patients with atherosclerotic lesions of the carotid arteries established by duplex scanning, including 28 post stroke patients and 10 patients with asymptomatic atherosclerosis, were examined. Lipoprotein (a) was determined by immunosorbent assay in the serum and supernatant after 3-day cultivation of neutrophils. RESULTS AND CONCLUSION: There was a correlation between serum lipoprotein (a) and endothelium-dependent vasodilation of the brachial artery, and the relationship of culture lipoprotein (a) with the severity of atherosclerotic lesions of precerebral arteries and prothrombin time. Thus, the effect of lipoprotein (a) on the atherogenesis may be mediated by endothelial dysfunction and the mechanism of realization of stroke development is prothrombogenic effects on hemostasis.


Assuntos
Aterosclerose , Doenças das Artérias Carótidas , Aterosclerose/metabolismo , Artéria Braquial , Artérias Carótidas , Doenças das Artérias Carótidas/metabolismo , Endotélio Vascular , Humanos , Lipoproteína(a)/fisiologia , Vasodilatação
5.
Eur Heart J ; 38(32): 2490-2498, 2017 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-28449027

RESUMO

Aims: As promising compounds to lower Lipoprotein(a) (Lp(a)) are emerging, the need for a precise characterization and comparability of the Lp(a)-associated cardiovascular risk is increasing. Therefore, we aimed to evaluate the distribution of Lp(a) concentrations across the European population, to characterize the association with cardiovascular outcomes and to provide high comparability of the Lp(a)-associated cardiovascular risk by use of centrally determined Lp(a) concentrations. Methods and results: Based on the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE)-project, we analysed data of 56 804 participants from 7 prospective population-based cohorts across Europe with a maximum follow-up of 24 years. All Lp(a) measurements were performed in the central BiomarCaRE laboratory (Biokit Quantia Lp(a)-Test; Abbott Diagnostics). The three endpoints considered were incident major coronary events (MCE), incident cardiovascular disease (CVD) events, and total mortality. We found lower Lp(a) levels in Northern European cohorts (median 4.9 mg/dL) compared to central (median 7.9 mg/dL) and Southern European cohorts (10.9 mg/dL) (Jonckheere-Terpstra test P < 0.001). Kaplan-Meier curves showed the highest event rate of MCE and CVD events for Lp(a) levels ≥90th percentile (log-rank test: P < 0.001 for MCE and CVD). Cox regression models adjusted for age, sex, and cardiovascular risk factors revealed a significant association of Lp(a) levels with MCE and CVD with a hazard ratio (HR) of 1.30 for MCE [95% confidence interval (CI) 1.15‒1.46] and of 1.25 for CVD (95% CI 1.12‒1.39) for Lp(a) levels in the 67‒89th percentile and a HR of 1.49 for MCE (95% CI 1.29‒1.73) and of 1.44 for CVD (95% CI 1.25‒1.65) for Lp(a) levels ≥ 90th percentile vs. Lp(a) levels in the lowest third (P < 0.001 for all). There was no significant association between Lp(a) levels and total mortality. Subgroup analysis for a continuous version of cube root transformed Lp(a) identified the highest Lp(a)-associated risk in individuals with diabetes [HR for MCE 1.31 (95% CI 1.15‒1.50)] and for CVD 1.22 (95% CI 1.08‒1.38) compared to those without diabetes [HR for MCE 1.15 (95% CI 1.08‒1.21; HR for CVD 1.13 (1.07-1.19)] while no difference of the Lp(a)- associated risk were seen for other cardiovascular high risk states. The addition of Lp(a) levels to a prognostic model for MCE and CVD revealed only a marginal but significant C-index discrimination measure increase (0.001 for MCE and CVD; P < 0.05) and net reclassification improvement (0.010 for MCE and 0.011 for CVD). Conclusion: In this large dataset on harmonized Lp(a) determination, we observed regional differences within the European population. Elevated Lp(a) was robustly associated with an increased risk for MCE and CVD in particular among individuals with diabetes. These results may lead to better identification of target populations who might benefit from future Lp(a)-lowering therapies.


