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
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
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 surgery Verrijcken. 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 Chobanian. JAMA. 2003.
Lifestyle Modification 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 MI ALLHAT. 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.