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1.
N Engl J Med ; 382(3): 244-255, 2020 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-31893580

RESUMO

BACKGROUND: Lipoprotein(a) levels are genetically determined and, when elevated, are a risk factor for cardiovascular disease and aortic stenosis. There are no approved pharmacologic therapies to lower lipoprotein(a) levels. METHODS: We conducted a randomized, double-blind, placebo-controlled, dose-ranging trial involving 286 patients with established cardiovascular disease and screening lipoprotein(a) levels of at least 60 mg per deciliter (150 nmol per liter). Patients received the hepatocyte-directed antisense oligonucleotide AKCEA-APO(a)-LRx, referred to here as APO(a)-LRx (20, 40, or 60 mg every 4 weeks; 20 mg every 2 weeks; or 20 mg every week), or saline placebo subcutaneously for 6 to 12 months. The lipoprotein(a) level was measured with an isoform-independent assay. The primary end point was the percent change in lipoprotein(a) level from baseline to month 6 of exposure (week 25 in the groups that received monthly doses and week 27 in the groups that received more frequent doses). RESULTS: The median baseline lipoprotein(a) levels in the six groups ranged from 204.5 to 246.6 nmol per liter. Administration of APO(a)-LRx resulted in dose-dependent decreases in lipoprotein(a) levels, with mean percent decreases of 35% at a dose of 20 mg every 4 weeks, 56% at 40 mg every 4 weeks, 58% at 20 mg every 2 weeks, 72% at 60 mg every 4 weeks, and 80% at 20 mg every week, as compared with 6% with placebo (P values for the comparison with placebo ranged from 0.003 to <0.001). There were no significant differences between any APO(a)-LRx dose and placebo with respect to platelet counts, liver and renal measures, or influenza-like symptoms. The most common adverse events were injection-site reactions. CONCLUSIONS: APO(a)-LRx reduced lipoprotein(a) levels in a dose-dependent manner in patients who had elevated lipoprotein(a) levels and established cardiovascular disease. (Funded by Akcea Therapeutics; ClinicalTrials.gov number, NCT03070782.).


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Hipolipemiantes/administração & dosagem , Lipoproteína(a)/sangue , Oligonucleotídeos/administração & dosagem , Adulto , Idoso , Doenças Cardiovasculares/sangue , Colesterol/sangue , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipolipemiantes/efeitos adversos , Hipolipemiantes/uso terapêutico , Análise dos Mínimos Quadrados , Masculino , Pessoa de Meia-Idade , Oligonucleotídeos/efeitos adversos , Fatores de Risco
2.
Angiology ; 71(2): 160-166, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31722547

RESUMO

Little is known about the association between lipoprotein(a) [Lp(a)] levels and future ischemic cardiovascular events in patients with premature acute coronary syndrome (ACS). A total of 1464 consecutive patients who underwent coronary angiography for premature ACS (males <45 years and females <55 years) were enrolled in this study. Patients were divided into quartiles according to serum Lp(a) levels (Q1: ≤11.1 nmol/L; Q2: 11.1-27.7 nmol/L; Q3: 27.7-79.3 nmol/L; and Q4: >79.3 nmol/L). Major adverse cardiovascular events (MACEs) increased with Lp(a) quartiles after 2-year follow-up (among quartiles, respectively; P = .001). Kaplan-Meier curves revealed significant differences in event-free survival rates among Lp(a) quartile groups (P = .001). Multivariate Cox proportional hazards regression analysis indicated that serum Lp(a) level was an independent predictor of MACE either as a continuous variable (hazard ratio [HR]: 1.002, 95% confidence interval [CI]: 1.001-1.004; P = .009) or as a categorical variable (HR: 1.443, 95% CI: 1.074-1.937; P = .015). Furthermore, Lp(a) levels (as a variable) significantly improved the prognostic value for MACE. These findings suggest that Lp(a) measurement has value for cardiovascular risk stratification in patients with premature ACS.