Assuntos
Doenças Cardiovasculares/etiologia , Lipoproteína(a)/fisiologia , Adulto , Biomarcadores/metabolismo , Doenças Cardiovasculares/mortalidade , Europa (Continente)/epidemiologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Lipoproteína(a)/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Características de Residência/estatística & dados numéricos , Medição de Risco
6.
Eur Heart J ; 38(20): 1553-1560, 2017 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-28329241

RESUMO

In the mid-1990s, the days of lipoprotein(a) [Lp(a)] were numbered and many people would not have placed a bet on this lipid particle making it to the next century. However, genetic studies brought Lp(a) back to the front-stage after a Mendelian randomization approach used for the first time provided strong support for a causal role of high Lp(a) concentrations in cardiovascular disease and later also for aortic valve stenosis. This encouraged the use of therapeutic interventions to lower Lp(a) as well numerous drug developments, although these approaches mainly targeted LDL cholesterol, while the Lp(a)-lowering effect was only a 'side-effect'. Several drug developments did show a potent Lp(a)-lowering effect but did not make it to endpoint studies, mainly for safety reasons. Currently, three therapeutic approaches are either already in place or look highly promising: (i) lipid apheresis (specific or unspecific for Lp(a)) markedly decreases Lp(a) concentrations as well as cardiovascular endpoints; (ii) PCSK9 inhibitors which, besides lowering LDL cholesterol also decrease Lp(a) by roughly 30%; and (iii) antisense therapy targeting apolipoprotein(a) which has shown to specifically lower Lp(a) concentrations by up to 90% in phase 1 and 2 trials without influencing other lipids. Until the results of phase 3 outcome studies are available for antisense therapy, we will have to exercise patience, but with optimism since never before have we had the tools we have now to prove Koch's extrapolated postulate that lowering high Lp(a) concentrations might be protective against cardiovascular disease.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Lipoproteína(a)/efeitos dos fármacos , Estenose da Valva Aórtica/etiologia , Remoção de Componentes Sanguíneos/métodos , LDL-Colesterol/efeitos dos fármacos , Medicina Baseada em Evidências , Humanos , Hipercolesterolemia/prevenção & controle , Hiperlipidemias/prevenção & controle , Hipolipemiantes/uso terapêutico , Lipoproteína(a)/metabolismo , Lipoproteína(a)/fisiologia , Oligonucleotídeos Antissenso/uso terapêutico , Guias de Prática Clínica como Assunto , Pró-Proteína Convertase 9/antagonistas & inibidores , Fatores de Risco , Calcificação Vascular/etiologia
7.
J Am Coll Cardiol ; 69(6): 692-711, 2017 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-28183512

RESUMO

Evidence that elevated lipoprotein(a) (Lp[a]) levels contribute to cardiovascular disease (CVD) and calcific aortic valve stenosis (CAVS) is substantial. Development of isoform-independent assays, in concert with genetic, epidemiological, translational, and pathophysiological insights, have established Lp(a) as an independent, genetic, and likely causal risk factor for CVD and CAVS. These observations are consistent across a broad spectrum of patients, risk factors, and concomitant therapies, including patients with low-density lipoprotein cholesterol <70 mg/dl. Statins tend to increase Lp(a) levels, possibly contributing to the "residual risk" noted in outcomes trials and at the bedside. Recently approved proprotein convertase subtilisin/kexin-type 9 inhibitors and mipomersen lower Lp(a) 20% to 30%, and emerging RNA-targeted therapies lower Lp(a) >80%. These approaches will allow testing of the "Lp(a) hypothesis" in clinical trials. This review summarizes the current landscape of Lp(a), discusses controversies, and reviews emerging therapies to reduce plasma Lp(a) levels to decrease risk of CVD and CAVS.


Assuntos
Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/terapia , Lipoproteína(a)/fisiologia , Doenças Cardiovasculares/epidemiologia , Humanos , Prognóstico , Fatores de Risco
9.
J Lipid Res ; 57(8): 1339-59, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27074913

RESUMO

Lipoprotein (a) [Lp(a)] has attracted the interest of researchers and physicians due to its intriguing properties, including an intragenic multiallelic copy number variation in the LPA gene and the strong association with coronary heart disease (CHD). This review summarizes present knowledge of the structure, function, and genetics of Lp(a) with emphasis on the molecular and population genetics of the Lp(a)/LPA trait, as well as aspects of genetic epidemiology. It highlights the role of genetics in establishing Lp(a) as a risk factor for CHD, but also discusses uncertainties, controversies, and lack of knowledge on several aspects of the genetic Lp(a) trait, not least its function.


