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Role of cell adhesion molecules and oxidative stress in essential hypertension in Asian Indians
Abstracts
habitual salt intake and both stroke and total cardiovascular outcomes (CVD). Data sources and study selection: We performed a systematic search of publications through online databases and relevant reviews. According to pre-defined selection criteria, 13 studies were included in the meta-analysis. Data extraction: For each study, relative risks (RR) and 95% C.I. were extracted and pooled using a random effect model, weighting for the inverse of the variance. Heterogeneity, publication bias, subgroup and meta-regression analyses were performed as necessary. Results: Overall, there were 19 independent cohort samples, with 177,025 participants (follow-up range 3.5 to 19 years) and over 11,000 vascular events. Higher salt intake was associated with greater risk of stroke (pooled RR: 1.23; 95% CI 1.06 to 1.43; p = 0.007) and CVD (1.14; 0.99 to 1.32; p = 0.07), with no significant evidence of publication bias. For CVD, sensitivity analysis showed that the exclusion of a single study led to a pooled estimate of 1.17 (1.02 to 1.34); p = 0.02. The associations observed were greater the greater the difference in sodium intake and the longer the study follow-up period. Conclusions: High salt intake is associated with significantly greater risk of both stroke and total CVD. These results support the role of a population reduction in salt intake for the prevention of cardiovascular disease. doi:10.1016/j.ijcard.2009.09.175 EP000137 Calcitonin gene-related peptide alpha (CALCA) gene haplotypes and circulating CGRP levels significantly associate with risk of essential hypertension in Chinese subjects GUANG-WEI ZHONGa, WEI LIa, CHANG-GAO ZHONGb, CHENG ZHANGc, TAO ZHOUd a Research Institute of Integrated Traditional Chinese and Western Medicine, Xiang Ya Hospital, Central South University, China b Department of Cardiovascular, Xiang Ya Hospital Medicine School, Central South University, China c Department of Cardiology, Second of Hunan Province People's Hospital, China d Department of Cardiology, Second of Xiang Ya Hospital, Central South University, China Objective: To assess whether the promoter region of the calcitonin gene-related peptide gene alpha (CALCA) polymorphisms and haplotypes are associated with essential hypertension in Chinese men and explore the genetic mechanism concerning the pathogenesis of this disorder. Methods: We investigated the role of the − 9241 T/C, − 5357 G/A, −3580 T/G and −692 T/C polymorphisms of the CALCA and CGRP levels in 452 consecutive unrelated subjects comprising 247 patients of essential hypertension and 215 controls. The polymorphisms were investigated independently and as haplotypes. Plasma calcitonin generelated peptide (CGRP) activity and concentration were measured. Results: Genotype frequencies for the − 5357 G/A, − 3580 T/G and −692 T/C polymorphisms differed significantly (P < 0.01) between patients and controls and were associated with an increased risk of hypertension (OR = 2.0, OR = 3.8, OR = 1.6, respectively). The 4-locus haplotypes TATC (H1), TGTT (H2), and CGTC (H3) were significantly associated with essential hypertension and served as susceptible haplotypes (P ≤ 0.01). On the other hand, haplotypes CATT (H4) and CGGT (H5) were negatively associated with hypertension and served as protective haplotypes (P < 0.01). CGRP levels were significantly lower in patients than controls (P < 0.01). The individual polymorphisms showed marginal association with CGRP level; however, the susceptible haplotype H2 associated significantly with lower CGRP levels in patients (P < 0.01) and conversely the haplotype H4 with higher CGRP levels in controls (P < 0.01). Conclusion: In conclusion, the − 5357 G/A, − 3580 T/G and − 692 T/C polymorphisms were identified as the determinants modifying the risk of hypertension. This study identifies the CALCA variants and haplotypes as genetic risk
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factors and as useful markers of increased susceptibility to the risk of essential hypertension in Chinese subjects. doi:10.1016/j.ijcard.2009.09.176 EP000153 Role of cell adhesion molecules and oxidative stress in essential hypertension in Asian Indians KAMNA SRIVASTAVA*a, RAJEEV NARANGb, V. SREENIVASc, NIBHRITI DASa a Department of Biochemistry, All India Institute of Medical Sciences, India b Department of Cardiology, All India Institute of Medical Sciences, India c Department of Biostatistics, All India Institute of Medical Sciences, India Objective: By the year of 2020, India will have the largest cardiovascular diseases (CVD) burden in the world. Hypertension is one of the important risk factor of CVD. In India, a large group of people suffer with hypertension. Endothelial dysfunction