RESUMO
BACKGROUND: Patients with rheumatoid arthritis (RA) have an increased risk for cardiovascular disease (CVD). No long-term intervention trials on CVD risk factors have been published, and a debate on the efficacy of controlling traditional risk factors in RA is ongoing. We aimed to evaluate a treat-to-target approach versus usual care regarding traditional CVD risk factors in patients with RA. METHODS: In this open-label, randomised controlled trial, patients with RA aged <70 years without prior CVD or diabetes mellitus were randomised 1:1 to either a treat-to-target approach or usual care of traditional CVD risk factors. The primary outcome was defined as change in carotid intima media thickness (cIMT) over 5 years, and the secondary outcome was a composite of first occurrence of fatal and non-fatal cardiovascular events. RESULTS: A total of 320 patients (mean age 52.4 years; 69.7% female) with RA underwent randomisation and 219 patients (68.4%) completed 5 years of follow-up. The mean cIMT progression was significantly reduced in the treat-to-target group compared with usual care (0.023 [95% CI 0.011 to 0.036] mm vs 0.045 [95% CI 0.030 to 0.059] mm; p=0.028). Cardiovascular events occurred in 2 (1.3%) of the patients in the treat-to-target group vs 7 (4.7%) in those receiving usual care (p=0.048 by log-rank test). CONCLUSION: This study provides evidence on the benefit of a treat-to-target approach of traditional CVD risk factors for primary prevention in patients with well-treated RA. TRIAL REGISTRATION NUMBER: NTR3873.
Assuntos
Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Aterosclerose/etiologia , Doenças Cardiovasculares/etiologia , Adulto , Idoso , Artrite Reumatoide/complicações , Artrite Reumatoide/fisiopatologia , Espessura Intima-Media Carotídea , Gerenciamento Clínico , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Planejamento de Assistência ao Paciente , Fatores de Risco , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: The binding of apolipoprotein (apo) B-containing lipoproteins to circulating erythrocytes (ery-apoB) is associated with a decreased prevalence of atherosclerosis. In this study, we evaluated ery-apoB as a possible prognostic factor in cardiovascular events and all-cause mortality, in a prospective cohort study. MATERIALS AND METHODS: Ery-apoB was measured by flow cytometry in subjects with and without cardiovascular disease (CVD). The primary endpoint was the cardiovascular event rate. Secondary endpoints were all-cause mortality and the combined endpoint of all-cause mortality and cardiovascular events (any event rate). A Cox regression analysis with univariate and multivariate analyses and Kaplan-Meier survival analysis was performed. RESULTS: Follow-up data were available of 384 subjects. Subjects were divided according to high (> 2·0 au, n = 60), intermediate (0·2-2·0 au, n = 274) or low (< 0·2 au, n = 50) ery-apoB. Median follow-up was 1767 days (IQR 1564-2001). In univariate analysis, low ery-apoB was associated with increased all-cause mortality [HR 9·9 (1·2-79·0), P = 0·031] and any event rate [HR 3·4 (95% CI 1·3-8·7), P = 0·012]. In a Cox regression analysis, only a history of CVD was significantly associated with any event rate [HR 3·6 (1·6-8·0), P = 0·002], while low ery-apoB showed a trend [HR 2·4 (0·9-6·4), P = 0·07]. In a subgroup analysis, in subjects with a history of CVD, ery-apoB was significantly associated with all-cause mortality (log rank P = 0·021) and any event rate (log rank P = 0·009). CONCLUSIONS: Low ery-apoB is associated with increased mortality and cardiovascular risk, especially in patients with a prior history of CVD. These subjects may benefit from more aggressive secondary prevention treatment.
