Hypertensive diabetic patients remain at high cardiovascular risk despite adequate blood pressure and glycemic control. Pulse pressure amplification (PPA) is expressed as the peripheral-to-central PP ratio and provides complementary information for use in assessing cardiovascular risk. The aim of our study was to determine the clinical and biological determinants of PPA in hypertensive and diabetic patients. A cross-sectional study was conducted in 624 patients. Applanation tonometry was used to determine hemodynamic parameters. Age, gender, and the association between hypertension and diabetes were the independent factors of PPA in our population (N = 624). A threshold of 55 years of age was chosen because of its link with menopause in our analysis. Multivariate regression analyses were performed to evaluate the independent determinants of PPA for hypertensive diabetic and hypertensive nondiabetic male and female patients. HbA1c level is the main factor of increased PPA regardless of age and gender (P < 0.05). Mean BP negatively regulates PPA in the overall study: men > 55 years (P = 0.0001) and women > 55 years (P = 0.03). The threshold calculated glomerular filtration rate (cGFR) < 60 mL/min/1.73 m2 was an independent and negative factor of PPA in hypertensive diabetic men regardless of age (P < 0.05) and in women > 55 years (P = 0.04). Mean BP negatively regulates PPA in hypertensive nondiabetic patients (P < 0.04) regardless of age and gender, except in women > 55 years, where cGFR < 60 (P = 0.04) negatively regulates the modulation of PPA. HbA1c and threshold cGFR < 60 have highly significant impacts on PPA in hypertensive diabetic patients, whereas mean BP appears as the main factor of PPA in hypertensive nondiabetic patients.
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Task Force for the management of arterial hypertension of the European Society of Hypertension, Task Force for the management of arterial hypertension of the European Society of Cardiology. 2013 ESH/ESC Guidelines for the Management of Arterial Hypertension. Blood Press. 2013;22:193–278. https://doi.org/10.3109/08037051.2013.812549.
Kaess BM, Rong J, Larson MG, Hamburg NM, Vita JA, Levy D, et al. Aortic stiffness, blood pressure progression, and incident hypertension. JAMA. 2012;308:875–81. https://doi.org/10.1001/2012.jama.10503.
Avolio AP, Van Bortel LM, Boutouyrie P, Cockcroft JR, McEniery CM, Protogerou AD, et al. Role of pulse pressure amplification in arterial hypertension: experts’ opinion and review of the data. Hypertension. 2009;54:375–83. https://doi.org/10.1161/HYPERTENSIONAHA.109.134379.
Neisius U, Bilo G, Taurino C, McClure JD, Schneider MP, Kawecka-Jaszcz K, et al. Association of central and peripheral pulse pressure with intermediate cardiovascular phenotypes. J Hypertens. 2012;30:67–74. https://doi.org/10.1097/HJH.0b013e32834e12d8.
Manisty C, Mayet J, Tapp RJ, Parker KH, Sever P, Poulter NR, ASCOT Investigators. et al. Wave reflection predicts cardiovascular events in hypertensive individuals independent of blood pressure and other cardiovascular risk factors: an ASCOT (Anglo-Scandinavian Cardiac Outcome Trial) substudy. J Am Coll Cardiol. 2010;56:24–30. https://doi.org/10.1016/j.jacc.2010.03.030.
Benetos A, Thomas F, Joly L, Blacher J, Pannier B, Labat C, et al. Pulse pressure amplification a mechanical biomarker of cardiovascular risk. J Am Coll Cardiol. 2010;55:1032–7. https://doi.org/10.1016/j.jacc.2009.09.061.
Cheng H-M, Chuang S-Y, Sung S-H, Yu W-C, Pearson A, Lakatta EG, et al. Derivation and validation of diagnostic thresholds for central blood pressure measurements based on long-term cardiovascular risks. J Am Coll Cardiol. 2013;62:1780–7. https://doi.org/10.1016/j.jacc.2013.06.029.
Williams B, Lacy PS, Thom SM, Cruickshank K, Stanton A, Collier D, CAFE Investigators, Anglo-Scandinavian Cardiac Outcomes Trial Investigators, CAFE Steering Committee and Writing Committee. et al. Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study. Circulation. 2006;113:1213–25. https://doi.org/10.1161/CIRCULATIONAHA.105.595496.
