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1.
Medicine (Baltimore) ; 98(51): e18510, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31861037

RESUMO

Statins therapy decrease both low-density lipoprotein cholesterol (LDL-C) levels and the risk of atherosclerotic cardiovascular disease (ASCVD) with considerable individual variability. Whether the amount of LDL-C lowering is a surrogate maker of statin responsiveness to ASCVD prevention has not been fully investigated. Among 2352 eligible patients with statin prescriptions in a cardiovascular center between January 2005 and February 2014, one-third of patients (33%) on statin therapy failed to achieve effective reductions in LDL-C (LDL-C level reduction of less than 15%). By using, propensity-score matched population (480 pairs, n = 960), the 5-year cumulative incidences of total major adverse cardiac events (MACE) were evaluated. The 5-year total MACE did not differ between normal cholesterol responders and non-responders (15.4% vs 16.1%, respectively; P = .860). In the subgroup analysis, male sex, older age, percutaneous coronary intervention, and heart failure were positive predictors, and dyslipidemia at the beginning of statin therapy was the only negative predictor of MACE in the 5-year follow-up (all P value < .05). However, cholesterol responsiveness after statin therapy did not influence the incidence of MACE (P = .860). The amount of LDL-C lowering did not predict beneficial effect on clinical outcomes of ASCVD after statin therapy. This result supports that given statin therapy, total ASCVD risk reduction should be tailored, which may not dependent to adherence to degree of LDL-C lowering or LDL-C goal based treatment.


Assuntos
Aterosclerose/sangue , LDL-Colesterol/sangue , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Idoso , Aterosclerose/tratamento farmacológico , Biomarcadores/sangue , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Fatores de Risco , Resultado do Tratamento
2.
JAMA ; 322(18): 1780-1788, 2019 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-31714986

RESUMO

Importance: Additional treatment options are needed for patients who do not achieve sufficient reduction in low-density lipoprotein cholesterol (LDL-C) level with available lipid-lowering therapies. Objective: To assess the efficacy of bempedoic acid vs placebo in patients at high cardiovascular risk receiving maximally tolerated lipid-lowering therapy. Design, Setting, and Participants: Phase 3, randomized, double-blind, placebo-controlled clinical trial conducted at 91 clinical sites in North America and Europe from November 2016 to September 2018, with a final date of follow-up of September 22, 2018. A total of 779 patients with atherosclerotic cardiovascular disease, heterozygous familial hypercholesterolemia, or both met randomization criteria, which included LDL-C level 70 mg/dL (1.8 mmol/L) or greater while receiving maximally tolerated lipid-lowering therapy. Interventions: Patients were randomized 2:1 to treatment with bempedoic acid (180 mg) (n = 522) or placebo (n = 257) once daily for 52 weeks. Main Outcomes and Measures: The primary end point was percent change from baseline in LDL-C level at week 12. Secondary measures included changes in levels of lipids, lipoproteins, and biomarkers. Results: Among 779 randomized patients (mean age, 64.3 years; 283 women [36.3%]), 740 (95.0%) completed the trial. At baseline, mean LDL-C level was 120.4 (SD, 37.9) mg/dL. Bempedoic acid lowered LDL-C levels significantly more than placebo at week 12 (-15.1% vs 2.4%, respectively; difference, -17.4% [95% CI, -21.0% to -13.9%]; P < .001). Significant reductions with bempedoic acid vs placebo were observed at week 12 for non-high-density lipoprotein cholesterol (-10.8% vs 2.3%; difference, -13.0% [95% CI, -16.3% to -9.8%]; P < .001), total cholesterol (-9.9% vs 1.3%; difference, -11.2% [95% CI, -13.6% to -8.8%]; P < .001), apolipoprotein B (-9.3% vs 3.7%; difference, -13.0% [95% CI, -16.1% to -9.9%]; P < .001), and high-sensitivity C-reactive protein (median, -18.7% vs -9.4%; difference, -8.7% [asymptotic confidence limits, -17.2% to -0.4%]; P = .04). Common adverse events included nasopharyngitis (5.2% vs 5.1% with bempedoic acid and placebo, respectively), urinary tract infection (5.0% vs 1.9%), and hyperuricemia (4.2% vs 1.9%). Conclusions and Relevance: Among patients at high risk for cardiovascular disease receiving maximally tolerated statins, the addition of bempedoic acid compared with placebo resulted in a significant lowering of LDL-C level over 12 weeks. Further research is needed to assess the durability and clinical effect as well as long-term safety. Trial Registration: ClinicalTrials.gov Identifier: NCT02991118.


