Abstract
Purpose
It is widely thought that excess pulsatile pressure from increased stiffness of large central arteries (macro-vasculature) is transmitted to capillary networks (micro-vasculature) and causes target organ damage. However, this hypothesis has never been tested. We sought to examine the association between macro- and micro-vasculature waveform features in patients with type 2 diabetes (i.e., those with elevated stiffness; T2D) compared with non-diabetic controls.
Methods
Among 13 T2D (68 ± 6 years, 39% male) and 15 controls (58 ± 11 years, 40% male) macro-vascular stiffness was determined via aortic pulse wave velocity (aPWV) and macro-vascular waveforms were measured using radial tonometry. Forearm micro-vascular waveforms were measured simultaneously with macro-vascular waveforms via low power laser Doppler fluxmetry. Augmentation index (AIx) was derived on macro- and micro-vascular waveforms. Target organ damage was assessed by estimated glomerular filtration rate (eGFR) and central retinal artery equivalent (CRAE).
Results
aPWV was higher among T2D (9.3 ± 2.5 vs 7.5 ± 1.4 m/s, p = 0.046). There was an obvious pulsatile micro-vascular waveform with qualitative features similar to macro-vasculature pressure waveforms. In all subjects, macro- and micro-vasculature AIx were significantly related (r = 0.43, p = 0.005). In T2D alone, micro-vasculature AIx was associated with eGFR (r = − 0.63, p = 0.037), whereas in controls, macro-vasculature AIx and AP were associated with CRAE (r = − 0.58, p = 0.025 and r = − 0.61, p = 0.015).
Conclusions
Macro- and micro-vasculature waveform features are related; however, micro-vasculature features are more closely related to markers of target organ damage in T2D. These findings are suggestive of a possible interaction between the macro- and micro-circulation.
Similar content being viewed by others
Abbreviations
- 24 ABPM:
-
24-h ambulatory BP monitoring
- AIx:
-
Augmentation index
- AP:
-
Augmentation pressure
- aPWV:
-
Aortic pulse wave velocity
- BMI:
-
Body mass index
- BP:
-
Blood pressure
- CRAE:
-
Central retinal artery equivalent
- CRVE:
-
Central retinal vein equivalent
- eGFR:
-
Estimated glomerular filtration rate
- LDF:
-
Laser Doppler fluxmetry
- T2D:
-
Type 2 diabetes
References
Angouras D, Sokolis DP, Dosios T, Kostomitsopoulos N, Boudoulas H, Skalkeas G, Karayannacos PE (2000) Effect of impaired vasa vasorum flow on the structure and mechanics of the thoracic aorta: implications for the pathogenesis of aortic dissection. Eur J Cardiothorac Surg 17(4):468–473
Benchimol A, Desser KB, Gartlan JL (1972) Bidirectional blood flow velocity in the cardiac chambers and great vessels studied with the Doppler ultrasonic flowmeter. The Am J Med Sci 52(4):467–473
Bračič M, Stefanovska A (1998) Wavelet-based analysis of human blood flow dynamics. Bull Math Bio 60(5):919–935
Chen C-H, Nevo E, Fetics B, Pak PH, Yin FC, Maughan WL, Kass DA (1997) Estimation of central aortic pressure waveform by mathematical transformation of radial tonometry pressure validation of generalized transfer function. Circulation 95(7):1827–1836
Cheung N, Sharrett AR, Klein R, Criqui MH, Islam FA, Macura KJ, Cotch MF, Klein BE, Wong TY (2007) Aortic distensibility and retinal arteriolar narrowing. Hypertension 50(4):617–622
Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ (2003) The Seventh Report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA 289(19):2560–2572
Choi Y-K, Kim K-W (2008) Blood-neural barrier: its diversity and coordinated cell-to-cell communication. BMB Rep 41(5):345–352
