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The Pharmacists’ Role in Treating Hypertension Thomas Owens, MD Saint Francis University CERMUSA Objectives 1. Enhance your understanding of hypertension to include cardiovascular risks, management, and goals for individual patients 2. Review and discuss the current pharmacotherapy standards of care for hypertension 3. Describe the pharmacist’s role in counseling patients on hypertensive medications Hypertension >140/90 mm Hg • United States: 65 million adults • Risk factors include: – Stroke, myocardial infarction, heart failure, peripheral vascular disease, aortic dissection, chronic renal failure • Hypertension price tag: $59.7 billion Wexler & Feldman, 2005 Hypertension • Typical onset – second decade of life • Primary Hypertension – identifiable behaviors • Secondary Hypertension – more discrete Cecil, 2004 Ethnic Groups • African Americans – 43% female & 39% male – Ratio 1:3 – Increase in sodium sensitivity? • Caucasians – 28% female – 29% male • Mexican Americans – Ratio 1:4 or 1:5 Cecil, 2004 DASH Diet Dietary Sodium Intake Salt Hypothesis? - Strong genetic underpinning ADA, 2005 Metabolic Syndrome • Risk of Hypertension increases with BMI • Obesity accounts for 50% to 60% of new cases of hypertension Cecil, 2004 Potential Causes of Hypertension • Expanded plasma volume plus sympathetic over activity – Peripheral vasoconstriction – Renal salt retention – Renal water retention Sleep Apnea www.sleepconsultants.com, 2007 Cecil, 2004 Blood Pressure Equation Blood Pressure = Cardiac Output x Peripheral Vascular Resistance Some pharmacologic agents lower Most pharmacologic agents lower Some pharmacologic agents lower both Cecil, 2004 Genetics of High BP • Sympathetic upregulation leads to a cascade of events – Peripheral vascular resistance • Genetic factors Discoveryedge.mayo.com, 2007; ADA, 2003 – 30% of cases – 2x as likely if parents have hypertension Systolic & Diastolic ?? • What is more important? – Depends on age • Live long enough almost all develop systolic hypertension 120 80 Cecil, 2004 systolic diastolic Age Dependant Rise in BP (Whelton & Rocella, 1995) Framingham Study (age: 50-79) (Khan, Wong, Larson, & Levy, 1999) Systolic Hypertension • Decreased distensibility of large arteries • Majority of uncontrolled hypertension – Due to focus on diastolic BP Cecil, 2004 Risk of cardiovascular mortality by systolic BP (National High Blood Pressure Education Program Working Group, 1993) Hypertension Study Results • Hypertension is excess of 140/90 mm Hg • Studies found – Increase risk when above 115 mm Hg systolic or 75 mm Hg diastolic – High normal BP had twice increased risk for cardio disease – More studies are needed to fully understand Cecil, 2004 The Silent Killer • 1/3 of adults do not know they have hypertension • Hypertension: 60% are treated – 45% of treated remain uncontrolled Despite over 75 different antihypertensive agents in 9 different classes! Cecil, 2004 Reclassification of BP Stages • Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC) Blood Pressure (mm Hg) Classification <120/80 Normal 120-139/80-89 Pre-hypertension ≥140/90 Hypertension – Pharmacotherapy not recommended 140-159/90-99 Stage 1 – Lifestyle modification recommended! 160-179/100-109 Stage 2 • New category “pre-hypertension” Cecil, 2004; JNC, 2007 JNC Drug Therapy Recommendations ≥130/80 (w/ heart and kidney disease or diabetes mellitus) recommendation (healthy) Blood Pressure (mm Hg) Classification <120/80 Normal 120-139/80-89 Pre-hypertension ≥140/90 Hypertension 140-159/90-99 Stage 1 160-179/100-109 Stage 2 JNC, 2007 Modest reduction in BP = big benefits !! • Decrease 5 mm Hg decreases risks – Small changes can have a big difference • Results of studies – Systolic surge 34 mm Hg = 3x increase of stroke – Systolic ≥135 mm Hg = 74% increase of cardio event Blood Pressure (mm Hg) Cardiovascular Risk Exceeds 115/75 Increases Each increase of 20/10 mm