Assuntos
Anticolesterolemiantes/uso terapêutico , Aterosclerose/tratamento farmacológico , Ácidos Dicarboxílicos/uso terapêutico , Ácidos Graxos/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemia Familiar Combinada/tratamento farmacológico , Idoso , Anticolesterolemiantes/efeitos adversos , Aterosclerose/sangue , Doenças Cardiovasculares/prevenção & controle , LDL-Colesterol/sangue , Ácidos Dicarboxílicos/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Ácidos Graxos/efeitos adversos , Feminino , Humanos , Hiperlipidemia Familiar Combinada/sangue , Masculino , Pessoa de Meia-Idade
3.
Medicine (Baltimore) ; 98(42): e17544, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626117

RESUMO

The protective role of serum total bilirubin, a widely recognized antioxidant, has been approved by numerous updating studies. However, regarding the effect of high serum total bilirubin level (STBL) in arteriosclerotic cardiovascular disease (ASCVD) are conflicting in different sources of data. We, therefore, performed this meta-analysis to evaluate the influence of STBL on risk of ASCVD.Four databases were used to identify the literature with a date of search of January, 2019. Finally, a total of 20 studies had been adopted. ASCVD was defined as acute coronary syndrome, stable angina, coronary revascularization, atherosclerotic stroke or transient ischemic attack, and peripheral arterial disease (PAD). All relevant data were collected from studies meeting the inclusion criteria.A total of 20 published studies (323,891 cases) met the inclusion criteria. The meta-analysis revealed that, in studies excluding heterogeneity, STBL was significantly positively related to in-hospital cardiovascular mortality (odds ratio [OR] 2.82, 95% confidence interval [CI] 1.83-4.36, Z = 4.69, P < .001) and major adverse cardiac events (OR 1.88, 95% CI 1.414-2.491, Z = 4.36, P < .001), also negatively associated with prognosis of acute myocardial infarction, pooled hazard ratio (HR) = 0.804 (95% CI 0.700-0.923, Z = 3.08, P = .002). The correlation similarity was also reflected in terms of patients with stroke (HR 0.78, 95% CI 0.70-0.88, Z = 4.24, P = .003). Combined analysis revealed that lower STBL was significantly associated with PAD, pooled OR = 0.91 (95% CI 0.85-0.98, Z = 2.39, P = .017). In general analysis, a conclusion can be drawn, that higher STBL was significantly negative correlated with cardiovascular disease, pooled HR = 0.83 (95% CI 0.73-0.94, Z = 3.02, P = .003).Higher STBL significantly improved the prognosis of ASCVD; furthermore, STBL was an important factor in the long-term prognosis of vascular-related disease prevention and can be used as a predictor in vascular-related disease risk prediction.


Assuntos
Aterosclerose/sangue , Bilirrubina/sangue , Doenças Cardiovasculares/sangue , Adulto , Idoso , Aterosclerose/mortalidade , Doenças Cardiovasculares/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Valor Preditivo dos Testes , Prognóstico , Medição de Risco/métodos , Fatores de Risco
5.
Toxicol Lett ; 316: 27-34, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31513887

RESUMO

OBJECTIVE: Atherosclerosis is an autoimmune inflammatory disease that is closely associated with long-term exposure to fine particulate matter (PM2.5). CD4+CD25+Foxp3+ regulatory T cells (Tregs) play a critical role in the regulation of T cell-mediated immune responses, and the depletion of CD4+CD25+Foxp3+ Tregs has been thought to play a prominent role in atherosclerosis. Therefore, we investigated the association between the CD4+CD25+Foxp3+ Tregs population and atherosclerotic development in ApoE-/- mice exposed to PM2.5. METHODS: We employed a real-world system to subject 40 ApoE-/- mice to ambient inhalation of PM2.5 (PM2.5 group, n = 20) or filtered air (FA group, n = 20) for 12 weeks. PM2.5 source apportionment, atherosclerotic lesions within aorta, lipid deposition and plaque accumulation in whole artery, serum level of inflammatory factors and lipid profiles, CD4+CD25+Foxp3+ Tregs population in splenocytes, Foxp3 protein and mRNA expressions in descending aorta and spleen were quantified, respectively. RESULTS: The daily average concentration of PM2.5 was 57.4 ± 25.6 µg/m3. Atherosclerotic lesions within aorta, lipid deposition and plaque accumulation in whole artery, serum levels of IL-6, TNF-α, TC and LDL-C in the PM2.5 group increased significantly compared to the FA group. Whereas, serum levels of IL-10 and TGF-ß, CD4+CD25+Foxp3+ Tregs population in splenocytes, Foxp3 protein and mRNA expressions in descending aorta and spleen in the PM2.5 group decreased significantly compared to the FA group. CONCLUSION: These results suggest that PM2.5 could accelerate the development of atherosclerosis in ApoE-/- mice, which is related to CD4+CD25+Foxp3+ Tregs down-regulation, as well as lipid deposition and systemic inflammation.


