Intra-uterine Growth Retardation and Development of Hypertension

Low birth weight (LBW) is defined as a birth weight of a liveborn infant of <2,500 gram. In developed countries, LBW is commonly caused by preterm birth; while in developing countries, it is mostly due to intrauterine growth retardation. The concept of developmental origins of adult diseases, particularly on late-onset diseases such as hypertension and kidney disease, implies that there is a correlation between intrauterine milieu, intrauterine growth retardation, premature birth and infant feeding. The ‘fetal origin hypothesis’ suggests that metabolic diseases are directly related to poor nutritional status in early life.There is an inverse association between LBW and later risk of hypertension. The pathomechanism that links LBW and hypertension is multifactorial including delayed nephrogenesis, genetic factors, sympathetic hyperactivity, endothel dysfunction, elastin deficiencies, insulin resistance and activation of renin-angiotension system

The Role of Endothelial Progenitor Cell in Cardiovascular Disease Risk Factors

Endothelial progenitor cells (EPCs) are cell derived from bone marrow and the cells circulate in peripheral blood. These cells have characteristics similar to stem cells, but their ability to proliferate and differentiate is more limited. EPC discovery has changed the old paradigm in the field of vascular biology and it brings huge implications in medicine as EPCs can mediate the processes of vasculogenesis and maintain the vascular integrity. Increasing amount of EPC in the circulation is important since it has positive correlation with reendothelialization and neovascularization and they are closely linked to cardiovascular health. Thus, EPC could potentially be used for treatment of disease caused by endothelial dysfunction.Key words: endothelial progenitor cell, endothelial dysfunction, vasculogenesis, reendothelialization

The Analysis of Asymetric Dimethylarginine and Homocysteine in Patients with Chronic Kidney Disease

BACKGROUND: Asymmetric dimethylarginine (ADMA) is a competitive inhibitor of nitric oxide synthase (NOS). ADMA reduces NO synthesis when its concentration elevates. ADMA is a novel risk factor for cardiovascular disease. Plasma ADMA accumulates in patients with endstage renal disease, due to reduced renal clearance. Hyperhomocysteinemia is often found in patients with chronic kidney disease (CKD). Homocysteine may cause ADMA to accumulate; however, the mechanism by which ADMA level elevates in hyperhomocysteinemia is still unclear. Objective of this study was to analyze the concentrations of homocysteine and ADMA and to assess the correlation between homocysteine and ADMA concentrations with the severity of chronic kidney disease.METHODS: This was a cross-sectional study on 75 patients with CKD, comprising men and women aged 40-70 years. Assessments were done on the concentrations of creatinine, homocysteine, ADMA, fasting blood glucose, cholesterol HDL and triglyceride.RESULTS: In later stage of CKD there was significantly higher tHcy concentration as compared with the earlier stage of CKD (p=0.0000). In CKD stage 2 to 4 there was a tendency for ADMA concentration to increase to a significant average (p=0.210), but ADMA concentration was lower at stage 5. There was increased ADMA along with increased tHcy concentration of around 20μ mol/L, and this then decreased. The inverse correlation between tHcy and ADMA concentrations started to appear in CKD stage 4, but this correlation was statistically insignificant (r2 =0.19; p=0.499).CONCLUSIONS: This study showed there was a correlation between homocysteine and ADMA concentrations in patients with CKD stage 2 to 5, although statistically not significant

The Mechanism of Coronary Artery Calcification in Centrally Obese Non-Diabetic Men: Study on The Interaction of Leptin, Free Leptin Index, Adiponectin, hs-C Reactive Protein, Bone Morphogenetic Protein-2 and Matrix Gla Protein

