ABSTRACT
OBJECTIVES: To compare the prevalence of carotid atherosclerosis in virologically suppressed HIV patients with that of a community sample, and to evaluate the capacity of various cardiovascular risk (CVR) equations for predicting carotid atherosclerosis. METHODS: This was a cross-sectional study with two randomly selected groups: HIV patients from an HIV unit and a control group drawn from the community. Participants were matched by age (30-80 years) and sex without history of cardiovascular disease. Carotid plaque, common carotid intima-media thickness (cc-IMT) and subclinical atherosclerosis (carotid plaque and/or cc-IMT > 75th percentile) were assessed by carotid ultrasound. The Systematic Coronary Risk Evaluation (SCORE), Framingham, REGICOR, reduced Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:D), and COMVIH equations were applied, and their abilities to predict carotid plaque were compared using the area under the curve (AUC). RESULTS: Each group included 379 subjects (77.8% men, age 49.7 years). Duration of antiretroviral therapy was 15.5 years. There were no differences between the groups for carotid plaque (HIV, 33.2%; control, 31.3%), mean cc-IMT (HIV, 0.63 mm; control, 0.61 mm) or subclinical atherosclerosis (HIV, 42.9%; control, 47.9%). Thymidine analogues were independently associated with subclinical atherosclerosis in HIV-infected patients. CVR equations revealed AUCs between 0.715 and 0.807 for prediction of carotid plaque; prediction was better in the control group and did not improve when HIV-adapted scales were used. CONCLUSIONS: The features of carotid atherosclerosis did not differ between the HIV-infected and the control group, although CVR equations were more predictive for carotid plaque in controls than in HIV-infected patients. HIV-specific equations did not improve prediction.
Subject(s)
Cardiovascular Diseases , Carotid Artery Diseases , HIV Infections , Adult , Aged , Aged, 80 and over , Carotid Artery Diseases/diagnostic imaging , Carotid Artery Diseases/epidemiology , Carotid Intima-Media Thickness , Cross-Sectional Studies , Female , HIV Infections/complications , HIV Infections/drug therapy , Heart Disease Risk Factors , Humans , Male , Middle Aged , Risk FactorsABSTRACT
OBJECTIVE: To assess the diagnostic performance of high-sensitivity troponin T (hs-TnT) in patients with suspected non-ST elevation acute coronary syndrome (NSTE-ACS); confirm whether it shortens the time to diagnosis; and analyze the clinical consequences derived from its use. METHOD: A prospective, longitudinal observational study was carried out in 5 emergency care departments. Patients seen for chest pain with suspected of NSTE-ACS were consecutively included. Patient care followed the internal protocols of the center, based on the consensus guidelines of the European Society of Cardiology. Serial conventional cardiac troponin (cTn) and hs-TnT determinations were made. RESULTS: A total of 351 patients were included in the study. A final diagnosis of acute myocardial infarction (AMI) was established in 77 patients, with unstable angina in 102, and no acute coronary syndrome in 172 patients. The hs-TnT values were above percentile 99% in a large number of patients without AMI. In the initial determination, the diagnostic sensitivity of the hs-TnT was significantly greater than that of cTn (87.0% vs. 42.9%), which led to a negative predictive value of 95.1%. CONCLUSIONS: High-sensitivity troponin T improves diagnostic performance compared with conventional troponin assay, shortens the time to diagnosis, and identifies a larger number of patients with smaller myocardial infarctions.
