Prajwal Gyawali

Erythrocyte aggregation and metabolic syndrome

Erythrocyte aggregation has been consistently associated with insulin resistance, central obesity and hypertension in the literature. Oxidative stress and chronic inflammation are almost always present in metabolic syndrome (MetS). Prooxidants and adipocytokines generated in MetS alter erythrocyte morphology, decrease erythrocyte deformability and increase whole blood viscosity (WBV). Increased WBV has been attributed to erythrocyte aggregation which in turn is greatly influenced by other rheological parameters, including its membrane surface charge and plasma fibrinogen concentration. The interplay of hemorheological factors, oxidative stress and inflammation has a detrimental effect in MetS due to the gross disturbance in microcirculation. The hemodynamic aspect of MetS needs further research and exploration.

Association of abnormal erythrocyte morphology with oxidative stress and inflammation in metabolic syndrome.

In carrying out their role of free radical scavenging, erythrocytes become damaged due to oxidation of membrane lipids and proteins. Such damage may change the morphology of the erythrocytes. The present study aims to demonstrate change in erythrocyte morphology in MetS and associate the changes with increased oxidative stress and inflammation that were shown in our recent study. One hundred participants were recruited from a rural town of Australia. Whole blood viscosity, erythrocyte aggregation, erythrocyte deformability, lipid profile and blood sugar level, oxidative stress markers (erythrocyte reduced glutathione, superoxide dismutase, urinary isoprostanes) and inflammatory markers (high sensitivity C-reactive protein) were measured. Erythrocyte morphological study was performed by scanning electron microscopy. Recruited participants were classified into MetS and non-MetS following the National Cholesterol Education Program Adult Treatment Panel III definition. Data were analyzed by IBM SPSS 20 software. The mean percentages of biconcave cells were decreased whereas acanthocytes, stomatocytes and echinocytes were increased in MetS group compared to healthy controls. Morphologically abnormal erythrocytes were significantly correlated with oxidative stress and chronic inflammation markers. Free radicals generated in increased concentration in MetS seem to damage erythrocyte changing its morphology which possibly could affect other hemorheological parameters.

Hemorheology, ankle brachial pressure index (ABPI) and toe brachial pressure index (TBPI) in metabolic syndrome

INTRODUCTION Microvascular dysfunction is associated with metabolic syndrome (MetS) and its components. The objective of our study was to assess macro and microvascular abnormalities in MetS and compare the strength of association of the ankle brachial pressure index (ABPI), toe brachial pressure index (TBPI) and hemorheological parameters with MetS. MATERIALS AND METHODS 100 participants were recruited from a rural Australian town. Anthropometric measurements were taken along with blood pressures (BP) at the arm, the ankle and the big toe for calculating ABPI and TBPI. Whole blood viscosity (WBV), erythrocyte aggregation, erythrocyte deformability, lipid profile and blood sugar level were analyzed. Recruited participants were classified into MetS and non-MetS following National Cholesterol Education Program Adult Treatment Panel III definition. Data were analyzed by IBM SPSS 20 software. RESULTS WBV and erythrocyte aggregation were higher whereas erythrocyte deformability was lower in participants with MetS when compared to participants without MetS. Age, sex and diabetes mellitus adjusted odds ratio for predicting MetS was not significant for ABPI and TBPI whereas it was significant for hemorheological parameters. Receiver Operating Characteristics curve showed that TBPI better classified MetS than ABPI but association of hemorheological parameters was superior to that of ABPI and TBPI with MetS. CONCLUSIONS Both microcirculation defects and macrovascular circulation defects were present in MetS. The concurrences of the components of MetS could have an additive effect in enhancing alterations in hemorheological parameters which may give rise to severe microvasculopathy. The association of hemorheological parameters was stronger than the association of TBPI and ABPI with MetS.

Erythrocyte morphology in metabolic syndrome

The study of erythrocyte morphology is of great importance in the field of hemorheology as the deformability of the circulating cells has a fundamental influence on the rheological properties of the blood. Diabetes mellitus, hypertension, dyslipidemia and obesity (mostly central obesity) are the major components of metabolic syndrome. In this review, we focus on the changes in erythrocyte morphology in different components of metabolic syndrome and also discuss the erythrocyte morphology in regards to oxidative stress – a common state of chronic diseases. This article also addresses the problem of inconsistency in the use of nomenclature and technique to identify the abnormal morphology and we recommend the use of standard terminology by all authors.