Hg Doubles Cecil, 2004; JNC, 2007 Clinical Presentation • No specific signs or symptoms • Possible symptoms – Occipital headache, dizziness, tinnitus, dimmed vision, palpitations, fatigue • Physical Exam – May reveal evidence Cecil, 2004 Hypertensive Retinopathy Grades of hypertensive retinopathy shown (Forbes, Jackson, 2003) Electrocardiogram (ECG or EKG) GOOD (Normal) BAD (Antero-Septal MI) physiol.umin.jp/cardiovasc, 2007 Counseling Patients: Proper BP Readings • At least 30 minutes before NO – Caffeine, decongestants, oral contraceptives, alcohol, tobacco • Sit down for at least 5 minutes Arm above heart level Falsely low blood pressure reading Arm below heart level Falsely elevated blood pressure reading Loose cuff or bladder = Falsely elevated blood pressure reading Cecil, 2004; ADA, 2005 Counseling Patients: Proper Fit of BP Cuff Length of bladder of the cuff at least 80% circumference of arm Bladder of cuff at least 40% circumference of arm Place the center of the bladder over the brachial artery Pump until radial pulse disappears, then continue for additional 30 mm Hg Help Patients Understand: White Coat Hypertension • Anxiety of going to doctor office raises BP – Recommend self-monitoring • Daytime: >135/85 mm Hg • Nighttime: >120/70 mm Hg • 24 hr: >130/80 mm Hg • Follow patients every 6 months for possible progression to persistent hypertension Cecil, 2004 Closely Monitor Medications with High-Risk Patients Cecil, 2004 Counseling Patients: Causes of Organ Damage Major Risk Factors Target Organ Damage Cigarette smoking Heart Obesity (BMI >30 kg/m2) * Left ventricular hypertrophy Physical inactivity Angina pectoris Dyslipidemia * Myocardial infarction Diabetes mellitus * Coronary revascularization Age Heart Failure Brain Stroke Men: Older than 55 Women: Older than 65 Family History of pre-mature CVD Men: Older than 55 Women: Older than 65 Transient ischemic attack Hypertensive nephrosclerosis GFR <60 mL/min Any chronic disease GFR <60 mL/min Urine protein >150 mg/24hr Urine protein >150 mg/24hr Retinopathy Peripheral atherosclerosis •Components of metabolic syndrome (The JNC 7 Report. JAMA 2003) Counseling Patients: Treatment Risk Group Mild Risk Treatment Lifestyle modification Free of CVD Low Risk Pre-hypertension or Stage 1 or 2 Moderate Risk Pre & Stage 1: Lifestyle modification Stage 2: Lifestyle modification and medications Lifestyle modification and medications 1 or more cardio risk factors High Risk Evident organ damage, diabetes, renal insufficiency Lifestyle modification and medications JNC, 2005 SUSPECTED DIAGNOSIS CLINICAL FEATURES DIAGNOSTIC TESTING Renal parenchymal hypertension Elevated serum creatinine or abnormal urinalysis 24-Hour urine creatinine and protein, renal ultrasound Renovascular disease New elevation in serum creatinine, marked elevation in serum creatinine with initiation of ACEI or ARB, refractory hypertension, flash pulmonary edema, abdominal bruit Captopril renogram, duplex Doppler sonography, magnetic resonance or CT angiogram, invasive angiogram Coarctation of the aorta Arm pulses > leg pulses, arm BP > leg BP, chest bruits, rib notching on chest radiograph MRI, aortogram Primary aldosteronism Hypokalemia, refractory hypertension Plasma renin and aldosterone, 24-hour urine potassium, 24-hour urine aldosterone and potassium after salt loading, adrenal CT scan Cushing's syndrome Truncal obesity, purple striae, muscle weakness Plasma cortisol, urine cortisol after dexamethasone, adrenal CT scan Pheochromocytoma Spells of tachycardia, headache, diaphoresis, pallor, and anxiety Plasma metanephrine and normetanephrine, 24-hour urine catechols, adrenal CT scan Obstructive sleep apnea Loud snoring, daytime somnolence, obesity Sleep study ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; BP = blood pressure; CT = computed tomography. (Williams & Wilkins, 2002) Counseling Patients: Lifelong Treatment • Objective: reduce BP and metabolic abnormalities • Pharmacotherapy & lifestyle modification – – – – – Reduce sodium intake Weight loss Exercise Moderating alcohol Reduce systolic BP by 21 to 55 mm Hg Cecil, 2004 Counseling Patients: Dietary Changes • Losing only 10 to 12 lbs lowers BP by 10/5 mm Hg • Reduce daily salt – 10 to 6 grams • Teach patients to read food labels • DASH Diet – www.nhlbi.nih.gov/health/public/heart/dash Cecil, 2004 Counseling Patients: Health Behaviors Lifestyle modification Recommendation Range of systolic blood pressure reduction (mm Hg) Weight loss Maintain a normal body weight based on BMI 5–20 Dietary Approaches Diet high in fruits and vegetables, and reduced fat 8–14 Low sodium diet Less than 6 grams 2–8 Exercise 30 min of aerobic activity at least 4 d/wk 4–9 Moderate Alcohol consumption 2 drinks or less per day for men, and 1 drink or less per day for women 2–4 JNC, 2005 Counseling Patients: Helpful Resources Barriers to Successful Health Behavior Modifications • Lack of education • Lack of access to safe places to exercise • Added salt in prepared foods and restaurant meals • Higher cost of foods low in salt Patient self-management is realistic and feasible! Cecil, 2004 Pharmacologic Therapy • Scientific proof lowering BP reduces organ damage • Certain classes of antihypertensive agents exert organoprotective effects – Not all medications equal Cecil, 2004; JNC, 2005 Major Challenges for Science 1. Identify the key geneenvironment interactions 2. Eliminate the patient and medical provider barriers ADA, 2003 Counseling Patients: Target Blood Pressure • Most patients below 140/90 mm Hg • Patients w/ diabetes or chronic disease 130/80 mm Hg • Help patients self-monitor BP – 1/3 do not know they are hypertensive • Research studies on targeting BP Cecil, 2004 Improve Hypertension Control Rates 1. Titrating blood pressure medications to achieve target goals 2. Most patients require 2 or 3 antihypertensive medications 3. Patient compliance with multi-drug regimens ADA, 2005 Patient Compliance and Quality of Life • Hypertension requires lifelong treatment • Medications can produce side effects – Men often concerned with sexual dysfunction • Patients with controlled BP, rate a significantly higher quality of life Cecil, 2004 Patient Compliance Principles 1. Titrating medical therapy based on home readings 2. Long-acting preparations w/ once daily dosing 3. Low dose combinations of medications from different drug classes 4. Fixed-dose combinations to reduce overall number of pills JNC, 2005 Drug Therapy • Old method: high-dose monotherapy • Recent studies (ex. ALLHAT) – At least 2 medications of different classes to treat mild hypertension – 3 or 4 different medications to treat more difficult cases • Thiazide-type antihypertensive medications costeffective • Initial treatment: – Beta blockers, Angiotensin-converting enzyme (ACE) inhibitors, Angiotensin receptor blockers, Calcium Cecil, 2004 antagonists Stage 2 Drug Therapy • JNC recommends: – 2 drug combination – Additional medications needed for each 10 mm Hg of systolic BP above goal – Great majority should include low-dose diuretic • High-risk conditions (heart failure/diabetes) – Angiotensin-converting enzyme inhibitors (ACE-Is) – Angiotensin receptor blockers (ARBs) Cecil, 2004 Cardio Events in Hypertensive Patients Verdecchia, Carin, Circo,2001 Left Ventricular Hypertrophy www.medem.com, 2007 Counseling Patients: Contradictions & Side Effects Considerations For Individualizing Antihypertensive Drug Therapy Hypertensive Sub-Populations • Hypertensive patients with nephrosclerosis • Diabetic hypertensive patients • Hypertensive patients with coronary artery disease • Isolated systolic hypertension in older persons • Hypertensive disorders of women – Oral contraceptives – Pregnancy Cecil, 2004 Hypertension Case Study How would we modify his treatment since he did not change his health behaviors (and he is diabetic)? 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