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

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

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

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  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

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