Association of altered hemorheology with oxidative stress and inflammation in metabolic syndrome

Abstract Objective We have shown increased whole blood viscosity (WBV), decreased erythrocyte deformability, and increased erythrocyte aggregation in metabolic syndrome (MetS) in our previous study. The objective of the study was to find out if the altered hemorheology shown in MetS in our previous study is associated with chronic inflammation and oxidative stress in the same subjects. Methods One hundred recruited participants were classified into three groups based on the number of the MetS components present following National Cholesterol Education Program, Adult Treatment Panel III definitions. WBV, erythrocyte aggregation, erythrocyte deformability, oxidative stress markers (erythrocyte reduced glutathione (GSH), superoxide dismutase (SOD), and urinary isoprostanes), inflammatory markers high-sensitivity C-reactive protein (hsCRP), and thrombotic marker D-dimer were measured. Data were analyzed by IBM SPSS 20 software. Results We found a significant association of altered hemorheology with chronic inflammation and oxidative stress in MetS. There was a linear increase in the level of hsCRP and a linear decrease in the level of SOD and GSH across the quartiles of erythrocyte aggregation. Similarly, the thrombotic marker D-dimer showed a linear increase and oxidative stress marker GSH showed a linear decrease trend across the quartiles of WBV. Discussion Alterations of hemorheology in MetS are probably due to the effect of chronic inflammation and oxidative stress. The negative effects of chronic inflammation and oxidative stress on the cardiovascular system could be due to the resulting altered hemorheology.

Whole Blood Viscosity and Metabolic Syndrome

Abstract Whole-blood viscosity (WBV) depends on vascular geometry and blood physiological constituents. Diabetes mellitus, hypertension, dyslipidemia and obesity – the major components of metabolic syndrome (MetS) – can independently affect blood vessels and microcirculation. MetS is the state of oxidative stress and systemic inflammation. Pro-oxidant and inflammatory cytokines induce endothelial dysfunction. Morphological alterations of erythrocytes could be a consequence of decreased erythrocytes deformability, oxidative stress and systemic inflammation. These events altogether lead to increased WBV. In this review, the effect of WBV in different components of the MetS and WBV with regard to oxidative stress and inflammation – common states in chronic disease – are discussed.

Non-high density lipoprotein cholesterol versus low density lipoprotein cholesterol as a discriminating factor for myocardial infarction

BackgroundSerum total cholesterol (TC) and LDL cholesterol (LDL-C) have been used as major laboratory measures in clinical practice to assess cardiovascular risk in the general population and disease management as well as prognosis in patients. However, some studies have also reported the use of non-HDL cholesterol (non-HDL-C). As non-HDL-C can be calculated by subtracting HDL-C from TC, both of which do not require fasting blood sample in contrast to LDL-C which requires fasting blood sample, we aimed to compare non-HDL-C with LDL-C as a predictor of myocardial infarction (MI).MethodsThis hospital based cross sectional study was undertaken among 51 cases of MI and equal number of controls. MI was diagnosed based on the clinical history, ECG changes and biochemical parameters. 5 mL of fasting blood sample was collected from each research participant for the analysis of lipid profile. Non-HDL-C was calculated by using the equation; Non-HDL-C = TC – HDL-C. Statistical analysis was performed using SPSS 14.0.Results42 MI cases were dyslipidemic in contrast to 20 dyslipidemic subjects under control group. The differences in the median values of each lipid parameter were statistically significant between MI cases and controls. The lipid risk factors most strongly associated with MI were HDL-C (OR 5.85, 95% CI 2.41-14.23, P value = 0.000) followed by non-HDL-C (OR 3.77, 95% CI 1.64-8.66, P value = 0.002), LDL-C/HDL-C (OR 3.38, 95% CI 1.44-7.89, P value = 0.005), TC/HDL-C (OR 2.93, 95% CI 1.36-7.56, P value = 0.026), LDL-C (OR 2.70, 95% CI 1.20-6.10, P value = 0.017), TC (OR 2.68, 95% CI 1.04-6.97, P value = 0.042) and Tg (OR 2.54, 95% CI 1.01-6.39, P value = 0.047). Area under the receiver operating curve was greater for non-HDL-C than for LDL-C. Non-HDL-C was also found to be more sensitive and specific than LDL-C for MI.ConclusionsHDL-C and non-HDL-C are better discriminating parameters than LDL-C for MI. Thus, we can simply perform test for HDL-C and non-HDL-C both of which do not require fasting blood sample rather than waiting for fasting blood sample to measure LDL-C.