Climie RE, Srikanth V, Beare R, Keith LJ, Fell J, Davies JE, Sharman JE (2014) Aortic reservoir characteristics and brain structure in people with type 2 diabetes mellitus; a cross sectional study. Cardiovasc Diabetol 13(1):143
Climie RE, Srikanth V, Keith LJ, Davies JE, Sharman JE (2015) Exercise excess pressure and exercise-induced albuminuria in patients with type 2 diabetes mellitus. Am J Physiol Heart Circ Physiol 308(9):H1136–H1142
Climie RE, Picone DS, Sharman JE (2017) Longitudinal changes in excess pressure independently predict declining renal function among healthy individuals—a pilot study. Am J Hypertens 30(8):772–775
Cruickshank K, Riste L, Anderson SG, Wright JS, Dunn G, Gosling RG (2002) Aortic pulse-wave velocity and its relationship to mortality in diabetes and glucose intolerance: an integrated index of vascular function? Circulation 106(16):2085–2090
Franklin SS (2005) Arterial stiffness and hypertension. Hypertension 45(3):349–351
García-Ortiz L, Recio-Rodríguez JI, Agudo-Conde C, Patino-Alonso MC, Rodríguez-Sánchez E, Maderuelo-Fernandez JA, Gómez-Marcos MA, EVIDENT Group (2015) The role of retinal vessels caliber as a marker of vascular aging in large arteries. J Hypertens 33(4):818–826
Gronenschild E, Muris D, Schram M, Karaca Ü, Stehouwer C, Houben A (2013) Semi-automatic assessment of skin capillary density: proof of principle and validation. Microvasc Res 90:192–198
Harloff A, Strecker C, Dudler P, Nuβbaumer A, Frydrychowicz A, Olschewski M, Bock J, Stalder AF, Stroh AL, Weiller C (2009) Retrograde embolism from the descending aorta. Stroke 40(4):1505–1508
Hashimoto J, Ito S (2011) Central pulse pressure and aortic stiffness determine renal hemodynamics pathophysiological implication for microalbuminuria in hypertension. Hypertension 58(5):839–846
Hashimoto J, Ito S (2013) Aortic stiffness determines diastolic blood flow reversal in the descending thoracic aorta potential implication for retrograde embolic stroke in hypertension. Hypertension 62(3):542–549
Ijzerman R, De Jongh R, Beijk M, Van Weissenbruch M, Delemarre-van de Waal H, Serne E, Stehouwer C (2003) Individuals at increased coronary heart disease risk are characterized by an impaired microvascular function in skin. Eur J Clin Invest 33(7):536–542
Keith LJ, Rattigan S, Keske MA, Jose M, Sharman JE (2013) Exercise aortic stiffness: reproducibility and relation to end-organ damage in men. J Hum Hypertens 27(8):516–522
Knudtson MD, Lee KE, Hubbard LD, Wong TY, Klein R, Klein BE (2003) Revised formulas for summarizing retinal vessel diameters. Curr Eye Res 27(3):143–149
Laakso M (2011) Heart in diabetes: a microvascular disease. Diabetes Care 34(Supplement 2):S145–S149
Laugesen E, Høyem P, Stausbøl-Grøn B, Mikkelsen A, Thrysøe S, Erlandsen M, Christiansen JS, Knudsen ST, Hansen KW, Kim WY (2013) Carotid-femoral pulse wave velocity is associated with cerebral white matter lesions in type 2 diabetes. Diabetes Care 36(3):722–728
Laurent S, Boutouyrie P (2015) The structural factor of hypertension. Circ Res 116(6):1007–1021
Laurent S, Cockcroft JR, Van Bortel LM, Boutouyrie P, Giannattasio C, Hayoz D, Pannier B, Vlachopoulos C, Wilkinson I, Struijker-Boudier H (2006) Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J 27(21):2588–2605
Laurent S, Briet M, Boutouyrie P (2009) Large and small artery cross-talk and recent morbidity-mortality trials in hypertension. Hypertension 54(2):388–392
Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150(9):604–612
