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1.
Indian Heart J ; 71(3): 184-198, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31543191

RESUMO

Malignant coronary artery disease (CAD) refers to a severe and extensive atherosclerotic process involving multiple coronary arteries in young individuals (aged <45 years in men and <50 years in women) with a low or no burden of established risk factors. Indians, in general, develop acute myocardial infarction (AMI) about 10 years earlier; AMI rates are threefold to fivefold higher in young Indians than in other populations. Although established CAD risk factors have a predictive value, they do not fully account for the excessive burden of CAD in young Indians. Lipoprotein(a) (Lp(a)) is increasingly recognized as the strongest known genetic risk factor for premature CAD, with high levels observed in Indians with malignant CAD. High Lp(a) levels confer a twofold to threefold risk of CAD-a risk similar to that of established risk factors, including diabetes. South Asians have the second highest Lp(a) levels and the highest risk of AMI from the elevated levels, more than double the risk observed in people of European descent. Approximately 25% of Indians and other South Asians have elevated Lp(a) levels (≥50 mg/dl), rendering Lp(a) a risk factor of great importance, similar to or surpassing diabetes. Lp(a) measurement is ready for clinical use and should be an essential part of all CAD research in Indians.


Assuntos
Doença da Artéria Coronariana/sangue , Hiperlipoproteinemias/complicações , Lipoproteína(a)/sangue , Adulto , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/mortalidade , Grupos Étnicos , Feminino , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco
2.
Indian J Ophthalmol ; 67(6): 954-957, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31124530

RESUMO

Familial combined hyperlipidemia, which presents as hypercholesterolemia or hypertriglyceridemia, is the commonest form of genetic hyperlipidemia and is associated with premature coronary artery disease. This is a rare case report of a 27 day-old neonate born out of a third-degree consanguineous marriage, with grade III lipemia retinalis secondary to familial-combined hyperlipidemia.


Assuntos
Hiperlipoproteinemias/complicações , Lipídeos/sangue , Retina/diagnóstico por imagem , Doenças Retinianas/etiologia , Biomarcadores/sangue , Humanos , Hiperlipoproteinemias/sangue , Hiperlipoproteinemias/diagnóstico , Recém-Nascido , Masculino , Doenças Retinianas/sangue , Doenças Retinianas/diagnóstico
4.
Circ Res ; 124(3): 405-415, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30702993

RESUMO

The prevalence of calcific aortic valve disease is increasing with aging of the population. Current treatment options for advanced or symptomatic aortic stenosis are limited to traditional surgical or percutaneous aortic valve replacement. Medical therapies that impact the progression of calcific aortic valve disease do not currently exist. New pathophysiological insights suggest that the processes leading to calcific aortic valve disease are metabolically active for many years before and during the clinical expression of disease. The identification of genetic and potentially causal mediators of calcific aortic valve disease allows opportunities for therapies that may slow progression to the point where aortic valve replacement can be avoided. Recent studies suggest that approximately one-third of aortic stenosis cases are associated with highly elevated lipoprotein(a) [Lp(a)] and pathways related to the metabolism of procalcifying oxidized phospholipids. Oxidized phospholipids can be carried by Lp(a) into valve leaflets but can also be formed in situ from cell membranes, lipoproteins, and apoptotic cells. This review will summarize the clinical data implicating the potential causality of Lp(a)/oxidized phospholipids, describe emerging therapeutic agents, and propose clinical trial designs to test the hypothesis that lowering Lp(a) will reduce progression aortic stenosis and the need for aortic valve replacement.


Assuntos
Estenose da Valva Aórtica/terapia , Calcinose/terapia , Hiperlipoproteinemias/complicações , Lipoproteína(a) , Fosfolipídeos/metabolismo , Estenose da Valva Aórtica/etiologia , Calcinose/etiologia , Causalidade , Ensaios Clínicos como Assunto , Implante de Prótese de Valva Cardíaca , Humanos , Oxirredução , Fatores de Risco
6.
Atheroscler Suppl ; 30: 174-179, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29096834