Assuntos
Apolipoproteínas B/metabolismo , Aterosclerose/mortalidade , Eritrócitos/metabolismo , Aterosclerose/metabolismo , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de RiscoRESUMO
OBJECTIVE: To investigate the prevalence of underdiagnosis and undertreatment of traditional cardiovascular risk factors in RA patients. METHODS: RA patients ⩽70 years of age without cardiovascular disease (CVD) or diabetes mellitus were included. Systolic blood pressure and a fasting lipid profile were measured. The 10-year CVD risk was estimated using the Dutch Cardiovascular Risk Management (CVRM) guideline and EULAR modifications of the Systemic Coronary Risk Evaluation tables. RESULTS: A total of 327 patients were included (female gender: 68%). The mean age was 53 (11) years [mean (s.d.)]. The median disease duration was 7 years (inter quartile range: 2-14 years). According to the CVRM guideline, 52% of the patients had a CVD risk ⩾20% and according to the EULAR guidelines, 18% of the patients had a CVD risk ≥ 20%. Low-density lipoprotein cholesterol (LDL-C) >2.5 mmol/l was found in >80% of the patients with a CVD risk ⩾10% as estimated by both the CVRM and EULAR guidelines, and 32-42% of the patients with a CVD risk ⩾10% had a systolic blood pressure >140 mmHg, depending on the risk model used. Statins were used in 6% and antihypertensives in 23-25%, and 50-86% of these patients did not reach the recommended treatment targets. CONCLUSION: Regardless of the adapted risk assessment model used, untreated hypertension and hypercholesterolaemia were frequently found in RA patients with increased CVD risk. Treatment of these cardiovascular risk factors deserves more attention in RA. TRIAL REGISTRATION: The Dutch Trial Register, www.trialregister.nl, NTR3873.
Assuntos
Artrite Reumatoide/complicações , Hipercolesterolemia/epidemiologia , Hipertensão/epidemiologia , Adulto , Anti-Hipertensivos/uso terapêutico , Artrite Reumatoide/sangue , Artrite Reumatoide/fisiopatologia , Pressão Sanguínea , Proteína C-Reativa/análise , LDL-Colesterol/sangue , Estudos Transversais , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/diagnóstico , Hipercolesterolemia/tratamento farmacológico , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prevalência , Medição de Risco/métodos , Fatores de RiscoRESUMO
BACKGROUND: Atherosclerosis is a pro-inflammatory condition, in which leucocyte activation plays an important role. The interaction between circulating leucocytes and apolipoprotein (apo) B-containing lipoproteins results in pro-inflammatory changes of these cells. We aimed to evaluate the relationship between apo B bound to circulating leucocytes and atherosclerosis. METHODS: Apo B on circulating leucocytes was measured by flow cytometry in subjects with and without cardiovascular disease (CVD), expressed as mean fluorescent intensity in arbitrary units (au). Carotid intima-media thickness (cIMT) was measured using B-mode ultrasound. Data are given as median (interquartile range). RESULTS: A total of 396 subjects were included, of whom 183 had a history of CVD. Compared to subjects without CVD, patients with CVD had lower apo B bound to neutrophils (12·7 au (9·8-16·2) and 14·2 au (10·1-17·5), respectively, P = 0·038) and to monocytes (2·5 au (1·7-3·1) and 2·7 (1·9-3·6) au, respectively, P = 0·025). No differences were found for lymphocyte-bound apo B. Neutrophil- and monocyte-bound apo B were inversely correlated with cIMT (Spearman's rho: -0·123, P = 0·017 and -0·108, P = 0·035, respectively). Both monocyte- and neutrophil-bound apo B were inversely associated with different factors related to the metabolic syndrome, such as body mass index, triglycerides and complement C3. There was a positive association between erythrocyte-bound apo B and apo B bound to each of the leucocyte classes, possibly reflecting a similar mechanism. Discontinuation of statins in 54 subjects did not influence leucocyte-bound apo B. CONCLUSION: Unexpectedly, the presence of noninternalized apo B-containing lipoproteins on circulating neutrophil and monocyte membranes may represent a protective mechanism against atherosclerosis.
