Isolated Systolic Hypertension in the elderly. Daniel Hayoz Clinique de Médecine Interne HFR-Hôpital Cantonal Fribourg

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1 Isolated Systolic Hypertension in the elderly Daniel Hayoz Clinique de Médecine Interne HFR-Hôpital Cantonal Fribourg

2 Case no 1 Man aged 75, from Kosovo, in CH since 1.5 years Former smoker (45 PY) BP: 168/78 mmhg Creat : 121 mmol/l (76 kg/166 cm) Clear: 50ml/min Lipids: LDL 5.6 mmol/l How do you proceed?

3 Cas no 1 Man aged 75, from Kosovo, in CH since 1.5 years Former smoker (45 PY) BP: 168/78 mmhg: pulse pressure = 90 mmhg Creat : 121 mmol/l (76 kg/166 cm) Lipids: LDL 5.6 mmol/l How do you proceed?

4 Cas no 1 Man aged 75, from Kosovo, in CH since 1.5 years Former smoker (45 PY) BP: 168/78 mmhg: pulse pressure = 90 mmhg Creat : 121 mmol/l (76 kg/166 cm) Lipids: LDL 5.6 mmol/l AGLA/GSLA: 60%...

5 Survival Role of initial PP on CV mortality N = Men; age (> 55 yrs): MAP > 107 mmhg p (Cox)= Corrected for cholesterol and smoking : PP < 45 mmhg 2: PP mmhg 3: PP mmhg 4: PP > 65 mmhg Follow-up (yrs) Benetos A et al. Hypertension. 1997;30:

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7 Prevalence of HTN with age % population With HTN Kannel WB. Am J Cardiol. 1996;77(suppl B):6B-11B. Age (years)

8 Distribution of Hypertension Categories by age 100% 90% 80% 70% 60% 50% 40% 30% HSI Combinée HDI 20% 10% 0% Sagie et al. NEJM 1993;329:

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10 Adapté de Franklin SS et al. Circulation 1997;96:

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12 Adapté de Franklin SS et al. Circulation 1997;96:

13 Fibers integrity Aging and large elastic arteries Rupture and degradation of fibers Increased collagen rigidity 1 2 Cardiac cycles (10 9 )

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15 Arterial stiffness and early reflected waves Compliant artery : Normal pulse wave velocity (8 m/sec) Systole Diastole (1) Heart-vessel coupling (2) coronary flow Systole Stiff artery : Elevated pulse wave velocity (12 m/sec) (1) Heart-vessel Mismatch (2) Reflected wave increases systolic central pressure at end of systole Increased afterload with increased risk of LVH Reduced coronary perfusion Increased O2 consumption of myocardium & subendocardial ischemia Increased turbulent flow inducing endothelial dysfunction Increase pulsatile deformation and plaque rupture

16 Smith a et al. J Am Soc Nephrol 16: , 2005

17 CHF and pulse pressure CHF Risk of CHF after controlling for age Mean age (78yrs) 55% HT DM 19% CHD 10% Follow up of 3.8 yrs 12% increase in risk/10mmhg SBP Chae CU et al. JAMA 1999;281:

18 Arterial stiffness Well identified CV risk factors age sex blood pressure (PP>SBP) lipids, smoking, diabetes, Poorly identified CV risk factors Infectioninflammation Low birth weight Genetics... Arterial stiffness = cumulative measure of previous exposure to CV risk factors

19 Arterial stiffness as a marker of CV risk : Cross-sectional study Risk score (European SCORE, Framingham Risk Score) Arterial stiffness

20 Case no 1 Man aged 75, from Kosovo, in CH since 1.5 years Former smoker (45 PY) BP: 168/78 mmhg Creat : 121 mmol/l (76 kg/166 cm) Lipids: LDL 5.6 mmol/l How do you proceed?

