Cardiovascular End Points and Mortality Are Not Closer Associated With Central Than Peripheral Pulsatile Blood Pressure Components

doi:10.1161/HYPERTENSIONAHA.120.14787

. 2020 Aug;76(2):350-358.

doi: 10.1161/HYPERTENSIONAHA.120.14787. Epub 2020 Jul 8.

Cardiovascular End Points and Mortality Are Not Closer Associated With Central Than Peripheral Pulsatile Blood Pressure Components

Qi-Fang Huang^#¹, Lucas S Aparicio^#², Lutgarde Thijs³, Fang-Fei Wei³, Jesus D Melgarejo³, Yi-Bang Cheng¹, Chang-Sheng Sheng¹, Wen-Yi Yang⁴, Natasza Gilis-Malinowska⁵, José Boggia², Teemu J Niiranen^{6

7}, Wiktoria Wojciechowska⁸, Katarzyna Stolarz-Skrzypek⁸, Jessica Barochiner⁹, Daniel Ackermann¹⁰, Valérie Tikhonoff¹¹, Belen Ponte^{12

13}, Menno Pruijm¹⁴, Edoardo Casiglia¹¹, Krzysztof Narkiewicz⁵, Jan Filipovský¹⁵, Danuta Czarnecka⁸, Kalina Kawecka-Jaszcz⁸, Antti M Jula⁶, Murielle Bochud¹⁶, Thomas Vanassche¹⁷, Peter Verhamme¹⁷, Harry A J Struijker-Boudier¹⁸, Ji-Guang Wang¹, Zhen-Yu Zhang^#³, Yan Li^#¹, Jan A Staessen^#^{3

19}; IDCARS (International Database of Central Arterial Properties for Risk Stratification) Investigators

Collaborators, Affiliations

Collaborators

IDCARS (International Database of Central Arterial Properties for Risk Stratification) Investigators:
L S Aparicio, J Barochiner, L Thijs, J A Staessen, F F Wei, W Y Yang, Z Y Zhang, Y B Cheng, Q H Guo, J F Huang, Q F Huang, Y Li, C S Sheng, J G Wang, J Filipovský, J Seidlerová, E P Juhanoja, A M Jula, A S Lindroos, T J Niiranen, S S Sivén, E Casiglia, A Pizzioli, V Tikhonoff, B S Chori, B Danladi, A N Odili, H Oshaju, W Kucharska, K Kunicka, N Gilis-Malinowska, K Narkiewicz, W Sakiewicz, E Swierblewska, K Kawecka-Jaszcz, K Stolarz-Skrzypek, A E Schutte, G R Norton, A J Woodiwiss, D Ackermann, M Bochud, B Ponte, M Pruijm, R Álvarez-Vaz, C Américo, C Baccino, L Borgarello, L Florio, P Moliterno, A Noboa, O Noboa, A Olascoaga, P Parnizari, M Pécora

Affiliations

¹ From the Center for Epidemiological Studies and Clinical Trials and Center for Vascular Evaluations, Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Ruijin Hospital (Q.-F.H., Y.-B.C., C.-S.S., J.-G.W., Y.L.).
² Shanghai Jiao Tong University School of Medicine, China; Servicio de Clínica Médica, Sección Hipertensión Arterial, Hospital Italiano de Buenos Aires, Argentina (L.S.A., J.B.).
³ Research Unit Hypertension and Cardiovascular Epidemiology (L.T., F.-F.W., J.D.M., Z.-Y.Z., J.A.S.), KU Leuven Department of Cardiovascular Sciences, University of Leuven, Belgium.
⁴ Department of Cardiology, Shanghai General Hospital (W.-Y.Y.).
⁵ Hypertension Unit, Department of Hypertension and Diabetology, Medical University of Gdańsk, Poland (N.G.-M., K.N.).
⁶ Population Studies Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland (T.J.N., A.M.J.).
⁷ Department of Medicine, Turku University Hospital and University of Turku, Finland (T.J.N.).
⁸ First Department of Cardiology, Interventional Electrocardiology and Hypertension, Jagiellonian University Medical College, Kraków, Poland (W.W., K.S.-S., D.C., K.K.-J.).
⁹ Centro de Nefrología and Departamento de Fisiopatología, Hospital de Clínicas, Universidad de la República, Montevideo, Uruguay (J.B.).
¹⁰ Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Switzerland (D.A.).
¹¹ Department of Medicine, University of Padua, Italy (V.T., E.C.).
¹² Division of Nephrology, University Hospital of Geneva, Geneva, Switzerland (B.P.).
¹³ Center for Primary Care and Public Health (B.P.), Unisanté, University of Lausanne, Switzerland.
¹⁴ Service of Nephrology and Hypertension, Lausanne University Hospital and University of Lausanne, Switzerland (M.P.).
¹⁵ Faculty of Medicine, Charles University, Pilsen, Czech Republic (J.F.).
¹⁶ Center for Primary Care and Public Health (M.B.), Unisanté, University of Lausanne, Switzerland.
¹⁷ Centre for Molecular and Vascular Biology (T.V., P.V.), KU Leuven Department of Cardiovascular Sciences, University of Leuven, Belgium.
¹⁸ Department of Pharmacology and Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, the Netherlands (H.A.J.S.-B.).
¹⁹ NPA Alliance for the Promotion of Preventive Medicine, Mechelen, Belgium (J.A.S.).