Assuntos
Doenças Cardiovasculares/genética , Lipoproteína(a)/química , Lipoproteína(a)/fisiologia , Animais , Frequência do Gene , Predisposição Genética para Doença , Humanos , Polimorfismo Genético , Domínios Proteicos
10.
J Lipid Res ; 57(5): 745-57, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26647358

RESUMO

Elevated plasma concentrations of lipoprotein (a) [Lp(a)] have been determined to be a causal risk factor for coronary heart disease, and may similarly play a role in other atherothrombotic disorders. Lp(a) consists of a lipoprotein moiety indistinguishable from LDL, as well as the plasminogen-related glycoprotein, apo(a). Therefore, the pathogenic role for Lp(a) has traditionally been considered to reflect a dual function of its similarity to LDL, causing atherosclerosis, and its similarity to plasminogen, causing thrombosis through inhibition of fibrinolysis. This postulate remains highly speculative, however, because it has been difficult to separate the prothrombotic/antifibrinolytic functions of Lp(a) from its proatherosclerotic functions. This review surveys the current landscape surrounding these issues: the biochemical basis for procoagulant and antifibrinolytic effects of Lp(a) is summarized and the evidence addressing the role of Lp(a) in both arterial and venous thrombosis is discussed. While elevated Lp(a) appears to be primarily predisposing to thrombotic events in the arterial tree, the fact that most of these are precipitated by underlying atherosclerosis continues to confound our understanding of the true pathogenic roles of Lp(a) and, therefore, the most appropriate therapeutic target through which to mitigate the harmful effects of this lipoprotein.


Assuntos
Doenças Cardiovasculares/sangue , Hiperlipidemias/sangue , Lipoproteína(a)/fisiologia , Trombose/sangue , Animais , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/terapia , Humanos , Hiperlipidemias/complicações , Lipoproteína(a)/química , Plasminogênio/química , Homologia Estrutural de Proteína , Trombose/terapia
11.
Med Hypotheses ; 85(5): 670-4, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26328479

RESUMO

Livedoid vasculopathy is a chronic disorder characterised by recurrent reticulated purpura on lower extremities, associated with painful purpuric or necrotic macules and ulcerations. Current knowledge indicates LV to be a thrombo-occlusive vasculopathy of cutaneous blood vessels; exact pathogenesis is yet to be understood. Elevated levels of lipoprotein(a) have been found in LV patients. To date, elevated plasma levels of lipoprotein(a) are considered an independent and causal genetic risk factor for the development of cardiovascular disease, as well as a relevant factor in hypercoagulable states. Because of its structural homology with plasminogen, Lp(a) might have important anti-fibrinolytic properties. Altered endothelial function and participation in immune and autoimmune processes, such as antiphospholipid syndrome, are also potential mechanisms of Lp(a) involvement in LV pathogenesis. Lp(a) is part of the wound healing process; the possibility of Lp(a) serum elevation to reflect an acute-phase reagent in LV scenario is also considered. The objective of this review is to examine the possible association of lipoprotein(a) with LV pathogenesis, based on its effects on thrombogenesis, fibrinolysis and autoimmunity.


Assuntos
Lipoproteína(a)/fisiologia , Trombofilia/fisiopatologia , Doenças Vasculares/fisiopatologia , Humanos , Modelos Teóricos
13.
Arq Bras Cardiol ; 103(1): 76-84, 2014 Jul.
Artigo em Inglês, Português | MEDLINE | ID: mdl-25120086