Assuntos
Aorta/efeitos dos fármacos , Doenças da Aorta/induzido quimicamente , Aterosclerose/induzido quimicamente , Fatores de Transcrição Forkhead/metabolismo , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Material Particulado/toxicidade , Linfócitos T Reguladores/efeitos dos fármacos , Animais , Aorta/imunologia , Aorta/metabolismo , Aorta/patologia , Doenças da Aorta/sangue , Doenças da Aorta/imunologia , Doenças da Aorta/patologia , Aterosclerose/sangue , Aterosclerose/imunologia , Aterosclerose/patologia , Biomarcadores/sangue , LDL-Colesterol/sangue , Citocinas/sangue , Modelos Animais de Doenças , Progressão da Doença , Fatores de Transcrição Forkhead/imunologia , Predisposição Genética para Doença , Mediadores da Inflamação/sangue , Subunidade alfa de Receptor de Interleucina-2/imunologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Tamanho da Partícula , Fenótipo , Placa Aterosclerótica , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/patologia , Fatores de Tempo
6.
Vasc Health Risk Manag ; 15: 209-220, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31371977

RESUMO

Cholesterol-embolization syndrome (CES) is a multisystemic disease with various clinical manifestations. CES is caused by embolization of cholesterol crystals (CCs) from atherosclerotic plaques located in the major arteries, and is induced mostly iatrogenically by interventional and surgical procedures; however, it may also occur spontaneously. Embolized CCs lead to both ischemic and inflammatory damage to the target organ. Therefore, anti-inflammatory agents, such as corticosteroids and cyclophosphamide, have been investigated as treatment for CES in several studies, with conflicting results. Recent research has revealed that CES is actually a kind of autoinflammatory disease in which inflammasome pathways, such as NLRP3 and IL1, are induced by CCs. These recent findings may have clinical implications such that colchicine and IL1 inhibitors, namely canakinumab, may be beneficial in the early stages of CES.


Assuntos
Aterosclerose , Colesterol/sangue , Embolia de Colesterol , Corticosteroides/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , Aterosclerose/sangue , Aterosclerose/diagnóstico , Aterosclerose/tratamento farmacológico , Aterosclerose/epidemiologia , Biomarcadores/sangue , Cristalização , Embolia de Colesterol/sangue , Embolia de Colesterol/diagnóstico , Embolia de Colesterol/epidemiologia , Embolia de Colesterol/prevenção & controle , Humanos , Imunossupressores/uso terapêutico , Inflamassomos/sangue , Mediadores da Inflamação/sangue , Interleucina-1/sangue , Proteína 3 que Contém Domínio de Pirina da Família NLR/sangue , Placa Aterosclerótica , Prognóstico , Fatores de Risco , Síndrome
7.
Rev Fac Cien Med Univ Nac Cordoba ; 76(3): 174-179, 2019 08 29.
Artigo em Espanhol | MEDLINE | ID: mdl-31465186

RESUMO

Background: Mortality from cardiovascular disease (CVD) is increased in rheumatoid arthritis, not explained by traditional cardiovascular risk factors (CVRF), suggesting a role of inflammation. This process would occur early. The common sonographic markers of subclinical atherosclerosis (SA), are increased carotid intima-media thickness (cIMT) or the presence of carotid atherosclerotic plaque and they are closely related to CVD. Aims: To evaluate sonographic markers and cardiovascular risk factors in early Arthritis (EA). Methods: A case control study of patients with EA, defined by 3 joints swollen with <1 year of evolution, served consecutively from January 2011 to may 2013, matched with healthy controls, by sex, age and cardiovascular risk factors (hypertension, diabetes mellitus, cardiovascular disease -IAM and ACV, dyslipidemia, family history of CVD) was conducted. We studied demographics data, cardiovascular risk factors, carotid ultrasound measuring increased cIMT or the presence of carotid atherosclerotic plaque in Common Carotid Artery (CCA) and Carotid Bulb (BC), laboratory test that included cholesterol, LDL, HDL, triglycerides in mg%, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR ), anti citrullinated peptide (ACCP), rheumatoid factor (RF), antinuclear antibodies (ANA). EA activity was measured by DAS 28, considering high disease activity (HDA) 5.1; moderate (MDA) from 5.1 to 3.2; and low (LDA) <3.2. Statistics: test Mann-Whitney and chi-square were used, p <0.05 was significant. Results: 25 women, 5 men, average age 43 years (DS 14.7) and 30 controls were included. The average DAS 28 was 4, 8 ± 1. 8; 47% had HDA, 33%MDA and 20%BDA. Both groups had similar values cIMT CCA (0, 57 ± 0.10 mm vs. 0.58 ± 0.15 mm, respectively, P = 0.82) and cIMT BC (0.18mm ± 0.67 vs 0.62 ± 0.15 mm respectively, P = 0.47). There were no carotid plaques. The median total cholesterol was 181,5 vs 183,5 (p = 0.35); triglycerides 99 vs 92,5 (p = 0.68); HDL 54,5 vs 52,5 (p = 0.921 and LDL 105 vs 110 (p = 0.27) in EA and controls respectively. The cIMT CCA and CB were not related to RF, ACCP, CRP, DAS 28 and smoking (NS). There was no difference in other cardiovascular risk factors Conclusions: Ultrasound evidence of atherosclerosis subclinical markers was not found in this study, suggesting that this process may occur after a year of diagnosis.


