Presented by Annie Ingram, MSN, NP-C  is the chronic elevation in that, long term, causes end- organ damage, and increases morbidity and mortality. It occurs due to the abnormal functioning of the arterial pressure related to the central nervous system, renin- angiotensin-aldosterone system, endothelial dysfunction, genetics, and environmental factors. Hypertension in the most common primary diagnosis in America, estimating 35 million office visits per year

The National Health and Nutrition Examination Survey estimates that 50 million or more Americans have hypertension Hypertension affects half of people age 60-69, and ¾ of people aged 70 and greater

Worldwide hypertension is estimated to be 1 billion people, with approximately 7.1 million deaths per year related to hypertension The Framingham heart study found that those with normal BP at age 55 have a 90% risk of developing hypertension in their lifetime

The World Health Organization reports that hypertension causes 62% of cerebrovascular disease and 49% of ischemic heart disease It is estimated that 30% of adults are unaware that they have hypertension, 40% with hypertension are not on medications, and 2/3 of individuals with hypertension are not controlled to BP <140/90

For people age 40-70, for every 20mmHg increase in systolic BP or 10mmHg increase in diastolic BP, there is a doubled risk of The higher the BP, the greater the risk of stroke, heart attack, heart failure, and kidney disease

Estimations state that for people with stage 1 hypertension, sustaining a 12mmHg reduction in SBP over 10 years will prevent 1 death in 11 people Antihypertensive therapy is associated with reductions in MI of approximately 20-25%, stroke 35-40%, and heart failure approximately 50%

Recent data suggests that the majority of people with hypertension with require two or more antihypertensive medications to achieve goal The pathophysiology of hypertension involves cardiac output, peripheral vascular resistance, the renin- angiotensin-aldosterone system, and the autonomic nervous system  To maintain a normal blood pressure, a balance of cardiac output and peripheral vascular resistance must be maintained. Most patients with primary hypertension have a normal cardiac output, but a raised peripheral resistance. Peripheral vascular resistance is determined by small , the walls of which contain smooth muscle cells. Contraction of these cells is thought to be related to a rise in intracellular calcium concentration. This may explain the vasodilatory effects of medications that block the calcium channels. Prolonged smooth muscle constriction causes thickening of the arteriolar vessel, leading to a rise in peripheral vascular resistance.

 The renin-angiotensin system is probably the most important endocrine system that affects blood pressure control. Renin is secreted from the juxtaglomerular apparatus of the kidney in response to glomerular underperfusion or a reduced salt intake. It is also released in response to stimulation from the sympathetic nervous system.  Renin is responsible for converting renin substrate (angiotensinogen) to angiotensin I, a physiologically inactive substance which is rapidly converted to angiotensin II by angiotensin converting enzyme. Angiotensin II is a potent vasoconstrictor, thus a rise in blood pressure is seen. In addition it stimulates the release of aldosterone from the adrenal gland, which results in a further rise in blood pressure related to sodium and water retention.

Sympathetic nervous system stimulation can cause both arteriolar constriction and arteriolar dilatation. Thus the autonomic nervous system has an important role in maintaining a normal blood pressure. It is also important in the mediation of short- term changes in blood pressure in response to stress and physical exercise.

Most likely, hypertension is related to an interaction between the autonomic nervous system and the renin-angiotensin system, together with other factors such as sodium, circulating volume, and genetics.  Normal - < 120/80 mm Hg  Pre-hypertension - 120-139/80-89 mm Hg  Hypertension Stage I - 140-159/90-99 mm Hg  Hypertension Stage II - >or= 160/100 mm Hg The diagnosis of hypertension should be made from at least 2 blood pressure readings one to two weeks apart

Patients should not smoke or consume caffeine for at least two hours before blood pressure measurement. The blood pressure should be measured in both arms, and the higher reading should be used Ambulatory blood pressure monitoring is an important tool if “white coat” hypertension is suspected, which occurs in about 15% of the population. Normal ambulatory blood pressure for awake periods is <135/85, asleep periods <120/70, and average over 24 hours of <130/80.

