hypertension1 HYPERTENSION and the use of ANTI-HYPERTENSIVES Joshua M.Crasner, DO,FACC,FACOI

hypertension2 DEFINITION the response of the left ventricle to increased peripheral resistance due to increased systemic arterial pressure

hypertension3 JNC-6 (old criteria) STAGESYSTOLIC BPDIASTOLIC BP or ≥180 or ≥ 110

hypertension4 JNC-7 Definition of HTN CATEGORYSYSTOLIC BPDIASTOLIC BP normal < 120 and < 80 Pre-HTN or Hypertension Stage or Stage 2 ≥ 160 or ≥ 100 JAMA 289; : 2003

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6 TYPES OF HYPERTENSION SYSTOLIC AND DIASTOLIC Primary(Essential, Idiopathic) Secondary Renal: Acute GN, Diabetic Nephropathy Endocrine: TSH, cortisol, calcium aortic coarctation pregnancy-induced neurologic: tumor, sleep apnea stress: surgery, burns, EtOH withdrawal,S.cell Drugs: decongestants, antidepressants, OCP

hypertension7 RED FLAGS FOR SECONDARY HYPERTENSION Abdominal bruit: renal artery stenosis Palps,HA,pallor,perspiration: pheochromocytoma Obesity,moon face,purple striae: Cushing’s Abd mass: polycystic kidney,hydroneph Obesity,hypersomnolence: OSAS Agitation, sweating: cocaine, ethanol Hypokalemia: hyperaldosteronism Hypercalcemia: hyperparathyroidism

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9 TYPES OF HYPERTENSION SYSTOLIC Increased Cardiac Output : –aortic regurgitation, PDA/AVF, thyrotoxicosis, Paget’s disease Aortic rigidity

hypertension10 HYPERTENSION WITH AGE Systolic BP rises continuously with age Diastolic rises up to age 50, then falls Pulse pressure then widens with age Vasan, et al.JAMA, 2002; 287(8):

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hypertension13 ETIOLOGY HTN “essential” > 90 % Genetics, environment African descent and elderly have low renin; more sensitive to salt and volume non-African/young pts. have high renin

hypertension14 ESSENTIAL HYPERTENSION Most common HBP( > 90 %)--multifactorial increased peripheral resistance perpetuates the process of high blood pressure and all of its secondary effects structural hypertrophy giving rise to smooth muscle hypercontractility pressure varies throughout the day major risk factor for coronary, renal, and cerebrovascular disease (50% of all USA deaths) leading cause of doctor’s visit carries prognostic value: 16X increased risk 40 y.o. smokes

hypertension15 TARGET ORGAN DAMAGE Left Ventricular Hypertrophy End result of hypertensive heart disease structural adaptation to pressure overload initially adaptive and later pathologic mass > g/m2

hypertension16 TARGET ORGAN DAMAGE LEFT VENTRICULAR HYPERTROPHY Eccentric: isotonic exercise, increased volume load mass/volume ratio low Concentric: isometric exercise, increased pressure load mass/volume ratio high degree does not correlate with blood pressure Prognostic value: sudden cardiac death, ischemia/decreased coronary flow, CHF, increased vascular tone Who? –Increases with age –2-3 more times likely in obese –athletes –African descent higher LV mass response

hypertension17 TARGET ORGAN DAMAGE LEFT VENTRICULAR DYSFUNCTION Diastolic dysfunction –reduced rate rapid early filling/incr.atrial portion –correlates with degree of LVH –CHF Systolic dysfunction –less common as BP tighter controlled –myofibril degeneration/lysis –occurs late –CHF: will predispose to other causes(CAD, valve)

hypertension18 TARGET ORGAN DAMAGE CORONARY ARTERY DISEASE HTN accelerates progression of CAD increased oxygen demand increased silent MI/sudden cardiac death/infarct size(33%) ischemia caused by diastolic dysfunction oxygen demand is different than for epicardial occlusion

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hypertension20 TARGET ORGAN DAMAGE RENAL DISEASE Increased intraglomerular hypertension loss of concentrating ability –nocturia –reduced creatinine clearance –albuminuria salt and water retention HTN is the leading cause of ESRD nephrosclerosis

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hypertension22 TARGET ORGAN DAMAGE CEREBRO/PERIPHERAL VASCULAR DISEASE major risk factor for CVA/TIA similar physiology

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hypertension25 DETECTION OF HYPERTENSIVE HEART DISEASE PHYSICAL EXAM ELECTROCARDIOGRAM 2-D ECHOCARDIOGRAM STRESS TESTING LAB TESTING

hypertension26 PHYSICAL EXAM Forceful sustained apical impulse early S4 gallop early S3 gallop later LV dilation: laterally displaced apical impulse

hypertension27 BP MEASUREMENT Patient seated/back supported/feet on floor Should rest 5 minutes prior Arm at heart level No recent caffeine, tobacco, cocaine Take medications as directed Cuff size important orthostatics

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hypertension29 ELECTROCARDIOGRAM All patients should have as baseline no LVH on ECG does not mean no LVH in vivo the presence of LVH suggests target end organ damage…….poorer prognosis Left atrial enlargement? Conduction abnormalities

hypertension30 2D ECHOCARDIOGRAM Wall thickness chamber size systolic and diastolic function valve pathology

hypertension31 2-D Echo (Parasternal Long Axis) RV IVS LV Mitral Valve Aortic Valve The parasternal long axis view is obtained from the left sternal border. Displayed in this view:  RV  IVS  LV  Aortic Valve (AV)  Mitral Valve (MV)  Left Atrium (LA) LV Apex Left Atrium

hypertension32 Motion Mode (M-Mode) In M-Mode, the motion of all cardiac structures along the sample line is displayed over time (left to right) Systole and Diastole are evident by the decrease in LV cavity size. The motion of the IVS and LV Posterior wall are synchronous in contraction.

