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Hypertension: Does it matter how to lower blood pressure?

Cardio Diabetes Master Class October 15-17, 2010, Dublin. Hypertension: Does it matter how to lower blood pressure?. Slide lecture prepared and held by:. Luis Ruilope, MD Hospital 12 de Octubre , Madrid, Spain. CARDIORENAL CONTINUUM . 1- CVRF 2- ASYMPTOMATIC TOD 3- SYMPTOMATIC TOD.

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Hypertension: Does it matter how to lower blood pressure?

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  1. Cardio Diabetes MasterClass October15-17, 2010, Dublin Hypertension:Does it matter how to lower blood pressure? Slide lecture prepared and held by: Luis Ruilope, MD Hospital 12 de Octubre, Madrid, Spain

  2. CARDIORENAL CONTINUUM 1- CVRF 2- ASYMPTOMATIC TOD 3- SYMPTOMATIC TOD

  3. ‘Double jeopardy’: type 2 diabetes and hypertension and cardiovascular risk 250 No diabetes Diabetes 200 150 CVD death rate (per 10,000 person-year) 100 50 0 < 120 120–139 140–159 160–179 180–199  200 Systolic blood pressure (mmHg)

  4. 1 75 % 2 3 25 % COST %EVENTS

  5. Treatment is effective • Results of antihypertensive therapy in randomised controlled trials Mean-DBP at randomisation 99 mm Hg, mean difference 5-6 mm Hg, n=37 000, mean time to event 2-3 years Collins et al. Lancet 1990;335:827

  6. BENEFIT OF BP CONTROL • A fixed amount of benefit corresponds to a fixed amount of drop in BP

  7. Risk Stratification

  8. Initiation of antihypertensive treatment

  9. Candesartan 04816 mg Candesartan Meta-Analysis based on US New Drug Application Evaluation Reports Reduction in diastolic BP (mmHg) -0 -2 -4 Losartan Valsartan -6 Irbesartan -8 -10 02550100 mgLosartan 080160320 mgValsartan 075150300 mgIrbesartan Elmfeldt et al 2002

  10. Valsartan and Amlodipine: Cardiovascular Endpoints in High-risk Hypertension1,2 ASCOTBPLA1 VALUEtrial2 Non-fatal MI (excluding silent) + fatal CHD Primary cardiac composite endpoint Total coronary endpoint Cardiac mortality Total CV events and procedures Cardiac morbidity All-cause mortality All MI CV mortality All congestive heart failure Fatal/non-fatal stroke All stroke Fatal/non-fatal HF All-cause death Development of renal impairment New-onset diabetes Development of diabetes 0.5 1 2 2 0.5 1 Favors valsartan Favors amlodipine Amlodipine-based better Atenolol-based better 1. Dahlöf et al. Lancet 2005;366:895–906; 2. Julius et al. Lancet 2004;363:2022–31

  11. Amlodipine/Valsartan Provides Powerful BP Reductions Across Hypertension Severities1,2 Moderate HTN1‡ Mild HTN1¶ Baseline SBP≥180 mmHg2 0 –10 –20 –30 –40 –50 0 –10 –20 –30 –40 –50 n=69 n=15 n=140 Mean change in MSSBPfrom baseline (mmHg) –20 –30 –43 Ad hoc analysis¶DBP 9099 mmHg, SBP 140159 mmHg‡DBP ≥100 mmHg, SBP ≥160 mmHg BP = blood pressure; DBP = diastolic BP; SBP = systolic BP; MSSBP = mean sitting SBP 1. Smith et al. J Clin Hypertens 2007;9:355–64 (Dose 10/160 mg) 2. Poldermans et al. Clin Ther 2007;29:279–89 (Dose 5–10/160 mg)