I have diagnosed hypertension… now what do I do??? past known blood pressure readings family history past or current symptoms or diagnosis of heart disease, CKD, asthma, COPD, diabetes, dislipidemia, or sleep apnea smoking history physical activity or inactivity excessive alcohol, , or sodium intake all medications currently prescribed or over-the-counter Risk factors for hypertension include:  family history  race (most common in blacks)  stress  obesity  a high diet in saturated or sodium  tobacco use  sedentary lifestyle  aging may result from:  renal  primary hyperaldestoronism  Cushing’s syndrome  thyroid, pituitary, or parathyroid dysfunction  coarctation of the aorta  pregnancy  neurologic disorders  use of hormonal contraceptives, cocaine, or some medications  Clozapine  Corticosteroids  Haemopoietic agents (darbepoetin, epoetin)  Immunomodifiers (cyclosporin, tacrolimus)  Leflunomide  Monoamine oxidase inhibitors: reversible  Non-steroidal anti-inflammatory drugs  Oral contraceptives  Oral decongestants (e.g. pseudoephedrine)  Sibutramine  Stimulants (dexamphetamine sulfate, methylphenidate hydrochloride)  Venlafaxine (dose-related)  Rebound hypertension may occur following abrupt withdrawal of the following: • bromocriptine • clonidine  American mistletoe  Angel’s trumpet  Butcher’s broom  Caffeine-containing products  (e.g. guarana, black tea, cola  nut, green tea, mate)  Ephedra (ma huang)  Gentian  Ginger preparations  Ginseng preparations  Licorice  Melatonin  Peyote  Phenylalanine  Sage  St John’s wort  Appropriate BP measurement  An optic fundi exam  A BMI calculation  Pulse rate, rhythm, and character  Jugular venous pulse and pressure  Ascultation for carotid, abdominal, and femoral bruits  Palpation of the thyroid gland  Evidence of cardiac enlargement (displaced apex, extra heart sounds)

 Crackles or wheezing in the lungs  Exam of the abdomen for enlarged kidneys, masses, or pulsations  Palpation of lower extremity pulses  Assessment for pedal edema  A neurologic assessment  ECG Urinalysis Blood glucose GFR Serum potassium, hemaglobin, and calcium Lipid panel Urine albumin and creatinine

The goal of antihypertensive treatment is to reduce cardiovascular and renal morbidity and mortality. Therefore the goal BP should be <140/90 for healthy adults, or <130/80 for those with diabetes or renal disease.

 Weight reduction in those overweight Adopting a DASH diet Lowering dietary sodium intake Increasing physical activity Smoking cessation Moderating alcohol consumption  The DASH (Dietary Approaches to Stop Hypertension) involves reducing dietary sodium and eating a variety of foods rich in nutrients that help lower blood pressure, such as potassium, calcium and magnesium.  It centers around eating whole grains, fruits, vegetables, and low-fat dairy items.  A 1600mg sodium DASH diet has been shown to be similar in its antihypertensive effects to single drug therapy.

 Regular physical activity has a strong cardioprotective effect. Regular aerobic exercise can lower SBP by an average of 4mmHg and DBP by 2.5mmHg. The recommended amount of activity is at least 30 minutes of moderate-intensity physical activity 3-5 days per week.

 For persons who are overweight, every 1% reduction in body weight lowers systolic BP by an average of 1mmHg. Weight loss of 10kg can reduce SBP by 6-10mmHg.

 Moderate to heavy alcohol intake can increase blood pressure, therefore in these patients, limiting alcohol consumption can substantially lower blood pressure. Alcohol intake should be limited to a maximun of 2 drinks per day for men, and 1 drink per day for women, with at least 2 alcohol free days per week.

 Initial drug choice should be based on the patient’s age, presence of associated comorbid conditions or end-organ damage, interactions with other medications, cost, and compliance.