Liao D, Wong TY, Klein R, Jones D, Hubbard L, Sharrett AR (2004) Relationship between carotid artery stiffness and retinal arteriolar narrowing in healthy middle-aged persons. Stroke 35(4):837–842
Liu JJ, Tavintharan S, Yeoh L, Sum C, Ng X, Pek S, Lee S, Tang W, Lim S (2014) High normal albuminuria is independently associated with aortic stiffness in patients with type 2 diabetes. Diabet Med 31(10):1199–1204
Lockhart CJ, McCann A, Pinnock R, Hamilton P, Harbinson M, McVeigh GE (2014) “Multimodal functional and anatomic imaging identifies preclinical microvascular abnormalities in type 1 diabetes mellitus”. Am J Physiol Heart Circ Physiol 307(12):H1729–H1736
MacMahon S, Peto R, Collins R, Godwin J, Cutler J, Sorlie P, Abbott R, Neaton J, Dyer A, Stamler J (1990) Blood pressure, stroke, and coronary heart disease: part 1, prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. The Lancet 335(8692):765–774
McEniery CM, Yasmin IR, Hall A, Qasem IB, Wilkinson JR, Cockcroft (2005) Normal vascular aging: differential effects on wave reflection and aortic pulse wave velocity: the Anglo-Cardiff Collaborative Trial (ACCT). J Am Coll Cardiol 46(9):1753–1760
McVeigh G, Brennan G, Johnston G, McDermott B, McGrath L, Henry W, Andrews J, Hayes J (1992) Impaired endothelium-dependent and independent vasodilation in patients with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 35(8):771–776
Megnien JL, Simon A, Valensi P, Flaud P, Merli I, Levenson J (1992) Comparative effects of diabetes mellitus and hypertension on physical properties of human large arteries. J Am Coll Cardiol 20(7):1562–1568
Meijer RI, de Boer MP, Groen MR, Eringa EC, Rattigan S, Barrett EJ, Smulders YM, Serné EH (2012) Insulin-induced microvascular recruitment in skin and muscle are related and both are associated with whole-body glucose uptake. Microcirculation 19(6):494–500
Mitchell GF (2008) Effects of central arterial aging on the structure and function of the peripheral vasculature: implications for end-organ damage. J Appl Physiol 105(5):1652–1660
Mitchell GF, Vita JA, Larson MG, Parise H, Keyes MJ, Warner E, Vasan RS, Levy D, Benjamin EJ (2005) Cross-sectional relations of peripheral microvascular function, cardiovascular disease risk factors, and aortic stiffness: the Framingham Heart Study. Circulation 112(24):3722–3728
Muiesan ML, Salvetti M, Rizzoni D, Paini A, Agabiti-Rosei C, Aggiusti C, Bertacchini F, Stassaldi D, Gavazzi A, Porteri E (2013) Pulsatile hemodynamics and microcirculation evidence for a close relationship in hypertensive patients. Hypertension 61(1):130–136
Nichols WW, O’Rourke MF (2005) McDonald’s Blood flow in arteries: theoretical, experimental and clinical principles, 5th edn. Hodder Arnold, London
Rajan V, Varghese B, van Leeuwen TG, Steenbergen W (2009) Review of methodological developments in laser Doppler flowmetry. Laser Med Sci 24(2):269–283
Rossi M, Taddei S, Fabbri A, Tintori G, Credidio L, Virdis A, Ghiadoni L, Salvetti A, Giusti C (1997) Cutaneous vasodilation to acetylcholine in patients with essential hypertension. J Cardiovasc Pharmacol 29(3):406–411
Schram M, Henry R, van Dijk R, Kostense P, Dekker J, Nijpels G, Heine R, Bouter L, Westerhof N, S. C (2004) Increased central artery stiffness in impaired glucose metabolism and type 2 diabetes: The Hoorn study. Hypertension 43:176–181
Schultz M, Climie R, Nikolic S, Ahuja K, Sharman J (2013) Persistent elevation of central pulse pressure during postural stress in patients with type 2 diabetes mellitus. J Hum Hypertens 27(7):437–444
