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Blood Pressure Variability – What Should I do? Professor Andrew Coats Joint Academic Vice-President and Director, Monash-Warwick Alliance Stroke and CHD Mortality Rate in Each Decade of Age versus Usual Systolic Blood Pressure at the Start of That Decade Age at risk (y): Stroke 256 Stroke mortality (floating absolute risk and 95% CI) 128 64 • • • • • • • •• • 32 • • • • • • 60-69 64 50-59 32 • • • • • • • • 16 • 120 140 160 180 Usual SBP (mmHg) • • • • • • • • • 80-89 • • • • •• • • • • •• • • •• •• • • • • •• •• • • 70-79 60-69 50-59 • 40-49 • • • • • • 9392 M 128 • • • • • • • 70-79 • 256 • • • • • • • 16 80-89 • Age at risk (y): CHD • • • 120 140 160 180 Usual SBP (mmHg) Lancet 2002; 360: 1903-1913 Metanalysis of Trials Comparing Different Treatments or Treatment vs Placebo in Hypertension Relative risk of outcome event 1.50 1.50 1.50 Stroke Major CVD CHD 1.25 1.25 1.25 1.00 1.00 1.00 0.75 0.75 0.75 0.50 0.50 0.50 0.25 0.25 0.25 -10 -8 -6 -4 -2 -10 -8 1.50 -6 -4 -2 -10 -8 -6 -4 -2 1.50 CVD death Total mortality 1.25 1.25 1.00 1.00 0.75 0.75 0.50 0.50 0.25 0.25 -10 -8 -6 -4 -2 -10 -8 -6 -4 -2 SBP difference between randomized groups (mmHg) 7939 = 6398 M mod BP Trialists’ Coll Group, Lancet 2003 Measuring Blood Pressure Standardise the environment and provide a relaxed, temperate setting with the person quiet and seated When using an automated device: –palpate the radial or brachial pulse before measuring blood pressure If pulse if irregular measure blood pressure manually –ensure that the device is validated* and an appropriate cuff size for the person’s arm is used –never assume a single measurement is accurate 24h Intra-Arterial BP mmHg 200 100 19 11258 = 4156 M mod 22 Hours 10 13 16 19 White Coat Effect If you recommend life long therapy, make sure you got the diagnosis correct When using the following to confirm diagnosis, ensure: ABPM: –at least two measurements per hour during the person’s usual waking hours, average of at least 14 measurements to confirm diagnosis HBPM: –two consecutive seated measurements, at least minute apart –blood pressure is recorded twice a day for at least days and preferably for a week –measurements on the first day are discarded – average value of all remaining is used BP variability as a risk factor for CV disease/complications? Causes of BP Variability Diurnal rhythm of blood pressure Duration of action of drug effects Visit to Visit Variation BP variability within the day (and frequencies thereof) Autonomic reflex control systems What is the True Blood Pressure? Daytime BP? Dipping Pattern? Nighttime BP? Morning Surge? 24 Hr Average BP? Clinic BP? Variability of BP? Home BP? Nocturnal BP Changes and CV Mortality: Ohasama study (Ohkubo et al; AJH 1997; 10: 1201) 3.69 3.5 Risk of CV Mortality 2.56 2.5 1.5 0.96 0.5 Extreme dippers Dippers Nondippers Risers Effects of Two ARBs Approved for Once Daily Dosing on 24 Hour Blood Pressure (Mancia et al AJC 1999: 84; 28S) Missed Dose Clinical Relevance of 24h BP Variability Study Parati, 1987 Palatini, 1992 Mancia, Parati, 2001 Liu, 2003 Frattola, Parati, 1993 Sander, 2000 Dawson, 2000 Kikuya, 2000 Pringle, Parati, 2003 Mena, 2005 Mancia, 2007 Tatasciore, Parati, 2007 Parati, 2009 Hansen, 2010 Design Endpoint Cross-sectional Cross-sectional Cross-sectional Longitudinal (rats) Longitudinal Longitudinal Longitudinal Longitudinal Longitudinal Longitudinal Longitudinal Cross-sectional Longitudinal Longitudinal TOD score TOD score Carotid IMT Cardiac /renal damage LV mass (echo) Carotid IMT / CV events Dead / dependency (after acute stroke) CV mortality Stroke CV events CV mortality Carotid IMT, LVMI CV events Only DBP for CV events / stroke Nocturnal BP Dipping Incidence of CV events, 24 h BP and Night/day SBP ratio in Syst Eur study Staessen JA, Parati G et al for the Systolic Hypertension in Europe (Syst-Eur) Trial Investigators JAMA 1999; 282: 539-546 CV Fatal Events in Relation with DBP Variability CV Events CV Events Mancia G, Short-Terma and Long-Term Blood Pressure Variability, In Special Issues in Hypertension, 2012, A Berbari and G Mancia BPV: Types and Prognostic Significance Parati G et al Nature Reviews Cardiology 2013.10:143-155 Comparison of Monotherapies 1.2 SBP Smoothness index 1.0 * DBP † * § 0.8 † 0.6 † § ‡ 0.4 0.2 §§ 0.0 Placebo (n = 160) L50 R10 V80 V160 T40 T80 A5 (n = 50) (n = 712) (n = 197) (n = 430) (n = 140) (n = 2033) (n = 206) L50, losartan 50 mg; R10, ramipril 10 mg; V80–160, valsartan 80–160 mg; T40–80, telmisartan 40–80 mg; A5, amlodipine mg *p < 0.05; †p < 0.01; ‡p < 0.001; §p < 0.0001 vs telmisartan 80 mg Parati G et al J.Hypertens 2010; 28: 2177-2183 Mean SBP Variability of SBP and Risk of Stroke and CHD in ASCOT-BPLA Stroke Mean SBP amlodipine ± perindopril atenolol ± thiazide Coefficient of variation in SBP Rothwell PM, et al Lancet 2010;375:895-905 CHD amlodipine ± perindopril atenolol ± thiazide Within-visit variability of systolic blood pressure in ASCOT-BPLA 6083 P PM Rothwell et al., www.thelancet.com/neurology Published online March 12, 2010 Conclusions Ambulatory average BP values more closely related to TOD and future events than office readings BP variability increases with age, diabetes, smoking, and in those with established vascular disease Higher 24 h BP Variability = Higher CV risk Long lasting CCBs seem to reduce short term and long term BPVmore than (non-vasodilating) BB’s Prospective outcome studies needed to confirm that treatment-induced reduction in BPV improves outcome
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