Assuntos
Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico por imagem , Angiografia Coronária , Lipoproteína(a)/sangue , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
3.
Biomed Res Int ; 2019: 4834202, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31637257

RESUMO

Coronary artery spasm (CAS) is one of the mechanisms of angina pectoris. Unlike the diagnosis of acute myocardial infarction which is based on the elevation of cardiac markers, the diagnosis of CAS is difficult and sometimes requires sophisticated and risky provocative test which is not widely accepted in China. There is no well-established biomarker for the diagnosis or prediction of CAS. However, there are some biomarkers proven to be associated with the occurrence of CAS. For example, inflammatory factors including C-reactive protein and cytokines, lipoprotein (a), and cystatin-C might be precipitating factor for CAS. Rho-kinase as a mediator involved in multiple mechanisms of CAS, serotonin, and endothelin-1 as powerful vasoconstrictors leading to vasospasm were all observed being elevated in patients with CAS. Thioredoxin and nitrotyrosine reflected the oxidative status and could be observed to be elevated after the occurrence of CAS. In some cases doubted to be CAS without the evidence of provocative test, the blood test for the biomarkers mentioned above could be useful for the diagnosis of CAS.


Assuntos
Angina Pectoris/sangue , Biomarcadores/sangue , Vasoespasmo Coronário/sangue , Infarto do Miocárdio/sangue , Acetilcolina/sangue , Proteína C-Reativa/metabolismo , China , Vasoespasmo Coronário/patologia , Vasos Coronários/patologia , Cistatina C/sangue , Citocinas/sangue , Humanos , Lipoproteína(a)/sangue
4.
Nutr Metab Cardiovasc Dis ; 29(11): 1168-1175, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31582198

RESUMO

BACKGROUND AND AIM: Although some earlier studies have indicated the effect of phytosterol (PS) supplementation on serum lipoprotein(a) (Lp(a)) and free fatty acid (FFA) concentration, findings are still conflicting. We aimed to assess the impact of PS supplementation on serum Lp(a) and FFA concentration through a systematic review and meta-analysis of available RCTs. METHODS AND RESULTS: We performed a systematic search of all available RCTs conducted up to 21 February 2019 in the following databases: PubMed, Scopus, and Cochrane. The choice of fixed- or random-effect model for analysis was determined according to the I2 statistic. Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence interval (CI). Pooling of 12 effect sizes from seven articles revealed a significant reduction of Lp(a) levels following PS supplementation (MD: -0.025 mg/dl, 95% CI: -0.045, -0.004, p = 0.017) without significant heterogeneity among the studies (I2 = 0.0%, p = 0.599). Also, PS supplementation significantly lowered FFA (MD: -0.138 mg/dl, 95% CI: -0.195, -0.081, p = 0.000) without significant heterogeneity among the studies (I2 = 0.0%, p = 0.911). The results for meta-regression and sensitivity analysis were not significant. CONCLUSION: The meta-analysis suggests that oral PS supplementation could cause a significant reduction in serum Lp(a) and FFA.


Assuntos
Suplementos Nutricionais , Dislipidemias/tratamento farmacológico , Ácidos Graxos não Esterificados/sangue , Hipolipemiantes/uso terapêutico , Lipoproteína(a)/sangue , Fitosteróis/uso terapêutico , Adulto , Biomarcadores/sangue , Suplementos Nutricionais/efeitos adversos , Regulação para Baixo , Dislipidemias/sangue , Dislipidemias/diagnóstico , Feminino , Humanos , Hipolipemiantes/efeitos adversos , Masculino , Pessoa de Meia-Idade , Fitosteróis/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
5.
Rev Port Cardiol ; 38(7): 485-493, 2019 07.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31530423

