Relationship between peripheral arterial disease, carotid intima-media thickness and C-reactive protein in elderly diabetic patients
Author(s)
Moatassem Salah Amer,
Samia Ahmed Abdul-Rahman,
Wafaa Mostafa Abd-El Gawad,
Ibrahim Ahmad Abdel Aal,
Ahmad Abdel Khalek Abdel Razek Mohamed,
Wessam El-Huseiny Moustafa Abdel Wahab
Affiliation(s)
Geriatrics and Gerontology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt. Radiodiagnosis Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt. Geriatrics and Gerontology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Geriatrics and Gerontology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt. Radiodiagnosis Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt. Geriatrics and Gerontology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
ABSTRACT
Purpose: To study the association between carotid intima media thickness (CIMT) and high sensitivity CRP (hs-CRP) level as markers for PAD in elderly patients with DM. Subjects: A case-control study on 90 participants aged 60 years and older divided into 60 cases (30 patients with DM alone and 30 patients with DM and comorbidities) and 30 healthy controls. All were assessed by measuring CIMT, ankle brachial index (AB), and markers for cardiovascular disease such as high-sensitivity CRP (hs-CRP), total cholesterol (TC), triglycerides (TG), high density lipoprotein (HDL), and low density lipoprotein (LDL). Results: hs-CRP levels showed statistically significant difference being highest among patients with DM and comorbidities and lowest among controls (P < 0.001). Also, symptoms of PAD were significantly higher among cases than controls. ABI was able to detect PAD in many asymptomatic patients. Color changes were present in only 43.30% (n = 26) of positive PAD cases while delayed wound healing, claudication pain, rest pain, cold extremities, and trophic changes were present in 23.30% (n = 14), 16.71% (n = 10), 16.71% (n = 10), 45.00% (n = 27), and 21.7% (n = 13). Using logistic regression analysis revealed that DM, CIMT, and hs-CRP were independent predictors for PAD (OR = 4.194, 7.236, 1.003; P value = 0.044, 0.25, 0.031) after adjustment of other coronary risk factors such as sex, smoking, hypertension, TC, and TG. Conclusion: Diabetic elderly have higher prevalence of asymptomatic PAD thannon-diabetics using solely ABI. DM, CIMT, and hs-CRP are independent predictors for the occurrence of PAD. Hs-CRP levels are highest among diabetics with comorbidities.
Purpose: To study the association between carotid intima media thickness (CIMT) and high sensitivity CRP (hs-CRP) level as markers for PAD in elderly patients with DM. Subjects: A case-control study on 90 participants aged 60 years and older divided into 60 cases (30 patients with DM alone and 30 patients with DM and comorbidities) and 30 healthy controls. All were assessed by measuring CIMT, ankle brachial index (AB), and markers for cardiovascular disease such as high-sensitivity CRP (hs-CRP), total cholesterol (TC), triglycerides (TG), high density lipoprotein (HDL), and low density lipoprotein (LDL). Results: hs-CRP levels showed statistically significant difference being highest among patients with DM and comorbidities and lowest among controls (P < 0.001). Also, symptoms of PAD were significantly higher among cases than controls. ABI was able to detect PAD in many asymptomatic patients. Color changes were present in only 43.30% (n = 26) of positive PAD cases while delayed wound healing, claudication pain, rest pain, cold extremities, and trophic changes were present in 23.30% (n = 14), 16.71% (n = 10), 16.71% (n = 10), 45.00% (n = 27), and 21.7% (n = 13). Using logistic regression analysis revealed that DM, CIMT, and hs-CRP were independent predictors for PAD (OR = 4.194, 7.236, 1.003; P value = 0.044, 0.25, 0.031) after adjustment of other coronary risk factors such as sex, smoking, hypertension, TC, and TG. Conclusion: Diabetic elderly have higher prevalence of asymptomatic PAD thannon-diabetics using solely ABI. DM, CIMT, and hs-CRP are independent predictors for the occurrence of PAD. Hs-CRP levels are highest among diabetics with comorbidities.
Cite this paper
Amer, M. , Abdul-Rahman, S. , Gawad, W. , Aal, I. , Mohamed, A. and Wahab, W. (2013) Relationship between peripheral arterial disease, carotid intima-media thickness and C-reactive protein in elderly diabetic patients. Advances in Aging Research, 2, 115-120. doi: 10.4236/aar.2013.24017.