Assuntos
Apolipoproteínas B/metabolismo , Aterosclerose/etiologia , Leucócitos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/tratamento farmacológico , Espessura Intima-Media Carotídea , Estudos Transversais , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Fatores de Risco , Adulto JovemRESUMO
Lipoproteins can induce complement activation resulting in opsonization and binding of these complexes to complement receptors. We investigated the binding of opsonized native LDL and acetylated LDL (acLDL) to the complement receptor 1 (CR1). Binding of complement factors C3b, IgM, C1q, mannose-binding lectin (MBL), and properdin to LDL and acLDL were investigated by ELISA. Subsequent binding of opsonized LDL and acLDL to CR1 on CR1-transfected Chinese Hamster Ovarian cells (CHO-CR1) was tested by flow cytometry. Both native LDL and acLDL induced complement activation with subsequent C3b opsonization upon incubation with normal human serum. Opsonized LDL and acLDL bound to CR1. Binding to CHO-CR1 was reduced by EDTA, whereas MgEGTA only reduced the binding of opsonized LDL, but not of acLDL suggesting involvement of the alternative pathway in the binding of acLDL to CR1. In vitro incubations showed that LDL bound C1q, whereas acLDL bound to C1q, IgM, and properdin. MBL did neither bind to LDL nor to acLDL. The relevance of these findings was demonstrated by the fact that ex vivo up-regulation of CR1 on leukocytes was accompanied by a concomitant increased binding of apolipoprotein B-containing lipoproteins to leukocytes without changes in LDL-receptor expression. In conclusion, CR1 is able to bind opsonized native LDL and acLDL. Binding of LDL to CR1 is mediated via the classical pathway, whereas binding of acLDL is mediated via both the classical and alternative pathways. Binding of lipoproteins to CR1 may be of clinical relevance due to the ubiquitous cellular distribution of CR1.
Assuntos
Ativação do Complemento , Complemento C3b/metabolismo , Lipoproteínas LDL/metabolismo , Receptores de Complemento 3b/metabolismo , Animais , Apolipoproteínas B/metabolismo , Células CHO , Células Cultivadas , Complemento C1q/metabolismo , Via Alternativa do Complemento , Via Clássica do Complemento , Cricetinae , Cricetulus , Ácido Edético/farmacologia , Citometria de Fluxo , Humanos , Imunoglobulina M/metabolismo , Leucócitos/citologia , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Lipopolissacarídeos/farmacologia , Proteínas Opsonizantes/metabolismo , Properdina/metabolismo , Ligação Proteica/efeitos dos fármacos , Receptores de Complemento 3b/genéticaRESUMO
The diagnosis of myelodysplastic syndromes (MDS) requires a high clinical index of suspicion to prompt bone marrow studies as well as subjective assessment of dysplastic morphology. We sought to determine if data collected by automated hematology analyzers during complete blood count (CBC) analysis might help to identify MDS in a routine clinical setting. We collected CBC parameters (including those for research use only and cell population data) and demographic information in a large (>5,000), unselected sequential cohort of outpatients. The cohort was divided into independent training and test groups to develop and validate a random forest classifier that identifies MDS. The classifier effectively identified MDS and had a receiver operating characteristic area under the curve (AUC) of 0.942. Platelet distribution width and the standard deviation of red blood cell distribution width were the most discriminating variables within the classifier. Additionally, a similar classifier was validated with an additional, independent set of >200 patients from a second institution with an AUC of 0.93. This retrospective study demonstrates the feasibility of identifying MDS in an unselected outpatient population using data routinely collected during CBC analysis with a classifier that has been validated using two independent data sets from different institutions.