hypertension33 DIASTOLIC DYSFUNCTION

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hypertension38 DIASTOLIC DYSFUNCTION

hypertension39 DIASTOLIC DYSFUNCTION

hypertension40 DIASTOLIC DYSFUNCTION

hypertension41 STRESS TESTING Detects patients at increased risk silent ischemia/subclinical CAD hypertensive response portends poor prognosis

hypertension42 LAB TESTING Urine analysis Chemistry panel Cholesterol CBC Endocrine Drug screen?

hypertension43 GOALS AT FIRST EVAL. Diagnose secondary or remediable causes Uncover target organ damage Identify coexisting risk factors that could affect treatment plans

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hypertension45 TREATMENT OF HYPERTENSION Prevent development/progression of LVH JNC-7: 120/80 optimal reduction of target organ damage: brain, heart, kidney, eyes pharmacologic Lifestyle modifications

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hypertension47 LIFESTYLE MODIFICATION Weight reductionMaintain BMI kg/m² 5-10 mm Hg / 10 kg loss DASH dietFruits, veggies, low fats 8-14 mm Hg Sodium restrict2.4 g sodium/day 2-8 mm Hg Physical activityAerobic 30min/day 4-9 mm Hg Alcohol1 oz.Etoh2-4 mm Hg

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hypertension51 PHARMACOLOGIC TREATMENT OF HYPERTENSION inhibitors of the renin-angiotensin system a must in diabetic, renal, or CAD patients identify co-morbidities (slide 19) ACE inhibitors/A-II blockers Calcium channel blockers Beta blockers diuretics alpha blockers central agents vasodilators

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hypertension54 PHARMACOLOGIC TREATMENT Heart failure: ACEi, A-II, diuretics, B-blockers Diabetes: ACEi, A-II CAD/post-MI: B-blockers, ACEi, +/- calcium blocker Systolic HTN: ACEi/A-II with diuretic, B- blocker, calcium blocker Pregnancy: labetalol, methydopa, calcium blocker Prostate enlargement: alpha blocker Renal disease: ACEi or A-II blocker »SJHG Heartbeat “Update on Hypertension”; July/Aug ‘02 »Mario Maiese,DO,FACC,FACOI

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ACCOMPLISH: A Novel Hypertension Trial Traditional approach to hypertension management: –Initiate monotherapy then sequentially add medications to achieve target BP ACCOMPLISH: –Initiate single tablet combination therapy in high- risk hypertension –Specific combinations may confer target organ protection in addition to their BP-lowering effects

Duke Clinical Research Institute/ Brigham and Women’s Hospital Marc A. Pfeffer Scott D. Solomon Kenneth Mahaffey Kenneth Jamerson Eric Velazquez Victor Shi, Novartis Jitendra Gupte, Novartis CentralClinicalLabs Henry R. Black, Chair Lloyd Fisher, Ph.D., Statistician Suzanne Oparil, M.D., Member Stevo Julius, M.D., Sc.D., Member Lars H. Lindholm, Member Novartis Trial Team Investigational Sites Novartis Vendors ACCOMPLISH Organizational Structure Operations Committee DSMB Kenneth Jamerson, Chair George L. Bakris Björn Dahlöf Bertram Pitt Eric Velazquez Michael A. Weber Steering Committee Sverre Kjeldsen Jan Östergren Jaakko Tuomilehto Hans Ibsen William C. Cushman Richard Devereux Brent Egan Barry M. Massie Shawna D. Nesbitt Elizabeth Ofili Vasilios Papademetriou Matthew R. Weir Jackson T. Wright, Jr. Independent Statistician Tom Greene Endpoint Committee Endpoint Coordinating Center Executive Committee

Primary Endpoint and Components Composite CV mortality/morbidity Cardiovascular mortality Non-fatal MI Non-fatal stroke Hospitalization for unstable angina Coronary revascularization procedure Resuscitated sudden death Incidence of adjudicated primary endpoints, based upon cut-off analysis date 3/24/2008 (Intent-to-treat population) Risk Ratio (95%) Favors CCB / ACEI Favors ACEI / HCTZ 0.80 (0.72–0.90) 0.81 ( ) 0.81 ( ) 0.87 ( ) 0.74 ( ) 0.85 ( ) 1.75 ( ) INTERIM RESULTS Mar 08

Conclusions ACCOMPLISH achieved exceptional BP control with combination therapy providing a new option for cardiovascular risk reduction to millions of patients with hypertension. The results of ACCOMPLISH provide compelling evidence for initial combination therapy with ACEI / CCB and challenge current diuretic-based guidelines.

hypertension65 10 KEY POINTS “white coat” HTN contributes to vascular risk BMI may be the strongest predictor of pre-HTN (SBP and/or DBP 80-89) with 10-15% per 1 kg/m2 Pre-HTN carries increased CV risk Arterial stiffness independent risk marker for target organ damage, cognition, CV and renal events When SBP > 220 and/or DBP > 120, 15-20% reduction first day Excess EtOH, OSAS/sleep deprivation, salt all contribute »JACC; 51:

hypertension66 REVIEW POINTS Familiarity with target end-organ damage What is ideal BP? Causes of secondary hypertension Ideal agents for condition(s) Familiarity with treatment options