Amer, M. , Abdul-Rahman, S. , Gawad, W. , Aal, I. , Mohamed, A. and Wahab, W. (2013) Relationship between peripheral arterial disease, carotid intima-media thickness and C-reactive protein in elderly diabetic patients. Advances in Aging Research, 2, 115-120. doi: 10.4236/aar.2013.24017.
References
[1] International Diabetes Federation (2003) Diabetes Atlas. 2nd Edition, International Diabetes Federation, Brussels. http://dx.doi.org/10.2337/diacare.25.5.894 [2] Adler, A.I., Stevens, R.J., Neil, A., Stratton, I.M., Boulton, A.J.M., and Holman, R.R. (2002) UKPDS 59: Hyperglycemia and other potentially modifiable risk factors for peripheral vascular disease in type 2 diabetes. Diabetes Care, 25, 894-899. http://dx.doi.org/10.2337/diacare.25.5.894 [3] Held, C., Hjemdahl, P., Eriksson, S.V., Bjorkander, I., Forslund, L. and Rehnqvist, N. (2001) Prognostic implications of intima media thickness and plaques in the carotid and femoral arteries in patients with stable angina pectoris. European Heart Journal, 22, 62-72.
http://dx.doi.org/10.1053/euhj.1999.2006 [4] Libby, P. (2002) Inflammation in atherosclerosis. Nature, 420, 868-874.
http://dx.doi.org/10.1038/nature01323 [5] Lucas, A.R., Korol, R. and Pepine, C.J. (2006) Inflammation in atheroscelerosis: Some thoughts about acute coronary syndromes. Circulation, 113, 728-732.
http://dx.doi.org/10.1161/CIRCULATIONAHA.105.601492 [6] Danesh, J., Wheeler, J.G., Hirschfield, G.M., Eda, S., Eiriksdottir, G., Rumley, A., et al. (2004) C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. The New England Journal of Medicine, 350, 1387-1397. http://dx.doi.org/10.1056/NEJMoa032804 [7] Krishnaswamy, B., Raja, N. and Deepa, S. (2006) A study of peripheral vascular disease in elderly and its association with coronary artery disease. Journal of the Indian Academy of Geriatrics, 2, 10-13. [8] Rhee, S.Y., Guan, H., Liu, Z.M., Cheng, S.W., Waspadji, S., Palmes, P., et al. (2007) Multi-country study on the prevalence and clinical features of peripheral arterial disease in Asian type 2 diabetes patients at high risk of atherosclerosis. Diabetes Research and Clinical Practice, 76, 82-92. http://dx.doi.org/10.1016/j.diabres.2006.07.029 [9] Hirsch, A.T., Criqui, M.H., Treat-Jacobson, D., Regensteiner, J.G., Creager, M.A., Olin, J.W., et al. (2001) Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA, 286, 1317-1324. http://dx.doi.org/10.1001/jama.286.11.1317 [10] Belch, J.J., Topol, E.J., Agnelli, G., Bertrand, M., Califf, R.M., Clement, D.L., et al. (2003) Critical issues in peripheral arterial disease detection and management: A call to action. Archives International Medicine, 163, 884-892. http://dx.doi.org/10.1001/archinte.163.8.884 [11] Murabito, J.M., Evans, J.C. and Nieto, K. (2002) Prevalence and clinical correlates of peripheral arterial disease in the Framingham Offspring Study. American Heart Journal, 143, 961-965.
http://dx.doi.org/10.1067/mhj.2002.122871 [12] Greenland, P., Abrams, J., Aurigemma, F.P., Bond, M.G., Clark, L.T., Criqui, M.H., et al. (2000) Prevention conference V: Beyond secondary prevention identifying the high risk patient for primary prevention: Noninvasive tests of atherosclerotic burden; writing group III. Circulation, 101, E16-E22. http://dx.doi.org/10.1161/01.CIR.101.1.e16 [13] Hirsch, A.T., Haskal, Z.J. and Hertzer, N.R. (2006) ACC/ AHA guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): A collaborative report from the American associations for vascular surgery/society for vascular surgery, society for cardiovascular angiography and interventions, society for vascular medicine and biology, society of interventional radiology, and the ACC/ AHA task force on practice guidelines (writing committee to develop guidelines for the management of patients with peripheral arterial disease)—Summary of recommendations. Journal of Vascular and Interventional Radiology, 17, 1383-1397. http://dx.doi.org/10.1097/01.RVI.0000240426.53079.46 [14] Grenon, M.S., Gagnon, J. and Hsiang, Y. (2009) AnkleBrachial index for assessment of peripheral arterial disease. The New England Journal of Medicine, 361, Article ID: e40.
