Early morning BP surge

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Early morning surge of BP and its clinical significance

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Early morning BP surge

  1. 1. Morning surge in blood pressure in hypertension- clinical relevance, prognostic significance and therapeutic approach Dr. Mohammed Sadiq Azam M.D. Assistant Professor of Medicine Department of Medicine Deccan College of Medical Sciences, Hyderabad
  2. 2. Definition • Dippers : Subjects experiencing physiological nocturnal BP drop during sleep. BP drop achieved is more than 10% of the BP values obtained during the awake period. • Extreme Dippers: Subjects experiencing exaggerated nocturnal BP drop i.e., more than 20% of the BP values obtained during the awake period. • Non Dippers: Subjects with a blunted nocturnal drop, i.e., less than 10% drop. • Risers : Subjects who register higher BP values during the night than the daytime. • MBPS: Rise in systolic BP (≥ 50mmHg) and/ or diastolic BP (≥ 22mmHg) during the early morning (06:00 –10:00) compared with the mean BP during the night [ Def. based on study by Gosse et al.](Gosse P . Lasserre R, Minifie C et al –2004. J Hypertens 22:1113--1118 )
  3. 3. Factors Influencing Dipping Status • Physical activity during day • Sleep duration and quality • Ethnicity • Sympathetic nervous system • Glucocorticoids • Sodium/volume factors • Renal disease • Diabetes
  4. 4. Evidence based support Sl. no Name of study / study group Duration Subjects involved 1 Jichi Medical University School of Medicine— ambulatory blood pressure monitoring (JMS-ABPM)(2003) 6 mnths—1 year 519 2 Gosse et al.( 2004) 1 year 507 3 Ohasama study (2006) 10 year 1430 4 Dublin out come study (2008) 5year 3 months 11,291 5 Amici A, cicconetti P. Sagrafoli C et al (2009) 5years 42 6 LI et al.—( International Database on Ambulatory Blood Pressure in Relation to Cardiovascular Outcome-- IDACO) (2010) unknown 5645 7 Iqbal P, Stevenson L (2011) 1—2 years 1187 8 Israel S et al (2011) unknown 2627
  5. 5. Figure 1. Definition of morning surge in BP. Kario K. Hypertension 2010;56:765-773 Copyright © American Heart Association
  6. 6. Figure 2. Risk factors and target organ damage associated with morning surge in BP. The corresponding reference numbers are shown as superscripts. Kario K. Hypertension 2010;56:765-773 Copyright © American Heart Association
  7. 7. Figure 3. Reproducibility of morning surge in BP and cardiovascular risk. Kario K. Hypertension 2010;56:765-773 Copyright © American Heart Association
  8. 8. Figure 4. Definition of morning BP surge reactivity. Kario K. Hypertension 2010;56:765-773 Copyright © American Heart Association
  9. 9. MORNING vs EVENING BP Morning bp predicts CV outcomes better than others
  10. 10. Issues 1. 2. 3. 4. Diurnal rhythm of blood pressure Diurnal rhythm of CV events Duration of action of drugs Effects of drugs on diurnal rhythm of blood pressure 5. Effects of timing of administration of drugs
  11. 11. Issues 1. 2. 3. 4. Diurnal rhythm of blood pressure Diurnal rhythm of CV events Duration of action of drugs Effects of drugs on diurnal rhythm of blood pressure 5. Effects of timing of administration of drugs
  12. 12. 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?
  13. 13. Ambulatory BP Differences for Normotensives, and Mild and Established HTN Patients 120110- Diastolic 10090Blood Pressure 80- (mm Hg) Mild hypertensives 70- Normotensives 60- 0Clinic Work Home Sleep
  14. 14. Clinical situations in which the normal diurnal rhythm of BP may be lost Autonomic Dysfunction Syndromes Diabetes Mellitus Renal Failure Secondary forms of hypertension e.g. Cushing’s disease Drugs, e.g. cyclosporine African-American ethnicity
  15. 15. Nocturnal BP Changes and CV Mortality: Ohasama study (Ohkubo et al; AJH 1997; 10: 1201) 4 3.69 3.5 3 Risk of CV Mortality 2.56 2.5 2 1.5 1 0.96 1 0.5 0 Extreme dippers Dippers Nondippers Risers
  16. 16. Issues 1. 2. 3. 4. Diurnal rhythm of blood pressure Diurnal rhythm of CV events Duration of action of drugs Effects of drugs on diurnal rhythm of blood pressure 5. Effects of timing of administration of drugs
  17. 17. Circadian Rhythm of Ischemic & Hemorrhagic Strokes Gallerani et al, Acta Neurol Scand 1993; 87: 482) 45 40 35 % of strokes Ischemic Hemorrhagic 30 25 20 15 10 5 0 1-6 6 -12 12-18 18-24 Hour of day
  18. 18. Analysis of The Influence of the Morning Surge of BP on Stroke Incidence (Kario, Pickering et al, Circ 2003; 107:1401)) Cox regression analysis for clinical stroke events Covariates Age (10 yrs) Male gender BMI 24 hr SBP Morning BP surge* Nocturnal BP fall* Lowest sleep BP * per 10 mmHg RR 1.80 (1.21-2.69) 1.42 (0.76-2.67) 0.98 (0.90-1.07) 1.37 (1.16-1.63 1.29 (1.10-1.51) 0.88 (0.73-1.06) 1.05 (0.65-1.71) P value 0.004 0.266 0.663 0.003 0.001 0.167 0.837
  19. 19. Issues 1. 2. 3. 4. Diurnal rhythm of blood pressure Diurnal rhythm of CV events Duration of action of drugs Effects of drugs on diurnal rhythm of blood pressure 5. Effects of timing of administration of drugs
  20. 20. Efficacy: ARB(telmisartan) vs CCB (amlodipine) using 24-h ABPM Placebo (n=58) Week 12, SBP Telmisartan (40-120 mg) (n=62) Amlodipine (5-10 mg) (n=65) BP (mm Hg) 160 140 120 100 0 0800 1200 1600 2000 Time 2400 0400 0800 Lacourcière Y et al, in press
  21. 21. Issues 1. 2. 3. 4. Diurnal rhythm of blood pressure Diurnal rhythm of CV events Duration of action of drugs Effects of drugs on diurnal rhythm of blood pressure 5. Effects of timing of administration of drugs
  22. 22. Do different drug classes have different effects on Daytime vs. Night time BP?
