260/150. Hypertension JNC 8. "The president was the worst-looking man I ever saw who was still alive."

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1 Hypertension JNC 8 WILLIAM R. SONNENBERG, MD TITUSVILLE, PA Disclosure Dr. William Sonnenberg has no conflict of interest, financial agreement, or working affiliation with any group or organization. 260/150 "The president was the worst-looking man I ever saw who was still alive." 1

Hypertension - 1945 The treatment of the hypertension itself is a difficult and almost hopeless task in the present state of our

.. the hypertension may be an important compensatory mechanism which should not be tampered with, even were it certain that we

2 Hypertension The treatment of the hypertension itself is a difficult and almost hopeless task in the present state of our knowledge, and in fact for aught we know... the hypertension may be an important compensatory mechanism which should not be tampered with, even were it certain that we could control it Dr. Paul Dudley White, 1931 FDR Blood Pressure A Little History In the 1940 s, treating hypertension was considered malpractice FDR s BP was 290/130 "I have a terrific pain in the back of my head." 2

Hypertension - Prevalence Most common reason for OV in non-pregnant patients 1/3 of adults > 18 years 67-78 million USA adults

throughout life By age 50, usually high Primary Focus Systolic more important than diastolic, except under 50 Majority of

3 Hypertension - Prevalence Most common reason for OV in non-pregnant patients 1/3 of adults > 18 years million USA adults Increasing Elderly ½ Obesity epidemic JAMA 2010;303: Hypertension Hypertension under 50 Usually Diastolic Systolic rises throughout life By age 50, usually high Primary Focus Systolic more important than diastolic, except under 50 Majority of hypertension over age 50 Risk reduction BP just a number Rule out secondary causes Appropriate therapeutic selections Consider overall cardiovascular risk 3

Hypertension by Age Number Needed to Treat Cholesterol treatment is typically 40-200

Increases Morbidity and Mortality 140 Treatment Decreases Morbidity and Mortality 50

4 Hypertension by Age Number Needed to Treat Cholesterol treatment is typically NNT is 11 if >65 One comorbid disease Hypertension Bad, Treatment Good Hypertension Increases Morbidity and Mortality 140 Treatment Decreases Morbidity and Mortality 50 CHD Incidence/1000 Patient years 120 Normotensive 100 Hypertensive Men Women Framingham Study Ann Int Med. 1961: 55:33-59 Cumulative Fatal & Nonfatal Endpoints Placebo Treated Vet. Study II JAMA. 1970; 213:

5 Why Treat Hypertension? Better Outcomes! 0% CHF Stroke LVH CV CAD -10% -20% -30% -21% -16% -40% -38% -35% -50% -60% -52% JNC 7 Target BPs Subgroup Target SBP Target DBP < Most Patients <140 <90 > 18 years with Chronic Kidney Disease <130 <90 > 18 years with Diabetes <130 <90 JNC 8 Target BPs Subgroup Target SBP Target DBP 60 years <150 <90 < 60 years <140 <90 > 18 years with Chronic Kidney Disease <140 <90 > 18 years with Diabetes <140 <90 5

6 JNC 8 Recommendations Nonblack populations Thiazides, CCB, ACEI, or ARB initially Black population Thiazide or CCB initially Chronic kidney disease Treatment to include ACEI or ARB Follow-up, increase and add meds Don t use ACEI and ARB together > 3 meds refer JNC 8 Background 5 trials (HDFP, MRC, HTN-Stroke Cooperative, ANBP, MRC) Ages lowering DBP below 90 reduces CV, HF, and overall mortality DBP < 90 as only goal for young? SBP of 140 may be unnecessarily low, 2 trials shows no improvement of 140 compared to 150 or 160 α-blockers or β-blockers not first line One trial showed more CV events with β-blocker compared to ARB Another trial showed more CV events with α-blocker compared to diuretic Less Hypertension Hypertension younger adults (18-59) 20.3% 19.2% Hypertension older adults ( 60) 68.9% 61.2% 25% more adults now at goal Navar et al. JAMA. 2014;311(14):

Overtreatment in Elderly- Hip Fractures 301,591 Ontario elderly with newly treated hypertension

increase with thiazides take 12 weeks for maximal effect Start low and go slow Butt DA et al.