http://dx.doi.org/10.1056/NEJMvcm0807012 [15] Smith, G.D., Shipley, M.J. and Rose, G. (1990) Intermittent claudication, heart disease risk factors, and mortality. The Whitehall study. Circulation, 82, 1925-1931.
http://dx.doi.org/10.1161/01.CIR.82.6.1925 [16] Eagle, K.A., Rihal, C.S., Foster, E.D., Mickel, M.C. and Gersh, B.J. (1994) Long-term survival in patients with coronary artery disease: Importance of peripheral vascular disease. The coronary artery surgery study (CASS) investigators. Journal of the American College of Cardiology, 23, 1091-1095. http://dx.doi.org/10.1016/0735-1097(94)90596-7 [17] McDermott, M.M., Fried, L., Simonsick, E., Ling, S. and Guralnik, J.M. (2000) Asymptomatic peripheral arterial disease is independently associated with impaired lower extremity functioning: The women’s health and aging study. Circulation, 101, 1007-1012. http://dx.doi.org/10.1161/01.CIR.101.9.1007 [18] Chen, Y.J., Lin, M.S., Hsu, K.Y., Chen, C.R., Chen, C.M. and Chen, W. (2013) Prevalence of asymptomatic peripheral arterial disease and related risk factors in younger and elderly patients in Taiwan. Angiology, in Press. http://dx.doi.org/10.1177/0003319713480842 [19] Zieman, S.J., Melenovsky, V. and Kass, D.A. (2005) Mechanisms, pathophysiology, and therapy of arterial stiffness. Arteriosclerosis, Thrombosis, and Vascular Biology, 25, 932-943.
http://dx.doi.org/10.1161/01.ATV.0000160548.78317.29 [20] Zieman, S.J. and Kass, D.A. (2004) Advanced glycation endproduct crosslinking in the cardiovascular system: Potential therapeutic target for cardiovascular disease. Drugs, 64, 459-470. http://dx.doi.org/10.2165/00003495-200464050-00001 [21] American Diabetes Association (2003) Peripheral arterial disease in people with diabetes. Diabetes Care, 26, 33333341. http://dx.doi.org/10.2337/diacare.26.12.3333 [22] Bild, D.E., Selby, J.V., Sinnock, P., Browner, W.S., Braveman, P. and Showstack, J.A. (1989) Lower-extremity amputation in people with diabetes. Epidemiology and prevention. Diabetes Care, 12, 24-31. http://dx.doi.org/10.2337/diacare.12.1.24 [23] Burke, A.P., Tracy, R.P., Kolodgie, F., Malcom, G.T., Zieske, A., Kutys, R., et al. (2002) Elevated C-reactive protein values and atherosclerosis in sudden coronary death: Association with different pathologies. Circulation, 105, 2019-2023. http://dx.doi.org/10.1161/01.CIR.0000015507.29953.38 [24] Tracy, R.P., Lemaitre, R.N., Psaty, B.M., Ives, D.G., Evans, R.W., Cushman, M., et al. (1997) Relationship of C-reactive protein to risk of cardiovascular disease in the elderly. Results from the cardiovascular health study and the rural health promotion project. Arteriosclerosis, Thrombosis, and Vascular Biology, 17, 1121-1127. http://dx.doi.org/10.1161/01.ATV.17.6.1121 [25] Roivainen, M., Viik-Kajander, M., Palosuo, T., Toivanen, P., Leinonen, M., Saikku, P., et al. (2000) Infections, inflammation, and the risk of coronary heart disease. Circulation, 101, 252-257. http://dx.doi.org/10.1161/01.CIR.101.3.252 [26] Verma, S., Wang, C.H., Li, S.H., Dumont, A.S., Fedak, P.W.M., Badiwala, M.V., et al. (2002) A self-fulfilling prophecy: C-reactive protein attenuates nitric oxide production and inhibits angiogenesis. Circulation, 106, 913-919. http://dx.doi.org/10.1161/01.CIR.0000029802.88087.5E [27] Venugopal, S.K., Devaraj, S., Yuhanna, I., Shaul, P. and Jialal, I. (2002) Demonstration that C-reactive protein decreases eNOS expression and bioactivity in human aortic endothelial cells. Circulation, 106, 1439-1441. http://dx.doi.org/10.1161/01.CIR.0000033116.22237.F9
[1] International Diabetes Federation (2003) Diabetes Atlas. 2nd Edition, International Diabetes Federation, Brussels. http://dx.doi.org/10.2337/diacare.25.5.894 [2] Adler, A.I., Stevens, R.J., Neil, A., Stratton, I.M., Boulton, A.J.M., and Holman, R.R. (2002) UKPDS 59: Hyperglycemia and other potentially modifiable risk factors for peripheral vascular disease in type 2 diabetes. Diabetes Care, 25, 894-899. http://dx.doi.org/10.2337/diacare.25.5.894 [3] Held, C., Hjemdahl, P., Eriksson, S.V., Bjorkander, I., Forslund, L. and Rehnqvist, N. (2001) Prognostic implications of intima media thickness and plaques in the carotid and femoral arteries in patients with stable angina pectoris. European Heart Journal, 22, 62-72.