  23. 23. Meta-Analysis of Effects of Antihypertensive Drug Classes on Daytime & Nighttime BP Weiner, Rieckmann, & Pickering, 2005 • Medline search of trials in which effects of antihypertensive drugs on daytime, nighttime, and 24 hr BP were described • 55 trials satisfied criteria, & were grouped into 3 classes: ACEI, ARBs, Beta blockers (n=10), CCBs & Diuretics (n=35), and combinations (n=10). • Across all studies, the absolute change of daytime BP (14/8 mmHg) was significantly greater than the change of nighttime BP (12.5/4.5 mmHg, p<0.01). • The magnitude of the difference between the daytime & nighttime changes did not differ between the groups (p>0.7).
  24. 24. Meta-Analysis of Effects of Antihypertensive Drug Classes on Daytime & Nighttime BP Weiner, Rieckmann, & Pickering, 2005 ARB+D ACEI+D D ARB Night Day ACEI CCB-nonDHP CCB-DHP 0 5 10 15 20 Change of SBP with Treatment mmHg 25
  25. 25. Meta-Analysis of Effects of Antihypertensive Drug Classes on Daytime & Nighttime BP Weiner, Rieckmann, & Pickering, 2005 ACEI, ARBs 40 CCBs, Diuretics Day: B=.07 (p=0.53) Night: B=.04 (p=0.63) 40 35 35 30 BP Change 25 mmHg 20 30 15 15 10 10 5 Day: B=.55 (p<0.001) Night: B=.55 (p<0.001) 5 0 100 25 20 120 140 160 180 0 200 100 DAY 120 140 NIGHT Baseline Systolic BP mmHg 160 180 200
  26. 26. Are there class differences in thresholds for lowering BP? (Sekino et al, J Hum Hypertens 1998: 12: 719) Drug Amlodipine Bisoprolol Lisinopril Combination1 Average Effect on BP Level CBP ABP -20 -15 -19 -12 -20 -19 -20 -14 Threshold BP* Daytime Nighttime 127 106 124 110 97 108 128 106 * Estimated from regression line of baseline BP versus change 1- ACEI + CCB- Fagard et al Am J Hypertens 1993: 6: 648
  27. 27. Diuretics Convert Non-Dippers to Dippers (Uzu & Kimura Circ 1999; 100:1635) 150 Day Night 140 Systolic pressure mmHg 130 120 110 100 No Rx Dippers HCTZ No Rx HCTZ Non-Dippers
  28. 28. Diuretics Convert Non-Dippers to Dippers (Uzu & Kimura Circ 1999; 100:1635) 150 Day Night 140 Systolic pressure mmHg 130 120 110 100 No Rx Dippers HCTZ No Rx HCTZ Non-Dippers
  29. 29. Regression of Carotid Atherosclerosis by Controlling Morning BP (Marfella et al, Am J Hypertens 2005: 18: 308) Clinic Day Night Morning 0 Carotid IMT 0 SBP -5 mm Hg -10 0 IMT mm-0.01 NS -15 -0.02 0.02 NS -20 -0.03 -25 -30 NS Metoprolol Carvedilol <0.02 <0.001 -0.04 -0.04
  30. 30. Effects of Alpha-Blockade on the Morning Surge of Blood Pressure (Kario, Pickering, et al Am J Hypertens 2004;17; 668) No Rx Doxazosin
  31. 31. Effects of graded release Diltiazem vs. Enalapril on Morning BP (White et al, Am Heart J 2004: 148: 628) Ramipril Diltiazem ER
  32. 32. Issues 1. 2. 3. 4. Diurnal rhythm of blood pressure Diurnal rhythm of CV events Duration of action of drugs Effects of drugs on diurnal rhythm of blood pressure 5. Effects of timing of administration of drugs
  33. 33. Effects of Time of Administration of ARB(Valsartan )on Diurnal Changes of BP (Hermida et al Hypertens 2003: 42:283) 0 -2 Change of SBP -4 mmHg Day Night 24 hour -6 -8 -10 -12 Awakening Bedtime -14 -16 -18 -20 P=0.041 P=0.402 P=0.174
  34. 34. Daytime BP Reduction mmHg 160 p<0.001 p<0.001 p<0.001 N.S. 150 Blood pressure level 140 130 120 8/7 7/7 10 / 8 11 / 8 110 100 90 80 n = 18 Extreme dippers n = 46 Dippers n = 48 Non-dippers n=6 Risers
  35. 35. Nighttime BP Reduction mmHg 160 p<0.01 N.S. N.S. p<0.001 150 140 Blood pressure level 130 120 12 / 9 110 18 /12 1/2 100 4/2 90 80 70 60 n = 18 Extreme dippers n = 46 Dippers n = 48 Non-dippers n=6 Reverse dippers