^# Contributed equally.

PMID: 32639894
PMCID: PMC7340226
DOI: 10.1161/HYPERTENSIONAHA.120.14787

Cardiovascular End Points and Mortality Are Not Closer Associated With Central Than Peripheral Pulsatile Blood Pressure Components

Qi-Fang Huang et al. Hypertension. 2020 Aug.

. 2020 Aug;76(2):350-358.

doi: 10.1161/HYPERTENSIONAHA.120.14787. Epub 2020 Jul 8.

Authors

Collaborators

IDCARS (International Database of Central Arterial Properties for Risk Stratification) Investigators:
L S Aparicio, J Barochiner, L Thijs, J A Staessen, F F Wei, W Y Yang, Z Y Zhang, Y B Cheng, Q H Guo, J F Huang, Q F Huang, Y Li, C S Sheng, J G Wang, J Filipovský, J Seidlerová, E P Juhanoja, A M Jula, A S Lindroos, T J Niiranen, S S Sivén, E Casiglia, A Pizzioli, V Tikhonoff, B S Chori, B Danladi, A N Odili, H Oshaju, W Kucharska, K Kunicka, N Gilis-Malinowska, K Narkiewicz, W Sakiewicz, E Swierblewska, K Kawecka-Jaszcz, K Stolarz-Skrzypek, A E Schutte, G R Norton, A J Woodiwiss, D Ackermann, M Bochud, B Ponte, M Pruijm, R Álvarez-Vaz, C Américo, C Baccino, L Borgarello, L Florio, P Moliterno, A Noboa, O Noboa, A Olascoaga, P Parnizari, M Pécora

Affiliations

¹ From the Center for Epidemiological Studies and Clinical Trials and Center for Vascular Evaluations, Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Ruijin Hospital (Q.-F.H., Y.-B.C., C.-S.S., J.-G.W., Y.L.).
² Shanghai Jiao Tong University School of Medicine, China; Servicio de Clínica Médica, Sección Hipertensión Arterial, Hospital Italiano de Buenos Aires, Argentina (L.S.A., J.B.).
³ Research Unit Hypertension and Cardiovascular Epidemiology (L.T., F.-F.W., J.D.M., Z.-Y.Z., J.A.S.), KU Leuven Department of Cardiovascular Sciences, University of Leuven, Belgium.
⁴ Department of Cardiology, Shanghai General Hospital (W.-Y.Y.).
⁵ Hypertension Unit, Department of Hypertension and Diabetology, Medical University of Gdańsk, Poland (N.G.-M., K.N.).
⁶ Population Studies Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland (T.J.N., A.M.J.).
⁷ Department of Medicine, Turku University Hospital and University of Turku, Finland (T.J.N.).
⁸ First Department of Cardiology, Interventional Electrocardiology and Hypertension, Jagiellonian University Medical College, Kraków, Poland (W.W., K.S.-S., D.C., K.K.-J.).
⁹ Centro de Nefrología and Departamento de Fisiopatología, Hospital de Clínicas, Universidad de la República, Montevideo, Uruguay (J.B.).
¹⁰ Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Switzerland (D.A.).
¹¹ Department of Medicine, University of Padua, Italy (V.T., E.C.).
¹² Division of Nephrology, University Hospital of Geneva, Geneva, Switzerland (B.P.).
¹³ Center for Primary Care and Public Health (B.P.), Unisanté, University of Lausanne, Switzerland.
¹⁴ Service of Nephrology and Hypertension, Lausanne University Hospital and University of Lausanne, Switzerland (M.P.).
¹⁵ Faculty of Medicine, Charles University, Pilsen, Czech Republic (J.F.).
¹⁶ Center for Primary Care and Public Health (M.B.), Unisanté, University of Lausanne, Switzerland.
¹⁷ Centre for Molecular and Vascular Biology (T.V., P.V.), KU Leuven Department of Cardiovascular Sciences, University of Leuven, Belgium.
¹⁸ Department of Pharmacology and Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, the Netherlands (H.A.J.S.-B.).
¹⁹ NPA Alliance for the Promotion of Preventive Medicine, Mechelen, Belgium (J.A.S.).

