Hypertension

Case 1

• A 31 year old Burmese male presents with shortness of breath x2 weeks. His blood pressure is 210/130 and he has evidence of volume overload. The creatinine is 2.0 and he has severe LV dysfunction on an echo.

Case 1

• After initiating appropriate therapy, which of the following studies should you consider ordering next?– MRI of the renal arteries– 24 hour urine for catecholamines and

metanephrines– 24 urine for cortisol– Plasma renin activity and aldosterone levels

Case 1

• What is the best first choice for management of this patients hypertension?– Hydrochlorothiazide– Lisinopril– Hydralazine, isosorbide mononitrate and

furosemide– Carvedilol and lisinopril– Diltiazem and furosemide

Case 2

• A 55 year old male smoker recently diagnosed with diabetes presents for a follow-up office visit. His blood pressure on the last 3 visits has been 148/85, 152/89 and 148/92. He is asymptomatic. Laboratory studies and a urinalysis are unremarkable. An EKG shows sinus rhythm.

Case 2

• What is the next best step in management of this patient?– Council him to loose weight, stop smoking and

exercise more– Start lisinopril 10 mg daily– Start hydrochlorothiazide 25 mg daily– Start metoprolol tartrate 25 mg BID– Order an echocardiogram for LV function

HTN Is A Common And Costly Problem

• Most common reason for non-pregnant patients to visit MD office

• Most common reason for use of prescription drugs• 29-31% incidence in population > age 18• 56-65 million hypertensives vs 43.3 million in 1990• Only 34% have controlled blood pressure• Costs: 37 billion annually, 15.5 billion for Rx• Projected to affect 1.5 billion worldwide by 2025

Cutler. Hypertension. 2008.ALLHAT. JAMA. 2002.Kearny. Lancet. 2005.

HTN Is Associated With Significant Morbidity

• Estimated lifetime risk of HTN is 90%• Most common modifiable risk factor for

– MI– Stroke– Aortic dissection– Heart failure – Atrial fibrillation– Peripheral arterial disease

Vasan. JAMA. 2002.

Definitions

• Normal blood pressure– SBP < 120 and DBP < 80

• Prehypertension– SBP 120-139 or DBP 80-90

• Hypertension– Stage I: SBP 140-159 or DBP 80-89– Stage 2: SBP > 160 or DBP > 100

Age Related Changes in Blood Pressure

Burt. Hypertension. 1995.

HTN Is A Risk Factor For Death Worldwide

http://www.who.int/healthinfo/global_burden_disease/GlobalHealthRisks_report_full.pdf

HTN Is A Top Risk Factor For Death At Every Income Level

http://www.who.int/healthinfo/global_burden_disease/GlobalHealthRisks_report_full.pdf

Global Mortality and Disease and Risk Factor Burden: Age 30

HTN Compounds Risk Regardless Of The Presence Of Other Risk Factors

Chobanian. JAMA. 2003.

Heart Disease Risk Increases With Minimal BP Elevation

Chobanian. JAMA. 2003.

Stroke Risk Increases With Minimal BP Elevation

Chobanian. JAMA. 2003.

Minimal BP Elevation Is Associated With Increased Mortality

Chobanian. JAMA. 2003.

HTN Treatment And Awareness In the US Has Improved

Kotchen. Circulation. 2010

Reduction Blood Pressure Leads to Clinical Benefits

Law. BMJ. 2009.

Physiology of Vascular Control• Goal: Maintain blood flow to important organs

– Local tissue controls and overall adjustments of cardiac pumping and vascular tone

• Short term blood pressure control– Cardiac output=Stroke volume x HR– Mechanisms

• Arterial baroreceptors, chemoreceptors, CNS (brain ischemia)• Fluid shifts, RAS activation, vasodilator systems

• Long term blood pressure control– Pressure natriuresis and diuresis– Infinite gain feedback control– All hypertension somehow alters this mechanism

Determinant of Blood Pressure

Klabunde. CV Physiology Concepts. 2005.

Time Dependence of BP Control

Fuster. Hurst’s the Heart. 12th Ed.

Mechanisms of HTN

Kaplan. Lancet. 2006.

Sympathetic Nervous System

Libby. Braunwald’s Heart Disease. 8th Ed.

Short Term BP Control

Mohrman. Cardiovascular Physiology. 6th Ed.

Long Term BP Control: Volume

Mohrman. Cardiovascular Physiology. 6th Ed.

