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1.
Medicine (Baltimore) ; 100(9): e24962, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33655963

RESUMO

ABSTRACT: Lipoprotein a (Lp (a)) and coronary artery calcification (CAC) are markers of coronary artery and cardiovascular diseases. However, the association between Lp (a) and CAC in asymptomatic individuals remains unclear. In this study, we aimed to determine the influence of Lp (a) on CAC in asymptomatic individuals.We included 2019 asymptomatic Korean adults who underwent testing for a coronary artery calcium score (CACS) and Lp (a) at the Gangnam Severance Hospital Health Checkup Center in Korea from January 2017 to August 2019. Participants were divided into 2 groups: CACS = 0 and CACS > 0. Factors affecting the CACS were analyzed by sex. Because age is a major risk factor for atherosclerosis, ≥45 years in men and ≥55 years in women, we further divided participants into 4 subgroups (≥45 and <45 in men, ≥55 and <55 in women). Factors affecting the CACS in the 4 groups were analyzed.There was a positive correlation between the CACS and traditional cardiovascular risk factors. Lp (a) positively correlated with the CACS in men (P < .01) and remained significant after multivariable logistic regression (P < .01). The same result was observed in men aged ≥45 years (P < .01).Lp (a) is an independently associated factor of CAC and a marker of coronary atherosclerosis in asymptomatic men aged ≥45 years. In asymptomatic men aged ≥45 years, Lp (a) should be measured, and intensive Lp (a)-lowering treatment should be considered.


Assuntos
Doença da Artéria Coronariana/sangue , Vasos Coronários/diagnóstico por imagem , Lipoproteína(a)/sangue , Programas de Rastreamento/métodos , Calcificação Vascular/sangue , Doenças Assintomáticas , Biomarcadores/sangue , Angiografia Coronária , Doença da Artéria Coronariana/epidemiologia , Estudos Transversais , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Calcificação Vascular/epidemiologia
2.
Curr Opin Endocrinol Diabetes Obes ; 28(2): 159-173, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33534258

RESUMO

PURPOSE OF REVIEW: Summarize recent recommendations on clinical management of adults and youth with elevated lipoprotein(a) [Lp(a)] who are at-risk of or affected by cardiovascular disease (CVD). RECENT FINDINGS: There is ample evidence to support elevated Lp(a) levels, present in approximately 20% of the general population, as a causal, independent risk factor for CVD and its role as a significant risk enhancer. Several guidelines and position statements have been published to assist in the identification, treatment and follow-up of adults with elevated levels of Lp(a). There is growing interest in Lp(a) screening and strategies to improve health behaviors starting in youth, although published recommendations for this population are limited. In addition to the well established increased risk of myocardial infarction, stroke and valvular aortic stenosis, data from the coronavirus pandemic suggest adults with elevated Lp(a) may have a particularly high-risk of cardiovascular complications. Lp(a)-specific-lowering therapies are currently in development. Despite their inability to lower Lp(a), use of statins have been shown to improve outcomes in primary and secondary prevention. SUMMARY: Considerable differences exist amongst published guidelines for adults on the use of Lp(a) in clinical practice, and recommendations for youth are limited. With increasing knowledge of Lp(a)'s role in CVD, including recent observations of COVID-19-related risk of cardiovascular complications, more harmonized and comprehensive guidelines for Lp(a) in clinical practice are required. This will facilitate clinical decision-making and help define best practices for identification and management of elevated Lp(a) in adults and youth.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Hiperlipoproteinemias/terapia , Lipoproteína(a)/sangue , Guias de Prática Clínica como Assunto , Adolescente , Adulto , Idade de Início , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/epidemiologia , Estenose da Valva Aórtica/terapia , /complicações , /terapia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Criança , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemias/sangue , Hiperlipoproteinemias/diagnóstico , Hiperlipoproteinemias/epidemiologia , Lipoproteína(a)/fisiologia , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Fatores de Risco , Adulto Jovem
3.
Metabolism ; 116: 154706, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33421505

RESUMO

BACKGROUND: Elevated plasma lipoprotein (a) [Lp(a)] and coronary artery calcification (CAC) are established cardiovascular risk factors that correlate with each other. We hypothesized that other cardiovascular risk factors could affect their relationship. METHODS: We tested for interactions of 24 study variables related to dyslipidemia, diabetes, insulin resistance, hypertension, inflammation and coagulation with baseline Lp(a) on change in CAC volume and density over 9.5 years in 5975 Multi-Ethnic Study of Atherosclerosis (MESA) participants, free of apparent cardiovascular disease at baseline. RESULTS: Elevated Lp(a) was associated with larger absolute increase in CAC volume (3.21 and 4.45 mm3/year higher for Lp(a) ≥30 versus <30 mg/dL, and Lp(a) ≥50 versus <50 mg/dL, respectively), but not relative change in CAC volume. No association was found with change in CAC density when assessing continuous ln-transformed Lp(a). The association between elevated Lp(a) (≥30 mg/dL) and absolute change in CAC volume was greater in participants with higher circulating levels of interleukin-2 soluble receptor α, soluble tumor necrosis factor alpha receptor 1 and fibrinogen (15.33, 11.81 and 7.02 mm3/year in quartile 4, compared to -3.44, -0.59 and 1.91 mm3/year in quartile 1, respectively). No significant interaction was found for other study variables. Similar interactions were seen when assessing Lp(a) levels ≥50 mg/dL. CONCLUSIONS: Elevated Lp(a) was associated with an absolute increase in CAC volume, especially in participants with higher levels of selected markers of inflammation and coagulation. These results suggest Lp(a) as a potential biomarker for CAC volume progression.


