Arterial stiffness and central BP as goals for antihypertensive therapy in pre- and elderly Piotr Jankowski I Department of Cardiology and Hypertension CM UJ, Kraków, Poland piotrjankowski@interia.pl Vienna, 09.07.2017
Outline Some pathophysiology Prognostic value of arterial stiffness and central BP 24-hour monitoring of central BP Modification od arterial stiffness and central BP
Some pathophysiology
The concept of Windkessel Left ventricle Aorta
The concept of Windkessel Windkessel literally means air chamber and is a German translation of a concept described by Stephen Hales, who linked the effect of the elastic arteries in dampening the arterial pulse to that of an air chamber in 18th century fire engines
Arterial stiffness CV risk Increases systolic and decreases diastolic BP. Increases pulsatile component of central BP. Damages microvasculature leading to coronary slow flow, kidney failure, etc. Induces atherosclerosis development
Forces acting on the vessel wall
Forces acting on the vessel wall Wall Circumferential tension Blood pressure Wall stress = Pr/h
Ruptured coronary plaque V. Fuster, JACC 2005.
Pulse wave velocity Safar M, Jankowski P. Atherosclerosis 2011; 218: 263
Central blood pressure
Patient A.K., 55 y dgn.: CAD Sys. BP 122 134 mmhg Diast. BP 81 80 mmhg Mean BP 99 98 mmhg Ascending aorta Brachial artery
pressure in aorta Pulse wave in the aorta Primary wave
In the arterial system, the secondary wave returns and interacts with the wave that created it, with a similar effect on the curve as seen on the bottom wave of the diagram.
mmhg pressure in aorta Pulse wave in the aorta augmentation of pressure wave Primary wave Secondary wave Ascending aorta Peripheral artery
Prognostic value of arterial stiffness
Probability of MACE Prognostic value of stiffness Aortic pulse wave velocity Years N=2232 Mitchell GF et al. Circulation 2010; 121: 505.
PWV CV risk Ben-Shlomo Y et al. JACC 2014; 63: 636. Vlachopoulos C et al. JACC. 2014; 63: 647.
Prognostic value of stiffness Arterial stiffening could be an integrate measure of the damages occurred at the vascular level over a long period. Boutouyrie P et al. Hypertension 2002; 39: 10.
Prognostic value of central BP
Central PP risk of death in end-stage renal disease 1 tertile 2 tertile 3 tertile months Safar M. et al. Hypertension 2002; 39:735.
Prognostic value of PP in CAD patients The Aortic Blood Pressure and Survival Study Probability of survival without MACEs 1,00 0,95 0,90 0,85 0,80 0,75 0,70 Central pulse pressure p = 0,0084 Central PP < median Central PP > median Probability of survival without MACEs 1,00 0,95 0,90 0,85 0,80 0,75 0,70 Brachial pulse pressure p = 0,7437 Brachial PP < mediany Brachial PP > mediany 0,65 0 500 1000 1500 2000 2500 DAYS 0,65 0 500 1000 1500 2000 2500 DAYS N = 1109, follow-up: 55,0 ± 17,2 months P. Jankowski et al. Hypertension 2008; 51: 848.
The Aortic Blood Pressure and Survival Study Variable Hazard ratio (95% confidence intervals) Wald statistics p Central PP (per 10 mmhg) 1.13 (1.05 1.22) 10.07 < 0.001 EF (per 10 %) 0.84 (0.75 0.94) 9.57 < 0.01 Mean coronary stenosis (per 10 %) Creatinine level (per 10 µmol/l) 1.18 (1.06 1.32) 9.14 < 0.01 1.03 (1.01 1.05) 5.05 < 0.01 Previous infarction 1.38 (1.03 1.86) 4.68 < 0.05 Sex 1.44 (1.03 2.02) 4.49 < 0.05 Diabetes 1.39 (1.00 1.95) 3.85 < 0.05 Central pulse pressure is the best predictor N=1109 Jankowski P. et al. Hypertension 2008; 51: 848.
Central vs peripheral BP The influence of central PP on CV risk Vlachopoulos C et al. EHJ 2010; 31: 1865.
Central vs peripheral BP CV events risk Vlachopoulos Pini C R i et wsp. al. JACC EHJ 2010; 2008; 51: 31: 2432. 1865.