Assuntos
Contagem de Células Sanguíneas , Programas de Rastreamento/métodos , Síndromes Mielodisplásicas/sangue , Idoso , Algoritmos , Área Sob a Curva , Contagem de Células Sanguíneas/instrumentação , Contagem de Células Sanguíneas/estatística & dados numéricos , Plaquetas/ultraestrutura , Medula Óssea/patologia , Exame de Medula Óssea , Tamanho Celular , Estudos de Coortes , Árvores de Decisões , Impedância Elétrica , Índices de Eritrócitos , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/patologia , Pacientes Ambulatoriais , Curva ROC , Distribuição Aleatória , Estudos RetrospectivosRESUMO
Many risk factors have been identified as being responsible for the process of atherogenesis. Several of these risk factors are related to inflammation, which is an obligatory feature of the atherosclerotic plaque. Increasing evidence suggests that postprandial lipoproteins and glucose may be involved in the inflammatory process preceding the development of atherosclerosis. During the postprandial situation, remnants of chylomicrons and very low-density lipoproteins bind to circulating leukocytes and endothelial cells, leading to a state of acute activation with the expression of integrins on different cells, the generation of oxidative stress, production of cytokines and complement activation. Elevated plasma glucose levels may also induce leukocyte activation in humans. In addition, advanced glycation end products, formed during hyperglycemia, cause inflammation and endothelial damage. This chain of events results in a situation of acute inflammation causing endothelial dysfunction, which may be one of the earliest defects in atherogenesis. Interestingly, while this may occur several times each day after each meal, there is only limited information on the contribution of different nutrients on the postprandial inflammatory processes. In this review, we will focus on the available evidence and we will discuss the role of lifestyle and pharmaceutical interventions in modulating postprandial inflammation.
Assuntos
Aterosclerose/mortalidade , Glicemia/metabolismo , Quilomícrons/sangue , Lipoproteínas IDL/sangue , Placa Aterosclerótica/metabolismo , Período Pós-Prandial , Animais , Aterosclerose/patologia , Aterosclerose/terapia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Humanos , Inflamação/sangue , Inflamação/patologia , Leucócitos/metabolismo , Leucócitos/patologia , Estresse Oxidativo , Placa Aterosclerótica/patologia , Placa Aterosclerótica/terapiaRESUMO
PURPOSE OF REVIEW: This study reviews recent developments concerning the effects of alcohol on plasma triglycerides. The focus will be on population, intervention and metabolic studies with respect to alcohol and plasma triglycerides. RECENT FINDINGS: Alcohol consumption and fat ingestion are closely associated and stimulated by each other via hypothalamic signals and by an elevated cephalic response. A J-shaped relationship between alcohol intake and plasma triglycerides has been described. A normal body weight, polyphenols in red wine and specific polymorphisms of the apolipoprotein A-V and apolipoprotein C-III genes may protect against alcohol-associated hypertriglyceridemia. In contrast, obesity exaggerates alcohol-associated hypertriglyceridemia and therefore the risk of pancreatitis. SUMMARY: High alcohol intake remains harmful since it is associated with elevated plasma triglycerides, but also with cardiovascular disease, alcoholic fatty liver disease and the development of pancreatitis. Alcohol-induced hypertriglyceridemia is due to increased very-low-density lipoprotein secretion, impaired lipolysis and increased free fatty acid fluxes from adipose tissue to the liver. However, light to moderate alcohol consumption may be associated with decreased plasma triglycerides, probably determined by the type of alcoholic beverage consumed, genetic polymorphisms and lifestyle factors. Nevertheless, patients should be advised to reduce or stop alcohol consumption in case of hypertriglyceridemia.
Assuntos
Consumo de Bebidas Alcoólicas/sangue , Triglicerídeos/sangue , Consumo de Bebidas Alcoólicas/efeitos adversos , Animais , Etanol/efeitos adversos , Etanol/farmacologia , Predisposição Genética para Doença , Humanos , Hipertrigliceridemia/sangue , Hipertrigliceridemia/etiologia , Estilo de Vida , Metabolismo dos Lipídeos/efeitos dos fármacos , Pancreatite Alcoólica/sangue , Pancreatite Alcoólica/etiologiaRESUMO
Randomized studies support the closure of midline incisions with a suture length to wound length ratio (SL:WL) of more than 4, accomplished with small tissue bites and short stitch intervals to decrease the risk of incisional hernia and wound infection. We investigated practical aspects of this technique possibly hampering the introduction of this technique. Patient data, operative variables and SL:WL ratio were collected at two hospitals: Sundsvall Hospital (SH) and Erasmus University Medical Center (EMC). A structured implementation of the technique had been performed at SH but not at EMC. Personnel were interviewed by questionnaire. At each hospital, 18 closures were analyzed. Closure time was significantly longer (p = 0.023) at SH (median 18 minutes, range: 9-59) than at EMC (median 13 minutes, range: 5-23). An SL:WL ratio of more than 4 was achieved in 8 of 18 cases at EMC and in all 18 cases at SH. We conclude that calculation of an SL:WL ratio is easily performed. Suturing with the small bite-short stitch interval technique of SH required 5 minutes extra, outweighing the morbidity of incisional hernia. Without a structured implementation to suture with an SL:WL ratio of more than 4, a lower ratio is often achieved.
