Herbert L. Muncie, Jr., M.D.

1. Herbert L. Muncie, Jr., M.D. Evaluation and Treatment of Hypertensive Patients

2. Proper technique to measure Blood Pressure (JNC VII) • Sitting, back supported, arm at level of heart • Feet on floor, legs uncrossed • Rest at least five minutes • Proper cuff size (> 80% of arm with bladder) • Inflate & palpate radial pulse to approximate BP – deflate cuff • Inflate 20-30 mm above palpable systolic • Measure Korotkoff I (onset sounds - systolic) and V (disappearance sounds - diastolic)

3. WatchBP Office

4. 250 62 A 58 year old African American female with three separate BP readings averaging 164/92. According to JNC VII, what is her BP classification? Question • Normal • Prehypertension • Stage 1 hypertension • Stage 2 hypertension

5. Classification of Blood Pressure – JNC VII Highest value (systolic or diastolic) determines Stage

6. Treat Prehypertension? • It is not a disease category (JNC VII) • Treatment with ARB (candesartan) for 4 years • Relative risk reduction of developing Stage 1 hypertension 15.6% • Patients with prehypertension are not candidates for drug therapy (JNC VII)

7. Lifetime Risk • For men or women who are normotensive at age 55 or 65 and • Who survive to age 80 - 85 • 90% will develop hypertension

8. Tests after Initial Diagnosis • Target organ damage? • ECG • Urinalysis • CBC • BUN & creatinine • Secondary causes? • Electrolytes, calcium • Other cardiovascular risk factor? • Lipid profile, glucose

9. Whom to consider evaluating for 2o causes • Onset of hypertension before age 30 or after age 55 • Initial diastolic BP is > 110 mm • Patient with unexplained hypokalemia • Patient with resistant or difficult to control BP especially if initially good control • Signs of Cushing’s disease • Signs or symptoms of pheochromocytoma

10. Pheochromocytoma • Measure plasma free metanephrine (99% sensitive, 89% specific) • < 61 ng/L excludes diagnosis • > 236 ng/L confirms diagnosis • If 62 - 235 ng/L more testing required • 24 hour urine metanephrine alone highly sensitive and specific, but often incomplete collection

11. Renal artery stenosis • Abdominal bruit suggestive often absent • If high index of suspicion & normal renal function [Hartman 2009] • MRA • CTA • If high index of suspicion & diminished renal function • MRA • Duplex Doppler ultrasonography

12. Primary hyperaldosteronism • Screen with plasma aldosterone/renin ratio (cutoff > 25) • β-blockers & DHCCBs stop for 2 weeks • Spironolactone & loop diuretics stop for 6 weeks • Plasma aldosterone should be > 20 ng/dL to make the diagnosis (Nl – 2 – 16 ng/dL – supine) • Renin – nl 12 – 79 mu/dL (supine)

13. Cushing Syndrome • 24 hr urine free cortisol useful screening (cutoff > 90 mcg/day) • Sensitivity 41 – 70% • Specificity – almost 100% • Overnight dexamethasone suppression test equally sensitive, less specific • 1 mg dexamethasone midnight – plasma cortisol next morning (cutoff > 100 nmol)

14. What if you find a 2o Cause? • Renal artery stenosis • For atherosclerotic etiology • Medical therapy is cornerstone [Dworkin 2009] • Stenting no better than medical but more complications • May be helpful with recurrent CHF or pulmonary edema • For fibromuscular dysplasia – balloon angioplasty is worthwhile

15. White coat hypertension • Elevated office BP but normal outside office • Normal would be either 24-hour BP with mean < 125/79 or home BP < 132/82 • If out of office BP consistently < 130/80 & no evidence of target organ damage • 24 hour monitoring or drug therapy can be avoided (JNC VII) • Increased risk of progressing to sustained hypertension [Mancia 2009] White coat hypertension

16. Masked hypertension • Masked hypertension • Normal office BP but elevated outside office • Suspect if patient with normal office BP has cardiovascular event • Increased risk of cardiovascular events • Pharmacotherapy is indicated • Deserves “an aggressive diagnostic & therapeutic approach” [Messerli 2007]

17. Mrs. Jones • Mrs. Jones is a 58 year old white female treated for hypertension for the past 6 years. Her BP today in the office is 168/94. • Which number should you focus on in deciding on modifying treatment? • Systolic BP • Diastolic BP

18. Treatment of Patients > 50 y.o. • Patients > 50 years old achieve diastolic goal when systolic goal achieved • Focus on systolic control for patients > 50 years old because: • Systolic BP continues to rise with age • Diastolic BP levels off around age 50 & will remain at that level or fall after age 50

19. Weight reduction alone reduces BP • Regardless of weight - DASH diet helpful in lowering BP • Increase potassium (6-8 fruits or vegetables a day) • Increase fiber with whole grains (breads, cereals) • Increase calcium intake (low fat dairy) • Decrease salt (DASH-low Na) • No added salt Non-pharmacologic Therapy