RESUMO

OBJECTIVE: Elevated plasma levels of lipoprotein(a) [Lp(a)], referred to as lipoprotein(a)-hyperlipoproteinemia [Lp(a)-HLP], are an independent risk factor for atherosclerosis. Lipoprotein apheresis (LA) enables an effective reduction of Lp(a) plasma levels. The present study investigates the effects of LA in patients with Lp(a)-HLP and peripheral artery disease (PAD). METHODS: Ten patients with isolated Lp(a)-HLP and severe PAD and who had recently undergone a revascularization (index procedure) were prospectively included in this observational single center study. All patients received weekly LA. Ankle-brachial-index (ABI), transcutaneous partial oxygen pressure (tcpO2), pain level, and walking distance were assessed at baseline and at the follow ups scheduled 1, 3, 6, 12, and 24 months after initiation of LA. The number of revascularizations within 12 months prior and within 24 months after the index procedure was determined. RESULTS: As early as 1 month after initiation of LA, all investigated parameters had improved significantly compared to baseline. This improvement was further substantiated under LA throughout the entire follow-up period. Comparing baseline results with the 24-month follow-up, the average ABI increased from 0.53 ± 0.15 to 0.97 ± 0.08 (P < 0.001). The mean tcpO2 also increased from 42.9 ± 2.3 mmHg to 61 ± 4.6 mmHg (P < 0.001). The improved perfusion led to a reduction of the mean pain level from 7.0 ± 1.5 to 1.1 ± 0.4 (P < 0.001) on a visual analogue scale (VAS) and an extension of the mean walking distance from 87 ± 60 m to 402 ± 119 m (P < 0.001). All patients suffered from severe PAD with a high number of revascularizations in the 12 months prior to the index procedure (35 procedures in 120 patient-months). Since initiation of LA, the number of revascularizations dropped significantly and remained very low during the entire follow-up period (2 procedures in 229 patient-months, P < 0.001). CONCLUSION: In patients with Lp(a)-HLP and severe PAD, LA results in sustained improvement of circulation, pain level and walking distance. The number of repeat revascularizations is strongly reduced under LA treatment.


Assuntos
Remoção de Componentes Sanguíneos/métodos , Hiperlipoproteinemias/terapia , Lipoproteína(a)/sangue , Doença Arterial Periférica/terapia , Índice Tornozelo-Braço , Biomarcadores/sangue , Monitorização Transcutânea dos Gases Sanguíneos , Tolerância ao Exercício , Feminino , Seguimentos , Humanos , Hiperlipoproteinemias/sangue , Hiperlipoproteinemias/complicações , Hiperlipoproteinemias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Medição da Dor , Doença Arterial Periférica/sangue , Doença Arterial Periférica/etiologia , Doença Arterial Periférica/fisiopatologia , Projetos Piloto , Estudos Prospectivos , Recuperação de Função Fisiológica , Fluxo Sanguíneo Regional , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Caminhada
7.
Atheroscler Suppl ; 30: 180-186, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29096835

RESUMO

BACKGROUND: Dyslipidemia is a well-known risk factor for atherosclerosis and subsequent cardiovascular disease (CVD). While low density lipoprotein cholesterol (LDL-C) is well-established and taken into consideration for risk management and therapy, lipoprotein(a) is another established CVD risk factor frequently not undergoing screening due to a lack of medical treatment options. For patients suffering from CVD due to massive elevation of Lp(a) in presence of normal LDL-C levels, lipoprotein apheresis is the only available treatment option. While this constellation is an accepted indication for lipoprotein apheresis (LA) in Germany, prospective studies including a control group are still lacking. OBJECTIVE: Primary objective of this trial is to evaluate the clinical benefit of lipoprotein apheresis on myocardial infarction, PCI, CABG and death from cardiovascular disease in subjects with elevated Lp(a). This study evaluates the clinical benefit of weekly LA in subjects with progressive cardiovascular disease, as accepted by the German Federal Joint Committee (treatment group). Comparator will be well-matched subjects under maximum tolerated lipid lowering therapy without access to LA treatment (control group). METHODS: MultiSELECt, is a prospective, multicenter, multinational, two-arm matched-pair cohort study designed to directly compare subjects with significantly elevated Lp(a) approved for LA subsequently undergoing weekly apheresis treatment versus a continuation of maximal medical therapy. The follow-up period will be 2 years after the baseline visit and until at least 60 events of the primary end-point occurred in the control group. A central trial expert committee will review all subjects with respect to their potential indication for LA according to established German guidelines in a blinded fashion. All control subjects will be contacted monthly via telephone visits to compensate for the more frequent visits during apheresis. Approximately 150 matched pairs will be necessary to detect an event reduction of at least 10% in subjects under LA treatment. CONCLUSION: The MultiSELECt trial provides the unique opportunity to demonstrate the efficiency of LA on CVD in patients with elevated Lp(a) under strongly controlled conditions.