Subject(s)
Acute Coronary Syndrome/diagnosis , Myocardial Infarction/diagnosis , Troponin T/blood , Acute Coronary Syndrome/blood , Adult , Aged , Aged, 80 and over , Angina, Unstable/blood , Angina, Unstable/diagnosis , Biomarkers/blood , Female , Humans , Longitudinal Studies , Male , Middle Aged , Myocardial Infarction/blood , Non-ST Elevated Myocardial Infarction/blood , Non-ST Elevated Myocardial Infarction/diagnosis , Predictive Value of Tests , Prospective Studies , Sensitivity and Specificity , Time Factors , Troponin/bloodABSTRACT
PURPOSE: To analyse the capacity of whole-blood NGAL (wbNGAL) to stratify AKI in critically ill patients with and without sepsis. METHODS: Whole-blood NGAL was measured with a point-of-care device at admission and 48 hours later in patients admitted to a general ICU. Patients were classified by the AKIN and KDIGO classifications at admission and 24 and 48 hours. We performed an ROC curve analysis. wbNGAL values at admission were compared in patients with sepsis and septic shock. RESULTS: The study included 100 consecutively admitted patients (40 female) with mean age 59.1 ± 17.8 years. Thirty-three patients presented AKI at admission, and 10 more developed it in the next 48 h. Eighteen patients had AKI stage 3, 14 of them at admission. Nine patients required renal replacement therapy. According to KDIGO at admission, wbNGAL values were 78 µg/L (60-187) in stage 0 (n = 67), 263 µg/L (89-314) in stage 1 (n = 8), 484 µg/L (333-708) in stage 2 (n = 11), and 623 µg/L (231-911) in stage 3 (n = 14), p = 0.0001 for trend. Ten patients did not complete 48 hours of study: 6 of 10 were discharged (initial wbNGAL 130 µg/L (60-514)) and 4 died (773 µg/L (311-1010)). The AUROC curve of wbNGAL to predict AKI was 0.838 (95% confidence interval 0.76-0.92, p = 0.0001), with optimal cut-off value of 178 µg/L (sensitivity 76.7%, specificity 78.9%, p < 0.0001). At admission, twenty-nine patients had sepsis, of whom 20 were in septic shock. wbNGAL concentrations were 81 µg/L (60-187) in patients without sepsis, 481 (247-687) in those with sepsis, and 623.5 µg/L (361-798) in the subgroup of septic shock (p < 0.0001). CONCLUSIONS: Whole-blood NGAL concentration at ICU admission was a good stratifier of AKI in critically ill patients. However, wbNGAL concentrations were higher in septic patients irrespective of AKI occurrence.
Subject(s)
Acute Kidney Injury/blood , Lipocalin-2/blood , Acute Kidney Injury/pathology , Adult , Aged , Biomarkers/blood , Critical Illness , Female , Humans , Male , Middle AgedABSTRACT
PURPOSE: To analyse the usefulness of the composite index of the tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) as urinary biomarkers for the early prediction of AKI in septic and non-septic patients. METHODS: This is a prospective, observational study including patients admitted to ICU from acute care departments and hospital length of stay <48 h. The main exclusion criteria were pre-existing eGFR <30 mL/min/1.73 m2 and hospitalisation 2 months prior to current admission. The [TIMP-2]·[IGFBP7] index was analysed twice, within the first 12 h of ICU admission. RESULTS: The sample included 98 patients. AKI incidence during ICU stay was 50%. Sepsis was diagnosed in 40.8%. Baseline renal variables were comparable between subgroups except for a higher baseline eGFR in non-septic patients. Patients were stratified based on the presence of AKI and their highest level of [TIMP-2]·[IGFBP7] within the first 12 h of stay. [TIMP-2]·[IGFBP7] index values were dependent on the incidence of AKI but not of sepsis. [TIMP-2]·[IGFBP7] values were significantly related to AKI severity according to AKIN criteria (p < 0.0001). The AUROC curve to predict AKI of the worst [TIMP-2]·[IGFBP7] index value was 0.798 (sensitivity 73.5%, specificity 71.4%, p < 0.0001). Index values below 0.8 ruled out any need for renal replacement (NPV 100%), whereas an index >0.8 predicted a rate of AKI of 71% and AKIN ≥ 2 of 62.9%. CONCLUSIONS: In our study, urinary [TIMP-2]·[IGFBP7] was an early predictor of AKI in ICU patients regardless of sepsis. Besides, index values <0.8(ng/mL)2/1000 ruled out the need for renal replacement.
ABSTRACT
Primary graft dysfunction after heart transplantation (HTx) has a very high mortality rate, especially if the left ventricle (PGD-LV) is involved. Early diagnosis is important to select the appropriate therapy to improve prognosis. The value of high-sensitivity troponin T (HS-TNT) measurement obtained at patient arrival at the intensive care unit was analyzed in 71 HTx patients. Mild or moderate PGD-LV was defined by hemodynamic compromise with one of the following criteria: left ventricular ejection fraction <40%, hemodynamic compromise with right atrial pressure >15 mm Hg, pulmonary capillary wedge pressure >20 mm Hg, cardiac index <2.0 L/min/m2, hypotension (mean arterial pressure <70 mm Hg), and need for high-dose inotropes (inotrope score >10) or newly placed intra-aortic balloon pump. The mean recipient age was 54 ± 12 years (73% men), and donor age was 47 ± 11 years. Ischemic time was 200 ± 51 minutes, and coronary bypass time was 122 ± 31 minutes. Nine (13%) HTx patients were diagnosed with PGD-LV post-HTx, 8 with biventricular dysfunction. Four patients died, 2 with PGD-LV (22%) and 2 without PGD (4%). Mean HS-TNT before HTx was 158 ± 565 ng/L, and post-HT was 1621 ± 1269 ng/L. The area under the curve (receiver-operator characteristic) of HS-TNT to detect patients at risk of PGD-LV was 0.860 (P < .003). A cutoff value of HS-TNT >2000 ng/L had a sensitivity of 75% and specificity of 87% to identify patients at risk of PGD-LV. Multivariate analysis identified HS-TNT >2000 ng/L (P < .02) and coronary bypass-time (P < .01) as independent predictors of PGD-LV. HS-TNT >2000 ng/L at intensive care admission after HT and prolonged coronary bypass time were the most powerful predictors of PGD-LV. HS-TNT may be helpful for early detection of HTx patients at risk of PGD-LV.