2012;172(22):1739 1744 What s New in JNC 8 (Simplified) 150/90 for over age 60 140/90 for

7 Overtreatment in Elderly- Hip Fractures 301,591 Ontario elderly with newly treated hypertension 43% in first 45 days, highest day X increase with ACE inhibitors and β-blockers No increase with thiazides take 12 weeks for maximal effect Start low and go slow Butt DA et al. Arch Intern Med. 2012;172(22): What s New in JNC 8 (Simplified) 150/90 for over age /90 for everyone else More medication choices ACE ARB CCB Thiazide Diastolic Control in Older Patient Age 60, avoid DBP < 60 Age 70, avoid DPP < 70 85% of coronary flow occurs during diastole 7

Evaluation of Hypertension Initial Measurement Chair

bared, slightly flexed, relaxed Support entire

of circumference of mid upper arm Length twice the

8 Evaluation of Hypertension Initial Measurement Chair with back Feet on floor Rested for 5 minutes Arm bared, slightly flexed, relaxed Support entire forearm at heart level Cuff Size Bladder width 40% of circumference of mid upper arm Length twice the width Adjust for obese or thin patients Calibrated if not mercury 8

per second Korotkoff I and V Average 2-3

factors that influence therapy Establish

out secondary, surgically curable causes

9 Cuff Pressure Raise 30 mm Hg above when radial pulse disappears Release 2-3 mm per second Korotkoff I and V Average 2-3 readings 40% of patients normalize BP at second reading Further Evaluation Cardiovascular risk factors Assess factors that influence therapy Establish baseline Assess target organ damage Rule out secondary, surgically curable causes Personal History Dietary (sodium, fat) Habits Exercise, weight changes, grapefruit juice Tobacco, alcohol, cocaine, anabolic steroids Stress 9

Family History Coronary heart disease Stroke CHF Outcomes in: Men < 55 Women <65

gout, asthma, COPD Endocrine disease Diabetes, thyroid, adrenal, pituitary

Medications NSAID s COX-2 Estrogen BCP s Corticosteriods TCA s MAO Inhibitors

10 Family History Coronary heart disease Stroke CHF Outcomes in: Men < 55 Women <65 Past Medical History Stroke, TIA, CHF, angina, renal, vascular, hyperlipidemia, gout, asthma, COPD Endocrine disease Diabetes, thyroid, adrenal, pituitary Previous hypertension Age of onset Previous treatment Compliance Interfering Medications NSAID s COX-2 Estrogen BCP s Corticosteriods TCA s MAO Inhibitors Ergots Cocaine Erythropoietin Cyclosporine Nasal decongestants Appetite suppressants Ephedra or ma huang 10

weight, BMI Ocular fundi Auscultation and

nicking Arteriolar narrowing Hemorrhages

11 Physical Examination Blood pressure confirmation General appearance Height and weight, BMI Ocular fundi Auscultation and palpation of the neck, chest and lungs, abdomen, and extremities Neurologic examination Ocular Fundi Most cases just nicking Arteriolar narrowing Hemorrhages Exudates Papilledema Neck Distended veins Thyromegaly Bruits 11

12 Chest and Lungs Heart rate Cardiac enlargement Heaves Murmurs Arrhythmias Gallops Rales Abdomen Bruits renal arteries Enlarged kidneys Enlarged liver Dilated aorta Extremities Peripheral pulses Edema Ankle-brachial index 12

Diagnostic Testing Urinalysis, with microscopic examination

reach goal Lower than office readings Finger and wrist devices not

masked hypertension Ambulatory BP Measurement White coat

$Assessment of Refractory hypertension Episodic or labile$

13 Diagnostic Testing Urinalysis, with microscopic examination Electrocardiogram (ECG) Hct/Hgb or CBC Creatinine or estimated GFR Glucose Potassium Calcium Lipid profile Home BP Monitoring Adherence and feedback Twice weekly readings 4x more likely to reach goal Lower than office readings Finger and wrist devices not accurate 2x as likely to predict events as office readings 8% have masked hypertension Ambulatory BP Measurement White coat hypertension Better predictor of organ damage that office BP Assessment of Refractory hypertension Episodic or labile hypertension Suspected hypotensive episodes or autonomic dysfunction Should drop 10-20% during sleep 13

14 Management of Hypertension Goals Prevention: CHF Stroke CHF Renal disease Patient Education Asymptomatic nature Dangers of CHF, stroke, CHD, and renal disease Lifestyle modifications Need for lifelong therapy May or may not include medication 14

Education Materials Goals of therapy Goal in writing Instructions for

What to do if they occur Missed dose response Teaching Points Sporadic

Include family members Document education efforts Intermittent Use of

days 42% missed 3 days Fatal stroke risk 3.