Assuntos
Remoção de Componentes Sanguíneos/métodos , Hiperlipoproteinemias/terapia , Lipoproteína(a)/sangue , Infarto do Miocárdio/prevenção & controle , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Protocolos Clínicos , Ponte de Artéria Coronária , Europa (Continente) , Feminino , Humanos , Hiperlipoproteinemias/sangue , Hiperlipoproteinemias/complicações , Hiperlipoproteinemias/mortalidade , Hipolipemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/mortalidade , Intervenção Coronária Percutânea , Estudos Prospectivos , Projetos de Pesquisa , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
8.
Atheroscler Suppl ; 30: 187-192, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29096836

RESUMO

OBJECTIVE: To evaluate the association of lipoprotein(a) [Lp(a)] level with short- and long-term outcomes after coronary artery bypass grafting (CABG) and to assess the effect of a 12 month course of weekly lipoprotein apheresis on vein graft patency and coronary atherosclerosis course in post-CABG patients with hyperlipidemia. METHODS: This study was performed in patients after successful CABG and consisted of three parts: a) a retrospective part with computed tomography assessment of vein graft patency in patients with first-year recurrence of chest pain after CABG (n = 102); b) a prospective trial with evaluation of cardiovascular outcomes during follow up time up to 15 years in relation to baseline Lp(a) levels (n = 356); c) an 12-months interventional controlled study in 50 patients with low-density lipoprotein cholesterol (LDL-C) levels >2.6 mmol/L prior to the operation despite statin treatment that allocated into 2 groups: active (n = 25, weekly apheresis by cascade plasma filtration (CPF) plus atorvastatin), and control (n = 25, atorvastatin alone). RESULTS: Patients subjected to computed tomography were divided in two groups: 66 (65%) with at least one vein graft occlusion and 36 (35%) without occlusions. Lp(a) levels were significantly higher in patients with occluded grafts with a median (95% confidence intervals (CI)) of 24 (17-42) mg/dL vs. 12 (6-24) mg/dL in patients with patent grafts, p < 0.01. Over a mean of 8.5 ± 3.5 years (range 0.9-15.0 years), the primary and secondary endpoints were registered in 46 (13%) and 107 (30%) patients, respectively. Patients with Lp(a) ≥30 mg/dL were at significantly greater risk for the primary endpoint (hazard ratio (HR) 2.98, 95% confidence interval (CI) 1.76-5.03, p < 0.001) and secondary endpoint (HR 3.47, 95%CI 2.48-4.85, p < 0.001) than patients with Lp(a) values <30 mg/dL. During the CPF procedure LDL-C levels decreased by 59 ± 14%, Lp(a) levels by 49 ± 15. The frequency of vein graft occlusions at study end was 14.3% (11 of 77) in the apheresis group and 27.4% (23 of 84) in the control group, p < 0.05. Progression of atherosclerosis was obtained in 26 (14.2%) segments of native coronary arteries in the apheresis group and in 50 (25.0%) segments of the control group. Regression signs were found in 30 (16.4%) and 19 (9.5%) segments, stabilization in 127 (69.4%) and 131 (65.5%) segments, respectively (χ2 = 9.37, p < 0.01). A Lp(a) level higher than 30 mg/dL was associated with a three-fold increased risk of vein grafts occlusion during first year after CABG, p < 0.001. CONCLUSION: Our data suggest that elevated Lp(a) is associated with a significantly increasing rate of one-year vein graft occlusions and adverse long-term cardiovascular outcomes whereas the use of lipoprotein apheresis improves vein graft patency during the first year after CABG.


Assuntos
Ponte de Artéria Coronária , Doença da Artéria Coronariana/cirurgia , Hiperlipoproteinemias/terapia , Lipoproteína(a)/sangue , Plasmaferese/métodos , Adulto , Idoso , Atorvastatina/uso terapêutico , Biomarcadores/sangue , LDL-Colesterol/sangue , Angiografia por Tomografia Computadorizada , Angiografia Coronária/métodos , Ponte de Artéria Coronária/efeitos adversos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/etiologia , Feminino , Oclusão de Enxerto Vascular/diagnóstico por imagem , Oclusão de Enxerto Vascular/etiologia , Oclusão de Enxerto Vascular/fisiopatologia , Oclusão de Enxerto Vascular/prevenção & controle , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemias/sangue , Hiperlipoproteinemias/complicações , Masculino , Pessoa de Meia-Idade , Plasmaferese/efeitos adversos , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular
9.
Atheroscler Suppl ; 30: 246-252, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29096845