Assuntos
Artrite Reumatoide/diagnóstico por imagem , Aterosclerose/diagnóstico por imagem , Biomarcadores/sangue , Adulto , Artrite Reumatoide/sangue , Artrite Reumatoide/complicações , Aterosclerose/sangue , Aterosclerose/complicações , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/etiologia , Artéria Carótida Primitiva/diagnóstico por imagem , Artéria Carótida Primitiva/patologia , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Ultrassonografia
8.
Pan Afr Med J ; 32: 141, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31308859

RESUMO

Introduction: Sickle cell anaemia (SCA) is an inherited abnormality of haemoglobin associated with reduced life expectancy. Patients' complications include dyslipideamia. This study was aimed at determining the artherogenic index of plasma (AIP) in sickle cell anaemia patients and compares the value to HbAA controls value. A high AIP is strongly predictive of elevated cardiovascular risk. Methods: A comparative study was conducted among SCA patients attending the haematology clinic, Lagos State University Teaching Hospital (LASUTH) and HbAA Phenotype controls. A total of 304 participants were recruited consisting of equal numbers of SCA and HbAA controls. Single lipid profiles were done; logarithms of triglycerides/high density lipoprotein were calculated to obtain AIP and lipid profile ratios established for all participants. Results: There were lower mean values of Total Cholesterol (TC), High Density Lipoprotein(HDL) and Low Density Lipoprotein (LDL) amongst SCD participants than controls and higher mean values of triglycerides (TG) and Very Low Density Lipoprotein (VLDL) in SCD p < 0.05. The AIP in SCD ranges from -0.62 to 1.32 while that of controls ranges from -0.56 to 0.61.The mean AIP were 0.14 ± 0.29 and -0.009 ± 0.26 in SCD and controls respectively. P value = 0.002. Conclusion: AIP value is higher in sickle cell anaemia than controls, the former have lower mean values of TC, HDL and LDL and higher mean values of TG and VLDL.


Assuntos
Anemia Falciforme/complicações , Colesterol/sangue , Dislipidemias/epidemiologia , Lipídeos/sangue , Adolescente , Adulto , Anemia Falciforme/sangue , Aterosclerose/sangue , Aterosclerose/etiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Estudos de Casos e Controles , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Hospitais Universitários , Humanos , Masculino , Nigéria , Fatores de Risco , Adulto Jovem
9.
Nat Commun ; 10(1): 2631, 2019 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-31201301

RESUMO

Men and women differ in circulating lipids and coronary artery disease (CAD). While sex hormones such as estrogens decrease CAD risk, hormone replacement therapy increases risk. Biological sex is determined by sex hormones and chromosomes, but effects of sex chromosomes on circulating lipids and atherosclerosis are unknown. Here, we use mouse models to separate effects of sex chromosomes and hormones on atherosclerosis, circulating lipids and intestinal fat metabolism. We assess atherosclerosis in multiple models and experimental paradigms that distinguish effects of sex chromosomes, and male or female gonads. Pro-atherogenic lipids and atherosclerosis are greater in XX than XY mice, indicating a primary effect of sex chromosomes. Small intestine expression of enzymes involved in lipid absorption and chylomicron assembly are greater in XX male and female mice with higher intestinal lipids. Together, our results show that an XX sex chromosome complement promotes the bioavailability of dietary fat to accelerate atherosclerosis.


Assuntos
Transtornos 46, XX do Desenvolvimento Sexual/metabolismo , Aterosclerose/genética , Metabolismo dos Lipídeos/genética , Lipídeos/sangue , Cromossomo X/fisiologia , Transtornos 46, XX do Desenvolvimento Sexual/sangue , Animais , Aterosclerose/sangue , Aterosclerose/metabolismo , Dieta Aterogênica/efeitos adversos , Modelos Animais de Doenças , Feminino , Hormônios Esteroides Gonadais/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Intestino Delgado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ovário/metabolismo , Fatores Sexuais , Proteína da Região Y Determinante do Sexo/genética , Testículo/metabolismo
10.
High Blood Press Cardiovasc Prev ; 26(3): 199-207, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31236902