http://dx.doi.org/10.1053/euhj.1999.2006 [4] Libby, P. (2002) Inflammation in atherosclerosis. Nature, 420, 868-874.
http://dx.doi.org/10.1038/nature01323 [5] Lucas, A.R., Korol, R. and Pepine, C.J. (2006) Inflammation in atheroscelerosis: Some thoughts about acute coronary syndromes. Circulation, 113, 728-732.
http://dx.doi.org/10.1161/CIRCULATIONAHA.105.601492 [6] Danesh, J., Wheeler, J.G., Hirschfield, G.M., Eda, S., Eiriksdottir, G., Rumley, A., et al. (2004) C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. The New England Journal of Medicine, 350, 1387-1397. http://dx.doi.org/10.1056/NEJMoa032804 [7] Krishnaswamy, B., Raja, N. and Deepa, S. (2006) A study of peripheral vascular disease in elderly and its association with coronary artery disease. Journal of the Indian Academy of Geriatrics, 2, 10-13. [8] Rhee, S.Y., Guan, H., Liu, Z.M., Cheng, S.W., Waspadji, S., Palmes, P., et al. (2007) Multi-country study on the prevalence and clinical features of peripheral arterial disease in Asian type 2 diabetes patients at high risk of atherosclerosis. Diabetes Research and Clinical Practice, 76, 82-92. http://dx.doi.org/10.1016/j.diabres.2006.07.029 [9] Hirsch, A.T., Criqui, M.H., Treat-Jacobson, D., Regensteiner, J.G., Creager, M.A., Olin, J.W., et al. (2001) Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA, 286, 1317-1324. http://dx.doi.org/10.1001/jama.286.11.1317 [10] Belch, J.J., Topol, E.J., Agnelli, G., Bertrand, M., Califf, R.M., Clement, D.L., et al. (2003) Critical issues in peripheral arterial disease detection and management: A call to action. Archives International Medicine, 163, 884-892. http://dx.doi.org/10.1001/archinte.163.8.884 [11] Murabito, J.M., Evans, J.C. and Nieto, K. (2002) Prevalence and clinical correlates of peripheral arterial disease in the Framingham Offspring Study. American Heart Journal, 143, 961-965.
http://dx.doi.org/10.1067/mhj.2002.122871 [12] Greenland, P., Abrams, J., Aurigemma, F.P., Bond, M.G., Clark, L.T., Criqui, M.H., et al. (2000) Prevention conference V: Beyond secondary prevention identifying the high risk patient for primary prevention: Noninvasive tests of atherosclerotic burden; writing group III. Circulation, 101, E16-E22. http://dx.doi.org/10.1161/01.CIR.101.1.e16 [13] Hirsch, A.T., Haskal, Z.J. and Hertzer, N.R. (2006) ACC/ AHA guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): A collaborative report from the American associations for vascular surgery/society for vascular surgery, society for cardiovascular angiography and interventions, society for vascular medicine and biology, society of interventional radiology, and the ACC/ AHA task force on practice guidelines (writing committee to develop guidelines for the management of patients with peripheral arterial disease)—Summary of recommendations. Journal of Vascular and Interventional Radiology, 17, 1383-1397. http://dx.doi.org/10.1097/01.RVI.0000240426.53079.46 [14] Grenon, M.S., Gagnon, J. and Hsiang, Y. (2009) AnkleBrachial index for assessment of peripheral arterial disease. The New England Journal of Medicine, 361, Article ID: e40.
