Hypertension old and new

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1 Hypertension old and new Dr. Alexander Woywodt Consultant Physician and Nephrologist Lancashire Teaching Hospitals NHS Foundation Trust Preston, November 2007

2 Menu Hypertension (and the kidney) How to measure blood pressure Tips and pitfalls Non-pharmacological management Anti-hypertensive drugs

3 Blood pressure an evolving concept in the 18th century Stephen Hales In 1733 Hales inserted a glass tube into the carotid artery of a horse the blood column rose to 247 cm

4 Dropsy a deadly disease Richard Bright F.R.S "William Bonham, aet 55, a large man of florid complexion, living as a carter in the service of a cheesemonger [ ] his legs were most enormously swollen. [ ] He sunk and died on the sixth day after his admission. [ ] The heart remarkably enlarged; on the left side it was very thick and strong [ ] The kidneys were very small, and hard in consistence 1827

5 Dropsy in our catchment population 180 years later Catchment population 1.5 million patients with hypertension 12m / year on anti-hypertensive drugs 2400 deaths per year

6 End-organ damage revisited Messerli FH et al., Essential hypertension. Lancet 370: 501 (2007)

7 Hypertension and renal disease a symptom of renal parenchymatous disease a symptom of reno-vascular disease Hypertension Other 10% GN 13% Diabetes 50% Hypertension 27% a cause of end-stage renal disease worsens renal disease of any cause

8 Hypertension and risk for ESRD: The MRFIT study Age-Adjusted Rate of of ESRD Per 100,000 Person-Years <120 Systolic BP (mm Hg) < ,544 patients 16 years of follow-up Diastolic Diastolic BP BP (mm (mm Hg) Hg) Klag et al. N Engl J Med. 1996;334(1):13-18.

9 Renal disease and mortality 1,120,295 Patients Kaiser Permanente North California Go et al. N Engl J Med 2004;351:

10 How to measure blood pressure Karl von Vierordt Scipione Riva-Rocci Sfigmomanometro

11 How to measure blood pressure After 5 minutes of rest Arm on level of the heart No coffee or smoking Cuff size (obese patients) Both arms White coat hypertension Masked hypertension Home monitoring

12 Home monitoring Beware of: The irritable few The self-managers Those with higher BP at home Routine use of automated ambulatory blood pressure monitoring or home monitoring devices in primary care is not currently recommended because their value has not been adequately established; appropriate use in primary care remains an issue for further research. (NICE guidelines GC 34, 2006) Self-measurement of BP at home is of clinical value and its prognostic significance is now demonstrated. (2007 ESH guidelines)

13 24 hour BP Confirms that BP is on target Diagnostic for rise in BP at night

14 What blood pressure is good? Messerli et al., Lancet Aug 18; 370 (9587): That level of blood pressure at which investigation and treatment do more good than harm

15 Secondary forms common and rare

16 Baseline diagnostics in hypertension comprehensive investigations for secondary hypertension neither reasonable nor feasible in all patients with hypertension Blood pressure both arms Abdominal bruit? Labs: Serum creatinine and egfr, glucose, Na, K, venous blood gases, urine dipstick Thyroid function tests Fundi? ECG Echo? Carotid ultrasound? Lipids

17 Hypertension as a gateway to cardiovascular risk

18 Hypertension as a gateway to cardiovascular risk Hypertensive patients without overt cardiovascular disease but with high cardiovascular risk ( 20% risk of events in 10 years) should also be considered for statin treatment even if their baseline total and LDL serum cholesterol levels are not elevated Low-dose aspirin should also be considered in hypertensive patients without a history of cardiovascular disease if older that 50 years, with a moderate increase in serum creatinine or with a high cardiovascular risk. In all these conditions, the benefit-to-risk ratio of this intervention (reduction in myocardial infraction greater than the risk of bleeding) has been proven favorable ESH guidelines 2007

19 Non-pharmacological management of hypertension Weight reduction Stop smoking Exercise Alcohol: moderation Reduce stress Rubens: Bacchus, 1638 Reduce salt intake

20 Salt and hypertension Usually feasible: reduce extra salt and salty foods For those with good compliance (& prepared to suffer): salt-poor diet Yanomamo Indian, Venezuela

21 Hypertension and stress: A famous case report Franklin Delano Roosevelt Messerli FH al. NEJM 332: (1995)

22 Drug treatment of hypertension

23 Effects of treatment: 6 mm in systolic blood pressure MacMahon S et al. Hypertension. 1989;13(suppl 5):I45-I50.

24 Difficult hypertension I ve also been treating the high cholesterol and then I stopped the medicine because I got my cholesterol down low. And, I had in the past, a little [blood pressure] problem, which I treated and then I got it down (Former US President Clinton to Larry King Live from his hospital bed; posted Friday,Sept 3, 2004). Messerli FH et al.lancet 370: 501 (2007)

25 Compliance - The other drug problem punctual dosing few or no doses taken all doses taken erratic timing 5-20% of doses taken, monthly drug holidays 5-20% omitted many doses missed 3-4 drug holidays per year

26 Drug treatment of hypertension: Some tips and tricks Establish home monitoring Start new drugs on weekends Start new drugs in the evenings Do not start two drugs at once Patient must know that treatment is permanent If patient or compliance and/or doctorpatient relationship fragile: start with low risk drugs at low dose. Head for early (and visible) success Be passionate about plans, particulary with multiple prescribers Dosette for the elderly