RESUMO

OBJECTIVES: Lipoprotein(a) (Lp(a)) is an independent cardiovascular (CV) risk factor, predisposing to premature and progressive CV events. Lipoproteinapheresis (LA) is the only efficacious therapy for reducing Lp(a). Data comparing the clinical efficacy of LA with respect to reduction of CV events in subjects with elevated Lp(a) versus LDL-C versus both disorders is scarce. We aimed to perform this comparison in a multicenter observational study. METHODS: 113 LA patients from 8 apheresis centers were included (mean age 56.3 years). They were divided into 3 groups: Group I: Lp(a) < 600 mg/l, LDL-C > 2.6 mmol/l, Group II: Lp(a) > 600 mg/l, LDL-C < 2.6 mmol/l, and Group III: Lp(a) > 600 mg/l, LDL-C > 2.6 mmol/l. CV events were documented 2 years before versus 2 years after LA start. RESULTS: Before start of LA Group II showed the highest CV event rate (p 0.001). Group III had a higher CV event rate than Group I (p 0.03). During LA there was a significant reduction of CV events/patient in all vessel beds (1.22 ± 1.16 versus 0.33 ± 0.75, p < 0.001). The highest CV event rate during LA was seen in coronaries followed by peripheral arteries, cerebrovascular events were least common. Greater CV event reduction rates were achieved in patients with isolated Lp(a) elevation (-77%, p < 0.001) and in patients with Lp(a) and LDL-C elevation (-74%, p < 0.001) than in subjects with isolated hypercholesterolemia (-53%, p 0.06). CONCLUSION: This study demonstrates that patients with Lp(a) elevation benefit most from LA treatment. Prospective trials to confirm these data are warranted.


Assuntos
Remoção de Componentes Sanguíneos/métodos , Doenças Cardiovasculares/prevenção & controle , Hiperlipoproteinemias/terapia , Lipoproteína(a)/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Remoção de Componentes Sanguíneos/efeitos adversos , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , LDL-Colesterol/sangue , Feminino , Alemanha , Humanos , Hiperlipoproteinemias/sangue , Hiperlipoproteinemias/complicações , Hiperlipoproteinemias/diagnóstico , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima
10.
Med Hypotheses ; 106: 61-70, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28818274

RESUMO

In this article is given the new insight about the affection of stress on the increase of level of low density lipoproteins (LDL) in the blood, which is connected with the disturbance of hydrodynamics in the bloodstream, the attention was paid to the cylindrical cholesterol plaque, and it's classification. The disturbance of hydrodynamics of blood under the stress leads to the formation of a cylindrical cholesterol plaque, which repeats the contour of the vessel, and leads to the ischemic disorders of the heart and brain. The cylindrical cholesterol plaque goes through several stages of development: friable, yielding, dense, old. In the case of destruction of friable, fresh cholesterol plaque, releases a big quantity of low-density lipoproteins. This leads to the pathological increase of level of LDL in the blood. In the case of long disturbance of hydrodynamics, occurs the formation of strong links between low-density lipoproteins. Yielding cholesterol plaque is formed. Further maturation of cylindrical cholesterol plaque, leads to it's densifying and damage. We may emphasize, that short periods of strong contraction and expansion of vessels lead to the increase of level of LDL in the blood. Self-dependent restoration of normal level of LDL in blood occurs in the case of restoration of pressure in the limits of numbers, which are specific for particular person, and which don't exceed the physiological standard. Among patients with long duration of stress, the duration of vasospasm increases. LDL, without having a possibility to crumble, begin to stick together and form the yielding cylindrical plaque. It is characterized by having of not so strong connection with the vascular wall, and maintains only at the expanse of iteration of the vascular wall, it has cylindrical shape, is elastic and yellow. The thickness and length of walls depends on the degree of cross-clamping during the time of formation of yielding cylindrical plaque. In the case of stopping of spasm, yielding cylindrical plaque can resolve slowly. Among hypotensive and individuals, which have normal pressure, the increase of level of LDL isn't noted. There aren't such investigations, where such link was noted. The increasing of level of LDL among these people (especially under the stress) can say about cases of short-term increase of pressure, which could be unnoticed. These patients require pressure monitoring and, accordingly, the adjustment of the state of stress and anger.