^# Contributed equally.

PMID: 32639894
PMCID: PMC7340226
DOI: 10.1161/HYPERTENSIONAHA.120.14787

Abstract

Pulsatile blood pressure (BP) confers cardiovascular risk. Whether associations of cardiovascular end points are tighter for central systolic BP (cSBP) than peripheral systolic BP (pSBP) or central pulse pressure (cPP) than peripheral pulse pressure (pPP) is uncertain. Among 5608 participants (54.1% women; mean age, 54.2 years) enrolled in nine studies, median follow-up was 4.1 years. cSBP and cPP, estimated tonometrically from the radial waveform, averaged 123.7 and 42.5 mm Hg, and pSBP and pPP 134.1 and 53.9 mm Hg. The primary composite cardiovascular end point occurred in 255 participants (4.5%). Across fourths of the cPP distribution, rates increased exponentially (4.1, 5.0, 7.3, and 22.0 per 1000 person-years) with comparable estimates for cSBP, pSBP, and pPP. The multivariable-adjusted hazard ratios, expressing the risk per 1-SD increment in BP, were 1.50 (95% CI, 1.33-1.70) for cSBP, 1.36 (95% CI, 1.19-1.54) for cPP, 1.49 (95% CI, 1.33-1.67) for pSBP, and 1.34 (95% CI, 1.19-1.51) for pPP (P<0.001). Further adjustment of cSBP and cPP, respectively, for pSBP and pPP, and vice versa, removed the significance of all hazard ratios. Adding cSBP, cPP, pSBP, pPP to a base model including covariables increased the model fit (P<0.001) with generalized R² increments ranging from 0.37% to 0.74% but adding a second BP to a model including already one did not. Analyses of the secondary end points, including total mortality (204 deaths), coronary end points (109) and strokes (89), and various sensitivity analyses produced consistent results. In conclusion, associations of the primary and secondary end points with SBP and pulse pressure were not stronger if BP was measured centrally compared with peripherally.

Keywords: blood pressure; morbidity; mortality; population; risk.

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Figures

**Figure 1.**
Cumulative incidence of the primary end point by fourths of the distributions of central systolic blood pressure (cSBP) and peripheral systolic blood pressure (pSBP). Tabulated data are the number of participants at risk at 5-y intervals. P values for trend were derived by Cox proportional hazards regression. Estimates accounted for sex and age (A and B). There were no differences in hazard ratios between cSBP (A) and pSBP (B; P=0.86). Additional adjustment for pSBP (C) or cSBP (D) removed the significance.

**Figure 2.**
Heat maps depicting the 5-year risk of the primary end point in relation to central and peripheral systolic blood pressure (SBP) or pulse pressure (PP) in 5608 study participants. Heat maps were derived by Cox proportional hazard regression. Risk estimates were standardized to the average of the distributions in the whole study population (mean or ratio) of cohort identifier, sex, age, body mass index, smoking and drinking, the total-to-HDL (high-density lipoprotein) serum cholesterol ratio, the estimated glomerular filtration rate, intake of antihypertensive drug, history of cardiovascular disease, and diabetes mellitus. Numbers in grids A and C represent the percent of participants within each cross-classification category of central and peripheral SBP or PP. Numbers in grids B and D represent the 5-year risk of a primary end point.

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References

1. Murray CJ, Ezzati M, Flaxman AD, Lim S, Lozano R, Michaud C, Naghavi M, Salomon JA, Shibuya K, Vos T, et al. GBD 2010: design, definitions, and metrics. Lancet. 2012;380:2063–2066. doi: 10.1016/S0140-6736(12)61899-6. - PubMed
1. O’Rourke MF, Safar ME. Relationship between aortic stiffening and microvascular disease in brain and kidney: cause and logic of therapy. Hypertension. 2005;46:200–204. doi: 10.1161/01.HYP.0000168052.00426.65. - PubMed
1. Staessen JA, Gasowski J, Wang JG, Thijs L, Den Hond E, Boissel JP, Coope J, Ekbom T, Gueyffier F, Liu L, et al. Risks of untreated and treated isolated systolic hypertension in the elderly: meta-analysis of outcome trials. Lancet. 2000;355:865–872. doi: 10.1016/s0140-6736(99)07330-4. - PubMed
1. Mitchell GF, Wang N, Palmisano JN, Larson MG, Hamburg NM, Vita JA, Levy D, Benjamin EJ, Vasan RS. Hemodynamic correlates of blood pressure across the adult age spectrum: noninvasive evaluation in the Framingham Heart Study. Circulation. 2010;122:1379–1386. doi: 10.1161/CIRCULATIONAHA.109.914507. - PMC - PubMed
1. Kaess BM, Rong J, Larson MG, Hamburg NM, Vita JA, Cheng S, Aragam J, Levy D, Benjamin EJ, Vasan RS, et al. Relations of central hemodynamics and aortic stiffness with left ventricular structure and function: the framingham heart study. J Am Heart Assoc. 2016;5:e002693. doi: 10.1161/JAHA.115.002693. - PMC - PubMed