RESUMO

The chemical structure of lipoprotein (a) is similar to that of LDL, from which it differs due to the presence of apolipoprotein (a) bound to apo B100 via one disulfide bridge. Lipoprotein (a) is synthesized in the liver and its plasma concentration, which can be determined by use of monoclonal antibody-based methods, ranges from < 1 mg to > 1,000 mg/dL. Lipoprotein (a) levels over 20-30 mg/dL are associated with a two-fold risk of developing coronary artery disease. Usually, black subjects have higher lipoprotein (a) levels that, differently from Caucasians and Orientals, are not related to coronary artery disease. However, the risk of black subjects must be considered. Sex and age have little influence on lipoprotein (a) levels. Lipoprotein (a) homology with plasminogen might lead to interference with the fibrinolytic cascade, accounting for an atherogenic mechanism of that lipoprotein. Nevertheless, direct deposition of lipoprotein (a) on arterial wall is also a possible mechanism, lipoprotein (a) being more prone to oxidation than LDL. Most prospective studies have confirmed lipoprotein (a) as a predisposing factor to atherosclerosis. Statin treatment does not lower lipoprotein (a) levels, differently from niacin and ezetimibe, which tend to reduce lipoprotein (a), although confirmation of ezetimibe effects is pending. The reduction in lipoprotein (a) concentrations has not been demonstrated to reduce the risk for coronary artery disease. Whenever higher lipoprotein (a) concentrations are found, and in the absence of more effective and well-tolerated drugs, a more strict and vigorous control of the other coronary artery disease risk factors should be sought.


Assuntos
Lipoproteína(a)/fisiologia , Apolipoproteínas A/química , Apolipoproteínas A/genética , Humanos , Lipoproteína(a)/análise , Lipoproteína(a)/metabolismo , Fatores de Risco
14.
Arq. bras. cardiol ; 103(1): 76-84, 07/2014. tab
Artigo em Inglês | LILACS | ID: lil-718102

RESUMO

The chemical structure of lipoprotein (a) is similar to that of LDL, from which it differs due to the presence of apolipoprotein (a) bound to apo B100 via one disulfide bridge. Lipoprotein (a) is synthesized in the liver and its plasma concentration, which can be determined by use of monoclonal antibody-based methods, ranges from < 1 mg to > 1,000 mg/dL. Lipoprotein (a) levels over 20-30 mg/dL are associated with a two-fold risk of developing coronary artery disease. Usually, black subjects have higher lipoprotein (a) levels that, differently from Caucasians and Orientals, are not related to coronary artery disease. However, the risk of black subjects must be considered. Sex and age have little influence on lipoprotein (a) levels. Lipoprotein (a) homology with plasminogen might lead to interference with the fibrinolytic cascade, accounting for an atherogenic mechanism of that lipoprotein. Nevertheless, direct deposition of lipoprotein (a) on arterial wall is also a possible mechanism, lipoprotein (a) being more prone to oxidation than LDL. Most prospective studies have confirmed lipoprotein (a) as a predisposing factor to atherosclerosis. Statin treatment does not lower lipoprotein (a) levels, differently from niacin and ezetimibe, which tend to reduce lipoprotein (a), although confirmation of ezetimibe effects is pending. The reduction in lipoprotein (a) concentrations has not been demonstrated to reduce the risk for coronary artery disease. Whenever higher lipoprotein (a) concentrations are found, and in the absence of more effective and well-tolerated drugs, a more strict and vigorous control of the other coronary artery disease risk factors should be sought.


A partícula de lipoproteína (a) apresenta estrutura semelhante à da LDL, diferenciando-se pela presença da apolipoproteína (a) ligada por uma ponte dissulfeto à apolipoproteína B. Sua síntese ocorre no fígado e sua concentração plasmática varia de < 1 mg a > 1.000 mg/dL, podendo ser dosada de rotina em laboratório clínico por método baseado em anticorpos monoclonais. Acima de 20 a 30 mg/dL o risco de desenvolvimento de doença cardiovascular aumenta em cerca de duas vezes, o que não é válido para os afrodescendentes, que já apresentam normalmente níveis mais altos dessa lipoproteína, do que caucasianos e orientais. Entretanto, o risco para indivíduos negros também deve ser levado em conta. Gênero e idade exercem pouca influência na concentração de lipoproteína (a). A homologia com o plasminogênio, que interfere na cascata fibrinolítica, pode ser um mecanismo da aterogenicidade da lipoproteína (a). Entretanto, a deposição direta na parede da artéria também é um dos mecanismos possíveis, sendo a lipoprotrína (a) mais oxidável do que a LDL. De forma geral estudos prospectivos confirmam a lipoproteína (a) como fator predisponente à aterosclerose. O uso de estatinas não interfere no nível da lipoproteína (a), diferentemente da niacina e da ezetimiba, que promovem sua diminuição, embora essa última dependa de confirmação. Não está demonstrado que a redução de lipoproteína (a) resulte em diminuição de risco de doença arterial coronária. Diante de concentrações mais elevadas de lipoproteína (a) e na falta de medicações mais efetivas e de boa tolerabilidade, deve-se, pelo menos, procurar controlar, de forma mais rigorosa, os outros fatores de risco de doença arterial coronária.