Subject(s)
Heart Transplantation/adverse effects , Primary Graft Dysfunction/diagnosis , Troponin T/metabolism , Ventricular Dysfunction, Left/diagnosis , Biomarkers/metabolism , Coronary Artery Bypass/adverse effects , Early Diagnosis , Female , Heart Ventricles , Humans , Male , Middle Aged , Postoperative Complications/diagnosis , Prognosis , ROC Curve , Sensitivity and Specificity , Stroke Volume/physiology , Ventricular Dysfunction, Left/etiologyABSTRACT
Natriuretic peptides are a useful laboratory tool for the diagnosis, prognosis and treatment of patients with heart failure. Natriuretic peptides are used in various healthcare settings (consultations, emergency department, hospitalization, laboratory) and by various primary care and specialised professionals. However, their use in clinical practice is still scare and uneven. Properly using and interpreting natriuretic peptides in clinical practice requires a minimum of prelaboratory (pathophysiology), laboratory (methods) and postlaboratory (interpretation and integration of clinical data) expertise. The objective of this consensus document, developed by several scientific societies, is to update the necessary concepts and expertise on natriuretic peptides that enable its application in the diagnosis, prognosis and treatment of heart failure, in various healthcare environments.
ABSTRACT
BACKGROUND: Endomyocardial biopsy (EMB) remains the gold standard for detecting acute rejection (AR) after heart transplantation (HTx). Non-invasive detection of AR thus far remains a challenge. Several studies have demonstrated that highly sensitive cardiac troponin T (hs-cTnT) concentrations have a low positive predictive value for diagnosing AR. Nevertheless, hs-cTnT proved to be useful for ruling out AR after HTx. An hs-cTnT concentration <17 ng/L, a value close to that used for rule-in or rule-out myocardial infarction, was associated with a 100% negative predictive value of AR. However, the cost-effectiveness of a strategy with the use of hs-cTnT for ruling out AR in HTx patients remains to be proven. METHODS: The cost-effectiveness of hs-cTnT determination for ruling out AR was assessed, comparing the costs of hs-cTnT measurements in 305 blood samples obtained at the time of EMB. Eighteen samples were excluded because the EMB was not assessable. RESULTS: Hs-cTnT determination cost 16.00 per sample, whereas EMB cost 1752.00 per biopsy; cost estimations included direct and indirect (30%) charges. Thirty-nine (13.6%) of the 287 blood samples presented hs-cTnT concentrations <17 ng/L; in none of them was an AR >2R degree found in the EMB. The cost of the assessment in the 287 blood samples and biopsies was of 4592.00 for hs-cTnT and 502,824.00 for EMB. Hs-cTnT systematic measurement would have avoided 39 EMB, with a saving of 68,328.00, which represents the 13.5% of the total budget expended in these cases. CONCLUSIONS: The use of hs-cTnT values to rule out the need of EMB for AR diagnosis after HTx appears to be a cost-effective procedure.
Subject(s)
Graft Rejection/blood , Heart Failure/surgery , Heart Transplantation , Myocardium/pathology , Troponin T/blood , Adult , Aged , Biomarkers/blood , Biopsy , Cost-Benefit Analysis , Female , Graft Rejection/diagnosis , Humans , Male , Middle AgedABSTRACT
BACKGROUND: Electronegative LDL (LDL(−)), a modified LDL fraction found in blood, induces the release of inflammatory mediators in endothelial cells and leukocytes. However, the inflammatory pathways activated by LDL(−) have not been fully defined. We aim to study whether LDL(−) induced release of the first-wave proinflammatory IL-1ß in monocytes and monocyte-derived macrophages (MDM) and the mechanisms involved. METHODS: LDL(−) was isolated from total LDL by anion exchange chromatography. Monocytes and MDM were isolated from healthy donors and stimulated with LDL(+) and LDL(−) (100 mg apoB/L). RESULTS: In monocytes, LDL(−) promoted IL-1ß release in a time-dependent manner, obtaining at 20 h-incubation the double of IL-1ß release induced by LDL(−) than by native LDL. LDL(−)-induced IL-1ß release involved activation of the CD14-TLR4 receptor complex. LDL(−) induced priming, the first step of IL-1ß release, since it increased the transcription of pro-IL-1ß (8-fold) and NLRP3 (3-fold) compared to native LDL. Several findings show that LDL(−) induced inflammasome activation, the second step necessary for IL-1ß release. Preincubation of monocytes with K+ channel inhibitors decreased LDL(−)-induced IL-1ß release. LDL(−) induced formation of the NLRP3-ASC complex. LDL(−) triggered 2-fold caspase-1 activation compared to native LDL and IL-1ß release was strongly diminished in the presence of the caspase-1 inhibitor Z-YVAD. In MDM, LDL(−) promoted IL-1ß release, which was also associated with caspase-1 activation. CONCLUSIONS: LDL(−) promotes release of biologically active IL-1ß in monocytes and MDM by induction of the two steps involved: priming and NLRP3 inflammasome activation. SIGNIFICANCE: By IL-1ß release, LDL(−) could regulate inflammation in atherosclerosis.