15 Education Materials Goals of therapy Goal in writing Instructions for taking medications Description of potential side effects of drug therapy What to do if they occur Missed dose response Teaching Points Sporadic treatment ineffective Moderate salt restriction Weight reduction Exercise Include family members Document education efforts Intermittent Use of Medications Missed meds on monotherapy 42% missed one day 15% missed two days 42% missed 3 days Fatal stroke risk 3.8 times greater with intermittent use over 12 years Kimmo Herttua, et al. Eur Heart J. 2013;34(38):

Barriers to Success Complexity of therapy Expense of

Assess problems initially and periodically Therapeutic

Physical activity Sodium restriction to 2.

per day Reduce dietary fat DASH diet Tobacco DASH Diet 11/6

16 Barriers to Success Complexity of therapy Expense of medications Competing drugs Over-the-counter Side effects Assess problems initially and periodically Therapeutic Lifestyle Changes Weight reduction Each one kg loss reduces BP 1.2/1.0 2 mm reduction could save 70,000 Americans per year Physical activity Sodium restriction to 2.4 grams/day Keep ethanol to 1 oz. per day Reduce dietary fat DASH diet Tobacco DASH Diet 11/6 drop in BP Emphasizes fruits, vegetables, and low-fat dairy products, that includes whole grains, poultry, fish, and nuts Small amounts of red meat, sweets, and sugar-containing beverages 16

Lifestyle Changes How Much from Lifestyle?

diary 8-14 mm Hg Sodium 6 g/day 2-8 mm Hg Aerobic

17 Lifestyle Changes How Much from Lifestyle? Lifestyle Change Recommendation SBP Reduction Weight Loss BMI mmhg/10 kg Dash Diet Fruits, vegetables, lowfat diary 8-14 mm Hg Sodium 6 g/day 2-8 mm Hg Aerobic physical activity Moderation of alcohol 30 min/day Most days 2/day - men 1/day - women 4-9 mm Hg 2-4 mm Hg Drug Therapy 17

Outcome Improving Drugs Thiazide diuretics Β-blocker ACE

inhibitors Use in ACE intolerant Initial Therapy Stage One

response 60-70% may require 2 or more agents Stage Two

volume-depleted Diuretics Low dose effective Inexpensive

18 Outcome Improving Drugs Thiazide diuretics Β-blocker ACE inhibitors ARB s Target organ protection similar to ACE inhibitors Use in ACE intolerant Initial Therapy Stage One Monotherapy or low-dose combination Allow 1-3 months for response 60-70% may require 2 or more agents Stage Two Start with two agents Caution in elderly, diabetic, and volume-depleted Diuretics Low dose effective Inexpensive cheap as dirt Hypokalemia, hyperuricemia, increased glucose at 50 mg. or higher Restrict sodium Insulin resistance and lipids not clinically meaningful Good synergism with other agents 18

Diuretic Outcomes Reductions across all subgroups Stroke CHD CHF Sudden death More so in older

0 times more potent More hypokalemia Better with low GFR Good to GFR of 30-35 v.

19 Diuretic Outcomes Reductions across all subgroups Stroke CHD CHF Sudden death More so in older patients Higher doses (50 mg.) less effective HCTZ v. Chlorthalidone Chlorthalidone 1.5 to 2.0 times more potent More hypokalemia Better with low GFR Good to GFR of v. 40 Half life of 40 hours v. 17 hours 19% lower event rate with chlorthalidone Neff KM et al. Cardiol Rev Jan-Feb;18(1):51-6 β-blockers Reduces CHF and stroke Indicated for CAD and history of MI Mild to moderate CHF More effective in European-Americans Mask symptoms of hypoglycemia Helpful in migraine headaches 19

20 Misconceptions About β-blockers Asthma COPD Diabetes Mellitus Does not worsen control Equal to ACE in renal protection even for DM when proteinuria not already present Ethnicity β-blockers Once daily atenolol not preferred Vasodilatory β-blockers preferred Improved insulin resistance Less weight gain Less fatigue (nabivolol) Better cardiac output Calcium Channel Antagonists Smooth muscle dilators Negative inotropic effects on atrial and ventricular working myocardial cells Blood flow increased to myocardium and kidneys 20