Background: The calcium in the artery was thought to be the result of the imbalance or dysregulation of the promoter and inhibitor cytokines influenced by various subclinical and clinical conditions. This study aimed to investigate the interaction between central obesity, as an early subclinical condition, also known as a chronic low grade inflammation condition and coronary artery calcium (CAC) in non-diabetic population including the underlying pathomechanisms of a CAC in the early stage of atherosclerosis.Materials and Methods: This was a cross-sectional pathway analysis study enrolling 60 central obesity non-diabetic men that underwent coronary calcium score scan, anthropometrics and biomarker assays.Results: There was a positive correlation between increasing free leptin index/adiponectin (FLI/A) ratio and CAC (r=0.297; p<0.05). There was a positive correlation between increasing FLI/A ratio and plasma high sensitive C-reactive protein (hs-CRP) (r=0.318; p<0.05). Plasma hs-CRP and bone morphogenetic protein-2 (BMP-2)-matrix gla protein (MGP) dysregulation were positively correlated (r=0.221; p<0.05) after adjusted to risk factors including insulin resistance, hypertension, age, and dyslipidemia.Conclusion: The study found that one of the pathways involved in CAC in the centrally obese non-diabetic male is might be due to an increase of free leptin and decrease of adiponectin. The free leptin and adiponection ratio also increased hs-CRP, which partially correlated to the dysregulation of BMP-2 and MGP.Keywords: coronary artery calcification, central obesity, adipokines, bone regulator protein, pathomechanis

Correlation Between Homeostatic Model Assessment-estimated Insulin Resistance (HOMA-IR) with Asymmetric Dimethylarginine (ADMA) in Prehypertension

BACKGROUND: Not only hypertension, prehypertension has been reported to be linked with increased cardiovascular morbidity and mortality risks as well. Prehypertension has three-fold hypertension and two-fold cardiovascular risks. Pathomechanism that links hypertension with cardiovascular is related with endothelial dysfunction and insulin resistance. Endothelial dysfunction occurs when nitric oxide (NO) biological function was impaired, whereas shown by asymmetric dimethylarginine (ADMA). Subjects with prehypertension had higher insulin resistance events than normotension, whereas shown by homeostatic model assessment-estimated insulin resistance (HOMA-IR). This research was conducted to investigate the correlation of HOMA-IR with ADMA in prehyper- and normo-tension.METHODS: A cross-sectional comparative research was designed. Subjects were recruited and divided into prehyper- and normo-tensive groups. ADMA was measured using ELISA method, while HOMA-IR was calculated by the ratio of fasting insulin and glucose. Spearman 1-tail and Mann Whitney statistical analyses were performed.RESULTS: Comparing to normotensive group, elevated levels of HOMA-IR and ADMA in prehypertensive group were shown, but not significant. In prehypertensive group, we found significant correlation between HOMA-IR and ADMA.CONCLUSION: Insulin resistance and endothelial dysfunction was elevated in prehyper-compared to normotension

Role of 8-isoprostane, Matrix Gla Protein (MGP) and Bone Morphogenetic Protein-2 (BMP-2) in Vascular Calcification in Chronic Kidney Disease

BACKGROUND: Vascular calcification may be an important risk factor of cardiovascular disease in Chronic Kidney Disease (CKD). The pathobiology of vascular calcification in CKD is complex and involves some factors including inflammation, oxidative stress and balancing of calcification regulators. The aim of the study was to investigate the interaction between 8-isoprostane with calcification regulators such as matrix gla protein (MGP) and bone morphogenetic protein (BMP)-2 with vascular calciication in CKD.METHODS: A cross-sectional study was performed on 63 subjects undergoing haemodialysis maintenance for more than 3 months. Abdominal aortic calcification (AAC) was measured using a lateral abdominal X-ray for calcification in abdominal aorta, which is related to severity of calcific deposits at lumbar vertebral segment (L)1-L4. Serum levels of 8-isoprostane, MGP and BMP-2 were measured by enzyme-linked immunosorbent assay method.RESULTS: Results showed that 8-isoprostane levels were correlated with BMP-2 (r=0.266, p=0.018) and MGP levels (r=0.410, p≤0.001). MGP/BMP-2 levels ratio was correlated with AAC score (r=0.279, p=0.013). Subjects were then stratified into 3 groups based on AAC score: 0, 1-6 and ≥7. The highest mean of MGP levels was in AAC score 1-6 group, and the highest mean of 8-isoprostane levels was in AAC score ≥7. In the group of AAC score 0, 8-isoprostane levels were correlated with MGP levels (r=0.499, p=0.001) and MGP/BMP-2 levels ratio (r=0.291, p=0.034). In AAC score 1-6 group, 8-isoprostane levels were correlated with BMP-2 (r=0.661, p=0.005) and MGP levels (r=0.569, p=0.017). In AAC score ≥7 group, MGP levels were positively correlated with AAC score (r=0.608, p=0.041). With multivariate logistic regression analyses, we identified that increased MGP/BMP-2 levels ratio (OR=12.436; 95% CI=1.595-96.971) was an independent predictor in aortic calcification event.CONCLUSION: We concluded that regulators of calcification including calcification inhibitor and promoter related to oxidative stress, were associated with vascular calcification in CKD. MGP levels were increased in the early of calcification and MGP/BMP-2 levels ratio was a strong predictor for vascular calcification in CKD