Sharman JE, Fang ZY, Haluska B, Stowasser M, Prins JB, Marwick TH (2005) Left ventricular mass in patients with type 2 diabetes is independently associated with central but not peripheral pulse pressure. Diabetes Care 28(4):937–939
SphygmoCor Assuring quality of Pulse Wave Anlaysis Measurements. Technical Note No: 14. Features of the radial artery pressure waveform that identify a good quality waveform. Australia, pp 1–2
Stamler J, Stamler R, Neaton JD (1993) Blood pressure, systolic and diastolic, and cardiovascular risks: US population data. Arch Intern Med 153(5):598–615
Stehouwer C, Henry R, Ferreira I (2008) Arterial stiffness in diabetes and the metabolic syndrome: a pathway to cardiovascular disease. Diabetologia 51(4):527
Strain WD, Chaturvedi N, Hughes A, Nihoyannopoulos P, Bulpitt CJ, Rajkumar C, Shore AC (2010) Associations between cardiac target organ damage and microvascular dysfunction: the role of blood pressure. J Hypertens 28(5):952–958
Tikellis G, Wang J, Tapp R, Simpson R, Mitchell P, Zimmet P, Shaw J, Wong T (2007) The relationship of retinal vascular calibre to diabetes and retinopathy: the Australian Diabetes, Obesity and Lifestyle (AusDiab) study. Diabetologia 50(11):2263–2271
Triantafyllou A, Anyfanti P, Gavriilaki E, Zabulis X, Gkaliagkousi E, Petidis K, Triantafyllou G, Gkolias V, Pyrpasopoulou A, Douma S (2014) Association between retinal vessel caliber and arterial stiffness in a population comprised of normotensive to early-stage hypertensive individuals. Am J Hyperns 27(12):1472–1478
van Bussel BC, Schouten F, Henry RM, Schalkwijk CG, de Boer MR, Ferreira I, Smulders YM, Twisk JW, Stehouwer CD (2011) Endothelial dysfunction and low-grade inflammation are associated with greater arterial stiffness over a 6-year period. Hypertensionaha, Hypertension. 111.174557
Winer N, Folker A, Murphy JA, Hung E, Bard M, Perkelvald A, Sowers JR, Bakris GL (2005) Effect offixed dose ACE-inhibitor/calcium channel blocker combination therapy vs ACE–inhibitormonotherapy on arterial compliance in hypertensive patients with type 2 diabetes. Prev Cardiol 8(2):87–92
Woodard T, Sigurdsson S, Gotal JD, Torjesen AA, Inker LA, Aspelund T, Eiriksdottir G, Gudnason V, Harris TB, Launer LJ, Levey A, Mitchell G (2014) Mediation analysis of aortic stiffness and renal microvascular function. J Am Soc Nephrol: ASN. 2014050450
Author information
Authors and Affiliations
Contributions
This study was performed at the Blood Pressure Clinic at the Menzies Institute for Medical Research, Tasmania, Australia. REDC, DSP, AQ, SR and JES conceived the study, REDC, DSP, SB and SEK acquired and analyzed the data, REDC, DSP and JES interpreted the results, REDC drafted the manuscript and DSP, SB, SEK, AQ, SR and JES provided critical evaluation of the manuscript. All authors approved the final version of the manuscript and are accountable for all aspects of the work. All authors qualify for authorship.
Corresponding author
Ethics declarations
Conflict of interest
Ahmad Qasem is the principal scientist at AtCor medical, the manufacturer of non-invasive central pressure waveform analysis devices SphygmoCor and XCEL.
Additional information
Communicated by I. Mark Olfert.
Rights and permissions
About this article
Cite this article
Climie, R.E.D., Picone, D.S., Blackwood, S. et al. Pulsatile interaction between the macro-vasculature and micro-vasculature: proof-of-concept among patients with type 2 diabetes. Eur J Appl Physiol 118, 2455–2463 (2018). https://doi.org/10.1007/s00421-018-3972-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00421-018-3972-2