RESUMO

INTRODUCTION AND OBJECTIVE: Lipoprotein(a) [Lp(a)] is an independent cardiovascular risk factor but is closely associated with other similar risk factors that are manageable with appropriate treatment and guidance. We aimed to study the impact of using combined therapy for managing Lp(a) levels in patients at high cardiovascular risk but without major adverse cardiovascular events, in primary prevention. METHODS: We conducted a retrospective observational study in 516 patients randomly selected from a group of 1677 patients who attended cardiovascular risk and metabolism consultations between 1995 and 2015. The disorders observed and therapies used were classified into nosological and pharmacological groups, respectively. Cardiovascular risk was calculated based on the Framingham risk score, the European Society of Cardiology's SCORE and the American College of Cardiology's ASCVD Risk Estimator, and changes in patients' lifestyle were assessed. RESULTS: Significant differences (p<0.001) were found in almost all metabolic variables, except fasting insulin and C-peptide. Lp(a) levels were also significantly reduced (p<0.001). Carotid intima-media thickness improved, decreasing from 2.90 mm to 1.40 mm; however, there was no reduction in the number of cases of vascular stenosis. Of patients with hepatic steatosis (85.5%), 40.7% presented hepatomegaly, but liver function was only altered in a few patients (14.5%). Lipid-lowering therapy, especially statins, significantly decreased Lp(a), benefiting from synergy with other treatments. CONCLUSIONS: Lp(a) is a key overall indicator of vascular risk and should be considered a therapeutic target. Besides a healthy lifestyle, primary prevention should include combined drug therapies to address all cardiovascular risk factors and to delay the atherosclerotic process.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Hipolipemiantes/uso terapêutico , Lipoproteína(a)/sangue , Prevenção Primária/métodos , Adulto , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
6.
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
7.
Ren Fail ; 41(1): 800-807, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31498021

RESUMO

Background: This retrospective study investigated whether baseline serum lipoprotein(a) (Lp(a)) may predict subsequent stroke in patients under chronic peritoneal dialysis (PD). Methods: Eight hundred and sixty incident PD patients, treated from 1 November 2005 to 28 February 2017, were enrolled, and followed until discontinuation of PD, death, or 31 May 2017. Hemorrhagic or ischemic stroke was the primary outcome. The population was stratified by baseline serum Lp(a) tertile. The risk of each stroke subtype was analyzed using the Cox proportional hazard models. Adjustments were made for: age; gender; history of stroke and hypertension; systolic blood pressure; lipid-lowering, antiplatelet and antihypertensive medications; laboratory profiles including hemoglobin, serum albumin, calcium, triglyceride, total and low-density lipoprotein cholesterol; and apolipoprotein A1. Results: Among the 860 participants, 19.3% and 4.1% had diabetes mellitus and a history of stroke, respectively. The median baseline serum Lp(a) was 328 (172-585) mg/L. After 28 (14-41) months of follow-up, 33 (3.84%) and 12 (1.40%) patients developed hemorrhagic and ischemic stroke, respectively. Participants in the highest Lp(a) tertile had a significantly lower risk of hemorrhagic stroke compared with those in the lowest tertile (hazard ratio (HR) 0.3, 95% confidence interval (CI) 0.1-0.86; p = .026); the rates of ischemic stroke were comparable among the tertiles. Each 10 mg/L rise in serum Lp(a) was associated with a 2% (95% CI 0.96-1; p = .033) lower risk of hemorrhagic stroke. Conclusions: Among patients with incident PD, a higher serum Lp(a) level may predict a lower risk of hemorrhagic stroke.


Assuntos
Hemorragia Cerebral/epidemiologia , Falência Renal Crônica/sangue , Lipoproteína(a)/sangue , Diálise Peritoneal/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Adulto , Idoso , Hemorragia Cerebral/etiologia , China , Feminino , Seguimentos , Humanos , Incidência , Falência Renal Crônica/terapia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Acidente Vascular Cerebral/etiologia
8.
Clin Cardiol ; 42(10): 988-994, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31436336