21 Three Classes Dihydropyridines Verapamil Diltiazem Distinct receptor binding sites, resulting in various specific actions. Verapamil Slows cardiac conduction Decreases heart rate Not for second or third degree heart block Caution in CHF Negative inotropic effect Diltiazem - Benzothiapine Less negative inotropic effect than verapamil Decrease systemic vascular resistance No net impairment of ventricular performance Caution in CHF 21

Dihydropyridines No effect on conduction Reflex tachycardia as pressure drops Inferior in CHF or renal disease Postural hypotension Fluid retention

survival or outcome Use long acting agents In general, well tolerated Work better with HIGH salt!

22 Dihydropyridines No effect on conduction Reflex tachycardia as pressure drops Inferior in CHF or renal disease Postural hypotension Fluid retention Examples: Nifedipine Nicardipine Amlodipine Felodipine Isradipine Nisoldipine CCB Summary Second line for angina Relieve symptoms No help with survival or outcome Use long acting agents In general, well tolerated Work better with HIGH salt! ACE Inhibitors Superior to CCB s for diabetic patients Improved survival post myocardial infarction Indicated regardless of hypertension for patients with CHF or diabetic nephropathy (including microalbuminuria) 22

Ace Inhibitors Decrease total peripheral resistance Do not reflexively increase

patients with bilateral renal arterial disease Monitor creatinine and potassium

deterioration of renal function in DM, type 1 Reverse microvascular coronary

23 Ace Inhibitors Decrease total peripheral resistance Do not reflexively increase cardiac output, contractility, or rate Effective in low doses Caution in patients with bilateral renal arterial disease Monitor creatinine and potassium before and during treatment in renal insufficiency ACE Benefits Slows deterioration of renal function in DM, type 1 Reverse microvascular coronary disease in hypertension ACE Side Effects Hyperkalemia Dry cough Angioedema 3x more in Blacks Dysgeusia 23

Precautions Check creatinine in 1-2 weeks <30% increase ok >30% think RAS Avoid potassium-sparing diuretics Hyperkalemia Avoid in pregnancy NEJM

reduce development of CHF Seldom cause cough May cause angioedema ARB-MI Paradox Some prior studies showed increased CV risk with ARBs compared to placebo

24 Precautions Check creatinine in 1-2 weeks <30% increase ok >30% think RAS Avoid potassium-sparing diuretics Hyperkalemia Avoid in pregnancy NEJM 2002;347(16): ARBs Early trials may indicate outcome comparable benefits to ACE s Slows progression of renal disease with and without diabetes Appear to reduce development of CHF Seldom cause cough May cause angioedema ARB-MI Paradox Some prior studies showed increased CV risk with ARBs compared to placebo Meta-analysis 37 RCTs, 147,000 patients ARBs no better than placebo in CV outcomes MI 0.99 RR Death 1.00 RR CV Death 0.99 RR Sight help with DM, HF, stroke RR reduction <10% BMJ. 2011;26;342:d

25 ARBs Less Effective in DM? 35 RCTs in DM ACEs: All cause mortality RR 0.87, CV mortality 0.83, CV events 0.86, MI 0.79, HF 0.81 ARBs: HF 0.70 and nothing else Neither decreased stroke risks JAMA Intern Med 2014;174: Aliskiren - Tekturna Only Direct Renin Inhibitor Seems to help with proteinuria Moderate effective Don t combine with ACEI or ARB Vasodilators Hydralazine most common Usually third line after diuretics and second line agents Lower total peripheral resistance May increase heart rate and cardiac output Initiate in small doses Minoxidil with consultation 25

Other Adrenergic Inhibitors α-blockers no longer first line Initial dose postural

in noncompliant Methyldopa contraindicated in liver disease Fatigue, lethargy, and sexual

month Can add to ACE or ARB Am Fam Physician. 2009 May 15;79(10):863-869.