Alternations In Sodium Handling Result In HTN

Fuster. Hurst’s the Heart. 12th Ed.

Risk Factors: Essential Hypertension

• Black race• Family history• Salt intake• Excess alcohol intake• Obesity• Dyslipidemia• Personality traits

Diagnosis• Screening

– Every two years in normal– Every year in SBP > 120– Diagnose after 3-6 measurements

• “White coat hypertension”– 20-25% of mild office hypertension

• Ambulatory BP monitoring– White coat HTN– Episodic HTN– Resistant to increasing medication– Hypotensive symptoms on treatment– Autonomic dysfunction

Initial Assessment

• Extent of target organ damage• Assess overall cardiovascular risk• Rule out modifiable causes of HTN• History and physical• Studies

– EKG– Labs: UA, Hgb, Gluc, Cr, K+, Na+, lipids

Suspect Secondary Causes of HTN

• Suggested by: age, history, exam, severity, lab findings

• Poor response to drug therapy• Previously controlled becomes resistant• Sudden onset

Secondary Hypertension• Renal disease• Drugs and alcohol• Pheochromocytoma• Primary hyperaldosteronism• Renovascular• Cushings• Thyroid and parathyroid disease• Sleep disordered breathing• Coarctation of the aorta

Hints to Secondary Causes• Renal disease

– Increased creatinine or abnormal UA• OCPs, NSAIDS, diet pills, decongestants, stimulants, stroids,

herbals, calcineurin inhbitors, antidepressants• Pheochromocytoma

– HTN (paroxysmal), HA, palpitations, sweating• Primary aldosteronism

– Hypokalemia• Cushings

– Cushingoid facies, central obesity, proximal muscle weakness, ecchymosis

• Sleep apnea– Snoring and apnea, daytime somnolence, morning confusion ,

depression• Coarctation

– UE HTN, brachial-femoral delay, LW hypotension• Hypothyroidism and hyperparathyroidism

Screening Tests for Secondary Causes

Pheochromocytoma• Paroxysmal hypertension

in 50% of pheo patients• Present in about 0.2% of

patients with HTN• Headache, palpitations,

perspiration, pallor• Screen with 24 urine

– Metanephrines– Epinepherine

• Treat with surgeryVerrijcken. Am J Card. In Press.

Renal Artery Stenosis• Most common after obesity and

EtOH• Rare in mild HTN, 10-45% of

severe HTN• Renal artery stenosis

– HTN age < 30 without family history, severe HTN with onset after 55

– Abdominal bruit– Accelerated HTN– Progressively resistant HTN– Flash pulmonary edema– RF of uncertain etiology– ARF after ACE-I– Asymmetric kidney size

• Screen with RA CT, US or MRI• Treatment

– Medical – Angioplasty or stenting

Zhang. Progress in CV disease. 2009

Hyperaldosteronism• 10-20% in resistant HTN• 50% normokalemic • Screen

– Plasma renin activity (low)– Plasma aldo/renin (high)

• Confirmatory test• Surgery• Medical

– Mineralocorotoid antagonist

Kumar. Robbins and Cotran Pathologic Basis of Disease. 8th Ed.

Coarctation Of The Aorta• 6-8% of all congenital heart

defects• More common in males• Associated with bicuspid valve,

Turners syndrome, other congenital heart disease and intracranial aneurysms

• BP and pulse variation• 75% mortality at 46 years if

uncorrected• CT, echo diagnosis • Surgical or percutaneous repair

Libby. Braunwald’s Heart Disease. 8th Ed.

Sleep Apnea

• 15 million Americans affected

• Increased CV mortality• 50% of OSA have HTN• 30% of HTN have OSA• BP improves with OSA Tx

Somers. JACC, 2008.

Goals of Therapy

• Reduce cardiovascular and renal morbidity and mortality

• Treat to goal < 140/90• For diabetics and heart disease, <130/80

Benefits of Blood Pressure Lowering

• For stage I HTN (140-159/90-99) and one risk factor, sustained 12 mmHg lowering over 10 years prevents one death per 11 patients

Outcome Reduction

Stroke 35-40%

Heart failure >50%

Myoocardial infarction

20-25%

Chobanian. JAMA. 2003.

Lifestyle ModificationIntervention Recommendation SBP Reduction

Weight reduction Normal body weight (BMI 18.5-24.9)

5-20 mmHg/10 kg

DASH Diet High fruit/veg, low fat 8-14 mmHg

Low salt diet Less than 6 g NaCl 2-8 mmHg

Physical activity 30 min daily 4-9 mmHg

Moderate alcohol

≤2/1 drink/day M/F 2-4 mmHg

Chobanian. JAMA. 2003.