RESUMO

BACKGROUND: Previous studies have observed that high level of lipoprotein (a) [Lp(a)] was common in the phenotypic familial hypercholesterolemia (FH) and may explain part of the clinical diagnosis of FH. HYPOTHESIS: We aim to develop a modified model including Lp(a) and compare its diagnostic performance with Dutch Lipid Clinic Network (DLCN) criteria. METHODS: Data of 10 449 individuals were utilized for the model establishment (7806 for derivation and 2643 for validation) from January 2011 to March 2018. The novel score model was modified on the basis of DLCN. Furthermore, 718 patients were screened for LDLR, APOB, and PCSK9 gene mutations. RESULTS: The novel modified model consisted of untreated low-density lipoprotein cholesterol (LDL-C) level, Lp(a), personal premature coronary heart disease (CHD), tendon xanthomas and family history of CHD and/or hypercholesterolemia. It has shown high discrimination (area under curve [AUC] 0.991, 95% confidence interval [CI[ 0.988-0.994, P < .001) for distinguishing clinical FH from non-FH diagnosed using DLCN. Furthermore, a concordance analysis was performed to compare the modified model with DLCN and it showed a good agreement with DLCN (κ = 0.765). External validation of the novel model also showed good accordance (κ = 0.700). Further genetic analysis showed that the agreements between the new model and mutation improved a little compared to that between DLCN and mutation. CONCLUSIONS: The novel modified model, including Lp(a), could provide new insights into FH diagnosis in Chinese population with more concerns on the patients with high level of Lp(a).


Assuntos
Algoritmos , Hiperlipoproteinemia Tipo II/diagnóstico , Lipoproteína(a)/sangue , Biomarcadores/sangue , China/epidemiologia , Feminino , Seguimentos , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
9.
Biomed Environ Sci ; 32(7): 477-485, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31331432

RESUMO

OBJECTIVE: The association between lipoprotein (a) [Lp(a)] levels and metabolic syndrome (MetS) remains uncertain, especially in the Asian population. The purpose of this study was to demonstrate the association between Lp(a) levels and MetS in a middle-aged and elderly Chinese cohort. METHODS: A cross-sectional study of 10,336 Chinese adults aged 40 years or older was conducted in Jiading District, Shanghai, China. Logistic regression analysis was used to evaluate the association between serum Lp(a) levels and MetS. RESULTS: In the overall population, 37.5% of participants had MetS. Compared with individuals in the lowest quartile of serum Lp(a) levels, those in the highest quartile had a lower prevalence of MetS (30.9% vs. 46.9%, P for trend < 0.0001). Multivariate logistic regression analyses showed that compared with participants in the bottom quartile of serum Lp(a) levels, those in the top quartile had decreased odds ratio (OR) for prevalent MetS [multivariate-adjusted OR 0.45 (95% confidence interval 0.39-0.51); P < 0.0001]. Additionally, Lp(a) level was conversely associated with the risk of central obesity, high fasting glucose, high triglycerides, and low HDL cholesterol, but not with hypertension. Stratified analyses suggested that increasing levels of Lp(a) was associated with decreased risk of MetS in all the subgroups. CONCLUSION: Serum Lp(a) level was inversely associated with the risk of prevalent MetS in a middle-aged and elderly Chinese cohort.


Assuntos
Lipoproteína(a)/sangue , Síndrome Metabólica/sangue , Idoso , Grupo com Ancestrais do Continente Asiático , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade
10.
Lipids Health Dis ; 18(1): 150, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31286992