http://dx.doi.org/10.1056/NEJMvcm0807012 [15] Smith, G.D., Shipley, M.J. and Rose, G. (1990) Intermittent claudication, heart disease risk factors, and mortality. The Whitehall study. Circulation, 82, 1925-1931.
http://dx.doi.org/10.1161/01.CIR.82.6.1925 [16] Eagle, K.A., Rihal, C.S., Foster, E.D., Mickel, M.C. and Gersh, B.J. (1994) Long-term survival in patients with coronary artery disease: Importance of peripheral vascular disease. The coronary artery surgery study (CASS) investigators. Journal of the American College of Cardiology, 23, 1091-1095. http://dx.doi.org/10.1016/0735-1097(94)90596-7 [17] McDermott, M.M., Fried, L., Simonsick, E., Ling, S. and Guralnik, J.M. (2000) Asymptomatic peripheral arterial disease is independently associated with impaired lower extremity functioning: The women’s health and aging study. Circulation, 101, 1007-1012. http://dx.doi.org/10.1161/01.CIR.101.9.1007 [18] Chen, Y.J., Lin, M.S., Hsu, K.Y., Chen, C.R., Chen, C.M. and Chen, W. (2013) Prevalence of asymptomatic peripheral arterial disease and related risk factors in younger and elderly patients in Taiwan. Angiology, in Press. http://dx.doi.org/10.1177/0003319713480842 [19] Zieman, S.J., Melenovsky, V. and Kass, D.A. (2005) Mechanisms, pathophysiology, and therapy of arterial stiffness. Arteriosclerosis, Thrombosis, and Vascular Biology, 25, 932-943.
http://dx.doi.org/10.1161/01.ATV.0000160548.78317.29 [20] Zieman, S.J. and Kass, D.A. (2004) Advanced glycation endproduct crosslinking in the cardiovascular system: Potential therapeutic target for cardiovascular disease. Drugs, 64, 459-470. http://dx.doi.org/10.2165/00003495-200464050-00001 [21] American Diabetes Association (2003) Peripheral arterial disease in people with diabetes. Diabetes Care, 26, 33333341. http://dx.doi.org/10.2337/diacare.26.12.3333 [22] Bild, D.E., Selby, J.V., Sinnock, P., Browner, W.S., Braveman, P. and Showstack, J.A. (1989) Lower-extremity amputation in people with diabetes. Epidemiology and prevention. Diabetes Care, 12, 24-31. http://dx.doi.org/10.2337/diacare.12.1.24 [23] Burke, A.P., Tracy, R.P., Kolodgie, F., Malcom, G.T., Zieske, A., Kutys, R., et al. (2002) Elevated C-reactive protein values and atherosclerosis in sudden coronary death: Association with different pathologies. Circulation, 105, 2019-2023. http://dx.doi.org/10.1161/01.CIR.0000015507.29953.38 [24] Tracy, R.P., Lemaitre, R.N., Psaty, B.M., Ives, D.G., Evans, R.W., Cushman, M., et al. (1997) Relationship of C-reactive protein to risk of cardiovascular disease in the elderly. Results from the cardiovascular health study and the rural health promotion project. Arteriosclerosis, Thrombosis, and Vascular Biology, 17, 1121-1127. http://dx.doi.org/10.1161/01.ATV.17.6.1121 [25] Roivainen, M., Viik-Kajander, M., Palosuo, T., Toivanen, P., Leinonen, M., Saikku, P., et al. (2000) Infections, inflammation, and the risk of coronary heart disease. Circulation, 101, 252-257. http://dx.doi.org/10.1161/01.CIR.101.3.252 [26] Verma, S., Wang, C.H., Li, S.H., Dumont, A.S., Fedak, P.W.M., Badiwala, M.V., et al. (2002) A self-fulfilling prophecy: C-reactive protein attenuates nitric oxide production and inhibits angiogenesis. Circulation, 106, 913-919. http://dx.doi.org/10.1161/01.CIR.0000029802.88087.5E [27] Venugopal, S.K., Devaraj, S., Yuhanna, I., Shaul, P. and Jialal, I. (2002) Demonstration that C-reactive protein decreases eNOS expression and bioactivity in human aortic endothelial cells. Circulation, 106, 1439-1441. http://dx.doi.org/10.1161/01.CIR.0000033116.22237.F9