Effects Of Lifestyle Interventions On HTN: Premier Trial

Premier Collborative Group. JAMA, 2003.

Salt Reduction

Bibbins-Domingo. NEJM. 2010.

Approach to Medical Therapy• Major drug categories

– Thiazide diuretics– ACE-I or ARB– Calcium channel blockers– Beta blockers– Direct Vasodilators

• Blood pressure reduction is important NOT agent used• Wide interpatient variability in response to therapy• Find regimen that is most effective with fewest side

effects• Why we don’t succeed: lack of lifestyle modification,

inadequate drug dose, inappropriate drug combinations

ALL HAT Trial

• Designed to compare older cheaper agents with newer ones

• 33,357 subjects 55 or older• HTN and one additional cardiac RF• Randomly assigned to chlorthalidone,

amlodipine, lisinopril or doxazosin• Doxazosin stopped early for increased CHF• Primary outcome: fatal heart disease or non-

fatal MIALLHAT. JAMA. 2002.

Thiazide Diuretics First Are Best: ALLHAT

• Chlorthalidone– Lower heart failure than amlodipine and lisinopril– Lower combined CV disease than lisinopril– Benefits likely secondary to better BP control

• Chlorthalidone is different than HCTZ– Different potency and duration of action

Blood Pressure Achieved: ALLHAT

ALLHAT. JAMA. 2002.

CAD Mortality and Non-Fatal MI: ALLHAT

ALLHAT. JAMA. 2002

Primary Endpoint: ACCOMPLISH

Jamerson. NEJM. 2008.

Initial Monotherapy

• Unlikely to be effective if BP > 20/10 over goal• 60% of patients in ALLHAT required 2 drugs

Factors Affecting Choice of Initial Therapy

Agent Indication Precautions

ACE-I LV dysfunction, post MI, DM, proteinuria

Diuretics (loop) Heart failure Hypokalemia

CCB (non-dihydropyridine)

Rate control in AF, angina, reactive airway disease

Beta Blockers Post MI, HF, AF, Ishchemia ↑ stroke, CV events, diabetes in age > 60

Alpha Blockers Prostatism Increased HF and CV events

Sequential Monotherapy

• Largest benefit with initial low dose• Higher doses with marginal increased benefit

and increase AEs• Normalization with one drug in 30-50% of

patients with mild HTN• If not responsive to one, 50% chance or

response to another

Comparison of Two Drug Regimens: ACCOMPLISH

• 11, 506 patients• Randomized to benez + HCTZ or amlodipine

Jamerson. NEJM. 2008.

Blood Pressure Control Achieved: ACCOMPLISH

Jamerson. NEJM. 2008.

ACCOMPLISH: ACE-I and CCB Was Superior

Jamerson. NEJM. 2008.

Combination Therapy

• Long acting dihydropyridine + ACE-I/ARB• Consider stopping thiazide

Strategy for HTN Management

Libby. Braunwald’s Heart Disease. 2007.

Thiazides• Inhibits Na absorption in

DCT -> short term reduction in plasma volume

• Vasodilation long term• Adverse effects

– Erectile dysfunction– Hyperuricemia/gout– Hypo Na/K/Mg– Inc gluc or cholesterol– Sexual/sleep dysfunction

• Less effective with GFR <30

Libby. Braunwald’s Heart Disease. 2007.

Other Diuretics• Loop diuretics

– Useful in volume overload states

– Renal dysfunction• Aldo antagonists

– Hyperaldo• Amiloride

– K Sparing• Adverse effects

– Dig and Li toxicity– Inhibited by NSAIDS

Beta Antagonists

• Reduction in heart rate, contractility, cardiac output

• Reduction in renin release

• Initial drop in cardiac output, long term reduction in peripheral vascular resistance

Libby. Braunwald’s Heart Disease. 2007.

Calcium Channel Blockers

• Inhibit entry of calcium into smooth muscle through L-type channels

• DHP vs Non-DHP• Non-DHP:

contrainidcations– AV block– LV dysfunction

Epstein. NEJM, 1982.

ACE-Inhibitors or Angiotensin Receptor Blockers

• Inhibit angiotensin II or block its receptor

• Adverse effects– Hyperkalemia– Angioedema– Cough (4-10%)– Renal dysfunction

Zaman. Nature Reviews, 2002.