Assuntos
Humanos , Lipoproteína(a)/fisiologia , Apolipoproteínas A/química , Apolipoproteínas A/genética , Lipoproteína(a)/análise , Lipoproteína(a)/metabolismo , Fatores de Risco
15.
Eur Heart J ; 35(29): 1917-24, 2014 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-24917639

RESUMO

Epidemiological research over the last 50 years has discovered a plethora of biomarkers (including molecules, traits or other diseases) that associate with coronary artery disease (CAD) risk. Even the strongest association detected in such observational research precludes drawing conclusions about the causality underlying the relationship between biomarker and disease. Mendelian randomization (MR) studies can shed light on the causality of associations, i.e whether, on the one hand, the biomarker contributes to the development of disease or, on the other hand, the observed association is confounded by unrecognized exogenous factors or due to reverse causation, i.e. due to the fact that prevalent disease affects the level of the biomarker. However, conclusions from a MR study are based on a number of important assumptions. A prerequisite for such studies is that the genetic variant employed affects significantly the biomarker under investigation but has no effect on other phenotypes that might confound the association between the biomarker and disease. If this biomarker is a true causal risk factor for CAD, genotypes of the variant should associate with CAD risk in the direction predicted by the association of the biomarker with CAD. Given a random distribution of exogenous factors in individuals carrying respective genotypes, groups represented by the genotypes are highly similar except for the biomarker of interest. Thus, the genetic variant converts into an unconfounded surrogate of the respective biomarker. This scenario is nicely exemplified for LDL cholesterol. Almost every genotype found to increase LDL cholesterol level by a sufficient amount has also been found to increase CAD risk. Pending a number of conditions that needed to be fulfilled by the genetic variant under investigation (e.g. no pleiotropic effects) and the experimental set-up of the study, LDL cholesterol can be assumed to act as the functional component that links genotypes and CAD risk and, more importantly, it can be assumed that any modulation of LDL cholesterol-by whatever mechanism-would have similar effects on disease risk. Therefore, MR analysis has tremendous potential for identifying therapeutic targets that are likely to be causal for CAD. This review article discusses the opportunities and challenges of MR studies for CAD, highlighting several examples that involved multiple biomarkers, including various lipid and inflammation traits as well as hypertension, diabetes mellitus, and obesity.


Assuntos
Doença da Artéria Coronariana/genética , Análise da Randomização Mendeliana , Proteína C-Reativa/genética , Proteína C-Reativa/metabolismo , Proteínas de Transferência de Ésteres de Colesterol/genética , Proteínas de Transferência de Ésteres de Colesterol/fisiologia , HDL-Colesterol/genética , HDL-Colesterol/fisiologia , LDL-Colesterol/genética , LDL-Colesterol/fisiologia , Complicações do Diabetes/genética , Fibrinogênio/fisiologia , Marcadores Genéticos/genética , Pleiotropia Genética/genética , Humanos , Hipertensão/complicações , Hipertensão/genética , Desequilíbrio de Ligação/genética , Lipoproteína(a)/genética , Lipoproteína(a)/fisiologia , Obesidade/complicações , Obesidade/genética , Fosfolipases A2/genética , Fosfolipases A2/fisiologia , Polimorfismo de Nucleotídeo Único/genética , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores de Interleucina-6/genética , Fatores de Risco , Componente Amiloide P Sérico/genética , Telômero/genética , Triglicerídeos/genética , Triglicerídeos/fisiologia
16.
Clin Exp Rheumatol ; 31(3): 415-21, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23465067

