Asymmetric dimethylarginine and angiopoietin-like protein-2 are independent predictors of cardiovascular risk in pre-dialysis non-diabetic chronic kidney disease patients.

BACKGROUND: Chronic kidney disease (CKD) is associated with increased cardiovascular (CVD) morbidity and mortality. Hence, this study was carried out to assess the biomarkers of endothelial dysfunction and inflammation as predictors of CVD risk in Indian patients with CKD. METHODS: In this case control study, we recruited 43 patients with CKD and 43 healthy control volunteers. Circulating levels of endothelial dysfunction markers [asymmetric dimethylarginine (ADMA), angiopoietin-like protein-2 (ANGPTL2), matrix metallopeptidase 9 (MMP-9)] and systemic inflammation [high-sensitivity C-reactive protein (hs-CRP)] were assessed in the study population. All study participants underwent brachial artery flow mediated dilation (FMD) to estimate endothelial dysfunction. Disease severity (e-GFR) was assessed by a nephrologist. RESULTS: CKD patients showed markedly elevated levels of ADMA, ANGPTL2, MMP-9, and hs-CRP. FMD and eGFR were significantly decreased in cases, as compared to the controls. ADMA, ANGPTL2, MMP-9 and hs-CRP showed significant positive correlation with one another and significant negative correlation with FMD and disease severity. We also observed a significant negative correlation of FMD with disease severity and duration of CKD. In the multiple linear regression model, ADMA and ANGPTL2 were found to be independent predictors of FMD. CONCLUSION: In CKD patients, there is significantly increased endothelial dysfunction and systemic inflammation, which showed a positive correlation with disease severity. Thus, the markers of endothelial dysfunction such as ADMA and ANGPTL2 can be used as predictors of CVD risk in CKD.

Assessment of bone turnover markers to predict mineral and bone disorder in men with pre-dialysis non-diabetic chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is commonly associated with disturbances in mineral metabolism and bone disease. Bone biopsy is the gold standard in diagnosing mineral bone disorder. Hence the search for non-invasive assessment of bone health gains importance. We undertook to assess the bone health in men with stage 4 and 5 chronic kidney Disease. METHODS: We recruited 32 male subjects with Stage 4 and 5 chronic kidney disease and 32 age-matched healthy male controls. 25-hydroxyvitamin D, intact parathyroid hormone, and bone-specific alkaline phosphatase were assayed. Bone mineral density (BMD) was estimated using dual-energy X-ray absorptiometry. RESULTS: CKD is associated with significantly higher levels of bone-specific alkaline phosphatase and intact parathyroid hormone and lower levels of 25-hydroxyvitamin D and bone mineral density, when compared to controls. In the multivariate linear regression model, bone-specific alkaline phosphatase emerged as an independent predictor of reduced BMD. Receiver Operator Characteristic analysis for prediction of reduced BMD in CKD showed both intact parathyroid hormone and bone-specific alkaline phosphatase have significant predicting power. CONCLUSION: The combination of bone-specific alkaline phosphatase and intact parathyroid hormone has more significant predicting power and is a more reliable index for non-invasive assessment of bone health in men with chronic kidney disease, than either marker when used alone.

Is the Ratio of Antibodies Against Oxidized LDL to Oxidized LDL an Indicator of Cardiovascular Risk in Psoriasis?

OBJECTIVES: Psoriasis is a chronic inflammatory skin disease. Chronic inflammation results in increased oxidative stress and oxidizes lipoproteins, increasing their atherogenicity. This study sought to estimate the levels of oxidized low-density lipoprotein (ox-LDL) and antibodies against oxidized LDL (anti-ox-LDL) and compute the ratio of anti-ox-LDL/ox-LDL as a single composite parameter to assess the oxidative lipoprotein burden as an indicator of cardiovascular risk in patients with psoriasis. METHODS: This cross-sectional study included 45 patients with psoriasis. All patients were given a psoriasis severity index score and their ox-LDL and anti-ox-LDL estimated using ELISA. RESULTS: The results of this study show an elevation in the ratio of anti-ox-LDL to ox-LDL in patients with psoriasis, which initiate and perpetuate the pathogenesis of psoriasis and its comorbidity, atherosclerotic cardiovascular disease. CONCLUSIONS: Our results suggest that an elevated ratio of anti-ox-LDL/ox-LDL can serve as a composite parameter reflecting the total oxidative lipoprotein burden and cardiovascular risk in psoriasis patients.