Assuntos
Laparotomia/instrumentação , Laparotomia/métodos , Duração da Cirurgia , Técnicas de Sutura/instrumentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Suturas , Suécia , Resultado do TratamentoRESUMO
Background and aim: The presence of mechanical dyssynchrony on echocardiography is associated with reverse remodelling and decreased mortality after cardiac resynchronization therapy (CRT). Contrarily, myocardial scar reduces the effect of CRT. This study investigated how well a combined assessment of different markers of mechanical dyssynchrony and scarring identifies CRT responders. Methods: In a prospective multicentre study of 170 CRT recipients, septal flash (SF), apical rocking (ApRock), systolic stretch index (SSI), and lateral-to-septal (LW-S) work differences were assessed using echocardiography. Myocardial scarring was quantified using cardiac magnetic resonance imaging (CMR) or excluded based on a coronary angiogram and clinical history. The primary endpoint was a CRT response, defined as a ≥15% reduction in LV end-systolic volume 12 months after implantation. The secondary endpoint was time-to-death. Results: The combined assessment of mechanical dyssynchrony and septal scarring showed AUCs ranging between 0.81 (95%CI: 0.74-0.88) and 0.86 (95%CI: 0.79-0.91) for predicting a CRT response, without significant differences between the markers, but significantly higher than mechanical dyssynchrony alone. QRS morphology, QRS duration, and LV ejection fraction were not superior in their prediction. Predictive power was similar in the subgroups of patients with ischemic cardiomyopathy. The combined assessments significantly predicted all-cause mortality at 44 ± 13 months after CRT with a hazard ratio ranging from 0.28 (95%CI: 0.12-0.67) to 0.20 (95%CI: 0.08-0.49). Conclusions: The combined assessment of mechanical dyssynchrony and septal scarring identified CRT responders with high predictive power. Both visual and quantitative markers were highly feasible and demonstrated similar results. This work demonstrates the value of imaging LV mechanics and scarring in CRT candidates, which can already be achieved in a clinical routine.
RESUMO
BACKGROUND: Apolipoprotein (apo) B-containing lipoproteins are closely linked to atherogenesis. These lipoproteins are transported in plasma and are also associated with blood leucocytes. Our aim was to investigate whether apoB-containing lipoproteins are also present on the surface of erythrocytes and investigate the relationship with the presence of atherosclerosis in a cross-sectional study. MATERIALS AND METHODS: Erythrocyte-bound apoB (ery-apoB) was measured by flowcytometry in subjects with (CAD+) and without coronary artery disease (CAD-), based on coronary angiography or on a history of cardiovascular disease. Intima media thickness (IMT) measurements were carried out using B-mode ultrasound. The relationship between ery-apoB and clinical and subclinical atherosclerosis was evaluated with binary logistic regression. RESULTS: A total of 166 subjects were included (40 CAD+ and 126 CAD-). ApoB was detected on freshly isolated erythrocytes (range: 0·1-5·5 au; mean ± SEM 0·86 ± 0·09 au) in all but nine subjects (four CAD+ and five CAD-). Ery-apoB was lower in CAD+ (0·62 ± 0·09 au) compared to CAD- (1·18 ± 0·10 au; P < 0·001). Higher ery-apoB was associated with a lower risk of CAD (adjusted OR: 0·003 (95% CI: 0·001-0·08; P < 0·001), but the protective effect was diminished with increasing age (adjusted OR: 1·10 (95% CI: 1·04-1·16; P < 0·001). IMT was increased in CAD+ subjects (0·77 ± 0·13 mm) compared to CAD- (0·57 ± 0·14 mm; P < 0·001). A significant negative association was found between ery-apoB and IMT (ß = -0·214: 95% CI -0·284 to -0·145; P < 0·001). There was no association between ery-apoB and plasma apoB (Pearson's r = -0·45; P = 0·57). CONCLUSIONS: Human erythrocytes carry apoB-containing lipoproteins. Subjects with atherosclerosis have lower ery-apoB. High ery-apoB may be protective against atherosclerosis and may reflect an alternative blood cell-mediated lipoprotein transport system in the circulation, in which these lipoproteins less likely interact with the endothelium.