Assuntos
Isquemia Encefálica/sangue , Hiperlipoproteinemias/sangue , Lipoproteínas LDL/sangue , Isquemia Miocárdica/sangue , Isquemia Encefálica/etiologia , Colesterol/sangue , Hemorreologia , Humanos , Hidrodinâmica , Hiperlipoproteinemias/complicações , Modelos Cardiovasculares , Modelos Neurológicos , Isquemia Miocárdica/etiologia , Placa Aterosclerótica/sangue , Placa Aterosclerótica/etiologia , Placa Aterosclerótica/patologia
12.
Clín. investig. arterioscler. (Ed. impr.) ; 29(2): 98-102, mar.-abr. 2017. ilus
Artigo em Espanhol | IBECS | ID: ibc-161021

RESUMO

La lipoproteína (a) [Lp(a)] es una lipoproteína definida por presentar una apolipoproteína específica, la apoA, unida a la apoB-100 por diversos tipos de enlaces químicos, entre ellos un puente disulfuro. A pesar de que su mecanismo aterogénico no es completamente conocido, está demostrada su importancia en el desarrollo de ateroesclerosis prematura, mostrando múltiples estudios su papel como factor de riesgo cardiovascular asociado a enfermedad coronaria e ictus. Presentamos el caso de una paciente con diagnóstico de arteritis de Takayasu en la que se detectó una elevación masiva de Lp(a), y abordamos las implicaciones diagnósticas y terapéuticas que tuvo este hallazgo


Lipoprotein (a) [Lp(a)] is a lipoprotein defined by presenting a specific apolipoprotein, ApoA, linked to the ApoB-100 by different types of chemical bonds, including a disulfide bridge. Despite their atherogenic mechanism is not fully understood, its importance has been demonstrated in the development of premature aterosclerosis. Multiple studies have shown its role as a cardiovascular risk factor associated with heart disease and stroke. We report the case of a patient with a diagnosis of Takayasu arteritis in which a massive elevation of Lp(a) was detected. We emphasize its diagnostic and therapeutic implications


Assuntos
Humanos , Feminino , Adulto , Arterite de Takayasu/complicações , Hiperlipoproteinemias/complicações , Arteriosclerose/diagnóstico , Diagnóstico Diferencial , Hipertensão/complicações
13.
Clin Res Cardiol Suppl ; 12(Suppl 1): 50-54, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28160245

RESUMO

High concentrations of lipoprotein(a) (Lp(a)) represent an important independent and causal risk factor associated with adverse outcome in atherosclerotic cardiovascular disease (CVD). Effective Lp(a) lowering drug treatment is not available. Lipoprotein apheresis (LA) has been proven to prevent cardiovascular events in patients with Lp(a)-hyperlipoproteinemia (Lp(a)-HLP) and progressive CVD. Here we present the course of a male patient with established peripheral arterial occlusive disease (PAOD) at the early age of 41 and coronary artery disease (CAD), who during follow-up developed over 2 years a progressive syndrome of cerebellar and spinal cord deficits against the background of multifactorial cardiovascular risk including positive family history of CVD. Spastic tetraplegia and dependency on wheel chair and nursing care represented the nadir of neurological deficits. All conventional risk factors including LDL-cholesterol had already been treated and after exclusion of other causes, genetically determined Lp(a)-HLP was considered as the major underlying etiologic factor of ischemic vascular disease in this patient including spinal cord ischemia with vascular myelopathy. Treatment with an intensive regimen of chronic LA over 4.5 years now was successful to stabilize PAOD and CAD and led to very impressive neurologic and overall physical rehabilitation and improvement of quality of life.Measurement of Lp(a) concentration must be recommended to assess individual cardiovascular risk. Extracorporeal clearance of Lp(a) by LA should be considered as treatment option for select patients with progressive Lp(a)-associated ischemic syndromes.


Assuntos
Remoção de Componentes Sanguíneos , Hiperlipoproteinemias/terapia , Lipoproteína(a)/sangue , Isquemia do Cordão Espinal/etiologia , Adulto , Biomarcadores/sangue , Doença Crônica , Doença da Artéria Coronariana/etiologia , Avaliação da Deficiência , Progressão da Doença , Humanos , Hiperlipoproteinemias/sangue , Hiperlipoproteinemias/complicações , Hiperlipoproteinemias/diagnóstico , Masculino , Exame Neurológico , Doença Arterial Periférica/etiologia , Qualidade de Vida , Recuperação de Função Fisiológica , Isquemia do Cordão Espinal/diagnóstico , Isquemia do Cordão Espinal/fisiopatologia , Isquemia do Cordão Espinal/reabilitação , Fatores de Tempo , Resultado do Tratamento
14.
Clin Res Cardiol Suppl ; 12(Suppl 1): 22-26, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28233269

RESUMO

General lipoprotein (Lp) (a) screening can help to identify patients at high risk for cardiovascular disease. Non-invasive methods allow early detection of clinically asymptomatic incipient atherosclerotic disease. Medical treatment options are still unsatisfactory. Lp(a) apheresis is an established treatment in Germany for secondary prevention of progressive cardiovascular disease. Statin-based lowering of LDL cholesterol and thrombocyte aggregation inhibitors still represent the basis of medical treatment. Target levels for LDL-cholesterol should be modified in patients with hyperlipoproteinemia (a).


Assuntos
Remoção de Componentes Sanguíneos , Doenças Cardiovasculares/prevenção & controle , Hiperlipoproteinemias/terapia , Hipolipemiantes/uso terapêutico , Lipoproteína(a)/sangue , Prevenção Primária/métodos , Prevenção Secundária/métodos , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , LDL-Colesterol/sangue , Alemanha , Humanos , Hiperlipoproteinemias/sangue , Hiperlipoproteinemias/complicações , Medição de Risco , Fatores de Risco , Resultado do Tratamento
15.
Clin Res Cardiol Suppl ; 12(Suppl 1): 18-21, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28233270

RESUMO

Lipoprotein (a) (Lp (a)) is one risk factor for the development of cardiovascular diseases. Several studies have shown that Lp (a) hyperlipoproteinaemia has a particular influence on the development of coronary heart disease (CHD). A retrospective single-centre observation study was performed to evaluate the effectiveness of lipid apheresis on the basis of consecutively performed percutaneous coronary interventions (PCI) in patients with high Lp (a) values and angiographically documented CHD.In 23 pts (male 18, age 60.04 ± 0.58 years) with angiographically documented CHD (first manifestation 48.00 ± 9.41 years), elevated LDL cholesterol (144.39 ± 92.01 mg/dl) and Lp (a) (133.04 ± 39.68 mg/dl), 49 PCI and 3 coronary artery bypass grafting (CABG) procedures had been performed prior to the initiation of lipid apheresis. Following the initiation of weekly lipid apheresis, LDL cholesterol was 99.43 ± 36.53 mg/dl and Lp (a) 91.13 ± 33.02 mg/dl. In a time interval of 59.87 ± 49.49 months (median 51.00, range 1-153 months) 15 pts did not require an additional PCI. In 8 pts (7 pts 3­vessel disease, 1 pt 2­vessel disease) 14 PCI - no CABG - were performed after 69.38 ± 71.67 months (median: 32.50, range 17-232 months). The incidence of PCI could thus be reduced by 71.43%.


Assuntos
Remoção de Componentes Sanguíneos , Doença das Coronárias/prevenção & controle , Hiperlipoproteinemias/terapia , Lipoproteína(a)/sangue , Prevenção Secundária/métodos , Adulto , Biomarcadores/sangue , LDL-Colesterol/sangue , Doença das Coronárias/sangue , Doença das Coronárias/etiologia , Progressão da Doença , Feminino , Alemanha , Humanos , Hiperlipoproteinemias/sangue , Hiperlipoproteinemias/complicações , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Recidiva , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
16.
J Clin Lipidol ; 10(4): 1045-1049, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27578139

RESUMO

Herein, we describe a 69-year-old Japanese man with massive type III hyperlipoproteinemia (total cholesterol, 855 mg/dL; triglyceride, 753 mg/dL) presenting as a paraneoplastic manifestation of hepatitis B virus-associated hepatocellular carcinoma. The messenger RNA expression of sterol regulatory element-binding protein-2 and proprotein convertase subtilisin/kexin 9 in the tumor tissue was increased by 13-fold and 4-fold, respectively, compared with the non-tumor tissue. Serum level of active form of PCSK9 was 382 ng/mL (reference range: 253 ± 79 ng/mL). The non-tumor tissue had extremely low expression of low-density lipoprotein receptor and low-density lipoprotein receptor-related protein 1. Together, we speculate that marked overexpression of sterol regulatory element-binding protein-2 in the tumor may stimulate the secretion of PCSK9, which inhibits the lipoprotein receptors in the non-tumor tissue, thereby causing paraneoplastic hyperlipoproteinemia.


Assuntos
Carcinoma Hepatocelular/complicações , Hiperlipoproteinemias/complicações , Hiperlipoproteinemias/metabolismo , Neoplasias Hepáticas/complicações , Pró-Proteína Convertase 9/biossíntese , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de LDL/metabolismo
17.
Mol Med Rep ; 14(4): 3832-40, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27572484

RESUMO

Atherosclerosis, as a common arterial disease with high morbidity rate, is reported to be closely associated with adventitia angiogenesis. The present study aimed to investigate the effect of tongxinluo (TXL) on angiogenesis in the carotid adventitia of hyperlipidemic rabbits and the underlying mechanism. A total of 90 experimental rabbits were randomly assigned into the following six groups (n=15 per group): Normal group, model group, low­dose TXL group, moderate-dose TXL group, high­dose TXL group and atorvastatin group. The normal group was fed with a standard diet. The model and treatment groups were on a high cholesterol diet for 4 weeks. The serum lipid level of the model group was significantly higher compared with the normal group. TXL serum lipid level compared with the model group. Hematoxylin and eosin, and CD31 staining demonstrated that TXL inhibited adventitia angiogenesis in a dose­dependent manner. The dihydroethidium probe and fluorescence in situ hybridization results indicated that TXL reduced O2­ level and positive signal of gp91phox and p22phox mRNA in adventitia. Reverse transcription­polymerase chain reaction and western blot analysis determined that TXL treatment significantly downregulated the expression levels of the gp91phox, p22phox genes and the vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor-2 (VEGFR-2) proteins compared with the model group. TXL exhibited a dose­dependent inhibitory effect on angiogenesis in the carotid adventitia of hyperlipidemic rabbits. This may be associated with the downregulation of reactive oxygen species generation in the adventitia and the suppression of VEGF/VEGFR-2 expression.


Assuntos
Túnica Adventícia/irrigação sanguínea , Inibidores da Angiogênese/farmacologia , Artérias Carótidas/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Hiperlipoproteinemias/complicações , Neovascularização Patológica/complicações , Neovascularização Patológica/tratamento farmacológico , Túnica Adventícia/efeitos dos fármacos , Túnica Adventícia/metabolismo , Túnica Adventícia/patologia , Animais , Artérias Carótidas/metabolismo , Artérias Carótidas/patologia , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Hiperlipoproteinemias/sangue , Lipídeos/sangue , Masculino , NADPH Oxidases/análise , NADPH Oxidases/genética , Neovascularização Patológica/sangue , Neovascularização Patológica/metabolismo , Coelhos , Espécies Reativas de Oxigênio/metabolismo , Fator A de Crescimento do Endotélio Vascular/análise , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/análise , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
18.
PLoS One ; 11(8): e0160636, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27505464

RESUMO

Peroxisome proliferator activated receptor gamma (PPARγ) is a pleiotropic ligand activated transcription factor that acts in several tissues to regulate adipocyte differentiation, lipid metabolism, insulin sensitivity and glucose homeostasis. PPARγ also regulates cardiomyocyte homeostasis and by virtue of its obligate role in placental development is required for embryonic survival. To determine the postnatal functions of PPARγ in vivo we studied globally deficient neonatal mice produced by epiblast-restricted elimination of PPARγ. PPARγ-rescued placentas support development of PPARγ-deficient embryos that are viable and born in near normal numbers. However, PPARγ-deficient neonatal mice show severe lipodystrophy, lipemia, hepatic steatosis with focal hepatitis, relative insulin deficiency and diabetes beginning soon after birth and culminating in failure to thrive and neonatal lethality between 4 and 10 days of age. These abnormalities are not observed with selective PPARγ2 deficiency or with deficiency restricted to hepatocytes, skeletal muscle, adipocytes, cardiomyocytes, endothelium or pancreatic beta cells. These observations suggest important but previously unappreciated functions for PPARγ1 in the neonatal period either alone or in combination with PPARγ2 in lipid metabolism, glucose homeostasis and insulin sensitivity.


Assuntos
Diabetes Mellitus/metabolismo , Insulina/sangue , Lipodistrofia/metabolismo , PPAR gama/deficiência , Animais , Animais Recém-Nascidos , Feminino , Camadas Germinativas/metabolismo , Hepatite/complicações , Hepatomegalia/complicações , Homeostase , Hiperlipidemias/complicações , Hiperlipoproteinemias/complicações , Resistência à Insulina , Cetose/complicações , Lipodistrofia/complicações , Camundongos , Necrose , Placenta/metabolismo , Gravidez
19.
Atheroscler Suppl ; 18: 35-40, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25936302

RESUMO

Lipoprotein apheresis (LA) can lower LDL-cholesterol and Lp(a) by 60%-70% and is the final escalating option in patients with hyperlipoproteinemias involving LDL or Lp(a) particles. Major therapeutic effect of LA is preventing cardiovascular events. In Germany since 2008 a reimbursement guideline has been implemented accepting to establish the indication for LA not only for familial or severe forms of hypercholesterolemia but also based on Lp(a)-hyperlipoproteinemia associated with a progressive course of cardiovascular disease, that persists despite effective treatment of other concomitant cardiovascular risk factors. The Pro(a)LiFe-study confirmed with a prospective multicenter design that LA can be regarded as an important therapeutic approach to effectively reduce Lp(a) plasma levels and prevent cardiovascular events in this particular high-risk patient group. Results support that Lp(a) may be a major causal factor for precipitating mechanisms of accelerated progression of cardiovascular disease (CVD). Indication for LA based on measurement of Lp(a) as part of risk assessment is supported by the following conditions: progressive CVD as assessed clinically and with imaging techniques, established maximally tolerated lipid lowering drug treatment, recent cardiovascular events despite efficient drug treatment, out of the ordinary frequency of cardiovascular events, early CVD, or positive family history of early CVD. Still existing difficulties with Lp(a) laboratory measurement require a practical approach to establish the indication for LA considering the 60 mg/dl threshold of German guidelines with selecting an Lp(a) assay which has been calibrated for mass.


Assuntos
Remoção de Componentes Sanguíneos/métodos , Doenças Cardiovasculares/prevenção & controle , Hiperlipoproteinemias/terapia , Lipoproteína(a)/sangue , Biomarcadores/sangue , Doenças Cardiovasculares/etiologia , Progressão da Doença , Alemanha , Humanos , Hiperlipoproteinemias/sangue , Hiperlipoproteinemias/complicações , Hiperlipoproteinemias/diagnóstico , Valor Preditivo dos Testes , Estudos Prospectivos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
20.
Atheroscler Suppl ; 18: 41-4, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25936303

RESUMO

OBJECTIVE: In recent years the Federal Joint Committee (G-BA), a paramount decision-making body of the German health care system challenged the approval of diagnostic and therapeutic procedures for regular reimbursement, including lipoprotein apheresis therapy. Years before an interdisciplinary German apheresis working group, established by members of both German Societies of Nephrology (Verband Deutsche Nierenzentren (VDN), Deutsche Gesellschaft für Nephrologie (DGfN)), initiated a revision of the indication of lipoprotein apheresis therapy according to current guidelines and recommendations for the treatment of lipid disorders. This working group was convinced, that data derived from a registry would support lipoprotein apheresis as a therapy for severe hyperlipidemic patients suffering from progressive cardiovascular diseases. METHODS AND RESULTS: In 2009 the working group established the indication for lipoprotein apheresis with respect to current cardiovascular guidelines and scientific knowledge for the registry, which are in line with the reimbursement guidelines. In 2011 financing by sponsors was secured and an internet-based registry was created. A pilot project with 5 apheresis centers finished in 2012 - since then the registry is available to all German apheresis centers. CONCLUSIONS: There has been consensus between the medical societies and health care carriers regarding the need for a German Lipoprotein Apheresis Registry (GLAR). The launch of this registry complies with requirements of the Federal Joint Committee (G-BA). Complementing the Pro(a)LiFe-Study, first data from GLAR support the safety of the different apheresis treatment procedures. In addition these first data suggest, with respect to the results of Pro(a)LiFe-Study, effectiveness in preventing cardiovascular progression as well. Here, further data are needed to statistically substantiate these early findings.


Assuntos
Remoção de Componentes Sanguíneos/métodos , Hiperlipoproteinemias/terapia , Lipoproteínas/sangue , Sistema de Registros , Biomarcadores/sangue , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Alemanha , Humanos , Hiperlipoproteinemias/sangue , Hiperlipoproteinemias/complicações , Hiperlipoproteinemias/diagnóstico , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
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