N-Acetyl Transferase (NAT) 2 Polymorphisms and Susceptibility to Antituberculosis Drug-induced Hepatotoxicity in Indonesia

Tuberculosis (TB) treatment, based on the use of isoniazid (INH), rifampicin (RMP) and pyrazinamide (PZA), shown to cause drug-induced hepatotoxicity (DIH). Recent studies have demonstrated that genetic variations may associate with the risk of DIH, such as INH acetylation status, related to N-acetyl transferase (NAT) 2 polymorphism, which slow acetylation are more prone to side effects from drugs. The proportion of rapid and slow acetylator vary remarkably in populations of different ethnic or geographic origin which has been described in the various study, but, there is still limited information on our population. The objective of this study is to investigate the contribution of NAT2 polymorphisms to the anti-TB DIH in our population. This case-control study conducted at the Cipto Mangunkusumo Hospital, Jakarta and Omni Hospital Alam Sutera, Tangerang, Indonesia from January 201

The Relationship between Epicardial Adipose Tissue Thickness with Severity of Coronary Artery Disease in Indonesia

Epicardial adipose tissue (EAT), which is thought to be a componentof visceral adiposity, is associated with the metabolic syndrome and considered as an indicator of cardiovascular risk.Correlation of EAT with coronary artery disease (CAD) in Indonesia is unknown. To address this issue, we examined the relationship between EAT thickness with severity of coronary lesion in Indonesian patients with CAD. Results revealed that one hundred and thirty one consecutive patients who underwent transthoracic echocardiography (TTE) anddiagnostic coronary angiography were studied. The EAT thickness on the free wall of the right ventriclewas measured at end-diastole from the parasternal long-axis views. Coronary angiogramswere analyzed for severity of coronary artery disease using modified Gensini score. Accordingly, we classified the study population into two angiographic groups: patients with non-severe CAD (Gensini score ?13) and patients with severe CAD (Genisini score &gt;13). There were no significant differences between the groups with respect to anthropometric measurements, including body mass index and waist circumference (p=0.473 and 0.947, respectively). The patients in severe CAD group had greater EAT thickness compared with non-severe CAD group (mean EAT thickness was 8.

Neck Circumference Correlates to Coronary Calcification Better Than BMI and Waist Circumference in Insulin Resistance Obese Subjects

The association of obesity, insulin resistance, and chronic low-grade inflammation has been evident for years. Neck circumference (NC), a parameter of subcutaneous fat, is a unique storage depot and allegedly has an additional role for cardiovascular risk beyond the effect of abdominal circumference. Vascular calfication is identified at early stage of atherosclerosis and associated with cardiovascular events. The degree of calcification associated with local vascular inflammation and progression of atherosclerosis, however, there is no study linking NC independently to coronary calcification, an established parameter of subclinical atherosclerosis. This study carried out 60 obese non-diabetes men, consisted of 30 insluin-resistant (IR) and 30 non insulin-resistant (NIR) subjects. In IR subjects, there was a significant positive correlation between CAC score with NC, but none between CAC score with body mass index (BMI) or waist circumference. A significant correlation was found between hs-CRP with CAC score or NC in IR subjects, but none in NIR subjects. Interestingly, the correlation between NC and CACA score in IR subjects remained significant after each of BMI, hs-CRP, HOMA-IR, leptin or adiponectin being adjusted, lead to suggestion of another mechanisms might invlolve in the patho-mechanisms of coronary calcification in upper body obesity subjects. We concluded, in non-diabetic beyond the effect of BMI, low-grade inflammation, the degree of insulin resistance and adipokines such as leptin and adipocnetin