Assuntos
Apolipoproteínas B/sangue , Aterosclerose/sangue , Eritrócitos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/diagnóstico por imagem , Espessura Intima-Media Carotídea , Angiografia Coronária/métodos , Estudos Transversais , Feminino , Citometria de Fluxo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Most dyslipidemic conditions have been linked to an increased risk of cardiovascular disease. Over the past few years major advances have been made regarding the genetic and metabolic basis of dyslipidemias. Detailed characterization of the genetic basis of familial lipid disorders and knowledge concerning the effects of environmental factors on the expression of dyslipidemias have increased substantially, contributing to a better diagnosis in individual patients. In addition to these developments, therapeutic options to lower cholesterol levels in clinical practice have expanded even further in patients with familial hypercholesterolemia and in subjects with cardiovascular disease. Finally, promising upcoming therapeutic lipid lowering strategies will be reviewed. All these advances will be discussed in relation to current clinical practice with special focus on common lipid disorders including familial dyslipidemias.
Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Dislipidemias/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Dislipidemias/genética , Dislipidemias/metabolismo , Humanos , Lipídeos/antagonistas & inibidoresRESUMO
BACKGROUND AND AIMS: Rheumatoid arthritis (RA) has been associated with an increased risk of atherosclerosis. We aimed to evaluate the progression of carotid intima media thickness (cIMT) in RA patients subject to a cardiovascular treat-to-target intervention. In addition, the presence of the metabolic syndrome (MetS) on cIMT outcomes was evaluated. METHODS: We performed a cohort analysis of FRANCIS, in which RA patients ≤70 years without CVD or diabetes mellitus were randomized for either a treat-to-target intervention or usual care concerning CVD risk factors. MetS was scored at baseline. RESULTS: Three-year data was available in 212 well-controlled RA patients. The treat-to-target intervention resulted in a lower cIMT progression over three years compared to the usual care. However, there was no difference in cIMT at three years between groups. MetS was present in 40.1% of RA patients. Baseline cIMT was significantly higher in RA patients with MetS compared to those without (0.619 (0.112) versus 0.557 (0.104) mm; pâ¯<â¯0.001). After three years, cIMT progression was comparable (0.043 (0.071) versus 0.043 (0.072) mm; pâ¯=â¯0.96). In RA patients with MetS, the presence of plaques increased over three years from 12.9% to 23.5% (pâ¯=â¯0.01). The type of intervention had no effect on cIMT progression in RA patients with MetS. However, in subjects without MetS, treat-to-target resulted in a lower progression. CONCLUSIONS: RA patients with MetS showed an increased CVD risk profile based on both a higher prevalence of CVD risk factors and structural vascular changes. A treat-to-target approach of CVD risk factors reduced cIMT progression only in RA patients without MetS.