27 Drug treatment of hypertension Beta blockers Central alpha agonists Thiazide diuretics Angiotensin Receptor blockers ACE inhibitors Renin blocker Calcium antagonists Minoxidil Loop diuretics

28 Hypertension causes few symptoms unlike its treatment, creatinine!, creatinine! Impotence, depression

29 What the guidelines say (2,160,000 hits in Google) JNC VII (2003) NICE (2006) calcium antagonists, ACE inhibitors, angiotensin receptor antagonists and β- blockers are suitable for the initiation and maintenance of antihypertensive treatment, alone or in combination. β-blockers, especially in combination with a thiazide diuretic, should not be used in patients with the metabolic syndrome or at high risk of incident diabetes ESH (2007)

30 Diuretics, Beta blockers and the risk of Diabetes Cumulative Fatal CHD and Nonfatal MI event rate (%) No. at Risk Chlorthalidone Amlodipine Lisinopril ALLHAT Primary Outcome by Treatment Group Time to event, yrs Chlorthalidone Amlodipine Lisinopril ALLHAT Research Group. JAMA. 2002;288: Copyright 2002, American Medical Association Absolute risk of diabetes 3.5% higher with chlorthalidone Absolute risk of diabetes 2.5% higher with atenolol Equalling to extra cases of diabetes per year in USA (in USA 20 million patients are on thiazides and 20 million on diuretics)

31 Differential treatment after ALLHAT Diuretics Beta blockers ACE inhibitors ARBs CCBs Congestive heart failure MERIT-HF, COPERNICUS, CIBIS, SOLVD, AIRE, TRACE, ValHEFT, CHARM Post MI ACC/AHA guidelines, BHAT, SAVE, CAPRICORN, VALIANT, OPTIMAAL High risk / atherosclerosis ALLHAT, HOPE, ANBP2, LIFE, CONVINCE, EUROPA, INVEST Diabetes?? NKF + ADA guidelines, UKPDS, ALLHAT, VALUE, INVEST, ASCOT, LIFE Chronic renal failure Stroke? NKF + ADA guidelines, Captopril trial, RENAAL, IDNT, REIN, AASK PROGRESS, SCOPE, ACCESS, LIFE, SYSTEUR, MRC Trial

32 Differential treatment after ALLHAT Blood pressure treatment has to follow guidelines. vs. Most importantly, the blood Pressure has to come down. Individual patient characteristics?

33 Only add-on dizziness Excellent add-on e.g. evening Low potential for trouble Doxazosin Moxonidin CCB If compliant with diuretics and Beta-Bl. Admission? Mi no xi dil Alpha-MD Beta- Blocker Loop diuretics ACE-I ARB Thiazides If compliant + renovascular Unlikely Beware of spironolactone If other Indication or stress If pregnant If edema and thiazides not enough Low potential for trouble If mild edema Avoid if low clearance

34 Combination Thiazide diuretics β- blockers Angiotensin receptor antagonists α- blockers Calcium antagonists ACE inhibitors

35 A forefather of nephrology and hypertension Speculated that pale hypertension is mediated by factors secreted by the kidney This was later proven by Goldblatt Volhard also pioneered the saltfree diet A man of varied interests Franz Volhard

36 News from the renin angiotensin aldosterone system Escape

37 Aliskiren a novel renin inhibitor Renin Aliskiren Adapted from Wood JM, et al Angiotensinogen

38 Aliskiren a novel renin inhibitor These findings provide a clear rationale for further studies to investigate the potential effects of longterm treatment with the combination of aliskiren and valsartan,and combinations of aliskiren with other ARBs, on possible benefits beyond treating hypertension Oparil S, et al., The Lancet 2007; 370:

39 Aliskiren: Hyperkalemia > 5.5 > 6.0 Ramipril 10 mg Aliskiren 300 mg Ramipril 10 mg + Aliskiren 300 mg Novartis data

40 Aliskiren and renal impairment In patients with renal impairment: changes in aliskiren exposure did not correlate with the severity of renal disease or with creatinine clearance steady-state clearance of aliskiren was 60 70% of the values for matched healthy control subjects adjustment of the initial aliskiren dose is not necessary in patients with hypertension and renal impairment Low potential for interactions, long half-life Vaidyanathan S, et al. Clin Pharmacokinet. 2007;46(8):

41 Direct renin inhibitors Future studies: DRIs may find their place as adjunctive therapies, in combinations with ACE inhibitors or ARBs, or less commonly still, in patients intolerant to these. Direct renin inhibitors: the dawn of a new era, or just a variation on a theme? Segall et al. NDT 2007 Renin inhibition may offer protection of target organs such as the kidney beyond what can be achieved with current antihypertensive therapies this drug class may have great potential. Dominik N. Mueller and Friedrich C. Luft. Clin J Am Soc Nephrol 1: , 2006

42 The latest gadget Management of Uncontrollable Hypertension With a Carotid Sinus Stimulation Device Markus G. Mohaupt, Juerg Schmidli, Friedrich C. Luft Hypertension published online Sep 24, 2007

43 "For they taught us common sense Tried to teach us common sense Truth and God 's own common sense Which is more than knowledge."' Rudyard Kipling poem dedicated to his teachers