20. Non-pharmacologic Therapy • Stage 1 can be treated with lifestyle only (JNC VII) • For one year if no other risk factors • For 6 months with other risk factors • You do not have to start medication immediately with Stage 1 (BP < 160/100)

21. 250 65 Patients who successfully lose 3 - 9% of their body weight with lifestyle changes can expect to see their average BP decrease how many mm? Audience Question • 3 • 5 • 7 • 10

22. Weight loss & BP - EBM • Dieting to lose weight may lower BP in overweight people but the effects are modest & dieting may not be effective alone • Cochrane Review • 18 randomized trials found weight loss of 3-9% • Associated with decreases of roughly 3 mmHg systolic & diastolic • http://www.chochrane.org/reviews/en/ab000484.html

23. Lifestyle changes • Combining intensive lifestyle counseling & physician feedback was not successful long-term (18 month) in achieving BP control [Svetkey 2009] • Some early success (6 months) faded over time • Dietary choices influence control success • Salt restriction is central especially in those requiring intensive pharmacotherapy • Increase fresh fruits & vegtables • Maximum 1 restaurant meal/week

24. 250 57 A 50 yo African American male with BP 155/95 (avg.) requires initiating drug therapy. What would be your initial choice of medication class for this patient? Question • Thiazide diuretic • Calcium channel blocker (CCB) • Beta blocker • Angiotensin-converting enzyme inhibitor (ACE) • Angiotensin receptor blocker (ARB)

25. Initial Therapy • JNC VII – a thiazide-type diuretic should be initial therapy unless compelling indication • Most patients with Stage 1 will experience better BP control & lower CVD risk when taking a thiazide-type diuretic • Most patients with Stage 2 disease will experience better BP control & lower CVD risk when taking a multidrug regimen that includes a thiazide-type diuretic

26. Initial Therapy • No treatment alters the natural progression of the disease • BP will continue to rise as the patient ages regardless of which medications are used • Therefore, every patient will eventually need for more than one medication to control their BP

27. Initial Therapy • Dr. Chobanian (Chair JNC VII) now suggests flexibility in choice of initial drug [Chobanian 2009] – he suggests • Stage 1 – ACE, ARB, CCB or diuretic • Stage 2 – two of those 4 drugs to start • With exception of β-blockers after an MI & CCBs effect on CVA risk, all drugs lowered CVD events for a given reduction in BP [Law 2009]

28. Initial Therapy • To increase drug persistence & compliance with therapy [Friedman 2010] • Choose medications that will lower BP with few complications & is taken less often • Persistence is lower with more side effects • Compliance is lower in males, lower SES groups & in urban environments

29. A 50 yo African American male with BP 155/95 (avg.) requires initiating drug therapy. What would I choose? Thiazide diuretic Calcium channel blocker (CCB) Beta blocker Angiotensin-converting enzyme inhibitor (ACE) Angiotensin receptor blocker (ARB) 250 57 Question

30. STITCH Therapy • Simplified Treatment Intervention to Control Hypertension (STITCH) • STITCH vs Canadian Hypertension Education Program guideline (CHEP) • CHEP is similar to JNC VII approach

31. STITCH Treatment • Initiate therapy with ½ tablet of low dose combination - diuretic & ACEI or ARB • Increase that combination to highest dose tolerated • Then add CCB & increase to highest tolerated dose • Then add non-first-line agents • Alpha-blocker • Beta-blocker • Spironolactone

32. STITCH Therapy • At 6 months [Feldman 2009] • 64.7% controlled on STITCH • 52.7% controlled on CHEP (P = 0.03)

33. Pharmacologic Efficacy • Average reduction in BP for major classes of drugs • At standard dosage - 9.1 mm (SBP)/5.5 mm (DBP) drop • With half standard dosage - 7.1 mm (SBP)/4.4 mm (DBP) • When BP > 20 (SBP) or 10 mm (DBP) above goal (Stage 2) start two medications initially

34. A 52 year old African American female has not achieved BP control on diuretics. You add an ACE inhibitor to the regimen. You order electrolytes, BUN and creatinine in 1 week. Her creatinine increased from 0.9 baseline to 1.14 mg/dL, a 26.7% increase. What should you do about her ACEI? Discontinue the ACEI & add a different class Reduce the ACEI dose 50% Reduce the ACEI dose 25% Make no change in the ACEI dosage Question

35. Initiating Therapy – Change in Renal Function • After initiating treatment, common to get decline in renal function • If ≤ 30% non-progressive increase in creatinine • Represents a functional response (reduced intraglomerular pressure) & no change in treatment required • This response is associated with long-term renal protection • If > 30% increase in creatinine, D/C medication & choose another class