Assuntos
Artrite Reumatoide/epidemiologia , Doenças das Artérias Carótidas/epidemiologia , Artéria Carótida Primitiva , Síndrome Metabólica/epidemiologia , Adulto , Idoso , Anti-Hipertensivos/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/mortalidade , Artrite Reumatoide/terapia , Doenças Assintomáticas , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/mortalidade , Doenças das Artérias Carótidas/prevenção & controle , Artéria Carótida Primitiva/diagnóstico por imagem , Espessura Intima-Media Carotídea , Progressão da Doença , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Hipolipemiantes/uso terapêutico , Masculino , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/mortalidade , Síndrome Metabólica/terapia , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Placa Aterosclerótica , Prevalência , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Comportamento de Redução do Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Obesity is related to increased cardiovascular risk. It is unknown whether increasing levels of obesity also increase levels of cardiovascular risk factors and systemic inflammation. This study describes the relationship between classic cardiovascular risk factors and inflammatory markers with BMI in a group of obese and non-obese subjects. MATERIALS AND METHODS: Obese subjects (BMI ≥ 30 kg/m2; n = 576; mean ± SD BMI 43.8 ± 7.58 kg/m2) scheduled for bariatric surgery were included. The reference population consisted of non-obese volunteers (BMI < 30 kg/m2; n = 377, BMI 25.0 ± 2.81 kg/m2). The relationship between BMI quintiles and the levels of cardiovascular risk factors was analyzed. Adipose tissue volumetry was performed in 42 obese subjects using abdominal CT scans. RESULTS: The obese group included more women and subjects with type 2 diabetes mellitus, hypertension, and current smoking behavior. In obese subjects, HDL-C and triglycerides decreased with increasing BMI. Systolic and diastolic blood pressure, total cholesterol, LDL-C, and apoB were not related to BMI in the obese group, in contrast to the non-obese group. Inflammatory markers CRP, leukocyte count, and serum complement C3 increased with increasing BMI in the obese group, while these relations were less clear in the non-obese group. The subcutaneous adipose tissue surface was positively correlated to BMI, while no correlation was observed between BMI and visceral adipose tissue. CONCLUSIONS: Markers of inflammation are strongest related to BMI in obese subjects, most likely due to increased adipose tissue mass, while cardiovascular risk factors do not seem to deteriorate above a certain BMI level. Limited expansion capacity of visceral adipose tissue may explain these findings.
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Índice de Massa Corporal , Doenças Cardiovasculares , Obesidade Mórbida , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2 , Feminino , Humanos , Masculino , Obesidade Mórbida/complicações , Obesidade Mórbida/epidemiologia , Fatores de Risco , Gordura SubcutâneaRESUMO
AIMS: Routinely fasting is not necessary for measuring the lipid profile according to the latest European consensus. However, LDL-C tends to be lower in the non-fasting state with risk of misclassification. The extent of misclassification in secondary cardiovascular prevention with a non-fasting lipid profile was investigated. METHODS AND RESULTS: 329 patients on lipid lowering therapy for secondary cardiovascular prevention measured a fasting and non-fasting lipid profile. Cut-off values for LDL-C, non-HDL-C and apolipoprotein B were set at <1.8mmol/l, <2.6mmol/l and <0.8g/l, respectively. Study outcomes were net misclassification with non-fasting LDL-C (calculated using the Friedewald formula), direct LDL-C, non-HDL-C and apolipoprotein B. Net misclassification <10% was considered clinically irrelevant. Mean age was 68.3±8.5years and the majority were men (79%). Non-fasting measurements resulted in lower LDL-C (-0.2±0.4mmol/l, P<0.001), direct LDL-C (-0.1±0.2mmol/l, P=0.001), non-HDL-C (-0.1±0.4mmol/l, P=0.004) and apolipoprotein B (-0.02±0.10g/l, P=0.004). 36.0% of the patients reached a fasting LDL-C target of <1.8mmol/l with a significant net misclassification of 10.7% (95% CI 6.4-15.0%) in the non-fasting state. In the non-fasting state net misclassification with direct LDL-C was 5.7% (95% CI 2.1-9.2%), 4.0% (95% CI 1.0-7.4%) with non-HDL-C and 4.1% (95% CI 1.1-9.1%) with apolipoprotein B. CONCLUSION: Use of non-fasting LDL-C as treatment target in secondary cardiovascular prevention resulted in significant misclassification with subsequent risk of undertreatment, whereas non-fasting direct LDL-C, non-HDL-C and apolipoprotein B are reliable parameters.