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[1] Murray CJ, Ezzati M, Flaxman AD, Lim S, Lozano R, Michaud C, Naghavi M, Salomon JA, Shibuya K, Vos T, et al. GBD 2010: design, definitions, and metrics. Lancet. 2012;380:2063–2066. doi: 10.1016/S0140-6736(12)61899-6. - PubMed

[2] Murray CJ, Ezzati M, Flaxman AD, Lim S, Lozano R, Michaud C, Naghavi M, Salomon JA, Shibuya K, Vos T, et al. GBD 2010: design, definitions, and metrics. Lancet. 2012;380:2063–2066. doi: 10.1016/S0140-6736(12)61899-6. - PubMed

[3] O’Rourke MF, Safar ME. Relationship between aortic stiffening and microvascular disease in brain and kidney: cause and logic of therapy. Hypertension. 2005;46:200–204. doi: 10.1161/01.HYP.0000168052.00426.65. - PubMed

[4] O’Rourke MF, Safar ME. Relationship between aortic stiffening and microvascular disease in brain and kidney: cause and logic of therapy. Hypertension. 2005;46:200–204. doi: 10.1161/01.HYP.0000168052.00426.65. - PubMed

[5] Staessen JA, Gasowski J, Wang JG, Thijs L, Den Hond E, Boissel JP, Coope J, Ekbom T, Gueyffier F, Liu L, et al. Risks of untreated and treated isolated systolic hypertension in the elderly: meta-analysis of outcome trials. Lancet. 2000;355:865–872. doi: 10.1016/s0140-6736(99)07330-4. - PubMed

[6] Staessen JA, Gasowski J, Wang JG, Thijs L, Den Hond E, Boissel JP, Coope J, Ekbom T, Gueyffier F, Liu L, et al. Risks of untreated and treated isolated systolic hypertension in the elderly: meta-analysis of outcome trials. Lancet. 2000;355:865–872. doi: 10.1016/s0140-6736(99)07330-4. - PubMed

[7] Mitchell GF, Wang N, Palmisano JN, Larson MG, Hamburg NM, Vita JA, Levy D, Benjamin EJ, Vasan RS. Hemodynamic correlates of blood pressure across the adult age spectrum: noninvasive evaluation in the Framingham Heart Study. Circulation. 2010;122:1379–1386. doi: 10.1161/CIRCULATIONAHA.109.914507. - PMC - PubMed

[8] Mitchell GF, Wang N, Palmisano JN, Larson MG, Hamburg NM, Vita JA, Levy D, Benjamin EJ, Vasan RS. Hemodynamic correlates of blood pressure across the adult age spectrum: noninvasive evaluation in the Framingham Heart Study. Circulation. 2010;122:1379–1386. doi: 10.1161/CIRCULATIONAHA.109.914507. - PMC - PubMed

[9] Kaess BM, Rong J, Larson MG, Hamburg NM, Vita JA, Cheng S, Aragam J, Levy D, Benjamin EJ, Vasan RS, et al. Relations of central hemodynamics and aortic stiffness with left ventricular structure and function: the framingham heart study. J Am Heart Assoc. 2016;5:e002693. doi: 10.1161/JAHA.115.002693. - PMC - PubMed

[10] Kaess BM, Rong J, Larson MG, Hamburg NM, Vita JA, Cheng S, Aragam J, Levy D, Benjamin EJ, Vasan RS, et al. Relations of central hemodynamics and aortic stiffness with left ventricular structure and function: the framingham heart study. J Am Heart Assoc. 2016;5:e002693. doi: 10.1161/JAHA.115.002693. - PMC - PubMed

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Cardiovascular End Points and Mortality Are Not Closer Associated With Central Than Peripheral Pulsatile Blood Pressure Components

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Cardiovascular End Points and Mortality Are Not Closer Associated With Central Than Peripheral Pulsatile Blood Pressure Components

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