26 Other Adrenergic Inhibitors α-blockers no longer first line Initial dose postural hypotension Reserpine avoid in depression or PUD Clonidine, methyldopa, and a-blockers avoid in noncompliant Methyldopa contraindicated in liver disease Fatigue, lethargy, and sexual dysfunction Spironolactone, the Secret Weapon Reduces BP 20/10 in pts on 3 or more drugs One month Can add to ACE or ARB Am Fam Physician May 15;79(10): Good Combinations Adding spironolactone as a 4 th med ACE or ARB with diuretic ACE or ARB with CCB Β-blocker with diuretic 26

Bedtime Dosing One drug should be taken at night if on

Reduces events 12% over 5 years May reduce DM risk 50%

Diabetes Care, 2011 June 34(6):1270-6 BAD Combinations

β-blocker and sympatholytic (reserpine, clonidine) No

27 Bedtime Dosing One drug should be taken at night if on multiple meds 5 mmhg reduction in SBP during sleep Reduces events 12% over 5 years May reduce DM risk 50% (unpublished data) Hermida, R. Diabetes Care, 2011 June 34(6): BAD Combinations ACE and ARB together Hypotension Syncope Renal disease β-blocker and sympatholytic (reserpine, clonidine) No difference in BP β-blocker and verapamil or diltiazem Resistant Hypertension 27

$Refractory Hypertension$ Excessive salt Alcohol, NSAID s

28 Refractory Hypertension Adherence Inadequate dose Excessive salt Alcohol, NSAID s Secondary hypertension Consultation or referral Secondary Hypertension Poor response to optimal therapy Age, history, PE, labs Severity of hypertension Sudden onset of hypertension Controlled BP, now worse Bad, Fast, and Young Severe or malignant hypertension Sudden/acute BP rise Age under 30 28

Testing for Secondary Hypertension Auscultation

cells Creatinine Potassium 24 urine for VMA or

Hypertension Sleep apnea Most common cause

Glomerulonephritis Pyelonephritis Polycystic

Hyperadrenergic state Suspect when: Snores loud

29 Testing for Secondary Hypertension Auscultation for bruits Urinalysis for protein, cast, red cells Creatinine Potassium 24 urine for VMA or total metanephrines Causes Secondary Hypertension Sleep apnea Most common cause Renal disease Renal artery stenosis Glomerulonephritis Pyelonephritis Polycystic kidneys Obstructive uropathy (BPH) Sleep Apnea Hyperadrenergic state Suspect when: Snores loud Daytime somnolence Apnea during sleep Treatment may improve hypertension 29

Renovascular Hypertension Hypertension from insufficient blood

Trial in Renovascular Hypertension 947 with renal artery stenosis

1%-15% complication rate Coartation of Aorta Narrowing in aorta

30 Renovascular Hypertension Hypertension from insufficient blood supply to kidneys 1-5% of hypertensives Upper abdominal bruit CORAL Trial in Renovascular Hypertension 947 with renal artery stenosis randomized to medical therapy + stenting or medical therapy alone 43 month follow-up BP 2.3 mmhg lower with stenting No in CV/renal outcomes 11% restenosis 1%-15% complication rate Coartation of Aorta Narrowing in aorta Renal underperfusion Decreased femoral pulses Chest x-ray Notched ribs Dilation of aorta above and below constriction 30

Causes Secondary Hypertension Hyper and hypothyroidism

Zebras Pheochromocytoma Primary aldosteronism Coarctation

More cardiac output Hypothyroidism More rise in diastolic

aldosterone Causes salt and water retention Suppresses

31 Causes Secondary Hypertension Hyper and hypothyroidism Parathyroid disease hypercalcemia Steroids Drug abuse Zebras Pheochromocytoma Primary aldosteronism Coarctation Thyroid Disease Hyperthyroidism More elevation of systolic More cardiac output Hypothyroidism More rise in diastolic More vascular tone Primary Hyperaldosteronism Excessive aldosterone Causes salt and water retention Suppresses renin Increases excretion of potassium Suspect with low K+ and no diuretic 31

32 Black Licorice Glycyrrhizic acid 50 grams Water retention Edema Lower testosterone in males Mimics effect of excessive aldosterone Questions? 32

ADVANCES IN MANAGEMENT OF HYPERTENSION

ADVANCES IN MANAGEMENT OF HYPERTENSION Advances in Management of Robert B. Baron MD Professor of Medicine Associate Dean for GME and CME Declaration of full disclosure: No conflict of interest Current Status of Prevalence 29%; Blacks 33.5%