36. A 52 year old African American female has not achieved BP control on diuretics. You add an ACE inhibitor to the regimen. You order electrolytes, BUN and creatinine in 1 week. Her creatinine increased from 0.9 baseline to 1.14 mg/dL, a 26.7% increase. What should you do about her ACEI? Discontinue the ACEI & add a different class Reduce the ACEI dose 50% Reduce the ACEI dose 25% Make no change in the ACEI dosage Question

37. Diuretic - Classes • Thiazide • Hydrochlorothiazide (HCTZ) dosage best if ≤ 25 mg & preferably 12.5 mg • Outcome benefits have not been established for these dosages of HCTZ • Increasing to 50 mg minimally lowers BP further but significantly increases side effects • Hyponatremia & hypokalemia more common in women • 12 combinations with HCTZ available

38. Diuretic - Classes • Thiazide • Chlorthalidone 25 mg provided better 24 hr BP control than HCTZ 50 mg • Milligram for milligram twice as potent as HCTZ • Outcome data available regarding reduced CV events • Only 2 combinations available • Chlorthalidone/clonidine (Clorpres®) – 15/0.1,0.2, 0.3 • Atenolol/chlorthalidone (Tenoretic®) – 25/50, 25/100

39. Diuretic - Classes • Loop • If only treating hypertension - use loop diuretics only with renal insufficiency (CrCl < 30 - 40 ml/min) • Discontinue thiazides at this CrCl – not effective • Dosage frequency for BP treatment • Furosemide (Lasix®) – BID • QD dosage may lead to reactive Na+ retention mediated by renin/angiotensin system • Torsemide (Demadex®) – QD

40. Diuretic - Classes • Potassium sparing • Combined with thiazide - reduces risk sudden death and hypokalemia • Do not combine with continuous K+ supplements or give with renal insufficiency • Increased risk hyperkalemia • Especially with ACE or ARB combination • Should be stopped temporarily if diarrhea or vomiting occurs

41. Selective aldosterone receptor antagonist • Eplerenone (Inspra®) first approved in new class • Primary focus in heart failure • Add-on to anti-hypertensive Rx • Side effects • Hyperkalemia • Contraindicated with hyperkalemia, creatinine > 1.8 men, > 2.0 women, or creatinine clearance < 50 ml • Caution in use with ACE or ARB

42. Diuretics – diabetes & hyperlipidemia? • Diuretics can raise glucose & lipid levels short-term • However, no long-term adverse effects in diabetics • Fasting glucose increases in older adults regardless antihypertensive drug • Diuretics may be safely used in patients with diabetes or hyperlipidemia

43. Beta-Blockers • Available evidence does not support their use as 1st line treatment alone • Weak effect in reducing CVA • Absent effect on CAD [Wiysonge - Cochrane 2007] • Lower heart rate with beta-blocker therapy associated with increased risk CV events & death • Compelling indications (JNC VII) • Heart failure • Chronic stable angina • Post MI • Tachyarrhythmia

44. Beta-Blockers • Side effects • Increased risk developing type 2 DM • Decreased exercise tolerance • Increased risk of Raynaud’s phenomenon • Increased insomnia & risk of delirium • Abrupt withdrawal can precipitate myocardial ischemia in at risk patients

45. Beta-Blockers & Diabetes • In diabetics beta-blockers blunt heart rate & BP response to hypoglycemia • However, no increase in severe hypoglycemia in Type 1 or Type 2 DM • Do not worsen glycemic control when used with ACE/ARB • Carvedilol (Coreg®) & nebivolol (Bystolic®) have neutral or even favorable effect on CHO & lipid metabolism

46. Angiotensin-Converting Enzyme (ACE) Inhibitors • Compelling indications (JNC VII) • Heart failure • Post MI - systolic dysfunction • Diabetics with proteinuria • Reduce cardiovascular & all-cause mortality • As effectively as diuretics, β-blocker or CCB [SOR-A] • Diabetics may retain sodium • Add diuretic to enhance response

47. Side effects • Cough (5-15%) - women 2x men’s risk • Angioedema (0.1-0.2%) – African Americans and Asians 3 - 4 x risk increase • Hyperkalemia with renal insufficiency • If patient has bilateral renal artery stenosis • Can cause renal insufficiency • Measure creatinine initially & one week after starting ACE • If > 30% increase in creatinine or hyperkalemia 1st 2 months – D/C ACE ACE Inhibitors

48. Angiotensin Receptor Blocker (ARB) • Three trials found ARBs effective in reducing CV events (LIFE, SCOPE, VALUE) • But not as effectively as ACE • Reduce the risk end-stage renal disease in diabetics • No evidence reduce mortality in diabetics with renal disease • Reserve for patients who cannot tolerate ACE

49. Angiotensin Receptor Blocker (ARB) • Low incidence of dizziness or other side effects • Cough not a problem • Caution with renal insufficiency or K+ supplements

50. Angiotensin Receptor Blocker (ARB) • Less effective if high salt intake • Measure serum creatinine initially & 1 week after starting drug • Can worsen renal failure • Not proven to improve survival post MI • ACE & ARB should not be used in pregnancy