Serum bilirubin: a simple routine surrogate marker of the progression of chronic kidney disease.

BACKGROUND: Studies suggest that Chronic Kidney Disease (CKD) is a global burden health associated with significant comorbid conditions. Few biochemical parameters have gained significance in predicting the disease progression. The present work aimed to study the association of the simple biochemical parameter of serum bilirubin level with the estimated glomerular filtration rate (eGFR), and to assess their association with the co-morbid conditions in CKD. METHODS: We recruited 188 patients with CKD who attended a Nephrology out-patient department. eGFR values were calculated based on the serum creatinine levels using CKD-EPI formula. Various biochemical parameters including glucose, creatinine, uric acid, total and direct bilirubin were assayed in all study subjects. Study subjects were categorized into subgroups based on their eGFR values and their diabetic status and the parameters were compared among the different subgroups. RESULTS: We observed a significantly decreased serum bilirubin levels (p < 0.001) in patients with lower eGFR values, compared to those with higher eGFR levels. There was a significant positive correlation between the eGFR levels and the total bilirubin levels (r = 0.92). We also observed a significant positive correlation between the eGFR levels and the direct bilirubin levels (r = 0.76). On multivariate linear regression analysis, we found that total and direct bilirubin independently predict eGFR, after adjusting for potential confounders (p < 0.001). CONCLUSIONS: Our results suggest that there is significant hypobilirubinemia in CKD, especially with increasing severity and co-existing diabetes mellitus. This finding has importance in the clinical setting, as assay of simple routine biochemical parameters such as serum bilirubin may help in predicting the early progression of CKD and more so in diabetic CKD.

Association of neurotrophins, inflammation and stress with suicide risk in young adults.

BACKGROUND: Stress, anxiety and various neurobiological changes have been postulated to be associated with increased suicidal ideation. Hence, this study was undertaken to evaluate the serum concentrations of neurotrophins, inflammatory markers and stress concentrations as predictors of suicidal risk among young adults. METHODS: This cross-sectional study was conducted in a tertiary care referral center in South India from March 2014 to February 2015. We recruited 42 suicide attempters and 42 age- and gender-matched healthy controls. The serum concentrations of neurotrophins (BDNF and NT-3), inflammatory markers (hs-CRP and IL-6) were assessed. Stress severity was assessed by Presumptive Stressful Life Events scale (PSLE) and Daily Hassles and Uplifts Scale-revised (DHUS-R). Psychological distress and Suicide risk was assessed using Hospital Anxiety and Depression Scale (HADS) and Mini International Neuropsychiatric Interview (MINI) respectively. RESULTS: Suicide attempters tend to show significantly lower concentrations of neurotrophins and significantly higher concentrations of inflammatory markers. We observed significant negative correlation of neurotrophins with inflammatory markers, stress, and suicide risk. In multivariate linear regression model, hs-CRP [adjusted ß=0.333, p<0.0001], PSLE [adjusted ß=0.133, p=0.029], DHUS-R [adjusted ß=0.159, p=0.018] emerged as independent predictors of suicide risk (R(2)=0.76). CONCLUSION: Our results suggest that inflammation and stress scores have a moderate association with suicidal ideation.

Using optimal combination of teaching-learning methods (open book assignment and group tutorials) as revision exercises to improve learning outcome in low achievers in biochemistry.

Graduate medical students of India are taught Biochemistry by didactic lectures and they hardly get any opportunity to clarify their doubts and reinforce the concepts which they learn in these lectures. We used a combination of teaching-learning (T-L) methods (open book assignment followed by group tutorials) to study their efficacy in improving the learning outcome. About 143 graduate medical students were classified into low (<50%: group 1, n = 23), medium (50-75%: group 2, n = 74), and high (>75%: group 3, n = 46) achievers, based on their internal assessment marks. After the regular teaching module on the topics "Vitamins and Enzymology", all the students attempted an open book assignment without peer consultation. Then all the students participated in group tutorials. The effects on the groups were evaluated by pre and posttests at the end of each phase, with the same set of MCQs. Gain from group tutorials and overall gain was significantly higher in the low achievers, compared to other groups. High and medium achievers obtained more gain from open book assignment, than group tutorials. The overall gain was significantly higher than the gain obtained from open book assignment or group tutorials, in all three groups. All the three groups retained the gain even after 1 week of the exercise. Hence, optimal use of novel T-L methods (open book assignment followed by group tutorials) as revision exercises help in strengthening concepts in Biochemistry in this oft neglected group of low achievers in graduate medical education. © 2016 by The International Union of Biochemistry and Molecular Biology, 44(4):321-325, 2016.