 Most clinical trials have found Thiazide-type diuretics to be the basis of antihypertensive therapy

 In trials such a the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial, diuretics were shown to be number one in preventing the cardiovascular complications of hypertension  Diuretics are also more affordable than many other antihypertensive agents

 Thiazide-type diuretics should be used as initial therapy for most newly diagnosed hypertensive patients

 Other first-line treatment options are an ACE Inhibitor, ARB, or dihydropyridine Calcium Channel Blocker Thiazide diuretics inhibit the sodium and chloride transporter in the distal convoluted tubule of the kidney, thus increasing the excretion of sodium and water, as well as increasing potassium loss. This diuresis decreases blood volume and blood pressure. Side effects include: Hyperglycemia Hypokalemia Increased uric acid level Hypercalcemia Impotence Photosensitivity They should be used cautiously in patients at risk for developing diabetes. ACE inhibitors block the conversion of angiotensin I to angiotensin II, thus lowering peripheral arteriolar resistance and lowering blood pressure.

Side effects include:   Cough  Hyperkalemia  Headache  Dizziness  Fatigue  Nausea  Renal impairment  ACE inhibitors are contraindicated in pregnancy and bilateral renal .

ARBs are receptor antagonists that block angiotensin II receptors on blood vessels and other tissues such as the heart. These receptors stimulate vascular smooth muscle contraction. Because ARBs do not inhibit ACE, they do not cause an increase in bradykinin, which produces some of the side effects of ACE inhibitors (cough and angioedema).

Side effects include:  Hyperkalemia  Hypotension  Dizziness  Headache  Drowsiness  Diarrhea  Abnormal taste sensation (metallic or salty taste)  Rash  ARBs are contraindicated in pregnancy and bilateral .

 Calcium channel blockers work by blocking calcium channels in cardiac muscle and blood vessels. This decreases intracellular calcium leading to a reduction in muscle contraction.  In the heart, a decrease in calcium available for each beat results in a decrease in cardiac contractility, which in turn decreases cardiac output.  In blood vessels, a decrease in calcium results in less contraction of the vascular smooth muscle, causing vasodilatation and therefore decrease in peripheral vascular resistance. There are two types of Calcium Channel Blockers:

Dihydropyridine, such as amlodipine, nifedipine, and felodipine

Non-dihydropyridine, such as verapamil and diltiazem.

 Dihydropyridine CCBs reduce peripheral vascular resistance.  Side effects include dizziness, , bradycardia, headache, flushing, edema, and constipation.  Non-dihydropyridine CCBs reduce myocardial oxygen demand and reverse coronary vasospasm.  Side effects include excessive bradycardia, impaired electrical conduction (e.g., atrioventricular nodal block), and depressed contractility.

Beta-adrenergic blocking agents, or beta blockers, work by blocking the neurotransmitters norepinephrine and epinephrine (part of the sympathetic nervous system) from binding to receptors in different parts of the body. This causes smooth muscle cells to relax. There are three types of beta receptors: Beta1, located mainly in the heart and kidneys Beta2, located in the lungs, GI tract, liver, uterus, vascular smooth muscle, and skeletal muscle Beta3, located in fat cells

First generation beta blockers, such as propranolol and sotalol, are non- selective, therefore they will block the receptors of beta1 and beta2 cells.

Second generation beta blockers, such as metoprolol, are selective and will only block the receptors of beta1 cells. This reduces heart rate, force of contraction, and cardiac output.

Beta blockers also affect the production of renin, which in turn relaxes smooth muscle cells and lowers blood pressure.

Side effects of beta blockers include:  Bradycardia  Cold extremities  Fatigue  Insomnia  Dizziness  Wheezing  Digestive problems  Rash  Erectile dysfunction  They should be used cautiously in patients with asthma.