Assuntos
Doença da Artéria Coronariana/sangue , Lipoproteína(a)/sangue , Calcificação Vascular/sangue , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/sangue , Aterosclerose/epidemiologia , Aterosclerose/etiologia , Biomarcadores/sangue , Estudos de Casos e Controles , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/etiologia , Vasos Coronários/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Estados Unidos/epidemiologia , Calcificação Vascular/epidemiologia , Calcificação Vascular/etiologia
4.
Diabetes Res Clin Pract ; 171: 108622, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33316308

RESUMO

AIMS: Lipoprotein (a) [Lp(a)] has been considered a determinant of residual cardiovascular risk. We aimed to investigate associations between serum Lp(a) levels and carotid atherosclerosis. METHODS: This cross-sectional study included 662 type 2 diabetic patients without cardiovascular disease. The mean value of three right and left measurements was used to indentify increased carotid intima-media thickness (CIMT). A carotid plaque was defined as a focal wall thickening >50% of the surrounding IMT or its CIMT ≥1.5 mm. The presence of carotid atherosclerosis was defined as having CIMT ≥1.0 mm or carotid plaque. RESULTS: A total of 34.3% of patients had carotid atherosclerosis. The median Lp(a) level was significantly higher in subjects with carotid atherosclerosis (14.6 vs. 10.2 mg/dL, P < 0.001). The log-transformed Lp(a) level per 1-standard deviation increase was significantly associated with higher risk of the presence of carotid atherosclerosis (odds ratio [OR] 1.46; 95% confidence interval [CI] 1.16 - 1.84, P = 0.001) after adjusting other parameters. The log Lp(a) level was still significantly associated with the risk of carotid atherosclerosis in subjects with optimal low-density lipoprotein cholesterol (LDL-C) <100 mg/dL (OR 1.48; 95% CI 1.16 - 1.88, P = 0.001). Higher Lp(a) and LDL-C had an additive effect on the presence of carotid atherosclerosis. CONCLUSION: Elevated Lp(a) was significantly associated with the presence of carotid atherosclerosis in patients with type 2 diabetes, independent of conventional cardiometabolic risk factors.


Assuntos
Doenças Cardiovasculares/diagnóstico , Doenças das Artérias Carótidas/diagnóstico , Diabetes Mellitus Tipo 2/complicações , Lipoproteína(a)/sangue , Doenças Cardiovasculares/sangue , Doenças das Artérias Carótidas/sangue , Espessura Intima-Media Carotídea , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
5.
Stroke ; 51(10): 2972-2982, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32878565

RESUMO

BACKGROUND AND PURPOSE: General population studies have shown that elevated Lp(a) (lipoprotein[a]) levels are an emerging risk factor for cardiovascular disease and subsequent cardiovascular events. The role of Lp(a) for the risk of secondary MACE in patients undergoing carotid endarterectomy (CEA) is unknown. Our objective is to assess the association of elevated Lp(a) levels with the risk of secondary MACE in patients undergoing CEA. METHODS: Lp(a) concentrations were determined in preoperative blood samples of 944 consecutive patients with CEA included in the Athero-Express Biobank Study. During 3-year follow-up, major adverse cardiovascular events (MACE), consisting of myocardial infarction, stroke, and cardiovascular death, were documented. RESULTS: After 3 years follow-up, Kaplan-Meier cumulative event rates for MACE were 15.4% in patients with high Lp(a) levels (>137 nmol/L; >80th cohort percentile) and 10.2% in patients with low Lp(a) levels (≤137 nmol/L; ≤80th cohort percentile; log-rank test: P=0.047). Cox regression analyses adjusted for conventional cardiovascular risk factors revealed a significant association between high Lp(a) levels and 3-year MACE with an adjusted hazard ratio of 1.69 (95% CI, 1.07-2.66). One-third of MACE occurred within 30 days after CEA, with an adjusted hazard ratio for the 30-day risk of MACE of 2.05 (95% CI, 1.01-4.17). Kaplan-Meier curves from time point 30 days to 3 years onward revealed no significant association between high Lp(a) levels and MACE. Lp(a) levels were not associated with histological carotid plaque characteristics. CONCLUSIONS: High Lp(a) levels (>137 nmol/L; >80th cohort percentile) are associated with an increased risk of 30-day MACE after CEA. This identifies elevated Lp(a) levels as a new potential risk factor for secondary cardiovascular events in patients after carotid surgery. Future studies are required to investigate whether Lp(a) levels might be useful in guiding treatment algorithms for carotid intervention.