is associated with most forms of CVD including hypertension, coronary artery disease and heart failure etc. Oxidative stress is involved in the pathogenesis of a wide range of CVD including hypertension. There is growing evidence that endothelium derived cell adhesion molecules play crucial role in the regulation of blood pressure. Endothelium is the target for prevention of cardiovascular disorders. Keeping this in view, we aimed at assessing the relationship between essential hypertension, cell adhesion molecules and oxidative stress. Methods: Various parameters for oxidative stress and cell adhesion molecules were determined using standard procedures and R&D Elisa kits, respectively. Results: The increase in oxidative stress might be contributed by decline in the levels of superoxide dismutase and catalase activity and lower levels of nitric oxide and higher levels of malondialdehyde in patients with essential hypertension as compared to normal healthy individuals. The levels of E-selectin and S VCAM-1 in patients were higher as compared to controls. Conclusion: This study, first of its kind, from India suggested that oxidative stress is prevalent in patients with essential hypertension at lower age group. Nitric oxide emerged as protective factor against the disease. Oxidative stress and cell adhesion molecules emerged as key risk factors for essential hypertension. doi:10.1016/j.ijcard.2009.09.177 EP000175 Control of the cardiovascular risk factors in the Spanish population GREGORIO MEDIAVILLA, JESUS ITURRALDE, ALFONSO A. RODRÍGUEZ, JAVIER MARTINEZ, AMAYA RUIZ DE LOIZAGA, CARLOS PARRA, JULIAN LARRANAGA, JAVIER GARCIA, M. CARMEN NORIEGA, M. TERESA HERNANDEZ, MILAGROS ALONSO, JULEN OCHARAN Osakidetza, Spain Objetive: One of the main objectives in our effort to achieve a better diagnosis of the affected population is the early identification of a subject in a cardiovascular risk situation, by managing the cardiovascular risk factors. It is also taken into account that cardiovascular diseases are the first cause of death in the developed countries. The objective of this study is to assess the control of the Cardiovascular Risk Factors in our population. Methods: A descriptive transversal study was conducted in December 2008 to a population of 289,923 patients from C. Álava (Basque Country, Spain) using an analysis of the OSABIDE programme database. Results: An Hta screening was conducted to the 48.28% of the allocated population and to the 58.03 % of the patients who have come to our clinics at least
habitual salt intake and both stroke and total cardiovascular outcomes (CVD). Data sources and study selection: We performed a systematic search of publications through online databases and relevant reviews. According to pre-defined selection criteria, 13 studies were included in the meta-analysis. Data extraction: For each study, relative risks (RR) and 95% C.I. were extracted and pooled using a random effect model, weighting for the inverse of the variance. Heterogeneity, publication bias, subgroup and meta-regression analyses were performed as necessary. Results: Overall, there were 19 independent cohort samples, with 177,025 participants (follow-up range 3.5 to 19 years) and over 11,000 vascular events. Higher salt intake was associated with greater risk of stroke (pooled RR: 1.23; 95% CI 1.06 to 1.43; p = 0.007) and CVD (1.14; 0.99 to 1.32; p = 0.07), with no significant evidence of publication bias. For CVD, sensitivity analysis showed that the exclusion of a single study led to a pooled estimate of 1.17 (1.02 to 1.34); p = 0.02. The associations observed were greater the greater the difference in sodium intake and the longer the study follow-up period. Conclusions: High salt intake is associated with significantly greater risk of both stroke and total CVD. These results support the role of a population reduction in salt intake for the prevention of cardiovascular disease. doi:10.1016/j.ijcard.2009.09.175 EP000137 Calcitonin gene-related peptide alpha (CALCA) gene haplotypes and circulating CGRP levels significantly associate with risk of essential hypertension in Chinese subjects GUANG-WEI ZHONGa, WEI LIa, CHANG-GAO ZHONGb, CHENG ZHANGc, TAO ZHOUd a Research Institute of Integrated Traditional Chinese and Western Medicine, Xiang Ya Hospital, Central South University, China b Department of Cardiovascular, Xiang Ya Hospital Medicine School, Central South University, China c Department of Cardiology, Second of Hunan Province People's Hospital, China d Department of Cardiology, Second of Xiang Ya Hospital, Central South University, China Objective: To assess whether the promoter region of the calcitonin gene-related peptide gene alpha (CALCA) polymorphisms and haplotypes are associated with essential hypertension in Chinese men and explore the genetic mechanism concerning the pathogenesis of this