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Vascular dysfunction: At the heart of cardiovascular disease, cognitive impairment and depressive symptoms

Artery Research volume 19, pages 18–23 (2017)Cite this article

Abstract

Vascular dysfunction may be an important pathway through which ageing and other factors, such as diabetes and obesity, can cause diseases of the heart and brain. Vascular dysfunction includes dysfunction of large arteries (due to arterial stiffness), the microcirculation (microvascular dysfunction) and endothelium (endothelial dysfunction). We have investigated, in a series of epidemiological studies, the role of vascular dysfunction in the pathogenesis of cardiovascular disease, dementia and depression. Data were used of The Hoorn Study, The AGES-Reykjavik Study, The Maastricht Study and The SUVIMAX2 Study. In addition, we did two systematic reviews and an individual participant data meta-analysis.

References

  1. Vaupel JW. Biodemography of human ageing. Nature 2010;464: 536–42.

    Google Scholar 

  2. Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: part I: aging arteries: a “set up” for vascular disease. Circulation 2003;107: 139–46.

    Google Scholar 

  3. Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: part II: the aging heart in health: links to heart disease. Circulation 2003;107: 346–54.

    Google Scholar 

  4. Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 2013;31:1281–357.

    Google Scholar 

  5. Gorelick PB, Scuteri A, Black SE, Decarli C, Greenberg SM, Ladecola C, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011;42:2672–713.

    Google Scholar 

  6. Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J 2006;27:2588–605.

    Google Scholar 

  7. Yang EY, Chambless L, Sharrett AR, Virani SS, Liu X, Thang Z, et al. Carotid arterial wall characteristics are associated with incident ischemic stroke but not coronary heart disease in the Atherosclerosis Risk in Communities (ARIC) study. Stroke 2012;43:103–8.

    Google Scholar 

  8. Selwaness M, van den Bouwhuijsen Q, Mattace-Raso FU, Verwoert GC, Hofman A, Franco OH, et al. Arterial stiffness is associated with carotid intraplaque hemorrhage in the general population: the Rotterdam study. Arterioscler Thromb Vasc Biol 2014;34:927–32.

    Google Scholar 

  9. Maher EEM, Creane A, Lally C, Kelly DJ. Site specific inelasticity of arterial tissue. J Biomech 2012;8:1393–9.

    Google Scholar 

  10. van Sloten TT, Schram MT, van den Hurk K, Dekker JM, Nijpels G, Henry RM, et al. Local stiffness of the carotid and femoral artery is associated with incident cardiovascular events and all-cause mortality: the Hoorn study. J Am Coll Cardiol 2014;63:1739–47.

    Google Scholar 

  11. van Sloten TT, Sedaghat S, Laurent S, London GM, Pannier B, Ikram MA, et al. Carotid stiffness is associated with incident stroke: a systematic review and individual participant data meta-analysis. J Am Coll Cardiol 2015;66:2116–25.

    Google Scholar 

  12. Tzourio C, Laurent S, Debette S. Is hypertension associated with an accelerated aging of the brain? Hypertension 2014;63: 894–903.

  13. O’Rourke MF, Safar ME. Relationship between aortic stiffening and microvascular disease in brain and kidney: cause and logic of therapy. Hypertension 2005;46:200–4.

    Google Scholar 

  14. Mitchell GF. Effects of central arterial aging on the structure and function of the peripheral vasculature: implications for end-organ damage. J Appl Physiol 2008;105:1652–60.

    Google Scholar 

  15. Schillaci G, Bilo G, Pucci G, Laurent S, Maqcuin Mavier I, Boutouyrie P, et al. Relationship between short-term blood pressure variability and large-artery stiffness in human hypertension: findings from 2 large databases. Hypertension 2012;60:369–77.

    Google Scholar 

  16. Hughes TM, Kuller LH, Barinas-Mitchell EJ, McDade EM, Klunk WE, Cohen AD, et al. Arterial stiffness and beta-amyloid progression in nondemented elderly adults. JAMA neurol 2014;17:562–8.

    Google Scholar 

  17. Zhao C, Deng W, Gage FH. Mechanisms and functional implications of adult neurogenesis. Cell 2008;132:645–60.

    Google Scholar 

  18. Sabayan B, Westendorp RG, Grond J, Stott DJ, Sattar N, van Osch MJ, et al. Markers of endothelial dysfunction and cerebral blood flow in older adults. Neurobiol Aging 2014;35:373–7.

    Google Scholar 

  19. Wardlaw JM, Smith C, Dichgans M. Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging. Lancet Neurol 2013;12:483–97.

    Google Scholar 

  20. Alexopoulos GS, Meyers BS, Young RC, Campbell S, Silbersweig D, Charlson M. ‘Vascular depression’ hypothesis. Arch Gen Psychiatry 1997;54:915–22.

    Google Scholar 

  21. Pedersen CB, Mors O, Bertelsen A, Waltoft BL, Agerbo E E, McGrath JJ, et al. A comprehensive nationwide study of the incidence rate and lifetime risk for treated mental disorders. JAMA Psychiatry 2014;71:573–81.

    Google Scholar 

  22. Taragano FE, Bagnatti P, Allegri RF. A double-blind, randomized clinical trial to assess the augmentation with nimodipine of antidepressant therapy in the treatment of “vascular depression”. Int Psychogeriatr 2005;17:487–98.