Subject(s)
Inflammasomes/drug effects , Interleukin-1beta/metabolism , Lipoproteins, LDL/pharmacology , Macrophages/drug effects , Monocytes/drug effects , Apolipoprotein L1 , Apolipoproteins/pharmacology , Apolipoproteins B/pharmacology , CARD Signaling Adaptor Proteins , Carrier Proteins/genetics , Carrier Proteins/immunology , Caspase 1/genetics , Caspase 1/immunology , Cell Line , Cytoskeletal Proteins/genetics , Cytoskeletal Proteins/immunology , Gene Expression Regulation , Humans , Inflammasomes/immunology , Interleukin-1beta/immunology , Lipopolysaccharide Receptors/genetics , Lipopolysaccharide Receptors/immunology , Lipoproteins, HDL/pharmacology , Macrophage Activation/drug effects , Macrophages/cytology , Macrophages/immunology , Monocytes/cytology , Monocytes/immunology , NLR Family, Pyrin Domain-Containing 3 Protein , Potassium Channels/genetics , Potassium Channels/immunology , Primary Cell Culture , Signal Transduction , Static Electricity , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/immunology , Transcription, GeneticABSTRACT
BACKGROUND: There is clinical interest in identifying novel lipid biomarkers for evaluating cardiovascular risk and targeting lipid-lowering treatment. Low-density lipoprotein receptor-related protein 1 (LRP1) plays a crucial role in the dysregulated cholesterol transfer from modified lipoproteins to human coronary vascular smooth muscle cells (hVSMCs), promoting hVSMC-derived foam cell formation. LRP1 has a soluble and circulating form (sLRP1) generated from LRP1. Cholesterol modulates the release of the soluble form of LRP1. Using in vitro, ex vivo and patient-based approaches, we tested the association between circulating sLRP1 concentrations and hypercholesterolemia and the potential of sLRP1 as a biomarker of atherosclerosis. METHODS AND RESULTS: Circulating sLRP1 concentrations were higher in severe hypercholesterolemia compared to moderate hypercholesterolemia or normocholesterolemia (Study 1). Circulating sLRP1 was significantly associated with established pro-atherogenic lipid parameters in two different hypercholesterolemic populations (Studies 2 and 3). sLRP1 concentrations decreased after statin treatment and increased after statin withdrawal (Study 3). In vitro experiments showed that native LDL, aggregated LDL and VLDL+IDL lipoproteins induced the release of sLRP1 from hVSMC. sLRP1 levels were increased in the conditioned medium of coronary atherosclerotic plaque areas extracted from patients compared to non-atherosclerotic areas of the same coronary artery and patient. Circulating sLRP1 concentrations were independently associated with the occurrence of carotid atherosclerosis in a hypercholesterolemic population (Study 2). The later association was higher than that observed for other classical or novel lipid parameters. CONCLUSIONS: Circulating sLRP1 is a new lipid-related parameter potentially useful as a biomarker for atherosclerosis.