RESUMO

Proprotein convertase subtilisin/kexin type 9 (PCSK9)-related discoveries of the turn of the century have translated into substantial novelty in dyslipidemia treatment in the last 5 years. With chronic preventable atherosclerotic cardiovascular diseases (ASCVD) representing an epidemic of morbidity and mortality worldwide, low-density lipoprotein cholesterol (LDL-c) reduction represents a public health priority. By overcoming two major statin-related issues, namely intolerance and ineffectiveness, PCSK9 inhibitors have offered a safe and effective option in selected clinical settings where LDL-c reduction is required. Herein, we recapitulate recent findings, clinical applications, and ASCVD prevention potential of PCSK9 inhibition, with focus on anti-PCSK9 monoclonal antibodies, evolocumab and alirocumab.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Anticolesterolemiantes/uso terapêutico , Aterosclerose/prevenção & controle , LDL-Colesterol/sangue , Dislipidemias/tratamento farmacológico , Pró-Proteína Convertase 9/antagonistas & inibidores , Inibidores de Serino Proteinase/uso terapêutico , Animais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Anticolesterolemiantes/efeitos adversos , Aterosclerose/sangue , Aterosclerose/enzimologia , Aterosclerose/epidemiologia , Biomarcadores/sangue , Dislipidemias/sangue , Dislipidemias/enzimologia , Dislipidemias/epidemiologia , Humanos , Guias de Prática Clínica como Assunto , Pró-Proteína Convertase 9/metabolismo , Fatores de Risco , Inibidores de Serino Proteinase/efeitos adversos , Resultado do Tratamento
11.
BMC Med Genet ; 20(1): 97, 2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31164103

RESUMO

BACKGROUND: Metabolic syndrome (MetS) is characterized by a clustering of cardiovascular risk factors that include: abdominal obesity, dyslipidemia, hypertension and glucose intolerance. Angiopoietin-like protein 4 (ANGPTL4) is a circulating peptide that is an inhibitor of lipoprotein lipase, a key enzyme in lipid metabolism. The objective of this study was to investigate the association of ANGPTL4 gene variants (E40K) with fasting serum triglyceride levels and with cardiovascular risk factors, that included the presence of MetS in 817 subjects recruited from the Mashhad stroke and heart Atherosclerosis Disorders (MASHAD) cohort Study. METHOD: ANGPTL4 genotypes were determined using a TaqMan genotyping based real time PCR method. The association of the genetic variant with the risk of metabolic syndrome and its relationship with lipid profile were determined. RESULT: The frequency of GG, GA and AA genotypes were 96.9, 2.7 and 0.4% in individuals with MetS, and 78.8, 20.8, 0.4%, in those without MetS. The GA genotype of the rs116843064 polymorphism was associated with a lower risk for MetS (e.g., OR in Codominant genetic model: 0.14, 95% CI: (0.06-0.33), p < 0.0001). Subject with an A allele had a higher risk for MetS (OR: 6.72, 95% CI: (3.05-14.82), p < 0.0001). There was a significant difference in fasted lipid profiles across the genotypes for ANGPTL4. Carriers of the AG genotype had higher levels of serum HDL-cholesterol (HDL-C) and lower TG, compared to the GG homozygotes genotype. CONCLUSION: The G allele at the rs116843064 polymorphic locus of the ANGPTL4 gene was associated with a lower prevalence of MetS.


Assuntos
Proteína 4 Semelhante a Angiopoietina/genética , Aterosclerose/genética , Predisposição Genética para Doença/genética , Síndrome Metabólica/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Aterosclerose/sangue , Estudos de Coortes , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Síndrome Metabólica/sangue , Pessoa de Meia-Idade , Fatores de Risco , Triglicerídeos/sangue
12.
Chin Med J (Engl) ; 132(12): 1400-1405, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31205096

RESUMO

BACKGROUND: Necroptosis plays an important role in human atherosclerosis and atheroma development. Since receptor interacting protein kinase-3 (RIP3) acts as a key mediator of necroptosis, this study aimed to explore its relationship between plasma RIP3 levels and coronary artery disease (CAD) and discover a potential new biomarker for screening CAD subtypes and severity. METHODS: A total of 318 patients with CAD who had coronary angiography and 166 controls in Peking Union Medical College Hospital from September 2017 to January 2018 were enrolled in this study. Patients with CAD were divided into three subgroups: patients with stable coronary artery disease (SCAD), patients with unstable angina (UA), and patients with myocardial infarction (MI). The severity of atherosclerosis was determined by Gensini score (GSS). Logistic regression was used to determine the relationship between plasma RIP3 levels and CAD. The correlation between plasma RIP3 and GSS was calculated using multiple linear regression models. RESULTS: Overall, plasma RIP3 levels were significantly higher than serum RIP3 levels. Plasma RIP3 levels in patients with CAD were significantly higher than those in controls. Plasma RIP3 levels were strongly associated with CAD (odds ratio: 6.00, 95% confidence interval 3.04-11.81; P < 0.001). Plasma RIP3 levels increased linearly from controls to patients with SCAD, then patients with UA, and finally to patients with MI. We found a significantly positive correlation between proportion of cases of acute coronary syndrome in subjects and their plasma RIP3 level quartile. Plasma RIP3 levels were also associated with GSS (B 0.027; standard error 0.012; P < 0.05). CONCLUSIONS: Plasma RIP3 levels were independently associated with CAD. Plasma RIP3 levels could potentially supplement clinical assessment to screen CAD and determine CAD severity.