Assuntos
Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas/efeitos adversos , Lipoproteína(a)/sangue , Infarto do Miocárdio/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estenose das Carótidas/sangue , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Complicações Pós-Operatórias/etiologia , Prognóstico , Risco , Medição de Risco , Acidente Vascular Cerebral/etiologia , Fatores de Tempo
6.
Medicine (Baltimore) ; 99(38): e22037, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957322

RESUMO

To investigate the relationship between serum lipoprotein (a) (LP(a)) levels and breast cancer as well as the clinicopathologic characteristics of breast cancer in a Han Chinese population.This study included 314 breast cancer patients, 51 patients with benign breast tumors, and 185 healthy control subjects. All study subjects were Han Chinese with similar socio-economic backgrounds, who were local residents of Zhoushan, Zhejiang, China or who had lived in Zhoushan for a long period of time. Serum concentrations of LP(a) were determined using a latex-enhanced immunoturbidimetric assay. Clinicopathological characteristics of patients were retrieved from medical records, which included the histopathological type, grade, stage, and molecular subtype of the disease, the expression of estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki67, and the level of reproductive hormones. Correlations between 2 groups were evaluated using the Spearman correlation analysis. Associations among ≥3 groups were interpreted using the Kruskal-Wallis H test or the logistic regression test.Elevated serum LP(a) levels were detected in breast cancer patients compared with healthy control subjects, but no significant differences in LP(a) were detected between breast cancer and benign tumor or between benign tumor and healthy control. In breast cancer patients, serum LP(a) levels were inversely associated with HER2 expression, but they were not significantly correlated with any other clinicopathologic characteristics of breast cancer evaluated in this study.Elevated serum LP(a) levels were associated with breast cancer in a Han Chinese population.


Assuntos
Neoplasias da Mama/etnologia , Grupos Étnicos/estatística & dados numéricos , Hiperlipoproteinemias/etnologia , Lipoproteína(a)/sangue , China/epidemiologia , Feminino , Humanos , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Índice de Gravidade de Doença
7.
Nutr Metab Cardiovasc Dis ; 30(10): 1723-1731, 2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-32636121

RESUMO

AIMS: To investigate the associations between Lp(a), Apo A1, Apo B, and Apo B/Apo A1 ratio with micro- and macrovascular complications of diabetes. METHODS AND RESULTS: In this case-cohort study, 1057 patients with type 2 diabetes (T2DM) were followed in the diabetes clinic of Vali-Asr Hospital from 2014 to 2019. The association between serum Lp (a) and apolipoproteins with cardiovascular disease (CVD), neuropathy, and nephropathy were assessed by using binary regression analysis. The ROC curve analysis was used to evaluate the predictive properties of proteins. Youden index was used to calculate cutoff values. Among patients with T2DM, 242, 231, and 91 patients developed CVD, neuropathy, and nephropathy, respectively. The serum Lp (a) level was positively correlated with the development of all three. (P-values = 0.022, 0.042, and 0.038, respectively). The Apo A1 level was negatively correlated with nephropathy. Among the biomarkers, Lp(a) had the highest AUC for prediction of CVD, neuropathy, and nephropathy. Calculated cutoff values of Lp(a), and Apo A1 levels were higher than the standard cutoff values. CONCLUSION: Serum level of Lp(a) is a predictor for CVD, neuropathy, and nephropathy. Based on the calculated cutoff values in patients with T2DM, we should consider diabetic complications at higher levels of Lp(a).


Assuntos
Apolipoproteína A-I/sangue , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Angiopatias Diabéticas/epidemiologia , Nefropatias Diabéticas/epidemiologia , Neuropatias Diabéticas/epidemiologia , Dislipidemias/sangue , Lipoproteína(a)/sangue , Idoso , Apolipoproteína B-100/sangue , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Angiopatias Diabéticas/diagnóstico , Nefropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/diagnóstico , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Feminino , Humanos , Incidência , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco , Fatores de Risco
8.
Cardiovasc Diabetol ; 19(1): 111, 2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32646432

