Lidija Memon

High serum uric acid and low-grade inflammation are associated with smaller LDL and HDL particles

Elevated serum uric acid (UA) is associated with higher risk for cardiovascular disease (CVD). Smaller, denser low density lipoprotein (LDL) and high-density lipoprotein (HDL) particles are the potential risk factors for CVD, while the role and diagnostic value of inflammatory markers are firmly established. This current cross-sectional study investigates interrelationships between UA, high sensitivity C-reactive protein (hsCRP) and fibrinogen concentrations with LDL and HDL sizes in healthy middle-aged subjects. The outcomes-of-interest were smaller, denser LDL and HDL particles (LDL size <or=25.5nm and HDL size <or=8.8nm). Serum UA, hsCRP and plasma fibrinogen concentrations were measured by standard laboratory methods in a sample of 194 healthy volunteers (112 men and 82 women). LDL and HDL particle sizes were determined by gradient gel electrophoresis. The subjects in the highest UA tertile had significantly smaller LDL and HDL particle sizes (P<0.05 and P<0.01, respectively) and higher concentrations of fibrinogen and hsCRP (P<0.05 and P<0.01, respectively). Elevated UA (>or=318micromol/L) was a significant predictor of smaller, denser LDL and HDL particles (OR=3.09; P<0.01; n=19 and OR=4.40; P<0.001; n=23, respectively). The observed relationship with smaller HDL size persisted after adjustment for conventional cardiovascular risk factors. UA strongly correlated with both markers of inflammation. In addition, the higher hsCRP level correlated with smaller LDL size (P<0.05), while fibrinogen concentration was inversely related to HDL size (P<0.05). Multiple regression analysis revealed that HDL size and inflammatory markers remained independent determinants of UA concentration. In conclusion, higher serum UA and low-grade inflammation are closely linked to alterations in lipoprotein metabolism which may represent an early sign of atherosclerosis in asymptomatic subjects.

Small, dense LDL cholesterol and apolipoprotein B: Relationship with serum lipids and LDL size

OBJECTIVE Small, dense low-density lipoprotein-cholesterol (sdLDL-C) is a recently recognised marker of cardiovascular disease risk. On the other hand, the usefulness of sdLDL-apoB concentration determination in clinical practice offers grounds for further exploration. This study investigates the associations of sdLDL-C and sdLDL-apoB with serum lipid parameters and LDL size in healthy men and women. METHODS The concentrations of sdLDL-C and sdLDL-apoB were measured after heparin-magnesium precipitation of serum samples from ninety-five asymptomatic subjects (47 men, 30 premenopausal and 18 menopausal women). LDL size was determined by gradient gel electrophoresis and serum lipid and lipoprotein parameters were measured by routine laboratory methods. RESULTS Compared to premenopausal women, men had higher sdLDL-C (P<0.001) and sdLDL-apoB concentrations (P<0.001). No difference in the sdLDL-C concentration was found between men and menopausal women. Menopause status was associated with higher concentrations of both sdLDL-C (P<0.01) and sdLDL-apoB (P<0.05). Subjects with the LDL B phenotype had elevated sdLDL-C (P<0.01) and sdLDL-apoB concentrations (P<0.001). LDL size and triglycerides were independent determinants of both sdLDL-C and sdLDL-apoB concentrations. CONCLUSION Gender and menopausal status have significant impact on sdLDL-C and sdLDL-apoB concentrations. The variability in sdLDL-C and sdLDL-apoB levels is considerably influenced by changes in LDL size and triglyceride concentration. Our results suggest that the characterisation of sdLDL particles by evaluating sdLDL-C could be complemented with sdLDL-apoB determination.

Low paraoxonase 1 activity predicts mortality in surgical patients with sepsis.

Introduction. State of severe oxidative stress is encountered in sepsis. Paraoxonase 1 (PON1) protects against oxidative stress but also undergoes inactivation upon that condition. We investigated PON1 activity in surgical patients with sepsis in relation to oxidative stress status, inflammation, disease severity, and survival. Methods. Prospective observational study. Sixty-nine surgical patients with sepsis were compared to 69 age/sex matched healthy controls. PON1 paraoxonase and diazoxonase activities, selected biochemical, hematological and oxidative stress parameters were measured on admission to ICU and 24, 48, 72, and 96 hours later. Disease severity scores were calculated daily. Results. Septic patients had significantly lower PON1 activities compared to control group at all time points. PON1 activities had good capacity to differentiate septic patients from healthy controls. Low PON1 activities were associated with higher disease severity scores and higher risk of death. Correlation between PON1 activity and markers of inflammation failed to reach significance. Decrease in PON1 activity was correlated with an increase in reducing components in plasma. Conclusion. Our study demonstrated lower PON1 activity in surgical patients with sepsis compared to healthy controls. PON1 activity also reflected severity of the disease. Low PON1 activity was associated with higher mortality of surgical patients with sepsis.