Central vs peripheral BP The risk of CV death Peripheral SBP Central SBP 0,8 1,0 1,2 1,4 1,6 Hazard ratio N=1272 Wang KL et al. J Hypertens 2009; 27: 461.
24-hour monitoring of central BP
Central hemodynamics
24-hour systolic BP amplification N = 100 Jankowski P i wsp. Am J Hypertens 2013; 26: 27.
24-hour systolic BP amplification N = 100 Jankowski P i wsp. Am J Hypertens 2013; 26: 27.
Nighttime central BP and target organ damage Left atrium volume 130 LVMI 120 110 100 90 80 70 60 50 40 r = 0.45 p < 0.001 E/E` 13 12 11 10 9 8 7 30 90 60 70 80 90 100 6 110 120 130 140 150 5 Central systolic BP Centralne ciśnienie skurczowe 4 r = 0.35 p < 0.001 Objętość lewego przedsionka 110 100 80 70 3 60 60 70 80 90 100 110 120 130 140 150 50 Central systolic BP Centralne ciśnienie skurczowe 40 30 20 r = 0.30 p < 0.01 10 60 70 80 90 100 110 120 130 140 150 Centralne ciśnienie skuczowe Central systolic BP Bednarek A, Jankowski P i wsp. Am J Cardiovasc Dis. 2014; 4: 77.
Age - diurnal BP changes Healthy individuals, free from CV medications Brachial SBP Brachial DBP Dipping: -13% /-12% /-5% Dipping: -19% /-16% /-11%
Age - diurnal BP changes Healthy individuals, free from CV medications MAP Heart rate Dipping: -15% /-14% /-7% Dipping: -20% /-17% /-15%
Age - diurnal BP changes Healthy individuals, free from CV medications Brachial SBP Central SBP Dipping: -13% /-12% /-5% Dipping: -4% /-6% /-0%
Brachial PP Central PP Dipping: -2 %/-4 %/3% Dipping: 25% /14% /17% PP amplification Dipping: -21% /-16% /-12% Heart rate Dipping: -20% /-17% /-15%
Pulse pressure amplification Dipping: -21% /-16% /-12%
Treatment
Pulse wave velocity The COMPLIOR Study 12,0 Prędkość fali tętna m/s p<0,001 11.6 Compliance 11,0 10,0 10.5 Pulse wave velocity 0 Before treatment After 6 months of treatment with perindopril N = 2 187 Asmar R. et al. J Hypertens 2001; 19: 813.
Effect of vasodilatation No drug Vasodilatator Secondary wave Primary wave Artery Arteriole
Aortic pressure Aortic pressure Effect of vasodilatation The influence of vasodilatators on central systolic BP (the influence on MBP is not shown) No drug Vasodilatator effect of vasodilation Primary wave Reflected wave Primary wave Reflected wave
REASON Study Change of BP after 12 months of treatment (N = 181) mmhg 0,0 Perindopril/indapamid Atenolol -5,0-10,0-6,5-15,0-11,0-15,1-15,3 p<0,001-20,0 Peripheral SBP Central SBP London GM et al. JACC 2004, 43, 92.
mmhg Change of systolic BP after 7 days of treatment 0,0-12,5 p<0,0001 Central pressure Brachial pressure -25,0 5,0 0,0 p<0,01 Difference: 5,3 mmhg -2,0 p<0,0001 3,3 = - -5,0 Ramipril Atenolol N = 30 Hirata K i wsp. J Hypertens 2005, 23, 551.
Is this difference important? 5 mmhg difference in systolic BP is related to the increase of cardiovascular risk by 25 %. PSC: Lancet 2002, 360, 1903.
The effect of drugs on central BP mmhg The change of PP after 4 weeks of treatment vs placebo (N = 32) 0,0 Central pressure Peripheral pressure -5,0-3,9-3,0-4,5-10,0-15,0-9,0 p<0,05 p<0,05-11,2-12,0-10,0-10,7 ACE-I Atenolol Calcium Hydrochloroantagonists thiazide Morgan T. Am J Hypertens 2004; 17: 118
The effect of drugs on central BP The influence of nebivolol (5 mg) and metoprolol (50-100mg) on central pulse pressure after 12 months of treatment mmhg p<0,01 nebivolol metoprolol N = 63 Kampus P i wsp. Hypertension 2011; 57: 1122.