RESUMO

BACKGROUND: Merging studies have reported the association of lipoprotein(a) [Lp(a)] with poor outcomes of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM). However, the prognostic importance of Lp(a) for recurrent cardiovascular events (CVEs) is currently undetermined in patients with T2DM and prior CVEs. METHODS: From April 2011 to March 2017, we consecutively recruited 2284 T2DM patients with prior CVEs. Patients were categorized into low, medium, and high groups by Lp(a) levels and followed up for recurrent CVEs, including nonfatal acute myocardial infarction, stroke, and cardiovascular mortality. Kaplan-Meier, Cox regression and C-statistic analyses were performed. RESULTS: During 7613 patient-years' follow-up, 153 recurrent CVEs occurred. Lp(a) levels were significantly higher in patients with recurrent CVEs than counterparts (20.44 vs. 14.71 mg/dL, p = 0.002). Kaplan-Meier analysis revealed that the event-free survival rate was dramatically lower in high and medium Lp(a) groups than that in low group irrespective of HBA1c status (< 7.0%; ≥ 7.0%, both p < 0.05). Furthermore, multivariate Cox regression models indicated that Lp(a) was independently associated with high risk of recurrent CVEs [HR(95% CI): 2.049 (1.308-3.212)], such data remains in different HBA1c status (HR(95% CI): < 7.0%, 2.009 (1.051-3.840); ≥ 7.0%, 2.162 (1.148-4.073)). Moreover, the results of C-statistic were significantly improved by 0.029 when added Lp(a) to the Cox model. CONCLUSIONS: Our data, for the first time, confirmed that Lp(a) was an independent predictor for recurrent CVEs in T2DM patients with prior CVEs, suggesting that Lp(a) measurement may help to further risk stratification for T2DM patients after they suffered a first CVE.


Assuntos
Doenças Cardiovasculares/sangue , Diabetes Mellitus Tipo 2/sangue , Lipoproteína(a)/sangue , Idoso , Pequim/epidemiologia , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Causas de Morte , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Prospectivos , Recidiva , Medição de Risco , Fatores de Risco , Fatores de Tempo
9.
Am J Cardiol ; 128: 163-167, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32650914

RESUMO

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are novel drugs that provide striking lowering of low-density lipoprotein cholesterol (LDL-C) when added to maximum tolerated therapy in patients with hypercholesterolemia. Ceramides, novel cardiac risk markers, have been associated with increased cardiovascular mortality, independent of traditional cardiovascular risk factors. The Ceramide Risk Score (CRS) predicts the likelihood of adverse cardiovascular events within 1 to 3 years in patients with coronary artery disease. The effect of PCSK9 inhibition on plasma ceramides is not well known. The study examines the effect of PCSK9 inhibitors on plasma ceramides and CRS in patients with clinical indication for this therapy. Retrospective chart review of consecutive patients with hypercholesterolemia on PCSK9 inhibitors was conducted (n = 24; Mayo Clinic 2015 to 2018). Plasma ceramides were measured before the initiation of PCSK9 inhibitors and 2 to 12 months after treatment. CRS was calculated before and after therapy based on individual plasma concentrations of 4 ceramides. Treatment with PCSK9 inhibitors was associated with significant reduction in mean CRS and individual ceramides levels (p <0.0001). CRS significantly improved with PCSK9 therapy. PCSK9 inhibitors significantly decreased LDL-C levels by 63% (p <0.0001). The absolute reduction in CRS did not correlate with the absolute reduction in LDL-C (r = 0.31; confidence interval -0.10 to 0.64), indicating that CRS may evaluate a different pathway for risk reduction beyond LDL-C lowering. In conclusion, treatment with PCSK9 inhibitors is associated with significant reduction in CRS and distinct ceramide levels.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticolesterolemiantes/uso terapêutico , Ceramidas/sangue , Hipercolesterolemia/tratamento farmacológico , Pró-Proteína Convertase 9/antagonistas & inibidores , 1-Alquil-2-acetilglicerofosfocolina Esterase/sangue , Idoso , Apolipoproteína A-I/sangue , Apolipoproteínas B/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Hipercolesterolemia/sangue , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Lipoproteína(a)/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
10.
Intern Med ; 59(14): 1705-1710, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32669515

RESUMO

Objective Lipoprotein (a), or Lp (a), has been shown to be associated with the development of chronic kidney disease (CKD) in populations of various ethnicities. This study aimed to investigate the association between serum Lp (a) and CKD in Japanese patients. Methods A total of 6,130 subjects who underwent a serum Lp (a) level assessment for any reason (e.g. any type of surgery requiring prolonged bed rest or risk factors for atherosclerosis, such as hypertension or diabetes) were retrospectively investigated at Kanazawa University Hospital from April 2004 to March 2014. Of these, 1,895 subjects were excluded because of the lack of clinical data. Subjects were assessed for Lp (a), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, hypertension, diabetes, smoking, body mass index (BMI), coronary artery disease (CAD), and CKD (stage ≥3). Results When the study subjects were divided into quartiles of Lp (a) levels, significant trends were observed with regard to the presence of CKD (p = 2.7×10-13). A multiple regression analysis showed that Lp (a) was significantly associated with CKD [odds ratio (OR), 1.12; 95% confidence interval (CI), 1.08-1.17; p = 1.3×10-7, per 10 mg/dL], independent of other classical risk factors, including age, gender, BMI, hypertension, diabetes, smoking, LDL cholesterol, and triglycerides. Under these conditions, Lp (a) was significantly associated with CAD (OR = 1.11, 95% CI = 1.06-1.16; p = 1.7×10-6, per 10 mg/dL), independent of other risk factors. Conclusion Serum Lp (a) was associated with CKD, independent of other classical risk factors in a Japanese population.