Subject(s)
Atherosclerosis/blood , Atherosclerosis/diagnosis , Hypercholesterolemia/blood , Hypercholesterolemia/diagnosis , Low Density Lipoprotein Receptor-Related Protein-1/blood , Adult , Aged , Biomarkers/blood , Cells, Cultured , Female , Humans , Male , Middle Aged , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , Young AdultABSTRACT
BACKGROUND: This observational study was designed to evaluate and compare the usefulness of BNP and NT-proBNP concentrations to detect the existence and severity of left ventricular diastolic dysfunction (LVDD) in critically ill patients. METHODS: A prospective, observational study in a university hospital. The sample included 86 consecutive adult patients. Based on echocardiography data, LVDD were classified into normal, impaired relaxation, pseudonormal or restrictive patterns. Patients were classified according to whether filling pressures were elevated or non-elevated in the echocardiography. Sampling for natriuretic peptides was performed immediately before echocardiography. RESULTS: Fifty patients showed LVDD. The most frequently observed pattern was impaired relaxation (N.=35), followed by the restrictive (N.=9) and the pseudonormal (N.=6) patterns. BNP concentrations in restrictive and pseudonormal patterns were higher than in normal and impaired relaxation patterns, while NT-proBNP only showed differences between normal and pseudonormal or restrictive patterns. Cut-off values using ROC curve analyses to detect LVDD were 125 ng/L for BNP and 390 ng/L NT-proBNP. BNP and NT-proBNP concentrations were higher in the 15 patients with restrictive and pseudonormal patterns, suggesting elevated filling pressures. Cut-off values using ROC curve analyses to detect echocardiography signs of elevated filling pressures were 254 ng/L for BNP and 968 for NT-proBNP. Both natriopeptides performed in a similar way to detect LVDD and elevated filling pressures. CONCLUSION: Both BNP and NT-proBNP are useful screening tools to detect the presence of advanced degrees of LVDD, and especially to rule out elevated filling pressures.
Subject(s)
Heart Failure, Diastolic/diagnosis , Natriuretic Peptide, Brain , Ventricular Dysfunction, Left/diagnosis , Adult , Aged , Critical Illness , Female , Heart Failure, Diastolic/diagnostic imaging , Humans , Male , Middle Aged , Peptide Fragments , Pilot Projects , Prospective Studies , Ultrasonography , Ventricular Dysfunction, Left/diagnostic imagingABSTRACT
Polycystic ovary syndrome (PCOS) is associated with the metabolic syndrome (MetS). The metabolic disorders are not universal and may vary with race, age and phenotype. Our purpose was to determine the clinical and biochemical characteristics of Mediterranean PCOS women with MetS, compare them with non-MetS PCOS patients, and assess the ability of clinical data and biochemical tests to predict these abnormalities within our population. A total of 218 subjects, 196 PCOS women and 22 controls, undergo a physical examination and laboratory evaluation for a diagnosis of MetS. MetS was categorized according to NCEP ATP III guidelines. PCOS patients were analyzed separately and compared in three subgroups: three or more MetS criteria, two criteria, one or no criteria. The overall prevalence of MetS was 21.4%. Women with MetS had higher glucose (G) levels than PCOS women with two criteria (5.7 ± 1.5 vs 5 ± 0.4, p < 0.05). Both groups were comparable for all the other parameters. Waist circumference (WC), body mass index (BMI), systolic (SBP) and diastolic blood pressure (DBP), bioavailable testosterone (uT), triglycerides (TG) and insulin (I) levels were significantly higher and sex hormone-binding globulin (SHBG) levels, high-density lipoprotein (HDL), HOMA and QUICKI indexes significantly lower in both groups, MetS and patients with two criteria, compared with women with one or no criteria and the control group. WC, HDL and TG were the best predictors of PCOS patients at risk for MetS. In conclusion, we recommend considering PCOS patients with two criteria of MetS as having the same risk as patients with the full syndrome. Waist circumference with HDL and triglycerides is an efficient combined test to identify PCOS women at risk for metabolic and cardiovascular diseases.
Subject(s)
Blood Glucose , Metabolic Syndrome/complications , Obesity/complications , Polycystic Ovary Syndrome/complications , Adult , Body Mass Index , Female , Humans , Lipoproteins, HDL/blood , Metabolic Syndrome/blood , Metabolic Syndrome/epidemiology , Obesity/blood , Polycystic Ovary Syndrome/blood , Prevalence , Risk Factors , Triglycerides/blood , Waist Circumference , Women , Young AdultABSTRACT
BACKGROUND: The aim of this study was to compare the prevalence of metabolic syndrome in human immunodeficiency virus (HIV)-infected patients treated with highly active antiretroviral therapy (HAART), using the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), European Group for the Study of Insulin Resistance (EGIR), and International Diabetes Federation (IDF) definitions. METHODS: A cross-sectional study was carried out with 159 consecutive adult HIV-infected subjects (120 males and 39 females) under HAART. Anthropometric and laboratory parameters were measured by standard methods. Hyperinsulinemia was defined by a fasting concentration >75th percentile of values obtained in healthy individuals (107.5 pmol/L). RESULTS: The prevalence of ATP III-defined metabolic syndrome was 10.1%; it was 28.3% according to EGIR criteria and 15.1% using the IDF definition. The concordance between the definitions was low (kappa coefficient ranging between 0.134 and 0.296). All subjects with EGIR-defined metabolic syndrome had hyperinsulinemia, but only 50% of those with ATP III-defined metabolic syndrome and 62.5% in the IDF metabolic syndrome population had hyperinsulinemia. CONCLUSIONS: The inclusion of hyperinsulinemia as a criterion in the EGIR metabolic syndrome definition made it more discriminative than the ATP III definition, both in men and women, and than the IDF definition in men to identify metabolic syndrome in HIV-infected subjects under HAART.