Assuntos
Biomarcadores/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/metabolismo , Plasma/química , Proteína Serina-Treonina Quinases de Interação com Receptores/sangue , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Angina Instável/sangue , Angina Instável/metabolismo , Angina Instável/patologia , Aterosclerose/sangue , Aterosclerose/metabolismo , Aterosclerose/patologia , Biomarcadores/metabolismo , Doença da Artéria Coronariana/patologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade
13.
Transplant Proc ; 51(4): 1118-1120, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31101184

RESUMO

INTRODUCTION: Cardiovascular disease is the leading cause of mortality in kidney transplant recipients. Rituximab is widely used in kidney transplantation for a variety of situations, and rituximab may inhibit some cytokines and antibodies that may play an active role in the atherosclerotic process. The aim of the study was to evaluate the efficacy of rituximab on atherosclerosis biomarkers in kidney transplant recipients. METHODS: All patients, 18 years of age and older, who underwent kidney transplantation and received at least 1 dose of 375 mg/m2 rituximab were considered for participation in this study. The primary study endpoint was the development of cardiovascular diseases after rituximab therapy. The secondary endpoint was the onset of cytomegalovirus (CMV) disease or biopsy-confirmed BK virus nephropathy. In addition, comparison of atherosclerosis biomarkers was performed between study and control groups. RESULTS: There were no cardiovascular events observed during follow up. Only 8 patients in the study group suffered from CMV disease during follow up. Serum interleukin 10 levels were significantly higher in the rituximab group compared with the control group, although anti-oxidized low-density lipoprotein levels were lower in the rituximab group compared with the control group, though this did not achieve statistical significance. DISCUSSION: Rituximab treatment may increase the risk of CMV reactivation and decrease lymphocyte counts and interleukin 10 levels; however, significant decreases in all atherosclerotic-related biomarkers have not been shown in our study.


Assuntos
Aterosclerose/sangue , Imunossupressores/uso terapêutico , Transplante de Rim , Rituximab/uso terapêutico , Adolescente , Adulto , Aterosclerose/epidemiologia , Biomarcadores/sangue , Citomegalovirus/fisiologia , Infecções por Citomegalovirus/epidemiologia , Feminino , Humanos , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Transplantados , Ativação Viral/efeitos dos fármacos
14.
Maturitas ; 125: 5-10, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31133217

RESUMO

OBJECTIVE: Whether endogenous testosterone concentrations are associated with atrial fibrillation (AF) development is not well established. We assessed the association between plasma total testosterone concentrations and incident AF in a population-based longitudinal study. STUDY DESIGN: Using data from the prospective Atherosclerosis Risk in Communities (ARIC) study, we identified incident AF among 9282 participants who had plasma total testosterone measured by liquid chromatography tandem mass spectrometry at Visit 4 (1996-1998). MAIN OUTCOME MEASURES: AF cases were identified by electrocardiograms performed during study visits, hospital records/discharge codes, and death certificates through 2013. We estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) for incident AF across quartiles of plasma total testosterone, stratified by sex, with multivariable Cox models. RESULTS: The mean age of the participant sample at ARIC Visit 4 was 63 years (range 52-75); 54.5% were women. Mean (SD) plasma total testosterone levels were 537 ng/dL (213) for men and 27.6 ng/dL (34.7) for women. Over a mean of 13.7 years of follow-up, 1664 incident cases of AF were identified. Comparing those in the highest quartile of plasma total testosterone concentration to those in the lowest quartile and after adjustment for potential confounding variables, there was a positive association between plasma total testosterone and incident AF in men (HR 1.33, 95% CI 1.07, 1.66), but no such association in women (HR 0.99, 95% CI 0.80, 1.22). Conclusion A higher plasma total testosterone concentration was associated with a modestly greater incidence rate of AF in men.