Assuntos
Hiperlipidemias/complicações , Lipoproteína(a)/sangue , Insuficiência Renal Crônica/etiologia , Adulto , Idoso , Doenças Cardiovasculares/complicações , LDL-Colesterol/sangue , Doença da Artéria Coronariana/sangue , Feminino , Hospitalização , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Razão de Chances , Curva ROC , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Triglicerídeos/sangue
11.
Curr Atheroscler Rep ; 22(9): 48, 2020 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-32710255

RESUMO

PURPOSE OF REVIEW: The COVID-19 pandemic has infected over > 11 million as of today people worldwide and is associated with significant cardiovascular manifestations, particularly in subjects with preexisting comorbidities and cardiovascular risk factors. Recently, a predisposition for arterial and venous thromboses has been reported in COVID-19 infection. We hypothesize that besides conventional risk factors, subjects with elevated lipoprotein(a) (Lp(a)) may have a particularly high risk of developing cardiovascular complications. RECENT FINDINGS: The Lp(a) molecule has the propensity for inhibiting endogenous fibrinolysis through its apolipoprotein(a) component and for enhancing proinflammatory effects such as through its content of oxidized phospholipids. The LPA gene contains an interleukin-6 (IL-6) response element that may induce an acute phase-type increase in Lp(a) levels following a cytokine storm from COVID-19. Thus, subjects with either baseline elevated Lp(a) or those who have an increase following COVID-19 infection, or both, may be at very high risk of developing thromboses. Elevated Lp(a) may also lead to acute destabilization of preexisting but quiescent atherosclerotic plaques, which might induce acute myocardial infarction and stroke. Ongoing studies with IL-6 antagonists may be informative in understanding this relationship, and registries are being initiated to measure Lp(a) in subjects infected with COVID-19. If indeed an association is suggestive of being causal, consideration can be given to systematic testing of Lp(a) and prophylactic systemic anticoagulation in infected inpatients. Therapeutic lipid apheresis and pharmacotherapy for the reduction of Lp(a) levels may minimize thrombogenic potential and proinflammatory effects. We propose studies to test the hypothesis that Lp(a) may contribute to cardiovascular complications of COVID-19.


Assuntos
Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Inflamação/etiologia , Lipoproteína(a)/sangue , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Trombose/etiologia , Proteínas da Fase Aguda/análise , Proteínas da Fase Aguda/genética , Anticoagulantes/uso terapêutico , Apolipoproteína E4/genética , Aterosclerose/etiologia , Betacoronavirus , Biomarcadores/sangue , Pesquisa Biomédica , Remoção de Componentes Sanguíneos , Grupos de Populações Continentais/genética , Infecções por Coronavirus/epidemiologia , Genótipo , Humanos , Inflamação/prevenção & controle , Interleucina-6/antagonistas & inibidores , Interleucina-6/sangue , Lipoproteína(a)/genética , Pandemias , Pneumonia Viral/epidemiologia , Fatores Raciais , Fatores de Risco , Índice de Gravidade de Doença , Trombose/prevenção & controle
12.
Nutr Metab Cardiovasc Dis ; 30(8): 1382-1388, 2020 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-32513581

RESUMO

BACKGROUND AND AIM: Lipid abnormalities are common in peritoneal dialysis (PD) patients and no effective treatment to decrease serum lipoprotein (a) [Lp(a)] in dialysis patients is known so far. Therefore, this research was designed to investigate the effects of soy isoflavone supplement on serum lipids and Lp(a) in PD patients. METHODS & RESULTS: In this randomized, double-blind, placebo-controlled trial, 40 PD patients were randomly assigned to either the isoflavone or the placebo group. The patients in the isoflavone group received 100 mg soy isoflavone daily for 8 weeks, whereas the placebo group received corresponding placebos. At baseline and the end of the 8th week, 7 mL of blood was obtained from each patient and serum triglycerides, total cholesterol, low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), and Lp(a) were measured. Serum Lp(a) reduced significantly up to 10% in the isoflavone group at the end of week 8 compared to baseline (P < 0.05), and the reduction was significant in comparison with the placebo group (P < 0.05). Serum HDL-C increased significantly up to 11.5% in the isoflavone group at the end of week 8 compared to baseline (P = 0.05), and the increment was significant in comparison with the placebo group (P < 0.05). There were no significant differences between the two groups in mean changes of serum triglycerides, total cholesterol, and LDL-C. CONCLUSIONS: This study indicates that daily administration of 100 mg soy isoflavones reduces serum Lp(a) and increases HDL-C concentration which are two determinants of cardiovascular disease in PD patients. CLINICALTRIALS.GOV: NCT03773029. REGISTRATION NUMBER AND DATE: NCT03773029 - 2018.