Subject(s)
HIV Infections/complications , Metabolic Syndrome/complications , Metabolic Syndrome/epidemiology , Adult , Anthropometry/methods , Antiretroviral Therapy, Highly Active/methods , Cross-Sectional Studies , Diabetes Mellitus/diagnosis , Europe , Female , Humans , Hyperinsulinism/pathology , Insulin Resistance , Male , Metabolic Syndrome/diagnosis , Middle Aged , PrevalenceABSTRACT
A total of 1,429 serum samples from 389 consecutive patients with acute chest pain were analyzed with the goal to aid the rapid diagnosis of acute myocardial infarction. To the best of our knowledge this is the largest and most comprehensive study on mid-infrared spectroscopy in cardiology. We were able to identify those signatures in the mid-infrared spectra of the samples, which were specific to either acute myocardial infarction or chest pain of other origin (angina pectoris, oesophagitis, etc). These characteristic spectral differences were used to distinguish between the cause of the donor's acute chest pain using robust linear discriminant analysis. A sensitivity of 88.5% and a specificity of 85.1% were achieved in a blind validation. The area under the receiver operating characteristics curve amounts to 0.921, which is comparable to the performance of routine cardiac laboratory markers within the same study population. The biochemical interpretation of the spectral signatures points towards an important role of carbohydrates and potentially glycation. Our studies indicate that the "Diagnostic Pattern Recognition (DPR)" method presented here has the potential to aid the diagnostic procedure as early as within the first 6 hours after the onset of chest pain.
Subject(s)
Chest Pain/diagnosis , Spectrophotometry, Infrared/methods , Triage/methods , Adult , Aged , Aged, 80 and over , Chest Pain/metabolism , Female , Humans , Male , Middle Aged , ROC Curve , Reference Standards , Sensitivity and Specificity , Spectrophotometry, Infrared/standards , Time Factors , Triage/standards , Young AdultABSTRACT
BACKGROUND: Abdominal fat (both visceral and subcutaneous) accumulation is associated with an increased risk of developing insulin resistance. The latter stands as the basis upon which diabetes, hypertension, and atherogenic dyslipidemia tend to build up. Hence, abdominal liposuction (AL) could theoretically hold metabolic benefits. We undertook the present study to assess the effects of AL on carbohydrate and lipid metabolism. METHODS: This is a prospective study including 20 healthy volunteers (M2/F18) aged 39.6 +/- 7.7 years old (24-52), body mass index (BMI) = 25.3 +/- 4.7 kg/m(2) (19.8-36) who underwent AL. Before and 4 months after AL, we measured glucose and insulin concentrations, HOMA index [glucose (mM) x IRI (microUI/l)/22.5], free fatty acids (FFA), glycerol, total cholesterol and triglycerides, high-density lipoprotein (HDL)-cholesterol (HDL-c), low-density lipoprotein (LDL)-cholesterol (LDL-c), very low-density lipoprotein (VLDL)-cholesterol (VLDL-c) and apolipoproteins (apo) B, AI and AII, adiponectin (Adp), and ultra-sensitive C-reactive protein (CRP). RESULTS: Lipo-aspirate averaged 5.494 +/- 5.297 cc (600-19.000). Weight, BMI, and waist circumference decreased significantly 4 months after surgery by 4.6, 4.6 and 5.9%, respectively. There were significant decrements in FFA (-35%, p < 0.0001), glycerol (-63%, p < 0.0005), VLDL-c (-15.2%; p < 0.001), and triglycerides (-21.3%, p < 0.002), an increase in HDL-c (+10%, p < 0.03), Apo AI (+10.1%, p < 0.02), and Apo AII (+11.8%, p < 0.001). Total cholesterol, LDL-c, ApoB, and the LDL-c/ApoB ratio raised by +15% (p < 0.0005), +27.3% (p < 0.000), +15.1% (p < 0.008) and +2.76% (p < 0.008), respectively. Glucose, insulin, the HOMA index, Adp, and CRP were not significantly altered after AL. CONCLUSION: AL in healthy normal weight or slightly overweight subjects improves the major lipoprotein components of obesity-associated dyslipidemia. This improvement occurs independent of insulin sensitivity.