Thiazide-type diretics have been shown to slow the progression of osteoporosis. Beta Blockerss are also useful for the treatment of atrial tachyarrhythmias, migraine, thyrotoxicosis, essential tremor, and perioperative hypertension. Calcium Channel Blockers can be useful in Raynaud’s syndrome and certain arrhythmias.

Thiazide diuretics should be used cautiously in patients with a history of gout or hyponatremia.

BBs should be avoided in patients with reactive airway disease or 2nd or 3rd degree heart block. ACEIs and ARBs should not be given to women who are or may become pregnant. ACEIs should not be used in patients with a history of angioedema.

Thiazide diuretics have been associated with increased risk of new-onset diabetes, and should be used with caution in patients with glucose intolerance.  Start with the lowest recommended dose of the selected agent.  If the drug is not well tolerated, switch to a drug of a different class.  If target blood pressure is not reached, increase the first agent, or add a second agent.  Addition of a second agent should be considered when adaquate doses of the first agent have not produced adaquate results. It is better to add a second agent before maxing out a first, to decrease the likelihood of potential side effects that can be seen with higher doses.  If a patient is taking a midrange dose and is still >5-10mmHg above goal, adding a second agent is more litely to be effective than increasing the dose.  If blood pressure is still above target, increase one agent at a time. Trial each dose regimen for at leaset 6 weeks, because most drugs take at least 3-4 weeks to achieve maximum benefit.  Once a combination regimen is tolerated and doses are established, the patient could be switched to a combined preparation. If blood pressure remains elevated despite optimal doses of at least two agents after a reasonable time, consider the following potential reasons:  Non-compliance to therapy- compliance decreases as number of times per day dose increases (79% once daily, 69% BID, 65% TID, 51% QID)  Use of medications that may increase blood pressure (NSAIDS, stimulants, sympathomimetics, alcohol, contraceptives, estrogen, corticosteroids, licorice, caffeine pills, cold medicines, ephedra, ginseng, St. John’s wort)  secondary hypertension, such as CKD/obstructive uropathy, renovascular hypertension, aortic coarctation, cushing’s syndrome, thyroid disease  undiagnosed sleep apnea  undisclosed alcohol, tobacco, or drug use  undisclosed or unrecognized high sodium diets  “white coat” hypertension- for which 24 hour ambulatory blood pressure monitoring may be helpful

 Most people will require at lease two medications to control their hypertension  Guidelines recommend a combination therapy as initial therapy in high-risk hypertensive individuals, when initial BP is >20/10 above goal  Avoid: ACE Inhibitors plus potassium- sparing diuretics, Beta-blockers plus Verapamil, and ACE Inhibitors plus ARBs  ACEIs and CCBs: Lotrel (amlodipine- benazepril), Lexxel (trandolapril- verapamil)  ACEIs and diuretics: Lotensin HCT (Benazepril-HCTZ), Zestoretic (Lisinopril- HCTZ), Vaseretic (Enalapril-HCTZ)  ARBs and diuretics: Atacand HCT (Candesartan-HCTZ), Hyzaar (Losartan- HCTZ), Benicar HCT (Olmesartan-HCTZ), Diovan HCT (Valsartan-HCTZ)  BBs and diuretics: Tenoretic (Atenolol- chlorthalidone), Lopressor HCT (Metoprolol- HCTZ)  Diuretic and diuretic: Aldactazide (Aldactone-HCTZ), Maxzide (Triamterene- HCTZ) Follow-up should include monthly blood pressure checks until goal is reached. More frequent visits may be indicated for patients with stage II hypertension, or those with comorbid conditions. After blood pressure is shown to be at goal, visits can generally be moved to every 3 to 6 months Serum creatinine and potassium should be monitored 1-2 times per year Tobacco avoidance should be strongly encouraged Low dose aspirin therapy can be considered when a patient is at goal, but not sooner due to risk of hemorrhagic stroke with uncontrolled HTN  Patient motivation improves blood pressure control and should be encouraged at each visit. Home blood pressure monitoring can help patients take ownership of their hypertension, and so become motivated to adhere to treatment.  The cost of medications can also affect compliance. Wal-mart has a $4 drug list, that can be helpful for those without insurance.

