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Hand grip strength significantly predicts cardiovascular event risk in patients with type 2 diabetes mellitus
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Abstracts / Atherosclerosis 252 (2016) e1ee196
design by sex, age, and diabetes mellitus status. Outcome measure was allcause mortality at 10 years. Results: Mortality rates at 10 years were 29% in non-diabetic PAD patients (vs. 14% in controls; RR, 2.31; 95%CI, 1.54-3.47), and 58% in diabetic PAD patients (vs. 20% in controls; RR, 4.06; 95%CI, 2.67-6.18). We found the following independent predictors of death: in the 216 non-diabetic PAD patients, patients’ age>¼ 65years (RR, 2.15; 95%CI, 1.28-3.59), ankle brachial index <0.60 mmHg/mmHg (RR, 1.88; 95%CI, 1.14-3.08), history of PAD specific intervention (RR, 1.81; 95% CI, 1.10-2.97) and high-sensitivity C-reactive protein>¼5.0 mg/L (RR, 2.11; 95%CI, 1.28-3.47); and in the 115 diabetic PAD patients, patients’ age>¼ 65years (RR, 1.72; 95%CI, 1.05-2.83) and amino-terminal pro-B-type natriuretic peptide>¼125 ng/L (RR, 2.10; 95%CI, 1.22-3.60). Conclusions: In this study, mortality rates and predictors of death at 10 years were different in PAD patients <75 years with and without diabetes. Our findings suggest that distinct risk assessment and treatment strategies should be applied in the two PAD subgroups in future studies.
EAS16-0133, METABOLIC ABNORMALITIES AND ATHEROSCLEROSIS: DIABETES. HAND GRIP STRENGTH SIGNIFICANTLY PREDICTS CARDIOVASCULAR EVENT RISK IN PATIENTS WITH TYPE 2 DIABETES MELLITUS P. Rein 1, C. Saely 1, A. Vonbank 1, D. Zanolin 2, A. Leiherer 2, H. Drexel 1. 1 Academic Teaching Hospital Feldkirch, Medicine & Cardiology, Feldkirch, Austria; 2 Vivit-Institute, Vascular research, Feldkirch, Austria Objectives: Muscle fitness is an established indicator of overall health. The power of muscle strength to predict cardiovascular endpoints in patients with type 2 diabetes (T2DM) is unclear and is addressed in the present study. Methods: We studied a high-risk cohort of 209 patients with T2DM who underwent coronary angiography for the evaluation of stable coronary artery disease (CAD). Forearm muscle dynamometry was performed to determine hand grip strength in the dominant arm the day before angiography. Significant CAD was diagnosed in the presence of coronary stenoses with lumen narrowing 50%. T2DM was diagnosed according to the ADA criteria. Prospectively, we recorded vascular events over 5.5±2.2 years. Results: Grip strength, measured in kilograms, at baseline did not differ significantly between patients with significant CAD and those who did not have significant CAD (34±12 vs. 31±12 kg; p¼0.140). Prospectively, hand grip strength significantly predicted the incidence of major cardiovascular events (n¼65) after adjustment for age, gender, BMI, smoking, systolic and diastolic blood pressure, LDL cholesterol and HDL cholesterol (standardized adjusted HR 0.72 [0.52-0.99]; p¼0.042). This result was not attenuated after further adjustment for the angiographically determined baseline CAD state (HR 0.72 [0.53-0.99]; p¼0.046). Conclusions: We conclude that hand grip strength in patients with T2DM is inversely associated with vascular events independently both from well established cardiovascular risk factors and from the angiographically determined baseline CAD state.