Subject(s)
Insulin Resistance/physiology , Lipectomy , Lipid Metabolism/physiology , Overweight/metabolism , Overweight/surgery , Subcutaneous Fat, Abdominal/surgery , Adiponectin/blood , Adult , Blood Glucose/metabolism , C-Reactive Protein/metabolism , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective StudiesABSTRACT
AIMS/HYPOTHESIS: Chemical and biological characteristics of LDL(-) from type 1 diabetic subjects were analysed. The diabetic patients were studied during poor and optimised glycaemic control. MATERIALS AND METHODS: Total LDL was subfractionated into electropositive LDL(+) and electronegative LDL(-) by anion exchange chromatography and the lipid and protein composition of the two determined. RESULTS: LDL(-) differed from LDL(+) in that it had higher triglyceride, non-esterified fatty acids, apoE, apoC-III and platelet-activating factor acetylhydrolase (PAF-AH), as well as lower apoB relative content. No evidence of increased oxidation was observed in LDL(-). LDL(-) increased two-fold the release of interleukin 8 (IL-8) and monocyte chemotactic protein 1 (MCP-1) in endothelial cells, suggesting an inflammatory role. Optimisation of glycaemic control after insulin therapy decreased the proportion of LDL(-), but did not modify the composition of LDL subfractions, except for a decrease in PAF-AH activity in LDL(-). The possibility that LDL(-) could be generated by non-enzymatic glycosylation was studied. Fructosamine and glycated LDL content in LDL subfractions from type 1 diabetic patients was greater than in LDL subfractions isolated from normoglycaemic subjects, and decreased after glycaemic optimisation in both subfractions. However, no difference was observed between LDL(+) and LDL(-) before and after insulin therapy. CONCLUSIONS/INTERPRETATION: These results provide evidence that LDL(-) is not produced by glycosylation. Nevertheless, LDL(-) from diabetic patients displays inflammatory potential reflected by the induction of chemokine release in endothelial cells. This proatherogenic effect could be related to the high PAF-AH activity in LDL(-).
Subject(s)
1-Alkyl-2-acetylglycerophosphocholine Esterase/metabolism , Diabetes Mellitus, Type 1/metabolism , Inflammation/chemically induced , Lipoproteins, LDL/chemistry , Lipoproteins, LDL/toxicity , Apoproteins/chemistry , Blood Glucose/metabolism , Cells, Cultured , Chemical Phenomena , Chemistry, Physical , Chemokines/metabolism , Diabetes Mellitus, Type 1/pathology , Electrophoresis, Polyacrylamide Gel , Endothelial Cells/drug effects , Humans , Inflammation/pathology , Lipids/blood , Malondialdehyde/metabolism , Oxidation-Reduction , Transcription FactorsABSTRACT
In order to assess the effect of glycaemic improvement on lipoprotein concentrations, we studied 73 type 2 diabetic subjects before (HbA1c 10.1 (6.2-16)%) and after (HbA1c 6.6 (3.8-8.0)%) glycaemic improvement. Total triglyceride and cholesterol (c), LDLc, HDLc, non-HDLc and apolipoproteins AI (apoAI) and B (apoB) were measured. Bivariate correlations and step-wise, multivariate analysis were performed to find predictors of change in the different components of diabetic dyslipidaemia. Changes in HDLc (r = -0.358, P = 0.001), apoAI (r = -0.355, P = 0.003), apoAI/apoB ratio (r = -0.333, P = 0.005), weight (r = -0.245, P = 0.046) and BMI (r = -0.253, P = 0.039) correlated with that of HbA1c, but, in multivariate analysis, only changes in HDLc, apoAI and apoAI/apoB ratio were predicted by the decrease in HbA1c. For the median observed change in HbA1c (-3.3 percentage-points), the estimated changes were +0.14 mmol/l, +0.12 g/l and +0.20 for HDLc, apoAI and apoAI/apoB ratio, respectively, accounting for 81, 92 and 80% of the observed changes. In conclusion, for the component of diabetic dyslipidaemia for which less therapeutic tools are available, glycaemic improvement is most effective.
Subject(s)
Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/drug therapy , Hyperlipidemias/blood , Hypoglycemic Agents/therapeutic use , Aged , Apolipoprotein A-I/blood , Apolipoproteins B/blood , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Diabetes Mellitus, Type 2/complications , Female , Glycated Hemoglobin/metabolism , Humans , Hyperglycemia/blood , Hyperglycemia/complications , Hyperglycemia/drug therapy , Hyperlipidemias/etiology , Longitudinal Studies , Male , Middle Aged , Triglycerides/bloodABSTRACT
Subclinical hypothyroidism (SH) is a frequent condition that may be associated with increased cardiovascular risk. There is current interest in determining the effect, if any, of substitutive therapy with l-thyroxine (L-T4) on cardiovascular risk factors in SH and, particularly, on those associated with emerging cardiovacular risk, such as apolipoprotein (apo) B, lipoprotein (Lp) (a), total homocysteine (t-Hcy), and C-reactive protein (CRP). Thus, the aim of this study was to assess the impact of euthyroidism restoration on these emerging risk factors in SH. Forty-two patients diagnosed with SH were consecutively recruited before treatment. These patients were treated with L-T4 for 3 to 6 months with the dose necessary to restore euthyroidism. Lp(a), fasting and postmethionine (n = 28) t-Hcy, and CRP did not change with substitutive therapy, regardless of the respective baseline values, and the decrease in apo B paralleled that of low-density lipoprotein (LDL) cholesterol. Similarly, no treatment effect was observed on homocysteine or CRP in patients with thyrotropin-stimulating hormone (TSH) >10 mIU/L. Monitoring of emerging risk factors did not offer additional arguments for treating patients with SH and, thus, is not justified in their clinical management.
