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Update on the Management of Hypertention. Timothy A. Denton, M.D. Divisions of Cardiology and Cardiothoracic Surgery Cedars-Sinai Medical Center Los Angeles. Outline. Role of BP Etiology of HTN Evaluation JNC VI. Why do we need blood pressure?. Why do we need blood pressure?.
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Update on the Management of Hypertention Timothy A. Denton, M.D. Divisions of Cardiology and Cardiothoracic Surgery Cedars-Sinai Medical Center Los Angeles
Outline • Role of BP • Etiology of HTN • Evaluation • JNC VI
Why do we need blood pressure? • Get blood to the scalp • Distribute flow quickly
Classification of HTN • Primary • Secondary
Physiology of HTN • Primary Hypertension • ? Central / peripheral adrenergic • ? renal • ? hormonal • ? vascular
Physiology of HTN • Secondary • Wide Pulse Pressure Aortic compliance Stroke volume • Normal Pulse Pressure Renal Endocrine Neurogenic Misc
Etiology of HTN Normal Pulse Pressure • Renal Chronic pyelonephritis Glomerulonephritis Polycystic kidney Renovascular Other renal • Endocrine Oral contraceptives Adrenocortical (Cushing, hyperaldo, 17 hydroxylase, 11-hydroxylase) Pheochromocytoma Myxedema Acromegaly • Neurogenic Psychogenic Familial dysautonomia Polyneuritis Increased intracranial pressure Spinal cord section • Misc Coarctation Intravascular volume Polyarteritis nodosa Hypercalcemia Acute intermittent porphyria Pre-eclampsia
Etiology of HTN Wide Pulse Pressure • Decreased aortic compliance • Increased stroke volume AI Thyrotoxicosis Hyperkinetic heart syndrome Fever AV fistula / PDA
Epidemiology of HTN Harrison’s Principles of Internal Medicine, 12th Edition
JNC VI Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure JNC VI -- Arch Int Med 1997;157:2413
Classification of HTN JNC VI -- Arch Int Med 157:2413, 1997
Risk Classification JNC VI -- Arch Int Med 157:2413, 1997
Undertreatment of Hypertension Berlowitz, NEJM 1998;339:1957
Undertreatment of Hypertension Berlowitz, NEJM 1998;339:1957
Undertreatment of Hypertension Berlowitz, NEJM 1998;339:1957
Classes of Anti-Hypertensives (1999 PDR) Adrenergic blockers Alpha/Beta adrenergic blockers ACE inhibitors ACE + Ca blockers ACE + diuretics ARB’s ARB’s with diuretics Beta blockers Beta blockers with diuretics Calcium blockers Diuretics Rauwolfia derivatives Vasodilators
Preparations of Anti-Hypertensives by Class (1999 PDR) Adrenergic blockers Alpha/Beta adrenergic blockers ACE inhibitors ACE + Ca blockers ACE + diuretics ARB’s ARB’s with diuretics Beta blockers Beta blockers with diuretics Calcium blockers Diuretics Rauwolfia derivatives Vasodilators 6 5 11 4 5 4 2 15 6 25 24 2 18 Total = 127
Special Considerations In African-Americans: -- low probability of success with Beta blockers or ACE or ARB’s -- higher probability of success with diuretics or Ca blockers
If you have not achieved goal, you must change your therapy
You push a medication’s dose to EFFECT or SIDE EFFECT or maximal recommended dose
“The committee recognizes that the responsible clinician’s judgment of the individual patient’s needs remains paramount.” JNC VI -- Arch Int Med 1997;157:2413
Compelling Indications JNC VI -- Arch Int Med 157:2413, 1997
Pressure/Volume Relation Pressure = 150 mmHg Pressure = 120 mmHg Fluid Flux Fluid Flux Vasculature
Combination Drugs: A Different Animal • Beta blocker + diuretic • ACE + diuretic • ACE + calcium blocker • ARB + diuretic • Diuretic + diuretic • “other” + diuretic
HOPE Trial Heart Outcomes Prevention Evaluation Study NEJM 2000;342:145-153
Backgroud • Activation of renin-angiotensin- aldosterone system may be a mortality risk factor • ACE therapy can reduce MI’s Circ 1994;90:2056, Lancet 1992;340:1173,JNC VI NEJM 1992;327:669 HOPE Trial, NEJM 2000;342:145-153
Design • Prospective, randomized • Two-by-two factorial ramipril + vitamin E • 9,541 patients HOPE Trial, NEJM 2000;342:145-153
Inclusion Criteria • > 55 years old • CAD or CVA or PVD or DM + (HTN or high LDL or low HDL or cigarettes or microalbuminuria) HOPE Trial, NEJM 2000;342:145-153
Run-In • 10,576 patients • ramipril 2.5 mg qd 7-10 days then placebo 10-14 days • 1,035 excluded (noncompliance, side effects, creat, K, withdrawal) HOPE Trial, NEJM 2000;342:145-153
Follow-up • First follow-up 1 month • Subsequent follow-ups q 6 months • Scheduled for 5 years HOPE Trial, NEJM 2000;342:145-153
Outcome Measures • Primary endpoint: CV death or MI or CVA • Secondary endpoints: All cause mortality Revascularization Hospitalization for UA or CHF DM complications Worsening angina Cardiac Arrest any CHF UA with ECG changes DM development HOPE Trial, NEJM 2000;342:145-153
Results HOPE Trial, NEJM 2000;342:145-153
Angiotensinogen Inactive products Renin Inhibitor Renin increase nitric oxide, prostacyclin (improved endothelial function ? anti-atherosclerotic?) non-ACE alternative pathways (chymase, cathepsin G, chymostatin ATII generation) Angiotensin I ACE Inhibitor ACE ACE hypotension Angiotensin II Bradykinin ? angioedema AT1 receptor Inhibitor cough Vaso- constriction Vaso- dilatation Vasopressin Endothelin-1 Adapted, Bonn, D. Lancet 1998;352:378
Results HOPE Trial, NEJM 2000;342:145-153
Results HOPE Trial, NEJM 2000;342:145-153
Results HOPE Trial, NEJM 2000;342:145-153
Results HOPE Trial, NEJM 2000;342:145-153
Results HOPE Trial, NEJM 2000;342:145-153
Results HOPE Trial, NEJM 2000;342:145-153
Results HOPE Trial, NEJM 2000;342:145-153
Summary • Ramipril decreased CV mortality MI and CVA all-cause mortality Revascularization rates DM complications CHF Worsening angina New onset DM • Effects were see in all groups except those without cardiovascular disease HOPE Trial, NEJM 2000;342:145-153
Implications • We have a new standard of care • All patients with vascular disease should be considered for ACE inhibition (e.g., ramipril)
How to Initiate Therapy • Initial Evaluation • Good history and physical exam (note comorbidities) • Take BP in both arms • Take BP at least 2 min apart and average them • Take BP at least on two separate office visits • Look for end-organ damage • Stratify patient • Initiate drug therapy based on comorbidity and risk
Evidence of End-organ Damage Eyes spasm AV nicking exudates edema Lungs rales Neck bruits JVD thyroid Abd bruits masses Heart S4 S3 Murmur Labs Chem I CBC Lipids ECG Ext pulses edema
Long-term Therapy The patient must become expert on their own blood pressure
Write each BP down in a log • 1x / day • 2x / day • 3x / day • 3x / week • etc…..