    Google Scholar 

  23. van Sloten TT, Protogerou AD, Henry RM, Schram MT, Launer LJ, Stehouwer CD. Association between arterial stiffness, cerebral small vessel disease and cognitive impairment: a systematic review and meta-analysis. Neurosci Biobehav Rev 2015;53:121–30.

    Google Scholar 

  24. van Sloten TT, Sigurdsson S, van Buchem MA, Phillips CL, Jonsson PV, Ding J, et al. Cerebral small vessel disease and association with higher incidence of depressive symptoms in a general elderly population: the AGES-Reykjavik Study. Am J Psychiatry 2015;172:570–8.

    Google Scholar 

  25. van Sloten TT, Mitchell GF, Sigurdsson S, van Buchem MA, Jonsson PV, Garcia ME, et al. Associations between arterial stiffness, depressive symptoms and cerebral small vessel disease: cross-sectional findings from the AGES-Reykjavik Study. J Psychiatry Neurosci 2016;41:162–8.

    Google Scholar 

  26. van Sloten TT, Schram MT, Adriaanse MC, Dekker JM, Nijpels G, Teerlink T, et al. Endothelial dysfunction is associated with a greater depressive symptom score in a general elderly population: the Hoorn Study. Psychol Med 2014;44:1403–16.

    Google Scholar 

  27. Mitchell GF, Vita JA, Larson MG, Parise H, Keyes MJ, Warner E, et al. Cross-sectional relations of peripheral microvascular function, cardiovascular disease risk factors, and aortic stiffness: the Framingham Heart Study. Circulation 2005;112: 3722–8.

    Google Scholar 

  28. Kim ES, Moon SD, Kim HS, Lim DJ, Cho JH, Kwon HS, et al. Diabetic peripheral neuropathy is associated with increased arterial stiffness without changes in carotid intima-media thickness in type 2 diabetes. Diabetes Care 2011;34:1403–5.

    Google Scholar 

  29. Yasuno S, Ueshima K, Oba K, Fujimoto A, Hirata M, Ogihara T, et al. Is pulse pressure a predictor of new-onset diabetes in high-risk hypertensive patients? A subanalysis of the Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J) trial. Diabetes Care 2010;33:1122–7.

    Google Scholar 

  30. Giallauria F, Ling SM, Schreiber C, Maggio M, Shetty V, Muller D, et al. Arterial stiffness and bone demineralization: the Baltimore longitudinal study of aging. Am J Hypertens 2011;24: 970–5.

    Google Scholar 

  31. Holowatz LA, Thompson-Torgerson CS, Kenney WL. The human cutaneous circulation as a model of generalized microvascular function. J Appl Physiol 2008;105:370–2.

    Google Scholar 

  32. van Sloten TT, Czernichow S, Houben AJ, Protogerou AD, Henry RM, Muris DM, et al. Association between arterial stiffness and skin microvascular function: the SUVIMAX2 Study and the Maastricht Study. Am J Hypertens 2015;28:868–76.

    Google Scholar 

  33. Rothman KJGS, Lash TJ. Modern epidemiology. Philadelphia: Lippincott Williams and Wilkins; 2008.

  34. van Sloten TT, Henry RM, Dekker JM, Nijpels G, Unger T, Schram MT, et al. Endothelial dysfunction plays a key role in increasing cardiovascular risk in type 2 diabetes: the Hoorn study. Hypertension 2014;64:1299–305.

    Google Scholar 

  35. de Jager J, Dekker JM, Kooy A, Kostense PJ, Nijpels G, Heine RJ, et al. Endothelial dysfunction and low-grade inflammation explain much of the excess cardiovascular mortality in individuals with type 2 diabetes: the Hoorn Study. Arterioscler Thromb Vasc Biol 2006;26:1086–93.

    Google Scholar 

  36. Kim JA, Montagnani M, Koh KK, Quon MJ. Reciprocal relationships between insulin resistance and endothelial dysfunction: molecular and pathophysiological mechanisms. Circulation 2006;113:1888–904.

    Google Scholar 

  37. Schalkwijk CG, Stehouwer CD. Vascular complications in diabetes mellitus: the role of endothelial dysfunction. Clin Sci (Lond) 2005;109:143–59.

    Google Scholar 

  38. Paneni F, Beckman JA, Creager MA, Cosentino F. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part I. Eur Heart J 2013;34:2436–43.

    Google Scholar 

  39. Frankel DS, Meigs JB, Massaro JM, Wilson PW, O’Donnel CJ, D’Agostino RB, et al. Von Willebrand factor, type 2 diabetes mellitus, and risk of cardiovascular disease: the Framingham offspring study. Circulation 2008;118:2533–9.

    Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine and Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Prof. Debyelaan 25, 6229HX, Maastricht, The Netherlands

    T. T. van Sloten

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  1. T. T. van Sloten
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Correspondence to T. T. van Sloten.

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Review linked to Career Development Lecture, Artery Meeting, Copenhagen, 2016.

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van Sloten, T.T. Vascular dysfunction: At the heart of cardiovascular disease, cognitive impairment and depressive symptoms. Artery Res 19, 18–23 (2017). https://doi.org/10.1016/j.artres.2017.05.002

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Keywords

Artery Research

ISSN: 1876-4401

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