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22 Case no 2 Woman aged 78 years, in good general condition until 59 ans, when HTN is diagnosed. First treated with b-blocker, then with add. Amlo + HCTZ. Developed a moderate form of Parkinson Disease; and Madopar is introduced when rigidity becomes bothering. For the past 6 mo. several falls without loss of consciousness

23 What happens? On-off phenomenon due to anti-pd Orthostatic Hypotension Dysautonomia Arrythmia

24 PD: is a cause of primary dysautonomia HOWEVER: OH is often considered as an exclusion criteria for PD!!! Look for alternative diagnosis

25 Parkinson disease 20% of patients with PD suffer from OH when tested for orthostatism but it occures quite late..

26 Cause of OH in PD Medications Antiparkinson drugs Levodopa and dopaminergic agents splanchnic and renal vasodilatation) Reduce vasopressive effect released from CNS Diuretics Antidepressant drugs (imipramine), much less with SSRI

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28 HYVET Trial: Study Design 3845 patients > 80 years with continual hypertension and systolic blood pressure 160 mm Hg prior to randomization Prospective. Randomized. Double Blind. Placebo-Controlled. Mean follow-up 1.8yrs R Active Treatment 1.5 mg Indapamide (SR) n=1933 Placebo Matching Dose n= yrs. follow-up Primary Endpoint: fatal and non-fatal strokes Secondary Endpoints: death from: stroke, cardiovascular causes, cardiac causes and any cause Copyleft Clinical Trial Results. You Must Redistribute Slides N Engl J Med 2008;358/ACC 2008

29 HYVET Trial: Baseline Characteristics Characteristic Active Treatment (n=1933) Placebo (n=1912) Age (years SD) Female (%) 1174 (60.7) 1152 (60.3) Blood Pressure (mm Hg) While sitting Systolic Diastolic While standing Systolic Diastolic

30 15 mm Hg 6 mm Hg N ENGL J MED 358;18 may 1, 2008

31 All strokes (30% reduction) Placebo P=0.055 Indapamide SR ± perindopril Placebo Indapamide SR ± perindopril

32 Heart failure (64% reduction) Placebo P< Indapamide SR ± perindopril Placebo Indapamide SR ± perindopril

33 ITT results

34 % Time since randomisation (years) Staessen J et al. Lancet 1997; 350:

35 Major Clinical Trials Showing Benefit of Treating Isolated Systolic Hypertension SHEP Syst-Eur Syst-China (n=4736) (n=4695) (n=2394) Baseline / / / SBP/DBP (mm Hg) <90 <95 <95 BP reduction: 27/9 23/7 20/5 SBP/DBP (mm Hg) Drug therapy Chlorthalidone Nitrendipine Nitrendipine Atenolol Enalapril Captopril HCTZ HCTZ Outcomes (%) Stroke CAD CHF All CVR disease Journal of Clinical Hypertension Vol II, No. 5, page 336, September/October 2000.

36 Benefit of the treatment of ISH Fatal and nonfatal coronary events Staessen JA et al. Lancet 2000;355:865

37 GERD and dependent variables. Friedenberg FK et al. Dig Dis Sci 2010:55;

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40 Algorithm for Management of the Elderly Primarily Systolic Hypertension 1) Lifestyle changes 2) Low dose diuretic (12.5 mg HCTZ) CCB B-Blocker ACE or ARB 3) It takes time do not change dosages to early Let the Baroreceptors reset

41 Thank you for your attention

42 Thank you for your attention

43 Thank you for your attention

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45 Composantes dynamiques de la pression artérielle systolique Résistance (P = Q. R) Ondes de réflexion Rigidité artérielle (compliance) diastolique

46 Diminution de la compliance artérielle Découplage coeur-vaisseaux Dommage vasculaire Intima Dysfonction endothéliale) Media (altération de la fonction d amortissement) Accélération athérogenèse Favorise rupture de plaque Augmente vasoconstriction Diminution de la réserve vasodilatation Favorise thrombogenèse Evénements cardiovasculaires Pression Systolique Pulse pressure Pression Diastolique Ischémie Hypertrophie VG Insuffisance cardiaque Impedance

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49 Introduction Elevated risk of CVD together with increased prevalence of hypertension is the leading cause of mortality in the western world An age-related increase in arterial stiffness results in an increase in systolic blood pressure (SBP) and left ventricular hypertrophy. It is also a strong predictor of CVD-associated mortality in patients with hypertension

50 Very old patients > 80 yrs (primary end point: stroke) Treatment better Control better SHEP SHEP-Pilot STOP Syst-Eur Double-blind trials COOPE CASTEL Open label trials Total RR=0.64, p=0.01 RR=0.85, p=0.75 RR=0.67, p=0.01 Gueyffier Lancet 1999