RESUMO

BACKGROUND: Elevated lipoprotein (a) is recognized as a risk factor for incident cardiovascular events in the general population and established cardiovascular disease patients. However, there are conflicting findings on the prognostic utility of elevated lipoprotein (a) level in patients with coronary artery disease (CAD).Thus, we performed a meta-analysis to evaluate the prognostic value of elevated lipoprotein (a) level in CAD patients. METHODS AND RESULTS: A systematic literature search of PubMed and Embase databases was conducted until April 16, 2019. Observational studies reporting the prognostic value of elevated lipoprotein (a) level for cardiac events (cardiac death and acute coronary syndrome), cardiovascular events (death, stroke, acute coronary syndrome or coronary revascularisation), cardiovascular death, and all-cause mortality in CAD patients were included. Pooled multivariable adjusted risk ratio (RR) and 95% confidence interval (CI) for the highest vs. the lowest lipoprotein (a) level were utilized to calculate the prognostic value. Seventeen studies enrolling 283,328 patients were identified. Meta-analysis indicated that elevated lipoprotein (a) level was independently associated with an increased risk of cardiac events (RR 1.78; 95% CI 1.31-2.42) and cardiovascular events (RR 1.29; 95% CI 1.17-1.42) in CAD patients. However, elevated lipoprotein (a) level was not significantly associated with an increased risk of cardiovascular mortality (RR 1.43; 95% CI 0.94-2.18) and all-cause mortality (RR 1.35; 95% CI 0.93-1.95). CONCLUSIONS: Elevated lipoprotein (a) level is an independent predictor of cardiac and cardiovascular events in CAD patients. Measurement of lipoprotein (a) level has potential to improve the risk stratification among patients with CAD.


Assuntos
Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/mortalidade , Lipoproteína(a)/sangue , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/etiologia , Doença da Artéria Coronariana/complicações , Humanos , Prognóstico , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/etiologia
11.
Heart Lung Circ ; 28(7): 1009-1017, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31178022

RESUMO

BACKGROUND: Although lipoprotein(a) (Lp(a)) has been regarded as an independent risk factor for atherosclerotic cardiovascular disease (ASCVD), its predictive role in outcomes in stable coronary artery disease (CAD) has been undetermined. The aim of the present study was to investigate the relations of Lp(a) to the coronary severity and events in Chinese patients with angiography-proven stable CAD. METHODS: A total of 3,278 patients with stable CAD were consecutively enrolled and the coronary severity was evaluated by the Gensini Score (GS) system. Patients were divided into two groups according to the median of GS: high GS group (n=1,585) and low GS group (n=1,693). The associations of continuous Lp(a), Lp(a) ≥300mg/L, and tertiles of Lp(a) with GS and events were respectively evaluated. RESULTS: Patients in the high GS group had significantly higher concentrations of Lp(a). In addition, the multivariate Cox regression analysis indicated that elevated Lp(a) (odds ratio: 1.164, 95% confidence interval: 1.005-1.349), Lp(a) ≥300mg/L (odds ratio: 1.200, 95% confidence interval: 1.028-1.401), and the highest tertile of Lp(a) (odds ratio: 1.205, 95% confidence interval: 1.010-1.438) were statistically associated with GS after adjusted for potential confounders. However, although 215 (6.56%) events were established during a median of follow-up over 10,170 patient-years, no relationship between Lp(a) and events was found. CONCLUSIONS: In this Chinese cohort study on stable CAD with moderate sample size and follow-up duration, data showed that Lp(a) was significantly associated with the coronary severity while not with cardiovascular events, similar to several studies, suggesting that further study is needed regarding the role of Lp(a) in ASCVD.


Assuntos
Doença da Artéria Coronariana/sangue , Lipoproteína(a)/sangue , Índice de Gravidade de Doença , Idoso , China/epidemiologia , Doença da Artéria Coronariana/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade
12.
J Diabetes Res ; 2019: 9583286, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31089476