Subject(s)
Biomarkers/blood , Cardiovascular Diseases/etiology , Hypothyroidism/complications , Adult , Aged , Apolipoproteins B/blood , C-Reactive Protein/metabolism , Cardiovascular Diseases/blood , Female , Homocysteine/blood , Humans , Hypothyroidism/blood , Lipoprotein(a)/blood , Male , Middle Aged , Risk Factors , Thyrotropin-Releasing Hormone/bloodABSTRACT
Physical activity (PA) is associated with a reduced risk of coronary heart disease, and may favorably modify the antioxidant-prooxidant balance. This study assessed the effects of aerobic PA training on antioxidant enzyme activity, oxidized LDL concentration, and LDL resistance to oxidation, as well as the effect of acute PA on antioxidant enzyme activity before and after the training period. Seventeen sedentary healthy young men and women were recruited for 16 weeks of training. The activity of superoxide dismutase in erythrocytes (E-SOD), glutathione peroxidase in whole blood (GSH-Px), and glutathione reductase in plasma (P-GR), and the oxidized LDL concentration and LDL composition, diameter, and resistance to oxidation were determined before and after training. Shortly before and after this training period they also performed a bout of aerobic PA for 30 min. The antioxidant enzyme activity was also determined at 0 min, 30 min, 60 min, 120 min, and 24 h after both bouts of PA. Training induces an increase in GSH-Px (27.7%), P-GR (17.6%), and LDL resistance to oxidation, and a decrease in oxidized LDL (-15.9%). After the bout of PA, an increase in E-SOD and GSH-Px was observed at 0 min, with a posterior decrease in enzyme activity until 30-60 min, and a tendency to recover the basal values at 120 min and 24 h. Training did not modify this global response pattern. Regular PA increases endogenous antioxidant activity and LDL resistance to oxidation, and decreases oxidized LDL concentration; 30 min of aerobic PA decreases P-GR and B-GSH-Px activity in the first 30-60 min with a posterior recovery.
Subject(s)
Exercise/physiology , Glutathione Peroxidase/blood , Lipid Peroxidation/physiology , Lipoproteins, LDL/blood , Oxidative Stress/physiology , Superoxide Dismutase/blood , Adult , Biomarkers/analysis , Cohort Studies , Female , Humans , Linear Models , Male , Oxidation-Reduction , Particle Size , Physical Education and Training , Physical Fitness , Probability , Reference Values , Sensitivity and Specificity , Time FactorsABSTRACT
LDL phenotype B is a component of diabetic dyslipidaemia, but its diagnosis is cumbersome. Our aim was to find easily available markers of phenotype B in a group of type 2 diabetic subjects. We studied 123 type 2 diabetic patients (67.5% male, aged 59.3+/-10.1 years, mean HbA1c 7.4%). Clinical features and fasting total cholesterol, triglyceride, HDL cholesterol, LDL cholesterol (LDLc, using Friedewald's equation and an alternative formula), apolipoprotein B (apoB), lipoprotein (a) and LDL particle size (on gradient polyacrylamide gel electrophoresis) were assessed. Patients with phenotypes A (predominant LDL size > or =25.5 nm) and B (<25.5 nm) were compared, and regression analysis was performed to find the best markers of LDL particle. Cut-off points were obtained and evaluated as predictors of phenotype B (kappa index). Patients with phenotype B (36%) showed higher total cholesterol, triglyceride and apolipoprotein B, and lower HDL cholesterol and LDLc/apoB ratio. Triglyceride was the best predictor of LDL particle size (r=-0.632, p<0.01), but an LDLc/apoB ratio below 1.297 mmol/g detected phenotype B best (sensitivity 65.9%, specificity 92.4%, kappa=0.611). Although triglyceride concentration is the best predictor of LDL size in type 2 diabetes, LDLcholesterol/apolipoproteinB ratio is the best tool to detect phenotype B.