EAS16-0106, METABOLIC ABNORMALITIES AND ATHEROSCLEROSIS: DIABETES. TELMISARTAN ATTENUATES HYPERGLYCEMIA-AGGRAVATED VCAM-1 EXPRESSION AND MONOCYTES ADHESION IN TNFa-STIMULATED ENDOTHELIAL CELLS BY INCREASING GSK3b-SER9 PHOSPHORYLATION D.H. Cho 1, J.E. Lee 1, K.H. Song 2. 1 School of Medicine- Eulji University, Department of Pharmacology, Daejeon, Republic of Korea; 2 Konkuk University School of Medicine, Division of Endocrinology and MetabolismDepartment of Internal Medicine, Seoul, Republic of Korea Objectives: Uncontrolled hyperglycemia accelerates endothelial damage and vascular inflammation caused by proinflammatory cytokines including tumor necrosis factor a (TNFa), which leads to arteriosclerotic cardiovascular diseases. Glycogen synthase kinase 3b (GSK3b) is reported
to mediate TNFa-stimulated nuclear factor-kB (NF-kB) activation and expression of vascular adhesion molecules. Although a few clinical trials have suggested that telmisartan, an angiotensin II type 1 receptor blocker (ARB), decreases cardiovascular complications in diabetic patients, the molecular mechanism for the beneficial effects remains elusive. Here, we investigated a molecular mechanism mediating the telmisartan’s beneficial effects on vascular inflammation in hyperglycemia-treated endothelial cells. Methods: We performed real-time qRT-PCR, western blot analysis, THP-1 adhesion assay, and transfection of GSK3b-S9A constructs. Results: Telmisartan dose-dependently attenuated the hyperglycemiaaggravated vascular cell adhesion molecule-1 (VCAM-1) expression and THP-1 monocytes adhesion, which accompanied an increased GSK3b-Ser9 phosphorylation and a decreased NF-kB p65-Ser536 phosphorylation. Among ARBs, including losartan and fimasartan, only telmisartan induced GSK3b-Ser9 phosphorylation and showed the inhibitory effects on expression of VCAM-1 and phosphorylation of NF-kB p65-Ser536. The telmisartan’s beneficial effects were not changed by pretreatment with GW9662, a specific and irreversible peroxisome proliferator-activated receptor g (PPARg) antagonist, although GW9662 clearly inhibited rosiglitazone-induced CD36 expression. Finally, ectopic expression of GSK3bS9A, a constitutively active mutant of GSK3b, significantly restored telmisartan-attenuated VCAM-1 expression, NF-kB p65-Ser536 phosphorylation, and THP-1 monocytes adhesion. Conclusions: Telmisartan ameliorates the hyperglycemia-exacerbated vascular inflammation at least in part by increasing GSK3b-Ser9 phosphorylation, which mediates a decrease in VCAM-1 expression in a PPARgindependent manner. Telmisartan may be useful for the treatment of diabetes mellitus-associated vascular inflammation and cardiovascular diseases.
EAS16-0507, METABOLIC ABNORMALITIES AND ATHEROSCLEROSIS: DIABETES. GENETIC VARIANTS AND LIPID TRAITS IN THE HONG KONG CHINESE PATIENTS WITH TYPE 2 DIABETES M. Hu, C. Tam, W.Y. So, J. Chan, B. Tomlinson, R. Ma. The Chinese University of Hong Kong, Department of Medicine & Therapeutics, Shatin, Hong Kong China Objectives: The genetic basis for raised triglycerides and low HDL-C in metabolic syndrome and type 2 diabetes is partially understood. We conducted a GWAS of plasma HDL-C and triglyceride levels to identify genetic determinants of these lipid traits in Chinese patients with type 2 diabetes in the Hong Kong Diabetes Registry. Methods: Chinese patients with type 2 diabetes were genotyped using the Illumina HumanOmni2.5Exome-8 BeadChip. After quality control, 1,303,895 autosomal SNPs were included for analysis. Association analyses were conducted using a linear regression model adjusted for age, sex, body mass index, duration of diabetes and urine protein/creatinine ratio. Results: In 2,246 patients with type 2 diabetes (mean(±SD) age: 52.6±13.0 years, 968 males), the mean(±SD) baseline triglyceride and HDL-C levels were 1.77±1.72 mmol/L and 1.29±0.36 mmol/L, respecitvely. For plasma triglyceride levels, the strongest statistical association signals were at the BUD13-ZNF259-APOA5-APOA4-APOC3-APOA1 cluster (top SNP: beta¼0.21, P<510-26) and LPL (top SNP: beta¼-0.14, P<510-10). For plasma HDL-C levels, the most significant association was found with variants in CETP (top SNP: beta¼0.16, P<510-11) followed by SNPs in the BUD13-ZNF259APOA5-APOA4-APOC3-APOA1 cluster (top SNP: beta¼-0.06, P<510-10) and LPL (top SNP: beta¼0.08, P<510-9). We also identified several new loci which are potentially related to triglyceride levels or HDL-C levels (P<1010-5). Conclusions: This preliminary analysis identified the strongly associated variants in loci previously implicated in lipid metabolism and suggested the involvement of several new loci in lipid metabolism in patients with type 2 diabetes.