RESUMO

Both obstructive sleep apnea (OSA) and decreased serum lipoprotein(a) (Lp(a)) concentrations are associated with insulin resistance. However, their interaction effect on insulin resistance has never been investigated. Therefore, we performed a cross-sectional study on OSA-suspected Chinese Han participants. Laboratory-based polysomnographic variables, biochemical indicators, anthropometric measurements, and medical history were collected. Linear regression and binary logistic regression analyses with interaction terms were used to investigate the potential effects of the interaction between the severity of OSA (assessed by the apnea-hypopnea index (AHI)) and Lp(a) concentrations on insulin resistance (assessed by the homeostasis model assessment of insulin resistance (HOMA-IR)), after adjusting for potential confounders including age, gender, body mass index, waist-to-hip circumference ratio, mean arterial pressure, smoking status, drinking status, and lipid profiles. A total of 4,152 participants were enrolled. In the OSA-suspected population, AHI positively correlated with insulin resistance and serum Lp(a) concentrations independently and inversely correlated with insulin resistance. In addition, the interaction analysis showed that the linear association between lgAHI and lgHOMA-IR was much steeper and more significant in subjects with relatively low Lp(a) concentrations, suggesting a significant positive interaction between lgLp(a) and lgAHI on lgHOMA-IR (P = 0.013). Furthermore, the interaction on a multiplicative scale also demonstrated a significant positive interaction (P = 0.044). A stronger association between AHI quartiles and the presence of insulin resistance (defined as HOMA-IR > 3) could be observed for participants within lower Lp(a) quartiles. In conclusion, a significant positive interaction was observed between OSA and decreased Lp(a) with respect to insulin resistance. This association might be relevant to the assessment of metabolic or cardiovascular disease risk in OSA patients.


Assuntos
Resistência à Insulina/fisiologia , Lipoproteína(a)/sangue , Apneia Obstrutiva do Sono/sangue , Adulto , Glicemia/metabolismo , Índice de Massa Corporal , Doenças Cardiovasculares , China , Estudos de Coortes , Estudos Transversais , Feminino , Homeostase , Humanos , Resistência à Insulina/etnologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Polissonografia , Análise de Regressão , Risco , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/etnologia , Fumar
13.
J Assist Reprod Genet ; 36(6): 1091-1099, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31079266

RESUMO

PURPOSE: Proprotein convertase subtilisin/kexin type 9 (PCSK9) and lipoprotein (a) (Lp[a]) levels are associated with cardiovascular risk. To investigate PCSK9 and Lp(a) levels of children born after assisted reproduction technologies (ART) compared with naturally conceived (NC) controls. METHODS: In this exposure-matched cohort study, 73 racial-, sex-, and age-matched children (mean age 98 ± 35 months) of ART (intracytoplasmic sperm injection [ICSI] n = 33, classic in vitro fertilization [IVF] n = 40) and 73 NC children were assessed. Blood lipid profile, including PCSK9 and Lp(a) levels, was measured. Children were grouped according to age (< 8 years, 8-10 years, ≥ 10 years). RESULTS: In the overall population, PCSK9 levels were related to total cholesterol, low-density lipoprotein, and systolic blood pressure, while Lp(a) levels were related to age, apolipoprotein-B, birth weight, height, waist-to-hip ratio, insulin resistance, insulin, and high-sensitivity C-reactive protein. No significant differences were observed regarding lipid biomarkers between ART and NC children. However, a significant interaction was found between age groups and conception method (p < 0.001) showing that PCSK9 levels increase with age in ART children, while they decline with age in NC offspring. IVF children showed higher levels of adjusted mean Lp(a) than ICSI (13.5 vs. 6.8 mg/dl, p = 0.010) and NC children (12.3 vs. 8.3 mg/dl, p = 0.048). CONCLUSIONS: We show that PCSK9 levels increase with age in ART children, indicating a gradual deterioration of lipidemic profile that could lead to increased cardiovascular risk. Moreover, our results indicate that ART method may be of importance given that classic IVF is associated with higher levels of Lp(a).


Assuntos
Doenças Cardiovasculares/sangue , Lipoproteína(a)/sangue , Pró-Proteína Convertase 9/sangue , Técnicas de Reprodução Assistida/efeitos adversos , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/patologia , Criança , Pré-Escolar , Feminino , Fertilização In Vitro/efeitos adversos , Humanos , Resistência à Insulina/genética , Masculino , Fatores de Risco , Injeções de Esperma Intracitoplásmicas/efeitos adversos
14.
J Atheroscler Thromb ; 26(7): 583-591, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31061262

RESUMO

Lipoprotein(a) [Lp(a)], discovered in 1963, has been associated with atherosclerotic cardiovascular disease (ASCVD) independent of other traditional risk factors, including LDL cholesterol. Lp(a) is an apolipoprotein B (apoB)-containing lipoprotein, which contains an LDL-like particle. Unlike LDL, which is a primary therapeutic target to decrease ASCVD, current guidelines recommend measuring Lp(a) for risk assessments because there is no clear evidence demonstrating the clinical benefit of decreasing Lp(a) using classical drugs such as niacin. However, recent Mendelian randomization studies indicate that Lp(a) causally correlates with ASCVD. In addition, novel drugs, including PCSK9 inhibitors, as well as antisense oligonucleotide for apo(a), have exhibited efficacy in decreasing Lp(a) substantially, invigorating a discussion whether Lp(a) could be a novel therapeutic target for further ASCVD risk reduction. This review aims to provide current understanding, and future perspectives, of Lp(a), which is currently considered a mere biomarker but may emerge as a novel therapeutic target in future clinical settings.


Assuntos
Aterosclerose/sangue , Lipoproteína(a)/sangue , Apolipoproteínas B/sangue , Apolipoproteínas B/química , Aterosclerose/tratamento farmacológico , Biomarcadores/sangue , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lipoproteína(a)/química , Niacina/uso terapêutico , Oligonucleotídeos Antissenso/uso terapêutico , Pró-Proteína Convertase 9/antagonistas & inibidores , Medição de Risco , Fatores de Risco , Inibidores de Serino Proteinase
15.
Neurology ; 92(22): e2580-e2593, 2019 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-31043469

RESUMO

OBJECTIVE: To examine the association of specific lipoproteins/inflammatory enzyme with cognitive change. METHODS: We examined the association of apolipoprotein B (ApoB), small-dense low-density lipoprotein cholesterol (sdLDL-C), lipoprotein (a) (Lp[a]), and lipoprotein-associated phospholipase A2 (LpPLA2) activity with 15-year change in Delayed Word Recall Test, Digit Symbol Substitution Test (DSST), Word Fluency Test (WFT), and overall summary score in 9,350 participants in the Atherosclerosis Risk in Communities study. We assessed interaction by race, sex, education, APOE ε4 status, and statin use. We also addressed questions of informative missingness, the role of stroke, and the influence of fasting status. RESULTS: The mean (SD) age was 63.4 (5.7) years; 56.4% were women and 17.4% were black. We observed faster cognitive decline on DSST and global z scores with every 10-mg/dL higher sdLDL-C level (Δ DSST z score, -0.010; 95% confidence interval [CI] -0.017, -0.002 and Δ global z score, -0.011; -0.021, -0.001) and the highest vs the lowest ApoB quintiles (Δ DSST z score, -0.092; -0.0164, -0.019 and Δ global z score, -0.101; -0.200, -0.002). Association for the ApoB quintiles with Δ global z score (-0.10) was comparable with that of having 1 APOE ε4 allele (-0.11). Higher Lp(a) was associated with slower decline in DSST, WFT, and global z scores. LpPLA2 activity was not associated with cognitive change. Results were similar in sensitivity analyses. The associations of sdLDL-C or Lp(a) on cognitive change were more pronounced in statin users. CONCLUSIONS: Optimal control of atherogenic lipoproteins such as ApoB and sdLDL-C in midlife for cardiovascular health may also benefit late-life cognitive health.


Assuntos
1-Alquil-2-acetilglicerofosfocolina Esterase/sangue , Apolipoproteínas B/sangue , LDL-Colesterol/sangue , Cognição , Disfunção Cognitiva/sangue , Lipoproteína(a)/sangue , Apolipoproteína E4/genética , Aterosclerose/sangue , Aterosclerose/tratamento farmacológico , Aterosclerose/epidemiologia , Aterosclerose/psicologia , Biomarcadores/sangue , Cognição/efeitos dos fármacos , Cognição/fisiologia , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/prevenção & controle , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos Prospectivos
19.
Biomolecules ; 9(4)2019 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-30934954