  12. IGT Metabolic Syndrome Pre-Hypertension • OBJECTIVES: • Intensive diabetes control (HbA1c <6.5% or lower, PG fasting, postprandial) • Intensive BP control <130/80mmHg • RAS blockade • Lipid profile: TChol, LDL, HDL, TGL goals… • Microalbuminuria - Proteinuria • Serum creatinine, GFR • Eye examination, ECG Prevent Prevent • OBJECTIVES: • BP goal <140/90 mmHg with ACEi, ARBs, CCB’s • Other CVRF control, lipid profile • Spot urine albumin/creatinine ratio Hypertension Diabetes Prevent CKD Prevent Microalbuminuria Micro-albuminuria Chronic Kidney Disease Prevent Stroke/CVD Prevent ESRD • OBJECTIVES: • BP <130/80 mmHg (<125/75 mmHg if U/prot >1 g/24h) with ACEi, ARBs, CCB’s, diuretics • Start with 2 drug-fixed dose combination if SBP >20 mmHg and/or DBP >10 mmHg above target • Reduce proteinuria using ACEi, ARBs, Aldo-antagonists ndCCBs (dCCBs may increase proteinuria) • Slow GFR decline with ACEi, ARBs (dCCBs may not alter GFR decline, in the absence of an ACEi/ARB) • Reduce CV Risk with ACEi • ACEi, ARBs and diuretics reduce CHF, ACEi and ARBs do not worsen IR Prevent CVD/Stroke • OBJECTIVES: • BP goal <130/80 mmHg • ACEi, ARBs, combination • Treat other CRFs • Monitor urine Alb/Cr ratio annually R Ruilope et al, Blood Press 2007r Ruilope et al, Blood Press 2007

  13. Baseline BP predicts progression to hypertension4 year hypertension incidence rates,adjusted for sex, age, BMI, and baseline BP Optimal = <120/80 mm Hg Normal = 120-130/80-85 mm Hg High Normal = 130-139/85-89 mm Hg Vasan RS Lancet 2001

  14. Impact of high-normal BP on CV risk Cumulative incidence of CV events (%) 16 Men 14 High-normal BP PreHTN 12 Normal BP 10 8 6 Optimal BP 4 2 0 Cumulative incidence of CV events (%) 12 Women 10 High-normal BP 8 PreHTN 6 Normal BP 4 2 Optimal BP 0 0 2 4 6 8 10 12 Years Optimal BP: <120/80 mmHg Normal BP: 120-129/80-84 mmHg High-normal BP: 130-139/85-89 mmHg Vasan RS et al. N Engl J Med 2001;345:1291-7

  15. Kaplan-Meier curves of clinical hypertension in the two groupsNumbers under the graph refer to hypertension-free individuals 1.0 0.9 Candesartan Placebo 0.8 0.7 0.6 % Cumulative incidence 0.5 0.4 0.3 0.2 0.1 0 0 1 2 3 4 Years in study Candesartan 391 356 309 191 128 Placebo 381 269 184 118 85

  16. 1 mo 1 y 2 y 3 y Rand. 3 mo 6 mo ROADMAP BP goal (ie. < 130/80 mmHg):

  17. New-onset diabetes (n=362) No of patients HCTZ 9 Candesartan p<0.05 8 7 6 5 4 3 2 1 0 Lindholm LH, J Hypertens 2003

  18. Progression from hypertension to heart failure Obesity Diabetes LVH Diastolic dysfunction Hypertension HF Death Smoking Dyslipidaemia Diabetes Systolic dysfunction MI Normal LV structure and function Subclinical LV dysfunction LV remodelling Overt heart failure Time: decades Time: months

  19. 2.0%(1.9% to 2.2%) 2.8%(2.5% to 3.2%) 2.3%(1.5% to 3.0%) Annual Transition Rates Through Stages of DN No nephropathy 1.4%(1.3% to 1.5%) Microalbuminuria 3.0%(2.6% to 3.4%) DEATH Macroalbuminuria 4.6%(3.6% to 5.7%) Elevated plasma creatinine or Renal replacement therapy 19.2%(14.0% to 24.4%) DN = diabetic nephropathy. Adler et al. Kidney Int. 2003;63:225-232.