Assuntos
HDL-Colesterol/sangue , Suplementos Nutricionais , Isoflavonas/administração & dosagem , Nefropatias/terapia , Lipoproteína(a)/sangue , Diálise Peritoneal Ambulatorial Contínua , Soja , Biomarcadores/sangue , Suplementos Nutricionais/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Irã (Geográfico) , Isoflavonas/efeitos adversos , Isoflavonas/isolamento & purificação , Nefropatias/sangue , Nefropatias/diagnóstico , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal Ambulatorial Contínua/efeitos adversos , Soja/química , Fatores de Tempo , Resultado do Tratamento
13.
Prog Cardiovasc Dis ; 63(4): 496-502, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32526213

RESUMO

Calcific aortic valve stenosis (AS) is the most common form of acquired valvular heart disease needing intervention and our understanding of this disease has evolved from one of degenerative calcification to that of an active process driven by the interplay of genetic factors and chronic inflammation modulated by risk factors such as smoking, hypertension and elevated cholesterol. Lipoprotein(a) [Lp (a)] is a cholesterol rich particle secreted by the liver which functions as the major lipoprotein carrier of phosphocholine-containing oxidized phospholipids. Lp(a) levels are largely genetically determined by polymorphisms in the LPA gene. While there is an extensive body of evidence linking Lp(a) to atherosclerotic cardiovascular disease, emerging evidence now suggests a similar association of Lp(a) to calcific AS. In this article, we performed a systematic review of all published literature to assess the association between Lp(a) and calcific aortic valve (AV) disease. In addition, we review the potential mechanisms by which Lp(a) influences the progression of valve disease. Our review identified a total of 21 studies, varying from case-control studies, prospective or retrospective observational cohort studies to Mendelian randomized studies that assessed the association between Lp(a) and calcific AS. All but one of the above studies demonstrated significant association between elevated Lp(a) and calcific AS. We conclude that there is convincing evidence supporting a causal association between elevated Lp(a) and calcific AS. In addition, elevated Lp(a) predicts a faster hemodynamic progression of AS, and increased risk of AV replacement, especially in younger patients. Further research into the clinical utility of Lp(a) as a marker for predicting the incidence, progression, and outcomes of sclerodegenerative AV disease is needed.


Assuntos
Estenose da Valva Aórtica/sangue , Estenose da Valva Aórtica/epidemiologia , Valva Aórtica/patologia , Calcinose/sangue , Calcinose/epidemiologia , Lipoproteína(a)/sangue , Estenose da Valva Aórtica/patologia , Calcinose/patologia , Humanos
14.
Clin Chem ; 66(5): 727-736, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32353129

RESUMO

BACKGROUND: With increased interest in lipoprotein(a) (Lp[a]) concentration as a target for risk reduction and growing clinical evidence of its impact on cardiovascular disease (CVD) risk, rigorous analytical performance specifications (APS) and accuracy targets for Lp(a) are required. We investigated the biological variation (BV) of Lp(a), and 2 other major biomarkers of CVD, apolipoprotein A-I (apoA-I) and apolipoprotein B-100 (apoB), in the European Biological Variation Study population. METHOD: Serum samples were drawn from 91 healthy individuals for 10 consecutive weeks at 6 European laboratories and analyzed in duplicate on a Roche Cobas 8000 c702. Outlier, homogeneity, and trend analysis were performed, followed by CV-ANOVA to determine BV estimates and their 95% CIs. These estimates were used to calculate APS and reference change values. For Lp(a), BV estimates were determined on normalized concentration quintiles. RESULTS: Within-subject BV estimates were significantly different between sexes for Lp(a) and between women aged <50 and >50 years for apoA-I and apoB. Lp(a) APS was constant across concentration quintiles and, overall, lower than APS based on currently published data, whereas results were similar for apoA-I and apoB. CONCLUSION: Using a fully Biological Variation Data Critical Appraisal Checklist (BIVAC)-compliant protocol, our study data confirm BV estimates of Lp(a) listed in the European Federation of Clinical Chemistry and Laboratory Medicine database and reinforce concerns expressed in recent articles regarding the suitability of older APS recommendations for Lp(a) measurements. Given the heterogeneity of Lp(a), more BIVAC-compliant studies on large numbers of individuals of different ethnic groups would be desirable.


Assuntos
Apolipoproteína A-I/sangue , Apolipoproteína B-100/sangue , Variação Biológica Individual , Lipoproteína(a)/sangue , Adulto , Idoso , Apolipoproteína A-I/normas , Apolipoproteína B-100/normas , Feminino , Humanos , Lipoproteína(a)/normas , Masculino , Pessoa de Meia-Idade , Valores de Referência , Adulto Jovem
15.
Vasc Health Risk Manag ; 16: 125-132, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32308405