  36. 36. Effects of Time of Administration of CCBs on Diurnal Changes of BP (Lemmer BPM 1996: 1;169) Drug Amlodipine (1) Isradipine (2) Nifedipine GITS (3) Nitrendipine (4) Dose Time AM PM AM PM AM PM AM PM Day Effect on BP Night 24 hr Pattern Unchanged Unchanged Unchanged Unchanged Unchanged Unchanged Unchanged Unchanged 1. Mengden J Hypertens 1992:10 (supp 4); S136 2. Fogari Br J Clin Pharm 1993: 35:51 3. Lemmer Naunyn- Schmiederberg Arch Pharm 1994; 349(supp); R141 4. Meilhac Therapie 1992: 47: 205
  37. 37. Effects of Time of Administration of ACEIs on Diurnal Changes of BP (Lemmer BPM 1996: 1;169) Drug Benazepril (1) Enalapril (2) Quinapril (3) Dose Time AM PM AM PM AM PM Day Effect on BP Night 24 hr Pattern Nearly Unchanged Changed Nearly Unchanged Changed Nearly Unchanged Changed 1. Palatini Int J Clin Pharm Ther Toxicol 1993:31:295 2. Witte Clin Pharm Ther 1993: 54:177 3. Paltini Clin Pharm Ther 1992; 52: 378
  38. 38. Anti-HTN strategy targeting MBPS and morning HTN  Strict BP control <130/80  Adequate circardian rhythm  Suppression of elevated MBPS
  39. 39. How to achieve • Anti Hypertensives that decrease the pressor effects of neurohumoral factors (which are potentiated in the morning) like the sympathetic activity inhibitors. • In particular bedtime dosing ---- more extensive BP lowering effect in the morning.( Kario K. Pickering TG, Hoshide et al – 2004. Am J Hypertens 17:668--675)
  40. 40. Supportive studies: • JMS-1 ( Japan Morning Surge-1) study: (611 subjects) - Demonstrated that bed time dosing of alpha blocker( doxazosin) along with base line anti-HTN medication reduced morning BP and albuminuria. Kario K, Matsui Y, Shibasaki S et al. 2008. J Hypertens 26:1257-1265 • J-TOP ( Japan Morning Surge-Target organ Protection) study: (450 subjects) - Demonstrated bed time dosing of an ARB may be more effective in in reducing albuminuria as it may more potently suppress tissue RAS during the sleep –early morning period than awakening dosing . Kario K (2010) Atlas medical publishing of Oxford, Oxford. Pp 27—38
  41. 41. • MAPEC ( Monitorizacion Ambulatoria para Prediccion de Eventos Cardiovasculares) study : ( 2156 subjects) - Subjects ingesting one or more anti -hypertensive drugs at bed time exibited a significantly lower relative risk of total cardiovascular events than those ingesting all medications on awakening. Hermida RC , Ayala DE, Mojon A, Fernandez JR (2010). Chronobiol Int 27:1629—1651 .
  42. 42. Conclusions: Does the Pattern of Blood Pressure Effects During the Day Matter? 1. 2. 3. 4. 5. There is a pronounced diurnal rhythm of BP and cardiovascular events, with a peak of both in the morning hours, and a decrease during the night. In some categories of patients the normal dipping pattern of BP is lost or reversed; this may be associated with increased risk. Drugs approved for once daily dose may have different durations of action, particularly after missed doses. Most classes of antihypertensive drugs lower daytime BP more than nighttime BP. The effects of CCBs may be more closely related to baseline BP than ARBs/ACEI.
  43. 43. Conclusions: Does the Pattern of Blood Pressure Effects During the Day Matter? 6. Different antihypertensive drugs may have different effects on the morning surge of BP. 7. With some antihypertensive drugs the time of dosing may have significant effects on the diurnal pattern of BP. 8. The implications of these time-dependent differences of antihypertensive drugs for CV morbidity are largely unknown, and need to be more fully investigated. 9. Implications of BP-independent effects of antihypertensive drugs based on small differences of clinic BP may be unwarranted.
  44. 44. Thank You
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