  20. HR (95% CI) for ESRD associated with urine albumin excretion Hallan, S. I. et al. J Am Soc Nephrol 2009;20:1069-1077

  21. Primary composite endpoint of the LIFE stratified by time-varying albuminuria. Ibsen H et.al J Hypertension 2004;22:1805

  22. GUARD trial BP Results DBP SBP -9.97*† -13.05* Change in BP from baseline -18.75* -20.49* *P<0.0001 vs baseline; †P=0.0176 vs benazepril/amlodipine Bakris G et.al. Kidney International 19 March 2008; doi:10.1038/ki.2008.102

  23. PREVALENCE AND TREATMENT OF HYPERTENSION IN EUROPE 44% ( > 140/90 mmHg), age and sex adjusted > 200 million europeans are actually treated ACEi/ARB are the most widely used classes (30-50%) ESH-ESC Guidelines recomend ACEi/ARB as initial therapy whenever there is a high added risk Wolf-Maier et al, JAMA 2003; Wang et al, Arch Intern Med 2007; Falaschetti et al, Hypertension 2009; Corrao et al, J Hypertens 2008; Mancia et al, J Hypertens 2007.

  24. ONTARGET: Changes in urinary albumin excretion 0.019 Occurrence proteinuria 2,5 2 0.0009 <0.0001 1,5 1 0,5 0 UAE initial Second year Final (mg/mmol) Ratio to initial Ratio to initial Ramipril Telmisartan Ram+Telm Mann J et al. Lancet 2008

  25. Evolución de la proteinuria a lo largo del estudio J Am Soc Nephrol 2005;16:3038-3045

  26. CARDIORENAL CONTINUUM 1- CVRF 2- ASYMPTOMATIC TOD 3- SYMPTOMATIC TOD

  27. Systolic Pressures (mean + 95% CI) Mean # Meds Intensive: 3.2 3.4 3.5 3.4 Standard: 1.9 2.1 2.2 2.3 Average : 133.5 Standard vs. 119.3 Intensive, Delta = 14.2

  28. Systolic Blood Pressure Over Time ACEI/HCTZ N=5762 ACEI/CCB N=5744 N=5723 N=5700 mm Hg 130.0 mmHg 129.3 mmHg Month Jamerson K et.al. N Engl J Med 2008;359:2417-28

  29. Blood pressure control according to clinic-based measurement and ambulatory monitoring Clinic-based Control = 23.6% Ambulatory monitoring control = 51.6% Banegas JR, Segura J, Sobrino J, Ruilope LM, et al. Hypertension 2007;49:62-68.

  30. Discrepancies between office and ambulatory blood pressure: clinical implications José R. Banegas,a MD; Franz H. Messerli,b MD; Bernard Waeber,c MD; Fernando Rodríguez-Artalejo,a Alex de la Sierra,d MD; Julián Segura,e MD; Alex Roca-Cusachs,f MD; Pedro Aranda,g MD; Luis M. Ruilope,e MD aDepartment of Preventive Medicine and Public Health. Universidad Autónoma de Madrid, and CIBER en Epidemiología y Salud Pública (CIBERESP), Spain. bDivision of Cardiology, St Luke's-Roosevelt Hospital, Columbia University College of Physicians and Surgeons, New York, USA. cDivision of Clinical Pathophysiology, Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Lausanne, Switzerland.dHypertension Unit, Clinic Hospital, Barcelona, Spain. eHypertension Unit, Doce de Octubre Hospital, Madrid, Spain. fHypertension Unit, Department of Internal Medicine, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain. gNephrology Department, Hospital Regional Universitario Carlos Haya, Málaga, Spain. Am J Med 2009, december

  31. Number and percentage of treated high-risk hypertensive patients whose 24-h ambulatory blood pressure is controlled (<130/80 mm Hg), according to office blood pressure and type of associated disease N=4,729 Am J Med 2009; in press.

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