Abstracts / Atherosclerosis 252 (2016) e1ee196
design by sex, age, and diabetes mellitus status. Outcome measure was allcause mortality at 10 years. Results: Mortality rates at 10 years were 29% in non-diabetic PAD patients (vs. 14% in controls; RR, 2.31; 95%CI, 1.54-3.47), and 58% in diabetic PAD patients (vs. 20% in controls; RR, 4.06; 95%CI, 2.67-6.18). We found the following independent predictors of death: in the 216 non-diabetic PAD patients, patients’ age>¼ 65years (RR, 2.15; 95%CI, 1.28-3.59), ankle brachial index <0.60 mmHg/mmHg (RR, 1.88; 95%CI, 1.14-3.08), history of PAD specific intervention (RR, 1.81; 95% CI, 1.10-2.97) and high-sensitivity C-reactive protein>¼5.0 mg/L (RR, 2.11; 95%CI, 1.28-3.47); and in the 115 diabetic PAD patients, patients’ age>¼ 65years (RR, 1.72; 95%CI, 1.05-2.83) and amino-terminal pro-B-type natriuretic peptide>¼125 ng/L (RR, 2.10; 95%CI, 1.22-3.60). Conclusions: In this study, mortality rates and predictors of death at 10 years were different in PAD patients <75 years with and without diabetes. Our findings suggest that distinct risk assessment and treatment strategies should be applied in the two PAD subgroups in future studies.
EAS16-0133, METABOLIC ABNORMALITIES AND ATHEROSCLEROSIS: DIABETES. HAND GRIP STRENGTH SIGNIFICANTLY PREDICTS CARDIOVASCULAR EVENT RISK IN PATIENTS WITH TYPE 2 DIABETES MELLITUS P. Rein 1, C. Saely 1, A. Vonbank 1, D. Zanolin 2, A. Leiherer 2, H. Drexel 1. 1 Academic Teaching Hospital Feldkirch, Medicine & Cardiology, Feldkirch, Austria; 2 Vivit-Institute, Vascular research, Feldkirch, Austria Objectives: Muscle fitness is an established indicator of overall health. The power of muscle strength to predict cardiovascular endpoints in patients with type 2 diabetes (T2DM) is unclear and is addressed in the present study. Methods: We studied a high-risk cohort of 209 patients with T2DM who underwent coronary angiography for the evaluation of stable coronary artery disease (CAD). Forearm muscle dynamometry was performed to determine hand grip strength in the dominant arm the day before angiography. Significant CAD was diagnosed in the presence of coronary stenoses with lumen narrowing 50%. T2DM was diagnosed according to the ADA criteria. Prospectively, we recorded vascular events over 5.5±2.2 years. Results: Grip strength, measured in kilograms, at baseline did not differ significantly between patients with significant CAD and those who did not have significant CAD (34±12 vs. 31±12 kg; p¼0.140). Prospectively, hand grip strength significantly predicted the incidence of major cardiovascular events (n¼65) after adjustment for age, gender, BMI, smoking, systolic and diastolic blood pressure, LDL cholesterol and HDL cholesterol (standardized adjusted HR 0.72 [0.52-0.99]; p¼0.042). This result was not attenuated after further adjustment for the angiographically determined baseline CAD state (HR 0.72 [0.53-0.99]; p¼0.046). Conclusions: We conclude that hand grip strength in patients with T2DM is inversely associated with vascular events independently both from well established cardiovascular risk factors and from the angiographically determined baseline CAD state.