Product of serum calcium and phosphorus (Ca × PO4) as predictor of cardiovascular disease risk in predialysis patients.

OBJECTIVES The mortality rate of chronic kidney disease (CKD) patients is very high due to cardiovascular diseases (CVD) which cannot be fully justified by traditional CVD markers. Since, mineral bone disorder is common in CKD, product of serum calcium and phosphorus (Ca × PO4) can be a predictor of future CVD. So, our study aims to assess the utility of higher Ca × PO4 in prediction of CVD risk in predialysis CKD patients. DESIGN AND METHODS 150 CKD patients defined by NKF-KDOQI guideline not undergoing dialysis were recruited. Anthropometric and electrocardiographic parameters were recorded. We evaluated CVD risk by: i) Biochemical CVD markers, ii) NCEP ATP III guideline postulated risk factors and iii) Framingham risk scores. RESULTS Higher Ca × PO4 is associated with presence of Left Ventricular Hypertrophy, oxidative stress, microinflammation, hyperhomocysteinemia, hypercholesterolemia, hypertriglyceridemia and increased LDLc. Compared to cases with Ca × PO4 <55 mg2/dL2, cases with ≥55 mg2/dL2 had relative risk (RR) of 1.82 (95% CI 1.25-2.64) for CVD, 3.24 (95% CI 2.37-4.41) for stroke and 2.43 (95% CI 1.37-4.31) for coronary heart disease (CHD). Moreover, compared to lowest quartile of Ca x PO4, the highest quartile group had RR of 2.13 (95% CI 1.06-4.28) for CVD, 2.61(95% CI 1.80-3.75) for stroke and 2.84 (95% CI 1.15-7.0) for CHD. CONCLUSION In predialysis patients, higher Ca × PO4 is independent predictor of CVD risk.

Association of High Sensitivity C-Reactive Protein with the Components of Metabolic Syndrome in Diabetic and Non-Diabetic Individuals

BACKGROUND AND OBJECTIVES High sensitivity C-reactive protein (hsCRP) has been associated with metabolic syndrome (MetS) and its components. Several studies have suggested hsCRP to be used as a marker for the primary prevention of cardiovascular diseases. So, we aimed to evaluate the association between hsCRP levels and the components of MetS in diabetic and non-diabetic population. MATERIALS AND METHODS Type II diabetic patients (T2DM) (n= 121) and healthy controls (n= 121) were enrolled for the study. Anthropometric measurements were taken along with blood pressure from the arm. Ten ml of blood was collected after overnight fasting for the measurement of lipid profile, hsCRP, C-peptide and glucose levels. Insulin resistance (HOMA2-IR) was estimated by HOMA2 calculator utilizing glucose and C-peptide values. All participants were classified into two groups on the basis of the presence or absence of MetS. Data were analysed through SPSS 14 software. RESULTS hsCRP, C-peptide and HOMA2-IR were significantly higher in T2DM subjects when compared with controls. As the number of the components of MetS increased, there was a linear increase in hsCRP levels in whole study population (p trend <.001), diabetic subjects (p trend <.001), as well as in controls (p trend <.001). HOMA2-IR and hsCRP levels were found to be better than LDL cholesterol and waist circumference for predicting the presence of MetS. CONCLUSION hsCRP was found to be better than LDL cholesterol and waist circumference for the prediction of MetS. Hence, hsCRP could be used as a defining marker of MetS in the near future.

Hemorheological parameters better classify metabolic syndrome than novel cardiovascular risk factors and peripheral vascular disease marker

The present study compares the association of Metabolic Syndrome (MetS) with hemorheological parameters, oxidative stress, inflammation and peripheral arterial disease markers. 100 participants were recruited and participants were divided into three groups on the basis of absence or presence of MetS and its components. Odds ratio for correctly predicting MetS was highest for erythrocyte aggregation followed by erythrocyte deformability. ROC curve analysis demonstrated that all the hemorheological components significantly classified MetS participants. Area Under Curve was higher for the hemorheological parameters (erythrocyte aggregation and erythrocyte deformability) than for the oxidative stress, inflammation and peripheral arterial disease markers. The possibilities of the hemorheological components to be identified as better cardiovascular risk markers due to their strong association with MetS cannot be precluded from the present findings.