Assuntos
Aterosclerose/sangue , Fibrilação Atrial/sangue , Testosterona/sangue , Idoso , Eletrocardiografia , Feminino , Taxa de Filtração Glomerular , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais
15.
Artigo em Inglês | MEDLINE | ID: mdl-31049144

RESUMO

Given its role in many biochemical processes essential to life, cholesterol remains a topic of intense research. Of all the plasma lipids, cholesterol is distinctive because it is a precursor to steroidogenic molecules, some of which regulate metabolism, and its blood concentration in the form of low- and high-density lipoprotein cholesterol (HDL-C) are positive and negative risk factors for atherosclerotic cardiovascular disease (ASCVD). New research, however, has challenged the widely held belief that high HDL-C levels are atheroprotective and is showing that both low and high plasma HDL-C levels confer an increased risk of ASCVD. Furthermore, it is disputing the widely cited mechanism involved in reverse cholesterol transport. This review explores the evolution of cholesterol research starting with the Gofman and Framingham studies, the development of traditional and emerging lipid-lowering therapies, and the role of reverse cholesterol transport in HDL cardioprotection.


Assuntos
Anticolesterolemiantes/uso terapêutico , Aterosclerose/sangue , Aterosclerose/etiologia , Colesterol na Dieta/efeitos adversos , Colesterol na Dieta/sangue , HDL-Colesterol/efeitos adversos , HDL-Colesterol/sangue , LDL-Colesterol/efeitos adversos , LDL-Colesterol/sangue , Animais , Anticolesterolemiantes/efeitos adversos , Aterosclerose/genética , Aterosclerose/prevenção & controle , Transporte Biológico , Humanos , Placa Aterosclerótica , Prognóstico , Fatores de Proteção , Fatores de Risco
16.
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
17.
Niger J Clin Pract ; 22(5): 713-717, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31089028

RESUMO

Objective: To date, there have been no studies investigating whether or not there is a correlation between the serum endocan level and the atherosclerotic cardiovascular disease (ASCVD) risk score that is frequently used in the determination of the risk of cardiovascular disease. If a single parameter such as endocan can provide reliable results which could be used in the prediction of the cardiovascular disease risk, the workload of the clinician would be lightened. The aim of this study was to investigate whether or not there is an association between the serum endocan level and the ASVCD risk score. Materials and Methods: This prospective, cross-sectional study included individuals age 40-79 years with risk factors calculated using the ASVCD score and individuals without any of those risk factors. In accordance with ASCVD risk calculation, each participant was questioned with respect to age, gender, height, weight, and lifestyle habits such as smoking, diseases, and medications. Systolic blood pressure, diastolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and serum endocan levels were measured and recorded. The serum endocan levels and ASCVD scores were compared. Results: The study included 205 individuals, comprising 92 (44.9%) males and 113 (55.1%) females with a mean age of 50.7 ± 7.6 years. The 10-year atherosclerosis risk was determined as mean 6.32% ± 5.9% (range, 0.3%-27.3%). The mean serum endocan level was calculated as 1109.6 ± 1479.7 ng/mL. As the ASCVD risk score increased, no increase was detected in the serum endocan level. Conclusion: The results of the study suggested that the serum endocan level is not suitable for use in place of the ASCVD risk score as a predictor of cardiovascular disease risk.


Assuntos
Aterosclerose/sangue , Proteínas de Neoplasias/sangue , Proteoglicanas/sangue , Adulto , Pressão Sanguínea , HDL-Colesterol/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco/métodos , Fatores de Risco , Fumar
18.
J Diabetes Res ; 2019: 9727952, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30949516

RESUMO

Background: There is a lack of predictive preclinical animal models combining atherosclerosis and type 2 diabetes. APOE∗3-Leiden (E3L) mice are a well-established model for diet-induced hyperlipidemia and atherosclerosis, and glucokinase+/- (GK+/-) mice are a translatable disease model for glucose control in type 2 diabetes. The respective mice respond similarly to lipid-lowering and antidiabetic drugs as humans. The objective of this study was to evaluate/characterize the APOE∗3-Leiden.glucokinase+/- (E3L.GK+/-) mouse as a novel disease model to study the metabolic syndrome and diabetic complications. Methods: Female E3L.GK+/-, E3L, and GK+/- mice were fed fat- and cholesterol-containing diets for 37 weeks, and plasma parameters were measured throughout. Development of diabetic macro- and microvascular complications was evaluated. Results: Cholesterol and triglyceride levels were significantly elevated in E3L and E3L.GK+/- mice compared to GK+/- mice, whereas fasting glucose was significantly increased in E3L.GK+/- and GK+/- mice compared to E3L. Atherosclerotic lesion size was increased 2.2-fold in E3L.GK+/- mice as compared to E3L (p = 0.037), which was predicted by glucose exposure (R 2 = 0.636, p = 0.001). E3L and E3L.GK+/- mice developed NASH with severe inflammation and fibrosis which, however, was not altered by introduction of the defective GK phenotype, whereas mild kidney pathology with tubular vacuolization was present in all three phenotypes. Conclusions: We conclude that the E3L.GK+/- mouse is a promising novel diet-inducible disease model for investigation of the etiology and evaluation of drug treatment on diabetic atherosclerosis.