McEniery CM, Yasmin null, McDonnell B, Munnery M, Wallace SM, Rowe CV, Anglo-Cardiff Collaborative Trial Investigators. et al. Central pressure: variability and impact of cardiovascular risk factors: the Anglo-Cardiff Collaborative Trial II. Hypertension. 2008;51:1476–82. https://doi.org/10.1161/HYPERTENSIONAHA.107.105445.
Vlachopoulos C, Aznaouridis K, O’Rourke MF, Safar ME, Baou K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with central haemodynamics: a systematic review and meta-analysis. Eur Heart J. 2010;31:1865–71. https://doi.org/10.1093/eurheartj/ehq024.
Yannoutsos A, Ahouah M, Tubiana CD, Topouchian J, Touboul C, Safar ME, et al. Hemodynamic parameters in hypertensive diabetic patients. J Hypertens. 2016;34:1123–31. https://doi.org/10.1097/HJH.0000000000000898.
Kitagawa N, Ushigome E, Matsumoto S, Oyabu C, Ushigome H, Yokota I, et al. Prognostic significance of home pulse pressure for progression of diabetic nephropathy: KAMOGAWA-HBP study. Hypertens Res. 2018;41:363–71. https://doi.org/10.1038/s41440-018-0024-6.
Regnault V, Thomas F, Safar ME, Osborne-Pellegrin M, Khalil RA, Pannier B, et al. Sex difference in cardiovascular risk: role of pulse pressure amplification. J Am Coll Cardiol. 2012;59:1771–7. https://doi.org/10.1016/j.jacc.2012.01.044.
McEniery CM, Yasmin null, Hall IR, Qasem A, Wilkinson IB, Cockcroft JR, ACCT Investigators. Normal vascular aging: differential effects on wave reflection and aortic pulse wave velocity: the Anglo-Cardiff Collaborative Trial (ACCT). J Am Coll Cardiol. 2005;46:1753–60. https://doi.org/10.1016/j.jacc.2005.07.037.
Wilkinson IB, Franklin SS, Hall IR, Tyrrell S, Cockcroft JR. Pressure amplification explains why pulse pressure is unrelated to risk in young subjects. Hypertension. 2001;38:1461–6.
Jacob MP. Extracellular matrix remodeling and matrix metalloproteinases in the vascular wall during aging and in pathological conditions. Biomed Pharmacother Biomedecine Pharmacother. 2003;57:195–202.
Rossi P, Francès Y, Kingwell BA, Ahimastos AA. Gender differences in artery wall biomechanical properties throughout life. J Hypertens. 2011;29:1023–33. https://doi.org/10.1097/HJH.0b013e328344da5e.
Adler AI, Stratton IM, Neil HA, Yudkin JS, Matthews DR, Cull CA, et al. Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study. BMJ. 2000;321:412–9.
Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, Byington RP, Goff DC, Bigger JT, Buse JB, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545–59. https://doi.org/10.1056/NEJMoa0802743.
Safar ME, London GM, Asmar R, Frohlich ED. Recent advances on large arteries in hypertension. Hypertension. 1998;32:156–61.
Safar ME, Balkau B, Lange C, Protogerou AD, Czernichow S, Blacher J, et al. Hypertension and vascular dynamics in men and women with metabolic syndrome. J Am Coll Cardiol. 2013;61:12–19. https://doi.org/10.1016/j.jacc.2012.01.088.
Ogedegbe G, Pickering T. Principles and techniques of blood pressure measurement. Cardiol Clin. 2010;28:571–86. https://doi.org/10.1016/j.ccl.2010.07.006.
Vera-Cala LM, Orostegui M, Valencia-Angel LI, López N, Bautista LE. Accuracy of the Omron HEM-705 CP for blood pressure measurement in large epidemiologic studies. Arq Bras Cardiol. 2011;96:393–8.
Chen CH, Nevo E, Fetics B, Pak PH, Yin FC, Maughan WL, et al. Estimation of central aortic pressure waveform by mathematical transformation of radial tonometry pressure. Valid Gen Transf Funct Circ. 1997;95:1827–36.
Roman MJ, Saba PS, Pini R, Spitzer M, Pickering TG, Rosen S, et al. Parallel cardiac and vascular adaptation in hypertension. Circulation. 1992;86:1909–18.
Hashimoto J, Ito S. Pulse pressure amplification, arterial stiffness, and peripheral wave reflection determine pulsatile flow waveform of the femoral artery. Hypertension. 2010;56:926–33. https://doi.org/10.1161/HYPERTENSIONAHA.110.159368.
Safar ME, Levy BI, Struijker-Boudier H. Current perspectives on arterial stiffness and pulse pressure in hypertension and cardiovascular diseases. Circulation. 2003;107:2864–9. https://doi.org/10.1161/01.CIR.0000069826.36125.B4.
McEniery CM, Yasmin null, Maki-Petaja KM, McDonnell BJ, Munnery M, Hickson SS, Anglo-Cardiff Collaboration Trial Investigators. et al. The impact of cardiovascular risk factors on aortic stiffness and wave reflections depends on age: the Anglo-Cardiff Collaborative Trial (ACCT III). Hypertension. 2010;56:591–7. https://doi.org/10.1161/HYPERTENSIONAHA.110.156950.
Pini R, Cavallini MC, Palmieri V, Marchionni N, Di Bari M, Devereux RB, et al. Central but not brachial blood pressure predicts cardiovascular events in an unselected geriatric population: the ICARe Dicomano Study. J Am Coll Cardiol. 2008;51:2432–9. https://doi.org/10.1016/j.jacc.2008.03.031.
Segers P, Mahieu D, Kips J, Rietzschel E, De Buyzere M, De Bacquer D, Asklepios investigators. et al. Amplification of the pressure pulse in the upper limb in healthy, middle-aged men and women. Hypertension. 2009;54:414–20. https://doi.org/10.1161/HYPERTENSIONAHA.109.133009.
Lieber A, Millasseau S, Bourhis L, Blacher J, Protogerou A, Levy BI, et al. Aortic wave reflection in women and men. Am J Physiol Heart Circ Physiol. 2010;299:H236–242. https://doi.org/10.1152/ajpheart.00985.2009.
Protogerou AD, Vlachopoulos C, Thomas F, Zhang Y, Pannier B, Blacher J, et al. Longitudinal changes in mean and pulse pressure, and all-cause mortality: data from 71,629 untreated normotensive individuals. Am J Hypertens. 2017;30:1093–9. https://doi.org/10.1093/ajh/hpx110.
Yang H, Drummer TD, Carter JR. Sex differences in sympathetic neural and limb vascular reactivity to mental stress in humans. Am J Physiol Heart Circ Physiol. 2013;304:H436–443. https://doi.org/10.1152/ajpheart.00688.2012.
Lane-Cordova AD, Kalil GZ, Wagner CJ, Sindler AL, Fiedorowicz JG, Ajibewa T, et al. Hemoglobin A1c and C-reactive protein are independently associated with blunted nocturnal blood pressure dipping in obesity-related prediabetes. Hypertens Res. 2018;41:33–38. https://doi.org/10.1038/hr.2017.82.
Webb DR, Khunti K, Silverman R, Gray LJ, Srinivasan B, Lacy PS, et al. Impact of metabolic indices on central artery stiffness: independent association of insulin resistance and glucose with aortic pulse wave velocity. Diabetologia. 2010;53:1190–8. https://doi.org/10.1007/s00125-010-1689-9.
Johansen NB, Rasmussen SS, Wiinberg N, Vistisen D, Jørgensen ME, Pedersen EB, et al. Associations between glycaemic deterioration and aortic stiffness and central blood pressure: the ADDITION-PRO Study. J Hypertens. 2017;35:1832–40. https://doi.org/10.1097/HJH.0000000000001398.
Sell DR, Monnier VM. Molecular basis of arterial stiffening: role of glycation—a mini-review. Gerontology. 2012;58:227–37. https://doi.org/10.1159/000334668.
Huang Q-F, Sheng C-S, Kang Y-Y, Zhang L, Wang S, Li F-K, et al. Central and peripheral blood pressures in relation to plasma advanced glycation end products in a Chinese population. J Hum Hypertens. 2016;30:430–5. https://doi.org/10.1038/jhh.2015.60.
Takenaka T, Suzuki H, Eguchi K, Miyashita H, Shimada K.ABC-J II study group Elevated pulse amplification in hypertensive patients with advanced kidney disease.Hypertens Res. 2018;41:299–307.
Wassertheurer S, Burkhardt K, Heemann U, Baumann M. Aortic to brachial pulse pressure amplification as functional marker and predictor of renal function loss in chronic kidney disease. J Clin Hypertens Greenwich Conn. 2014;16:401–5. https://doi.org/10.1111/jch.12316.
Safar ME, Blacher J, Pannier B, Guerin AP, Marchais SJ, Guyonvarc’h P-M, et al. Central pulse pressure and mortality in end-stage renal disease. Hypertension. 2002;39:735–8.
Goupil R, Dupuis D, Agharazii M, Hamet P, Troyanov S, Madore F. Central blood pressures in early chronic kidney disease: an analysis of CARTaGENE. Nephrol Dial Transplant. 2017;32:976–83. https://doi.org/10.1093/ndt/gfw059.
Briet M, Boutouyrie P, Laurent S, London GM. Arterial stiffness and pulse pressure in CKD and ESRD. Kidney Int. 2012;82:388–400. https://doi.org/10.1038/ki.2012.131.
Blacher J, Guerin AP, Pannier B, Marchais SJ, London GM. Arterial calcifications, arterial stiffness, and cardiovascular risk in end-stage renal disease. Hypertension. 2001;38:938–42.
Toussaint ND, Lau KK, Strauss BJ, Polkinghorne KR, Kerr PG. Associations between vascular calcification, arterial stiffness and bone mineral density in chronic kidney disease. Nephrol Dial Transplant. 2008;23:586–93. https://doi.org/10.1093/ndt/gfm660.
Woodard T, Sigurdsson S, Gotal JD, Torjesen AA, Inker LA, Aspelund T, et al. Mediation analysis of aortic stiffness and renal microvascular function. J Am Soc Nephrol JASN. 2015;26:1181–7. https://doi.org/10.1681/ASN.2014050450.
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. https://doi.org/10.1161/01.HYP.0000168052.00426.65.
Hashimoto J, Ito S. Aortic blood flow reversal determines renal function: potential explanation for renal dysfunction caused by aortic stiffening in hypertension. Hypertension. 2015;66:61–67. https://doi.org/10.1161/HYPERTENSIONAHA.115.05236.
Theilade S, Claggett B, Hansen TW, Skali H, Lewis EF, Solomon SD, TREAT investigators. et al. Pulse pressure is not an independent predictor of outcome in type 2 diabetes patients with chronic kidney disease and anemia—the Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT). J Hum Hypertens. 2016;30:46–52. https://doi.org/10.1038/jhh.2015.22.
Protogerou AD, Stergiou GS, Vlachopoulos C, Blacher J, Achimastos A. The effect of antihypertensive drugs on central blood pressure beyond peripheral blood pressure. Part II: evidence for specific class-effects of antihypertensive drugs on pressure amplification. Curr Pharm Des. 2009;15:272–89.
Agnoletti D, Zhang Y, Borghi C, Blacher J, Safar ME. Effects of antihypertensive drugs on central blood pressure in humans: a preliminary observation. Am J Hypertens. 2013;26:1045–52. https://doi.org/10.1093/ajh/hpt081.
Tedesco MA, Natale F, Di Salvo G, Caputo S, Capasso M, Calabró R. Effects of coexisting hypertension and type II diabetes mellitus on arterial stiffness. J Hum Hypertens. 2004;18:469–73. https://doi.org/10.1038/sj.jhh.1001690.
Vallée A, Yannoutsos A, Temmar M, Dreyfuss TC, Spinu I, Zhang Y. et al.Determinants of the aortic pulse wave velocity index in hypertensive and diabetic patients: predictive and therapeutic implications.J Hypertens. 2018;36:2324–32.
Aisu H, Saito M, Inaba S, Morofuji T, Takahashi K, Sumimoto T, et al. Association of worsening arterial stiffness with incident heart failure in asymptomatic patients with cardiovascular risk factors. Hypertens Res. 2017;40:173–80. https://doi.org/10.1038/hr.2016.116.
Boutouyrie P, Lacolley P, Briet M, Regnault V, Stanton A, Laurent S, et al. Pharmacological modulation of arterial stiffness. Drugs. 2011;71:1689–701. https://doi.org/10.2165/11593790-000000000-00000.
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Vallée, A., Yannoutsos, A., Zhang, Y. et al. Determinants of pulse pressure amplification in hypertensive and diabetic patients. Hypertens Res 42, 374–384 (2019). https://doi.org/10.1038/s41440-018-0161-y
- Pulse pressure amplification
- glomerular filtration rate
Wave reflections and systemic vascular resistance are stronger determinants of pulse pressure amplification than aortic stiffness in drug-naïve hypertensives
Clinical and Experimental Hypertension (2019)