Elevated fibrinogen and lowered homocysteine-vitamin determinants and their association with left atrial thrombus in patients with rheumatic mitral stenosis.

Mitral stenosis (MS) causes stagnation of blood flow, leading to thrombus formation in the left atrium (LA), which may lead to systemic thrombo-embolic complications and stroke. We compared the alterations in echocardiographic and procoagulant parameters in patients with severe rheumatic MS with and without LA thrombus. The study was a cross-sectional study of patients with rheumatic MS, being evaluated for percutaneous mitral commisurotomy. Group 1 patients comprised of patients with rheumatic MS with LA thrombus (n=35) and Group 2 patients had rheumatic MS without LA thrombus (n = 45). Platelet aggregability, fibrinogen, homocysteine, vitamin B12 and folate; mitral valve area (MVA), mean mitral gradient and pulmonary artery pressure (PAP) were assessed in all study subjects. Significant increase in fibrinogen, homocysteine and platelet aggregation and fall in homocysteine-associated determinants were seen in Group 1, as compared with Group 2. Raised fibrinogen, lowered homocysteine-vitamin determinants and lowered mitral valve area were associated independently, with presence of LA thrombus in rheumatic MS. In this study, fibrinogen, vitamin B12 and folate were independently associated with the occurrence of thrombus in patients with rheumatic MS. Hence, our results suggest that increase in procoagulant mechanisms contribute to increased risk of thrombosis in the left atrium in patients with rheumatic MS.

Comprehensive lipid tetrad index, atherogenic index and lipid peroxidation: Surrogate markers for increased cardiovascular risk in psoriasis.

BACKGROUND AND OBJECTIVES: Recently, the concept of "psoriatic march" has come to the fore, in which chronic cutaneous inflammation in psoriasis leads to systemic inflammation which, in conjunction with increased oxidative stress, triggers a cascade of events resulting in increased cardiovascular risk in patients with severe psoriasis. We, therefore, decided to study the levels of some biochemical cardiovascular risk markers: lipid peroxidation (malondialdehyde), lipoprotein (a), lipid indices and atherogenic index, in patients with psoriasis and their association with disease severity. METHODS: Forty five patients with psoriasis and 45 age and gender-matched healthy controls were included in this cross-sectional study. Disease severity was assessed by the Psoriasis Area Severity Index (PASI). Serum malondialdehyde, lipoprotein (a) and fasting lipid profile were estimated in all study subjects. Lipoprotein ratios were computed using standard formulae. Atherogenic index was calculated as ratio of lipoprotein (a)/high-density lipoprotein. RESULTS: In psoriasis, we observed significantly higher levels of malondialdehyde, total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, lipoprotein (a), lipid ratios, atherogenic index and comprehensive lipid tetrad index, compared to controls. These levels were directly proportional to disease severity. Serum levels of malondialdehyde correlated positively with serum lipoprotein (a), comprehensive lipid tetrad index and atherogenic index. LIMITATIONS: Different morphological types of psoriasis were not included and follow-up post-therapy was not done. A larger sample size would have validated the results further. CONCLUSION: Our results indicate that psoriasis, especially the severe variants, are associated with increased oxidative stress and dyslipidemia, which correlate positively with atherogenic index and hence, an increased cardiovascular risk.

25-hydroxy vitamin D and ischaemia-modified albumin levels in psoriasis and their association with disease severity.