Assuntos
Apolipoproteína E3/genética , Aterosclerose/genética , Complicações do Diabetes/genética , Diabetes Mellitus Tipo 2/genética , Modelos Animais de Doenças , Dislipidemias/genética , Animais , Aterosclerose/sangue , Glicemia/metabolismo , Colesterol/sangue , Complicações do Diabetes/sangue , Diabetes Mellitus Tipo 2/sangue , Dislipidemias/sangue , Feminino , Heterozigoto , Inflamação , Lipídeos/sangue , Camundongos , Camundongos Knockout , Fenótipo , Risco , Pesquisa Médica Translacional , Triglicerídeos/metabolismo
19.
Lipids Health Dis ; 18(1): 99, 2019 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-30987629

RESUMO

OBJECTIVE: The value of atherogenic index of plasma (AIP) as a predictive biomarker for coronary artery disease (CAD) remains controversial. In addition, whether AIP is associated with the risk of acute coronary syndrome (ACS) in very young adults has not been well established. METHODS: We consecutively collected very young adults (≤35 years of age) undergoing coronary angiography (CAG) at Anzhen Hospital, between January 2008 and December 2017. Total of 1, 478 very young participants, including 1, 059 ACS patients and 419 non-CAD subjects, were enrolled in the present study. RESULTS: Very young patients with ACS had higher AIP level compared with non-CAD participants (0.35 ± 0.30 vs 0.21 ± 0.33, P < 0.001). According to Gensini Score (GS) and number of lesion vessel, patients were divided into four groups, respectively. With the elevated GS score and number of lesion vessels, the AIP level increased gradually (Pfor trend all< 0.05). Multivariate logistic regression analyses suggested that AIP remained to be independently associated with the presence of ACS and was superior to traditional lipid profiles (for AIP, OR = 2.930, 95% CI = 1.855-4.627, P < 0.001; for total cholesterol, OR = 1.152, 95% CI = 1.048-1.266, P = 0.003; for triglyceride, OR = 1.078, 95% CI = 0.991-1.172, P = 0.079; for low-density lipoprotein cholesterol, OR = 1.046, 95% CI = 1.015-1.078, P < 0.001), after adjustment for other traditional confounders. Moreover, the prevalence of ACS, acute myocardial infarction, unstable angina pectoris and the value of GS were also elevated as AIP quartiles increased (Pfor trend < 0.001). Subgroup analysis based on gender revealed that AIP was only independently associated with the ACS risk in male. CONCLUSIONS: AIP was independently associated with the presence and severity of ACS in very young patients in a gender-dependent manner, which might be superior to traditional lipid profiles.


Assuntos
Síndrome Coronariana Aguda/sangue , Angina Instável/sangue , Aterosclerose/sangue , Infarto do Miocárdio/sangue , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/fisiopatologia , Adulto , Idade de Início , Angina Instável/diagnóstico por imagem , Angina Instável/fisiopatologia , Aterosclerose/diagnóstico por imagem , Aterosclerose/fisiopatologia , Estudos de Casos e Controles , China , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Angiografia Coronária , Feminino , Hospitais , Humanos , Modelos Logísticos , Masculino , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/fisiopatologia , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Triglicerídeos/sangue
20.
Clin Chim Acta ; 495: 82-84, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30953613

RESUMO

The American Heart Association (AHA) and American College of Cardiology (ACC) recently published new guidelines for managing blood cholesterol. Five years from the publication of Pooled Cohort Equation to estimate 10-year risk of atherosclerotic cardiovascular disease (ASCVD), the newest guidelines put more focus on individualized risk assessment which necessitates increased participation of laboratory medicine in the prevention and management of ASCVD. This mini-review summarizes key ideas from the new guideline that influence laboratory practice, including the renewed low-density lipoprotein cholesterol (LDL-C) treatment targets in primary and secondary prevention, the use of non-fasting lipids, new calculations of LDL cholesterol, and recommendations on assessing risk-enhancing factors in certain populations to aid the decision on statin and non-statin therapy. The shift in strategies for monitoring and lowering LDL-C has created opportunities for clinical laboratorians to more actively contribute to better identification of individuals at risk for ASCVD and partner with physicians taking care of the patient.


Assuntos
American Heart Association , Análise Química do Sangue/métodos , Cardiologia , Colesterol/sangue , Guias de Prática Clínica como Assunto , Aterosclerose/sangue , Aterosclerose/prevenção & controle , Humanos , Estados Unidos
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