RESUMO

We sought to investigate whether levels of matrix metalloproteinases (MMPs) and their inhibitors predict coronary atherosclerotic plaque instability, as assessed by intravascular ultrasound (IVUS) virtual histology during coronary angiography. Blood samples were collected before angiography in 32 subjects (mean age 56 ± 8 years) with stable coronary heart disease (CHD) and elevated lipoprotein(a) (Lp(a), 94 ± 35 mg/dL). Levels of high-sensitivity C-reactive protein (hsCRP), apolipoprotein B100 (apoB100), MMP-7, MMP-9, tissue inhibitor of metalloproteinases (TIMP)-1, and TIMP-2 were determined using commercially available enzyme-linked immunosorbent assay kits. Results. The morphology of a total of sixty coronary lesions was assessed by virtual histology IVUS imaging. Eleven (18%) plaques in nine (28%) patients were classified as plaques with an unstable phenotype or a thin-cap fibroatheroma. Age, low-density lipoprotein cholesterol, apoB100, MMP-7, and MMP-9 levels were positively associated with necrotic core volume. Conversely, there was a negative relationship between MMP-7 and -9 levels and fibrous and fibro-fatty tissue volume. Multivariate regression analysis revealed that MMP-9 is a strong independent predictor of atherosclerotic plaque instability in stable CHD patients. In stable CHD patients with elevated Lp(a), MMP-9 levels are positively associated with the size of the necrotic core of coronary atherosclerotic plaques.


Assuntos
Angiografia Coronária , Doença das Coronárias/enzimologia , Lipoproteína(a)/sangue , Metaloproteinase 9 da Matriz/sangue , Placa Aterosclerótica/enzimologia , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/metabolismo , Doença das Coronárias/sangue , Doença das Coronárias/metabolismo , Feminino , Humanos , Lipoproteína(a)/metabolismo , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Placa Aterosclerótica/sangue , Placa Aterosclerótica/metabolismo , Software
20.
Acta Med Port ; 32(3): 202-207, 2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30946791

RESUMO

INTRODUCTION: High values of lipoprotein(a), related to atherosclerosis progression, are often considered a marker of thrombosis. We assessed the lipoprotein(a) profile in a group of patients with high vascular risk and no cardiovascular events, established its correlation with other cardiovascular risk factors and inferred the results for patients with metabolic disorders and, at least, two risk factors. MATERIAL AND METHODS: This longitudinal observational study included 516 patients, who had at least two cardiovascular risk factors and regularly attended, for at least two years, the outpatient consultations at a clinic of metabolism and vascular risk for primary prevention. Sociodemographic, clinical and anthropometric parameters were obtained at the baseline visit. Hepatic morphology was assessed in 509 patients (98.6%) by ultrasonography. The 10-year vascular risk was estimated using Framingham risk score, atherosclerotic cardiovascular disease and systematic coronary risk evaluation tables. RESULTS: Significant correlations were found between lipoprotein(a) levels and the addressed vascular risk factors, as well as between lipoprotein(a), and Framingham risk score, atherosclerotic cardiovascular disease and systematic coronary risk evaluation charts. Lipoprotein(a) values were also considerably higher in patients with steatosis. DISCUSSION: Increased lipoprotein(a) values were directly associated with all markers of cardiovascular risk and with non-alcoholic hepatic steatosis. CONCLUSION: Due to its high availability and low cost, lipoprotein(a) should become part of the routine evaluation of patients at vascular risk.


Assuntos
Doenças Cardiovasculares/sangue , Lipoproteína(a)/sangue , Adulto , Idoso , Biomarcadores/sangue , Composição Corporal , Doenças Cardiovasculares/etiologia , Feminino , Humanos , Estilo de Vida , Estudos Longitudinais , Masculino , Doenças Metabólicas/sangue , Pessoa de Meia-Idade , Portugal , Fatores de Risco , Fatores Socioeconômicos , Estatísticas não Paramétricas
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