RESUMO

Background: Risk stratification models with incorporation of biochemical markers have received attention recently. In acute myocardial infarction (AMI) one such marker is lipoprotein(a) (Lp(a)). Lp(a) has prothrombotic and proinflammatory properties. High levels of Lp(a) probably contribute to the additional adverse effects in AMI, as it enhances the damaging effect of acute thrombosis. This study aimed to evaluate serum Lp(a) as a predictor of major adverse cardiovascular events (MACE) in hospitalized-acute myocardial infarction patients. Methods: A prospective cohort study was conducted at Sanglah Hospital, Denpasar, during June-August 2018, among 66 people by consecutive sampling. Samples that met the inclusion and exclusion criteria were examined for serum Lp(a) at the time of admission and the occurrence of MACE during hospitalization was observed. Data regarding serum Lp(a), demography, smoking history, dyslipidemia, hypertension, diabetes mellitus, and MACE were collected. Log rank test and Cox proportional hazards regression were conducted with SPSS version 20 for Windows. Results: During observation, MACE occurred in 25 (38%) patients, including cardiogenic shock in 7 (10.6%) patients, heart failure in 20 (30.3%) patients, cardiovascular death in 5 (7, 6%) patients, malignant arrhythmias in 5 (7.6%) patients, and postinfarction angina in 5 (7.6%) patients. After the Log rank test, a significant difference in survival was observed (p = 0.001) between groups of high Lp(a) (survival rate of 60.6 hours; 95% CI 43.3-77.9) and low Lp(a) (average survival of 104.3 hours, 95% CI 91.4-117.2). The hazard ratio of high Lp(a) against MACE was 4.63 (p=0.002), and it increased to 4.69 in multivariate analysis with Cox proportional hazards regression test (p=0.003). Conclusion: The high level of Lp(a) in AMI patients was a risk factor for the occurrence of MACE during hospitalization. Patients with high Lp(a) also had worse survival compared to patients with low Lp(a).


Assuntos
Pacientes Internados , Lipoproteína(a)/sangue , Infarto do Miocárdio/sangue , Admissão do Paciente , Idoso , Biomarcadores/sangue , Feminino , Humanos , Indonésia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/terapia , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Regulação para Cima
16.
Prog Cardiovasc Dis ; 63(3): 219-227, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32277995

RESUMO

Elevated circulating concentrations of lipoprotein(a) [Lp(a)] is strongly associated with increased risk of atherosclerotic cardiovascular disease (CVD) and degenerative aortic stenosis. This relationship was first observed in prospective observational studies, and the causal relationship was confirmed in genetic studies. Everybody should have their Lp(a) concentration measured once in their lifetime. CVD risk is elevated when Lp(a) concentrations are high i.e. > 50 mg/dL (≥100 mmol/L). Extremely high Lp(a) levels >180 mg/dL (≥430 mmol/L) are associated with CVD risk similar to that conferred by familial hypercholesterolemia. Elevated Lp(a) level was previously treated with niacin, which exerts a potent Lp(a)-lowering effect. However, niacin is currently not recommended because, despite the improvement in lipid profile, no improvements on clinical outcomes have been observed. Furthermore, niacin use has been associated with severe adverse effects. Post hoc analyses of clinical trials with proprotein convertase subtilisin/kexin type-9 (PCSK9) inhibitors have shown that these drugs exert clinical benefits by lowering Lp(a), independent of their potent reduction of low-density lipoprotein cholesterol (LDL-C). It is not yet known whether PCSK9 inhibitors will be of clinical use in patients with elevated Lp(a). Apheresis is a very effective approach to Lp(a) reduction, which reduces CVD risk but is invasive and time-consuming and is thus reserved for patients with very high Lp(a) levels and progressive CVD. Studies are ongoing on the practical application of genetic approaches to therapy, including antisense oligonucleotides against apolipoprotein(a) and small interfering RNA (siRNA) technology, to reduce the synthesis of Lp(a).


Assuntos
Estenose da Valva Aórtica/sangue , Valva Aórtica/patologia , Artérias/metabolismo , Aterosclerose/sangue , Calcinose/sangue , Lipoproteína(a)/sangue , Placa Aterosclerótica , Animais , Estenose da Valva Aórtica/epidemiologia , Estenose da Valva Aórtica/patologia , Estenose da Valva Aórtica/terapia , Artérias/patologia , Aterosclerose/epidemiologia , Aterosclerose/patologia , Aterosclerose/terapia , Biomarcadores/sangue , Calcinose/epidemiologia , Calcinose/patologia , Calcinose/terapia , Humanos , Lipoproteína(a)/química , Prognóstico , Fatores de Risco , Regulação para Cima
17.
Zh Nevrol Psikhiatr Im S S Korsakova ; 120(3. Vyp. 2): 42-48, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32307429