RESUMO

OBJECTIVES: To examine the effect of methotrexate (MTX) with or without tumor necrosis factor alpha (TNF-α)-inhibitors on serum lipoprotein(a) (s-Lp(a)), and to explore a possible relationship between s-Lp(a) and endothelial function (EF) in terms of serum levels of adhesion molecules and reactive hyperaemic index (RHI) in patients with rheumatoid arthritis (RA). METHODS: Serum levels of Lp(a), endothelial adhesion molecules, RHI and inflammatory markers were studied in 64 RA patients, starting with either MTX (n=34) or MTX+TNF-α-inhibitor treatment (n=30) at baseline and after 6 weeks and 6 months. RESULTS: Compared to baseline values, s-Lp(a) was significantly reduced after 6 weeks (p=0.001) and 6 months (p=0.001) in RA patients treated with MTX, and after 6 weeks (p=0.001) in the MTX+TNF-α-inhibitor group. A non-significant reduction was found after 6 months (p=0.102) in the MTX+TNFα-inhibitor group. Serum E-selectin (s-E-selectin) was significantly reduced in both RA treatment groups at both control points. S-Lp(a) correlated positively with s-E-selectin at baseline (p=0.004), and change in s-E-selectin correlated with the change in s-Lp(a) during follow-up (p6weeks= 0.008, p 6months=0.009). No association was found between s-Lp(a) and the other adhesion molecules and RHI. CONCLUSIONS: MTX or MTX combined with a TNFα-inhibitor appears to significantly reduce Lp(a). This finding indicate that s-Lp(a) might be related to systemic inflammation, or that the examined drugs might reduce s-Lp(a) by other mechanisms. Anti-inflammatory treatment might be a novel therapeutic option to decrease s-Lp(a). The associations between s-E-selectin and s-Lp(a) suggest an interaction between these factors, or a common cause.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Selectina E/sangue , Lipoproteína(a)/sangue , Metotrexato/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab , Adulto , Idoso , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Reumatoide/sangue , Artrite Reumatoide/fisiopatologia , Estudos de Coortes , Quimioterapia Combinada , Selectina E/fisiologia , Etanercepte , Feminino , Humanos , Imunoglobulina G/uso terapêutico , Infliximab , Molécula 1 de Adesão Intercelular/sangue , Molécula 1 de Adesão Intercelular/efeitos dos fármacos , Molécula 1 de Adesão Intercelular/fisiologia , Lipoproteína(a)/fisiologia , Masculino , Pessoa de Meia-Idade , Receptores do Fator de Necrose Tumoral/uso terapêutico , Molécula 1 de Adesão de Célula Vascular/sangue , Molécula 1 de Adesão de Célula Vascular/fisiologia
17.
Metabolism ; 62(4): 479-91, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23040268

RESUMO

Lipoprotein(a) [Lp(a)] resembles low-density lipoprotein (LDL), with an LDL lipid core and apolipoprotein B (apoB), but contains a unique apolipoprotein, apo(a). Elevated Lp(a) is an independent risk factor for coronary and peripheral vascular diseases. The size and concentration of plasma Lp(a) are related to the synthetic rate, not the catabolic rate, and are highly variable with small isoforms associated with high concentrations and pathogenic risk. Apo(a) is synthesized in the liver, although assembly of apo(a) and LDL may occur in the hepatocytes or plasma. While the uptake and clearance site of Lp(a) is poorly delineated, the kidney is the site of apo(a) fragment excretion. The structure of apo(a) has high homology to plasminogen, the zymogen for plasmin and the primary clot lysis enzyme. Apo(a) interferes with plasminogen binding to C-terminal lysines of cell surface and extracellular matrix proteins. Lp(a) and apo(a) inhibit fibrinolysis and accumulate in the vascular wall in atherosclerotic lesions. The pathogenic role of Lp(a) is not known. Small isoforms and high concentrations of Lp(a) are found in healthy octogenarians that suggest Lp(a) may also have a physiological role. Studies of Lp(a) function have been limited since it is not found in commonly studied small mammals. An important aspect of Lp(a) metabolism is the modification of circulating Lp(a), which has the potential to alter the functions of Lp(a). There are no therapeutic drugs that selectively target elevated Lp(a), but a number of possible agents are being considered. Recently, new modifiers of apo(a) synthesis have been identified. This review reports the regulation of Lp(a) metabolism and potential sites for therapeutic targets.