Diagnostic Value of Matrix Metalloproteinase-9 and Tissue Inhibitor of Matrix Metalloproteinase-1 in Sepsis-Associated Acute Kidney Injury

Sepsis-associated acute kidney injury (SA-AKI) severely impacts morbidity and mortality in surgical patients with sepsis. Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) have an important role in pathophysiology of sepsis but they have been unexplored in SA-AKI. We aimed to investigate the role of MMP-9 and TIMP-1 in septic surgical patients with SA-AKI and to evaluate them as diagnostic biomarkers of SA-AKI. This prospective observational study compared 53 major abdominal surgery patients with sepsis divided into SA-AKI (n = 37) and non-SA-AKI (n =16) group to 50 controls without sepsis matched by age, gender, comorbidities and type of surgery. Blood and urine samples from septic patients were collected on admission to ICU and 24, 48, 72 and 96 h later and once from the controls. The levels of MMP-9, TIMP-1, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1, urea and creatinine were measured. MMP-9/TIMP-1 ratio and disease severity scores, such as Sequential Organ Failure Assessment (SOFA), were calculated. Septic patients with SA-AKI had higher serum TIMP-1 levels and lower serum MMP-9 levels and lower MMP-9/TIMP ratio, compared to septic patients without SA-AKI and controls. The levels of these biomarkers did not change significantly over time. MMP-9, TIMP-1 and MMP-9/TIMP-1 ratio correlated with urea, creatinine, NGAL, and SOFA scores. Moreover, using the area under ROC curve, we showed that TIMP-1 and MMP-9/TIMP-1 ratio, but not MMP-9, were good diagnostic biomarkers of SA-AKI. We report for the first time the potential diagnostic value of TIMP-1 and MMP-9/TIMP-1 ratio in SA-AKI.

Assessment of endothelial dysfunction: the role of symmetrical dimethylarginine and proinflammatory markers in chronic kidney disease and renal transplant recipients.

Objectives. The study was designed to evaluate associations between symmetric dimethylarginine (SDMA), inflammation, and superoxide anion (O2∙−) with endothelial function and to determine their potential for screening of endothelial dysfunction in patients with chronic kidney disease (CKD) and renal transplant (RT) recipients. Materials and Methods. We included 64 CKD and 52 RT patients. Patients were stratified according to brachial artery flow-mediated dilation (FMD). Results. Logistic regression analysis showed that high SDMA and high sensitive C-reactive protein (hs-CRP) were associated with impaired FMD in CKD and RT patients, after adjustment for glomerular filtration rate. The ability of inflammation, SDMA, and O2∙− to detect impaired FMD was investigated by receiving operative characteristic analysis. Hs-CRP (area under the curves (AUC) = 0.754, P < 0.001), IL-6 (AUC = 0.699, P = 0.002), and SDMA (AUC = 0.689, P = 0.007) had the highest ability to detect impaired FMD. SDMA in combination with inflammatory parameters and/or O2∙− had better screening performance than SDMA alone. Conclusions. Our results indicate a strong predictable association between hs-CRP, SDMA, and endothelial dysfunction in CKD patients and RT recipients. The individual marker that showed the strongest discriminative ability for endothelial dysfunction is hs-CRP, but its usefulness as a discriminatory marker for efficient diagnosis of endothelial dysfunction should be examined in prospective studies.

Are levels of NT-proBNP and SDMA useful to determine diastolic dysfunction in chronic kidney disease and renal transplant patients?

The aim of the study was to determine the clinical usefulness of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) and symmetric dimethylarginine (SDMA) for detection of renal and left ventricular (LV) diastolic dysfunction in chronic kidney disease (CKD) patients and renal transplant (RT) recipients.

Smaller HDL particles are associated with absence of obstructive coronary artery disease in stable angina pectoris patients

Background A research on novel cardiovascular risk factors is mainly focused on patients with clinically verified coronary artery disease (CAD), while less is known about their presence in symptomatic patients, but without angiographically proven occlusion of coronary arteries. The aim of this study was to compare plasma low-density lipoprotein (LDL) and high-density lipoprotein (HDL) size and subclasses in stable angina patients with and without significant obstructive CAD. Methods LDL and HDL subclasses were analysed in 100 stable angina patients with ≥50% of obstruction and 40 patients with less than 50% of luminal narrowing, as assessed by coronary angiography. Results Patients with <50% of obstruction had reduced mean HDL size and higher proportion of small HDL particles (P < 0.05). HDL size and proportion of small HDL particles were significant and independent predictors of obstructive CAD (P < 0.05, respectively). Conclusions Stable angina patients with <50% of coronary obstruction have more favourable HDL subclasses distribution than patients with significant coronary stenosis.

Matrix Metalloproteinase-9 and Tissue Inhibitor of Matrix Metalloproteinase-1 in Sepsis after Major Abdominal Surgery

Background The role of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in sepsis after major abdominal surgery and sepsis-associated organ dysfunction is unexplored. Materials and Methods Fifty-three patients with sepsis after major abdominal surgery were compared to 50 operated and 50 nonoperated controls. MMP-9, TIMP-1, biomarkers of inflammation, kidney and liver injury, coagulation, and metabolic disorders were measured daily during 96 h following diagnosis of sepsis and once in controls. MMP-9/TIMP-1 ratios and disease severity scores were calculated. Use of vasopressors/inotropes, mechanical ventilation, and survival were recorded. Results Septic patients had lower MMP-9 and MMP-9/TIMP-1 ratios but higher TIMP-1 levels compared to controls. AUC-ROC for diagnosis of sepsis was 0.940 and 0.854 for TIMP-1 and 0.924 and 0.788 for MMP-9/TIMP-1 ratio (sepsis versus nonoperated and sepsis versus operated controls, resp.). Lower MMP-9 and MMP-9/TIMP-1 ratio and higher TIMP-1 levels were associated with shorter survival. MMP-9, TIMP-1, and MMP-9/TIMP-1 ratio correlated with biomarkers of inflammation, kidney and liver injury, coagulation, metabolic disorders, and disease severity scores. Use of vasopressors/inotropes was associated with higher TIMP-1 levels. Conclusions MMP-9, TIMP-1, and MMP-9/TIMP ratio were good diagnostic or prognostic biomarkers of sepsis after major abdominal surgery and were linked to sepsis-associated organ dysfunction.