Assuntos
Análise Química do Sangue/normas , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/prevenção & controle , Jejum/sangue , Lipídeos/sangue , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Valores de ReferênciaRESUMO
CONTEXT: Cholecalciferol (vitamin D3) improves vascular function and inflammation, potentially providing an explanation for the proposed cardiovascular protection of vitamin D. OBJECTIVE: We investigated whether cholecalciferol supplementation reduces postprandial arterial dysfunction and inflammation. DESIGN: Randomized, 1:1, double-blind trial. SETTING: Diabetes and Vascular Center, Franciscus Gasthuis, Rotterdam, The Netherlands. PATIENTS: Twenty-four healthy, premenopausal, overweight or obese, vitamin D-deficient women. INTERVENTIONS: A single high (300,000 IU) or low dose (75,000 IU) of cholecalciferol. MAIN OUTCOME MEASURES: The effect of low- and high-dose cholecalciferol on postprandial leukocyte activation markers, pulse wave velocity (PWV), and augmentation index (AIx) during an oral fat loading test, expressed as area under the curve (AUC). RESULTS: High- and low-dose supplementation increased vitamin D by 163% ± 134% (P < 0.001) and 66% ± 59% (P < 0.001), respectively. Monocyte CD11b-AUC slightly increased after low but not high dose (6% ± 2%, P = 0.012, and 4% ± 1%, P = 0.339, respectively). There were no significant effects on postprandial PWV or AIx by high- or low-dose vitamin D. Fasting complement component 3 (C3) levels decreased by 5.9% (P = 0.004) in the high-dose group and by 4.0% (P = 0.018) in the low-dose group. CONCLUSION: A single dose of vitamin D does not seem to reduce arterial stiffness and leukocyte activation in overweight, vitamin D-deficient women. Vitamin D may decrease fasting C3. Possibly, higher vitamin D concentrations may be needed to decrease inflammation and improve vascular function in overweight or obese vitamin D-deficient women.
Assuntos
Colecalciferol/administração & dosagem , Obesidade/metabolismo , Período Pós-Prandial , Rigidez Vascular , Deficiência de Vitamina D/tratamento farmacológico , Vitaminas/administração & dosagem , Adulto , Apolipoproteína A-I/metabolismo , Apolipoproteínas B/metabolismo , Área Sob a Curva , Proteína C-Reativa/imunologia , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Complemento C3/imunologia , Método Duplo-Cego , Feminino , Humanos , Inflamação , Contagem de Leucócitos , Monócitos/imunologia , Neutrófilos/imunologia , Obesidade/complicações , Obesidade/fisiopatologia , Sobrepeso/complicações , Sobrepeso/metabolismo , Sobrepeso/fisiopatologia , Análise de Onda de Pulso , Triglicerídeos/metabolismo , Vitamina D/análogos & derivados , Vitamina D/metabolismo , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/metabolismo , Deficiência de Vitamina D/fisiopatologia , Adulto JovemRESUMO
BACKGROUND AND AIMS: The postprandial situation is a pro-inflammatory condition most likely linked to the development of atherosclerosis. We evaluated the relationship between apolipoprotein (apo) B48 and fasting and postprandial leukocyte activation markers. METHODS: Leukocyte activation markers and apo B48 were determined in 80 subjects with and without coronary artery disease (CAD). Twelve healthy subjects underwent an oral fat loading test (up to 8 h). RESULTS: Fasting apo B48 was significantly higher in patients with CAD (n = 47, 8.1 ± 5.2 mg/L) than in subjects without CAD (n = 33, 5.9 ± 3.9 mg/L, p = 0.022). Fasting apo B48 and triglycerides correlated positively with fasting monocyte CD11b and neutrophil CD66b expression. Plasma apo B48 and leukocyte activation markers increased after an oral fat load. No correlations were found between fasting or postprandial triglycerides and postprandial leukocyte activation markers. We observed no correlations between postprandial apo B48 and postprandial neutrophil CD11b or CD66b expression. CONCLUSION: This study suggests that chylomicron remnants may be responsible for postprandial leukocyte activation in the circulation. The postprandial chylomicron response may be a stronger mediator of postprandial inflammation than postprandial triglyceridemia.