Assuntos
Lipoproteína(a)/efeitos dos fármacos , Lipoproteína(a)/metabolismo , Animais , Apolipoproteínas A/metabolismo , Regulação da Expressão Gênica/fisiologia , Humanos , Lipoproteína(a)/biossíntese , Lipoproteína(a)/fisiologia , Receptores de LDL/metabolismo , Distribuição Tecidual
18.
J Cardiol ; 61(2): 99-106, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23165148

RESUMO

BACKGROUND AND PURPOSE: Lipoprotein (Lp) (a) is a neglected element of the blood lipid profile. It is now recognized as a determinant of coronary heart disease progression and its role in atherosclerosis and its ability to induce thrombosis make it potentially important in the course of normal and complicated pregnancies. Pregnancy involves a major transformation of metabolism to sustain fetal growth. Multiple studies have been conducted on Lp(a) in pregnancy, and it is timely to synthesize and evaluate this evidence. METHODS AND SUBJECTS: We reviewed the MEDLINE database for all articles published concerning "lipoprotein a" and "pregnancy" from May 2003 to May 2012. A previous comprehensive review assessed the literature up to May 2003. RESULTS: We critically analyzed 14 studies detailing the effect of complications in pregnancy on Lp(a) profile, and subsequent pregnancy outcomes where available. Studies evaluating the normal metabolic response to pregnancy, pregnancies complicated by pre-eclampsia and intra-uterine growth restriction were reviewed. CONCLUSIONS: A substantial mass of data has accumulated describing Lp(a) changes in pregnancy. The diversity of study design limits the ability to draw broad-ranging conclusions, but brings into focus the important questions remaining, which we discuss.


Assuntos
Lipoproteína(a)/sangue , Lipoproteína(a)/fisiologia , Complicações na Gravidez/sangue , Adulto , Colesterol/sangue , Feminino , Retardo do Crescimento Fetal/sangue , Humanos , Pré-Eclâmpsia/sangue , Gravidez , Resultado da Gravidez
20.
Arterioscler Thromb Vasc Biol ; 32(7): 1732-41, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22516069

RESUMO

OBJECTIVE: The aim of the present study was to determine whether lipoprotein(a) [Lp(a)], considered a causal risk factor for cardiovascular disease, primarily promotes thrombosis or atherosclerosis. METHODS AND RESULTS: Using a Mendelian randomization study design, we measured plasma Lp(a) and genetically elevated Lp(a) levels through the LPA kringle IV type 2 repeat genotype in 41231 individuals. We included 2 general population studies of both venous thrombosis and combined thrombosis and atherosclerosis in coronary arteries (=myocardial infarction), and 3 -case--control studies of atherosclerotic stenosis. Neither Lp(a) tertiles nor LPA kringle IV type 2 tertiles associated with the risk of venous thrombosis in general population studies (trend: P=0.12-0.76), but did each associate with risk of coronary, carotid, and femoral atherosclerotic stenosis in -case--control studies (trend: P<0.001 to 0.04). Lp(a) and LPA kringle IV type 2 tertiles also associated with the risk of myocardial infarction in general population studies (trend: P<0.001 to 0.003). For doubling of Lp(a) levels, instrumental variable estimates of hazard/odds ratios were 1.02 (95% CI 0.90-1.15) and 1.04 (0.93-1.16) for venous thrombosis in the 2 general population studies, 1.12 (1.01-1.25), 1.17 (1.05-1.32), and 1.16 (1.01-1.35), respectively, for coronary, carotid, and femoral atherosclerotic stenosis in -case-control studies, and 1.21 (1.10-1.33) and 1.17 (1.05-1.29) for myocardial infarction in general population studies. CONCLUSIONS: This supports that Lp(a) primarily promotes atherosclerotic stenosis rather than venous thrombosis.


Assuntos
Aterosclerose/etiologia , Lipoproteína(a)/fisiologia , Trombose Venosa/etiologia , Adulto , Idoso , Estenose das Carótidas/etiologia , Estudos de Casos e Controles , Estenose Coronária/etiologia , Feminino , Artéria Femoral , Genótipo , Humanos , Lipoproteína(a)/sangue , Lipoproteína(a)/genética , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA