Determinants of pulse pressure amplification in hypertensive and diabetic patients


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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Fig. 1


  1. 1.

    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.

    Article  Google Scholar 

  2. 2.

    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.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  3. 3.

    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.

    CAS  PubMed  Article  Google Scholar 

  4. 4.

    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.

    CAS  PubMed  Article  Google Scholar 

  5. 5.

    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.

    CAS  PubMed  Article  Google Scholar 

  6. 6.

    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.

    PubMed  Article  Google Scholar 

  7. 7.

    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.

    PubMed  Article  Google Scholar 

  8. 8.

    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.

    CAS  Article  Google Scholar 

  9. 9.

    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.

    CAS  PubMed  Article  Google Scholar 

  10. 10.

    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.

    PubMed  Article  Google Scholar 

  11. 11.

    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.

    CAS  PubMed  Article  Google Scholar 

  12. 12.

    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.

    PubMed  Article  Google Scholar 

  13. 13.

    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.

    PubMed  PubMed Central  Article  Google Scholar 

  14. 14.

    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.

    PubMed  Article  Google Scholar 

  15. 15.

    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.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  16. 16.

    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.

    CAS  Article  Google Scholar 

  17. 17.

    Rossi P, Francès Y, Kingwell BA, Ahimastos AA. Gender differences in artery wall biomechanical properties throughout life. J Hypertens. 2011;29:1023–33.

    CAS  PubMed  Article  Google Scholar 

  18. 18.

    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.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  19. 19.

    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.

    Article  Google Scholar 

  20. 20.

    Safar ME, London GM, Asmar R, Frohlich ED. Recent advances on large arteries in hypertension. Hypertension. 1998;32:156–61.

    CAS  PubMed  Article  Google Scholar 

  21. 21.

    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.

    PubMed  Article  Google Scholar 

  22. 22.

    Ogedegbe G, Pickering T. Principles and techniques of blood pressure measurement. Cardiol Clin. 2010;28:571–86.

    PubMed  PubMed Central  Article  Google Scholar 

  23. 23.

    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.

    PubMed  Article  Google Scholar 

  24. 24.

    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.

    CAS  Google Scholar 

  25. 25.

    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.

    CAS  Article  Google Scholar 

  26. 26.

    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.

    CAS  PubMed  Article  Google Scholar 

  27. 27.

    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.

    Article  Google Scholar 

  28. 28.

    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.

    CAS  PubMed  Article  Google Scholar 

  29. 29.

    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.

    PubMed  Article  Google Scholar 

  30. 30.

    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.

    CAS  PubMed  Article  Google Scholar 

  31. 31.

    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.

    CAS  PubMed  Article  Google Scholar 

  32. 32.

    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.

    PubMed  Article  Google Scholar 

  33. 33.

    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.

    CAS  PubMed  Article  Google Scholar 

  34. 34.

    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.

    CAS  PubMed  Article  Google Scholar 

  35. 35.

    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.

    CAS  PubMed  Article  Google Scholar 

  36. 36.

    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.

    CAS  PubMed  Article  Google Scholar 

  37. 37.

    Sell DR, Monnier VM. Molecular basis of arterial stiffening: role of glycation—a mini-review. Gerontology. 2012;58:227–37.

    CAS  PubMed  Article  Google Scholar 

  38. 38.

    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.

    CAS  PubMed  Article  Google Scholar 

  39. 39.

    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.

    PubMed  Article  Google Scholar 

  40. 40.

    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.

    Article  Google Scholar 

  41. 41.

    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.

    CAS  Article  Google Scholar 

  42. 42.

    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.

    CAS  PubMed  Article  Google Scholar 

  43. 43.

    Briet M, Boutouyrie P, Laurent S, London GM. Arterial stiffness and pulse pressure in CKD and ESRD. Kidney Int. 2012;82:388–400.

    PubMed  Article  Google Scholar 

  44. 44.

    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.

    CAS  Article  Google Scholar 

  45. 45.

    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.

    PubMed  Article  Google Scholar 

  46. 46.

    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.

    CAS  PubMed  Article  Google Scholar 

  47. 47.

    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.

    CAS  PubMed  Article  Google Scholar 

  48. 48.

    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.

    CAS  PubMed  Article  Google Scholar 

  49. 49.

    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.

    CAS  PubMed  Article  Google Scholar 

  50. 50.

    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.

    CAS  PubMed  Article  Google Scholar 

  51. 51.

    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.

    CAS  PubMed  Article  Google Scholar 

  52. 52.

    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.

    CAS  PubMed  Article  Google Scholar 

  53. 53.

    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.

    PubMed  Article  Google Scholar 

  54. 54.

    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.

    PubMed  Article  Google Scholar 

  55. 55.

    Boutouyrie P, Lacolley P, Briet M, Regnault V, Stanton A, Laurent S, et al. Pharmacological modulation of arterial stiffness. Drugs. 2011;71:1689–701.

    CAS  PubMed  Article  Google Scholar 

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Correspondence to Jacques Blacher.

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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).

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  • Pulse pressure amplification
  • hypertension
  • diabetes
  • HbA1c
  • glomerular filtration rate

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