disorder. Methods: We investigated the role of the − 9241 T/C, − 5357 G/A, −3580 T/G and −692 T/C polymorphisms of the CALCA and CGRP levels in 452 consecutive unrelated subjects comprising 247 patients of essential hypertension and 215 controls. The polymorphisms were investigated independently and as haplotypes. Plasma calcitonin generelated peptide (CGRP) activity and concentration were measured. Results: Genotype frequencies for the − 5357 G/A, − 3580 T/G and −692 T/C polymorphisms differed significantly (P < 0.01) between patients and controls and were associated with an increased risk of hypertension (OR = 2.0, OR = 3.8, OR = 1.6, respectively). The 4-locus haplotypes TATC (H1), TGTT (H2), and CGTC (H3) were significantly associated with essential hypertension and served as susceptible haplotypes (P ≤ 0.01). On the other hand, haplotypes CATT (H4) and CGGT (H5) were negatively associated with hypertension and served as protective haplotypes (P < 0.01). CGRP levels were significantly lower in patients than controls (P < 0.01). The individual polymorphisms showed marginal association with CGRP level; however, the susceptible haplotype H2 associated significantly with lower CGRP levels in patients (P < 0.01) and conversely the haplotype H4 with higher CGRP levels in controls (P < 0.01). Conclusion: In conclusion, the − 5357 G/A, − 3580 T/G and − 692 T/C polymorphisms were identified as the determinants modifying the risk of hypertension. This study identifies the CALCA variants and haplotypes as genetic risk
S53
factors and as useful markers of increased susceptibility to the risk of essential hypertension in Chinese subjects. doi:10.1016/j.ijcard.2009.09.176 EP000153 Role of cell adhesion molecules and oxidative stress in essential hypertension in Asian Indians KAMNA SRIVASTAVA*a, RAJEEV NARANGb, V. SREENIVASc, NIBHRITI DASa a Department of Biochemistry, All India Institute of Medical Sciences, India b Department of Cardiology, All India Institute of Medical Sciences, India c Department of Biostatistics, All India Institute of Medical Sciences, India Objective: By the year of 2020, India will have the largest cardiovascular diseases (CVD) burden in the world. Hypertension is one of the important risk factor of CVD. In India, a large group of people suffer with hypertension. Endothelial dysfunction is associated with most forms of CVD including hypertension, coronary artery disease and heart failure etc. Oxidative stress is involved in the pathogenesis of a wide range of CVD including hypertension. There is growing evidence that endothelium derived cell adhesion molecules play crucial role in the regulation of blood pressure. Endothelium is the target for prevention of cardiovascular disorders. Keeping this in view, we aimed at assessing the relationship between essential hypertension, cell adhesion molecules and oxidative stress. Methods: Various parameters for oxidative stress and cell adhesion molecules were determined using standard procedures and R&D Elisa kits, respectively. Results: The increase in oxidative stress might be contributed by decline in the levels of superoxide dismutase and catalase activity and lower levels of nitric oxide and higher levels of malondialdehyde in patients with essential hypertension as compared to normal healthy individuals. The levels of E-selectin and S VCAM-1 in patients were higher as compared to controls. Conclusion: This study, first of its kind, from India suggested that oxidative stress is prevalent in patients with essential hypertension at lower age group. Nitric oxide emerged as protective factor against the disease. Oxidative stress and cell adhesion molecules emerged as key risk factors for essential hypertension. doi:10.1016/j.ijcard.2009.09.177 EP000175 Control of the cardiovascular risk factors in the Spanish population GREGORIO MEDIAVILLA, JESUS ITURRALDE, ALFONSO A. RODRÍGUEZ, JAVIER MARTINEZ, AMAYA RUIZ DE LOIZAGA, CARLOS PARRA, JULIAN LARRANAGA, JAVIER GARCIA, M. CARMEN NORIEGA, M. TERESA HERNANDEZ, MILAGROS ALONSO, JULEN OCHARAN Osakidetza, Spain Objetive: One of the main objectives in our effort to achieve a better diagnosis of the affected population is the early identification of a subject in a cardiovascular risk situation, by managing the cardiovascular risk factors. It is also taken into account that cardiovascular diseases are the first cause of death in the developed countries. The objective of this study is to assess the control of the Cardiovascular Risk Factors in our population. Methods: A descriptive transversal study was conducted in December 2008 to a population of 289,923 patients from C. Álava (Basque Country, Spain) using an analysis of the OSABIDE programme database. Results: An Hta screening was conducted to the 48.28% of the allocated population and to the 58.03 % of the patients who have come to our clinics at least