Psoriasis is a T-helper-1 (Th1)/Th17-mediated chronic inflammatory skin disease, characterised by hyperproliferation of keratinocytes. Psoriasis and cardiovascular disease share similar pathogenic mechanisms such as vascular endothelial cell dysfunction, oxidative stress and metabolic syndrome. 25-hydroxy vitamin D is an immune-regulatory hormone, with the ability to reduce cellular proliferation in psoriasis. Ischaemia-modified albumin (IMA) is a marker of oxidative stress. This study examined 25-hydroxy vitamin D, IMA and high-sensitivity C-reactive protein (hs-CRP) levels in patients with psoriasis, in comparison with healthy controls and their possible association with disease severity. A total of 43 cases of psoriasis and 43 controls were included in this cross-sectional study, and severity grading was performed according to psoriasis area severity index (PASI) scoring. Serum 25-hydroxy vitamin D, IMA and hs-CRP were evaluated in all study subjects. In psoriasis, 25-hydroxy vitamin D showed a significant decline, while hs-CRP and IMA levels were significantly elevated, as compared with controls. Serum 25-hydroxy vitamin D showed a significant negative correlation with PASI score. hs-CRP and IMA showed a significant positive correlation with PASI score. Significant negative correlation was observed between 25-hydroxy vitamin D and hs-CRP; 25-hydroxy vitamin D and IMA levels in psoriasis. The results indicate that psoriasis is associated with significantly lowered 25-hydroxy vitamin D levels, along with increased systemic inflammation and oxidative stress, especially in severe disease. Thus, vitamin D supplementation might reduce systemic inflammation and oxidative stress and help in delaying the pathogenesis of co-morbidities associated with psoriasis.

Is enhanced platelet activation the missing link leading to increased cardiovascular risk in psoriasis?

BACKGROUND: Psoriasis is an immune mediated inflammatory skin disease associated with systemic inflammation resulting in increased risk for associated cardiovascular co-morbidities. The role of platelet activation in the pathophysiology of this condition has not been clearly studied. We undertook to study the platelet activation markers in psoriasis, as compared to controls and to identify its association with disease severity in psoriasis. METHODS: Sixty-two patients with psoriasis and 62 age and gender matched healthy controls were enrolled in this cross-sectional study. The severity of the disease was assessed using the psoriasis area severity index (PASI) scoring. The platelet indices [mean platelet volume (MPV) and platelet distribution width (PDW)] were estimated by an automated haematological laser optical analyzer. Plasma soluble P-selectin and platelet derived microparticle (PDMP) concentrations, serum high sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6 concentrations were estimated in all study participants. Platelet aggregation was assessed using adenosine diphosphate (ADP) as aggregating agent. RESULTS: We observed that there was significantly higher platelet indices (MPV and PDW) in patients with psoriasis, when compared to controls. Plasma soluble P-selectin concentrations, PDMP and platelet aggregation were significantly elevated in patients with psoriasis, as compared to controls. We also found significantly higher concentrations of hs-CRP and IL-6 in patients with psoriasis, as compared to controls. Platelet activation and systemic inflammation markers correlated positively with PASI, except PDW. We also observed significant positive correlation between platelet activation and systemic inflammation in psoriasis. CONCLUSION: Significant platelet activation and systemic inflammation were observed in patients with psoriasis, especially when associated with severe disease. The increased platelet activation might be the missing link between the persistent inflammation and the development of atherosclerotic plaque leading onto cardiovascular co-morbidities seen associated with psoriasis.

Hypomagnesemia and atherogenic dyslipidemia in chronic kidney disease: surrogate markers for increased cardiovascular risk.

BACKGROUND: Recent reports suggest that 40-70 % chronic kidney disease (CKD) patients receiving dialysis have significant coronary artery disease. Magnesium depletion is being considered as the missing link between the cardiovascular risk factors and atherosclerosis in CKD. The present work aimed to study the association between magnesium status and lipid alterations in pre-dialysis CKD patients attending the Nephrology Clinic in a tertiary care hospital in South India. METHODS: 90 cases of CKD and 90 age and gender matched healthy controls were included in the study. Framingham risk scoring was done and presence of metabolic syndrome was assessed. Lipid profile, serum and urine magnesium, blood glucose, calcium, phosphorus, urea and creatinine levels were assayed in all study subjects. RESULTS: In this study we observed a significantly lower serum magnesium levels and dyslipidemic alterations, a significantly raised total cholesterol and low-density lipoprotein and non-HDL in patients with CKD. We also observed a significant correlation between the lowered serum magnesium concentrations and atherogenic dyslipidemia, suggesting a link to increased cardiovascular risk in CKD patients. CKD patients had higher risk of cardiovascular disease (according to their Framingham risk score), which also showed significant correlation with the hypomagnesaemia. CONCLUSIONS: Our results suggest a strong association of hypomagnesemia and atherogenic dyslipidemia in patients with CKD. This gains particular importance in the high cardiovascular risk-borne CKD patients, as supplementing magnesium would go a long way in reducing the risk of cardiovascular morbidity and mortality in CKD.