RESUMO

INTRODUCTION: Lipoprotein(a) [Lp(a)] is a genetically determined risk factor of coronary heart disease and its complications. Meanwhile data about the role of Lp(a) in development of ischemic stroke are controversial. AIM: To investigate the association of Lp(a) with atherothrombotic ischemic stroke and stenotic (≥50%) atherosclerosis of carotid arteries. MATERIAL AND METHODS: The study included 490 patients (mean age 60 years, 53% male). The first group comprised 157 patients with ischemic stroke, the second group 68 patients with isolated stenotic atherosclerosis of carotid arteries, but without significant lesion of coronary and low limbs arteries. The control group included 265 patients without stroke, myocardial infarction, stenotic atherosclerosis of coronary, carotid and low limbs arteries according to instrumental examinations. The levels of Lp(a) and lipids were measured in blood serum of all patients. RESULTS: Lp(a) concentration was significantly higher in patients of the first and second groups in comparison with the control group (median [interquartile range]): 24 [9; 48], 20 [8; 55] vs 13 [5; 27] mg/dl, respectively (p<0,05 in both cases). Hyperlipoproteinemia(a) (Lp(a) ≥30 mg/dl) was more frequent in the group with stroke, stenotic atherosclerosis of carotid arteries, than in the control group: 43%, 40% vs 22% (p<0.01 in all cases). In patients with hyperlipoproteinemia(a), odds ratio (OR) for ischemic stroke was 2.7 (95% confidence interval (CI) 1.7-4.1), and OR for stenotic atherosclerosis of carotid arteries was 2.3 (95% CI 1.3-4.0) compared to the patients with Lp(a) level <30 mg/dl (p<0.01 in both cases). In logistic regression analysis adjusted for age, sex, hypertension, type 2 diabetes, smoking and Lp(a) concentration, the hyperlipoproteinemia(a) was associated with ischemic stroke and isolated stenotic carotid atherosclerosis. In the group with severe carotid atherosclerosis, 16 patients (24%) had ischemic stroke. Lp(a) concentration in these patients was higher 36 [20; 59] mg/dl, than in the patients with isolated carotid atherosclerosis without stroke 15 [7; 54] mg/dl (p=0.04). Other risk factors of atherosclerosis did not differ in patients with or without ischemic stroke. CONCLUSION: The study shows the association of elevated level of Lp(a) with ischemic stroke and isolated stenotic atherosclerosis of carotid arteries. In the presence of isolated stenotic carotid atherosclerosis, the median of Lp(a) concentration was significantly higher in patients with ischemic stroke than in patients without stroke.


Assuntos
Isquemia Encefálica/sangue , Doenças das Artérias Carótidas/sangue , Lipoproteína(a)/sangue , Acidente Vascular Cerebral/sangue , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Hipertensão/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco
19.
Am J Cardiol ; 126: 94-102, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32336532

RESUMO

Lipoprotein (a) [Lp(a)] is a low-density, cholesterol-containing lipoprotein that differs from other low-density lipoproteins due to the presence of apolipoprotein(a) bound to its surface apolipoprotein B100. Multiple epidemiologic studies, including Mendelian Randomization studies, have demonstrated that increasing Lp(a) levels are associated with increased risk of heart disease, including atherosclerotic cardiovascular disease and calcific aortic stenosis. The risk associated with elevations in Lp(a) appears to be independent of other lipid markers. While the current treatment options for elevated Lp(a) are limited, promising new therapies are under development, leading to renewed interest in Lp(a). This review provides an overview of the biology and epidemiology of Lp(a), available outcome studies, and insights into future therapies.


Assuntos
Doenças Cardiovasculares/sangue , Lipoproteína(a)/sangue , Biomarcadores/sangue , Remoção de Componentes Sanguíneos , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus/sangue , Predisposição Genética para Doença , Humanos , Lipoproteína(a)/genética , Oligonucleotídeos Antissenso/uso terapêutico , Doença Arterial Periférica/sangue , Prevenção Primária , Medição de Risco , Prevenção Secundária , Acidente Vascular Cerebral/sangue
20.
Rev Cardiovasc Med ; 21(1): 147-153, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32259914

RESUMO

The purpose of this study is to investigate the effect of lipoprotein(a) level on long-range prognosis after Percutaneous Coronary Intervention (PCI) in patients with low-density lipoprotein cholesterol (LDL-C) goal attainment. In this retrospective study, 350 patients in Coronary artery disease (CAD) with LDL-C less than 1.8 mmol/L were enrolled in the Guangdong Institute of Cardiovascular Diseases from January 2011 to December 2013. Follow-up was 1 year after PCI. According to the median value of the study population based on Lp(a), the patients were assigned to the high-level group and low-level group. The clinical data of the 2 groups were collected. We compared the baseline data between the 2 groups and the incidence rate of major cardiovascular events. After statistical analysis, the gender composition, hypertension, diabetes, and age of the patients between the 2 groups were similar, and the distinction was not significant. There was no significant distinction in cardio-vascular death, ischemic stroke, and recurrent myocardial infarction between the 2 groups, but the incidence of revascularization was higher in the high-level group (P < 0.05). High Lp(a) level predicts an increased incidence of revascularization of patients in CAD with LDL-C less than 1.8 mmol/L after PCI.


Assuntos
LDL-Colesterol/sangue , Doença da Artéria Coronariana/terapia , Lipoproteína(a)/sangue , Intervenção Coronária Percutânea , Idoso , Biomarcadores/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
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