EAS16-0106, METABOLIC ABNORMALITIES AND ATHEROSCLEROSIS: DIABETES. TELMISARTAN ATTENUATES HYPERGLYCEMIA-AGGRAVATED VCAM-1 EXPRESSION AND MONOCYTES ADHESION IN TNFa-STIMULATED ENDOTHELIAL CELLS BY INCREASING GSK3b-SER9 PHOSPHORYLATION D.H. Cho 1, J.E. Lee 1, K.H. Song 2. 1 School of Medicine- Eulji University, Department of Pharmacology, Daejeon, Republic of Korea; 2 Konkuk University School of Medicine, Division of Endocrinology and MetabolismDepartment of Internal Medicine, Seoul, Republic of Korea Objectives: Uncontrolled hyperglycemia accelerates endothelial damage and vascular inflammation caused by proinflammatory cytokines including tumor necrosis factor a (TNFa), which leads to arteriosclerotic cardiovascular diseases. Glycogen synthase kinase 3b (GSK3b) is reported
to mediate TNFa-stimulated nuclear factor-kB (NF-kB) activation and expression of vascular adhesion molecules. Although a few clinical trials have suggested that telmisartan, an angiotensin II type 1 receptor blocker (ARB), decreases cardiovascular complications in diabetic patients, the molecular mechanism for the beneficial effects remains elusive. Here, we investigated a molecular mechanism mediating the telmisartan’s beneficial effects on vascular inflammation in hyperglycemia-treated endothelial cells. Methods: We performed real-time qRT-PCR, western blot analysis, THP-1 adhesion assay, and transfection of GSK3b-S9A constructs. Results: Telmisartan dose-dependently attenuated the hyperglycemiaaggravated vascular cell adhesion molecule-1 (VCAM-1) expression and THP-1 monocytes adhesion, which accompanied an increased GSK3b-Ser9 phosphorylation and a decreased NF-kB p65-Ser536 phosphorylation. Among ARBs, including losartan and fimasartan, only telmisartan induced GSK3b-Ser9 phosphorylation and showed the inhibitory effects on expression of VCAM-1 and phosphorylation of NF-kB p65-Ser536. The telmisartan’s beneficial effects were not changed by pretreatment with GW9662, a specific and irreversible peroxisome proliferator-activated receptor g (PPARg) antagonist, although GW9662 clearly inhibited rosiglitazone-induced CD36 expression. Finally, ectopic expression of GSK3bS9A, a constitutively active mutant of GSK3b, significantly restored telmisartan-attenuated VCAM-1 expression, NF-kB p65-Ser536 phosphorylation, and THP-1 monocytes adhesion. Conclusions: Telmisartan ameliorates the hyperglycemia-exacerbated vascular inflammation at least in part by increasing GSK3b-Ser9 phosphorylation, which mediates a decrease in VCAM-1 expression in a PPARgindependent manner. Telmisartan may be useful for the treatment of diabetes mellitus-associated vascular inflammation and cardiovascular diseases.
EAS16-0507, METABOLIC ABNORMALITIES AND ATHEROSCLEROSIS: DIABETES. GENETIC VARIANTS AND LIPID TRAITS IN THE HONG KONG CHINESE PATIENTS WITH TYPE 2 DIABETES M. Hu, C. Tam, W.Y. So, J. Chan, B. Tomlinson, R. Ma. The Chinese University of Hong Kong, Department of Medicine & Therapeutics, Shatin, Hong Kong China Objectives: The genetic basis for raised triglycerides and low HDL-C in metabolic syndrome and type 2 diabetes is partially understood. We conducted a GWAS of plasma HDL-C and triglyceride levels to identify genetic determinants of these lipid traits in Chinese patients with type 2 diabetes in the Hong Kong Diabetes Registry. Methods: Chinese patients with type 2 diabetes were genotyped using the Illumina HumanOmni2.5Exome-8 BeadChip. After quality control, 1,303,895 autosomal SNPs were included for analysis. Association analyses were conducted using a linear regression model adjusted for age, sex, body mass index, duration of diabetes and urine protein/creatinine ratio. Results: In 2,246 patients with type 2 diabetes (mean(±SD) age: 52.6±13.0 years, 968 males), the mean(±SD) baseline triglyceride and HDL-C levels were 1.77±1.72 mmol/L and 1.29±0.36 mmol/L, respecitvely. For plasma triglyceride levels, the strongest statistical association signals were at the BUD13-ZNF259-APOA5-APOA4-APOC3-APOA1 cluster (top SNP: beta¼0.21, P<510-26) and LPL (top SNP: beta¼-0.14, P<510-10). For plasma HDL-C levels, the most significant association was found with variants in CETP (top SNP: beta¼0.16, P<510-11) followed by SNPs in the BUD13-ZNF259APOA5-APOA4-APOC3-APOA1 cluster (top SNP: beta¼-0.06, P<510-10) and LPL (top SNP: beta¼0.08, P<510-9). We also identified several new loci which are potentially related to triglyceride levels or HDL-C levels (P<1010-5). Conclusions: This preliminary analysis identified the strongly associated variants in loci previously implicated in lipid metabolism and suggested the involvement of several new loci in lipid metabolism in patients with type 2 diabetes.