The effect of drugs on central BP The change of BP after 5 weeks of treatment in comparison with placebo (N = 16) mmhg 10 5 Nebivolol Atenolol 0-5 -10-15 -20-25 -13-12 p = NS -6-4 p = NS Peripheral Central Peripheral Central SBP SBP PP PP -6-3 p = NS 1 5 p<0,05 Dhakam Z. et al. J Hypertens 2008; 26: 351
CAFE Study Brachial artery 2199 hypertensives and 3 risk factors Age: 63±8 years Ascending aorta Women: 19 % atenolol/thiazyd vs atenolol/thiazyd amlodipine/perindopril amlodipine/perindopril
mmhg CAFE Study Systolic pressure 140 135 130 125 Brachial pressure Ascending aortic pressure atenolol / thiazyd amlodipine / perindopril 133,9 133,2 125,5 120 115 (AUC) = 4,3 (3,3 5,4) mm Hg 0 0,5 1 1,5 2 2,5 3 3,5 4 4,5 5 5,5 6 years 121,2 p < 0,0001 CAFE Investigators: Circulation 2006, 113, 1213.
Is this difference important? 4 mmhg difference in systolic BP is related to the increase of cardiovascular risk by 20 %. PSC: Lancet 2002; 360: 1903.
Incidence (%) CAFE Study CAFE- composite end point 25,0 20,0 amlodipine / perindopril atenolol / thiazide 15,0 10,0 5,0 0,0 RRR = 16% HR = 0,84 (0,79 0,90) p < 0,0001 0,0 1,0 2,0 3,0 4,0 5,0 lata CAFE Investigators: Circulation 2006, 113, 1213.
The EXPLOR Study N = 393 Boutouyrie P et al. Hypertension 2010; 55: 1314.
The EXPLOR Study amlodipine/atenolol amlodipine/valsartan N = 393 Boutouyrie P et al. Hypertension 2010; 55: 1314.
Sacubitril/valsartan vs olmesartan (The PARAMETER Study) 454 patients aged 60 years, bpp>60 mmhg sacubitril/valsartan (200-400 mg) olmesartan (20-40 mg) (after 12 weeks amlodipine and hydrochlorothiazide could be added) Williams B et al. Hypertension 2017; 69: 411.
Sacubitril/valsartan vs olmesartan (The PARAMETER Study) 454 patients aged 60 years, bpp>60 mmhg sacubitril/valsartan (200-400 mg) olmesartan (20-40 mg) (after 12 weeks amlodipine and hydrochlorothiazide could be added) Williams B et al. Hypertension 2017; 69: 411.
Sacubitril/valsartan vs olmesartan (The PARAMETER Study) 454 patients aged 60 years, bpp>60 mmhg sacubitril/valsartan (200-400 mg) brachial olmesartan (20-40 mg) central brachial central Williams B et al. Hypertension 2017; 69: 411.
PWV [m/s] Yoga is beneficial 60 years, bpp>60 mmhg 15 10 p<0,001 11,65 11,39 10,73 11,71 5 0 Yoga Pre Post Brisk walking N = 60 Patil SG et al. Complement Ther Med. 2015; 23: 562.
Bathing in hot water improves wave reflections Mean age: 65.5 ± 9.7 years 5 mmhg N = 28 Ishikawa J et al. Blood Press Monit. 2016; 21: 80.
Bathing in hot water improves wave reflections N = 28 Ishikawa J et al. Blood Press Monit. 2016; 21: 80.
TAKE HOME MESSAGE (1) Arterial stiffness increases pulsatile load leading to increase in (central) pulse pressure and subsequently to target organ damage and reduced survival.
TAKE HOME MESSAGE (2) BP is not constant along the arterial tree. Conventional BP measurements may not detect significant changes of central BP.
TAKE HOME MESSAGE (3) 24-hour profile of central hemodynamics differs according to age.
TAKE HOME MESSAGE (4) Any intervention decreasing BP reduces arterial stiffness. Also in elderly.
TAKE HOME MESSAGE (5) CV drugs may influence brachial and central BP differentially.