 Amiloride-HCTZ 5mg-50mg  Doxazosin 1, 2, 4, 8mg tab  Atenolol-Chlorthalidone  Enalapril-HCTZ 5mg-12.5mg 100mg  Enalapril 2.5, 5, 10, 20mg tab  Atenolol 25, 50, 100mg tab  Furosemide 20, 40, 80mg tab  Benazepril 5, 10, 20, 40mg  Hydralazine 10, 25mg tab  Bisoprolol-HCTZ 2.5mg-6.25mg  Hydrochlorothiazide(HCTZ)12. tab 5mg cap  Bisoprolol-HCTZ 5mg-6.25mg  Hydrochlorothiazide (HCTZ)  Bisoprolol-HCTZ 10mg-6.25mg 25, 50mg tab tab  Indapamide 1.25, 2.5mg tab  Captopril 12.5, 25, 50, 100mg  Isosorbide Mononitrate 30,  Carvedilol 3.125, 6.25, 12.5, 60mg ER tab 25mg tab  Lisinopril-HCTZ 10mg-12.5mg  Clonidine 0.1, 0.2mg tab  Diltiazem 30, 60, 90, 120mg tab  Lisinopril-HCTZ 20mg-  Sotalol HCL 80mg tab 12.5mg  Spironolactone 25mg tab  Lisinopril-HCTZ 20mg-  Terazosin 1, 2, 5, 10mg 25mg cap  Lisinopril 2.5, 5, 10, 20mg  Triamterene-HCTZ 75mg- tab 50mg tab  Methyldopa 250mg tab  Triamterene-HCTZ  Metoprolol Tartrate 25, 37.5mg-25mg tab 50, 100mg tab  Verapamil 80, 120mg tab  Nadolol 20, 40mg tab  Prazosin HCL 1mg cap  Propranolol 10, 20, 40, 80mg

Withdrawl of antihypertensives may be considered in patients who have achieved target blood pressure at low doses and agree to continue lifestyle modifications, undergo regular blood pressure monitoring, and reinstitute antihypertensives if necessary.

Ischemic heart disease  The most common form of target organ damage associated with hypertension is Ischemic heart disease.  In patients with hypertension and stable angina, beta-blockers or long acting calcium-channel blockers are indicated.  In patients with ACS, treatment should be beta blockers and ace inhibitors, as well as nitrates.  For patients post-MI, beta blockers, ACEIs, and aldosterone antagonists have shown to be the most benificial. Aspirin and lipid therapy should also be initiated.

Heart failure  For paitents with systolic heart failure, or left ventricular dysfunction, ACEIs and BBs are recommended.  For those who are symptomatic or at end- stage heart disease, ACEIS, BBs, ARBs, aldosterone blockers, and loop diuretics are indicated.

Diabetic Hypertension  Usually a combination of two or more antihypertensives will be needed to achieve a blood pressure of <130/80.  Thiazide diuretics, BBs, ACEIs, ARBs, and CCBs have been shown to reduce Cardiovascular disease and stroke in diabetic patients.  ACEIs and ARBs have been shown to slow the progression of diabetic nephropathy and reduce albuminuria.

Chronic Kidney Disease  In patients with CKD, the goal of therapy is to slow deterioration of renal function, and prevent cardiovascular disease.  Target blood pressure in these patients is <130/80.  ACEIs and ARBs have shown to slow the progression of renal disease. A rise of as much as 35% above baseline in serum creatinine is found to be acceptable and should not cause discontinuation of therapy unless hyperkalemia develops.  With advanced renal disease, loop diuretics will also be necessary in combination with other antihypertensives.

Cerebrovascular disease  In an acute stroke, blood pressure is recommended to be maintained around 160/100 until the condition has stabilized.  A combination of thiazide-type diuretics and ACEIs have been shown to lower recurrent stroke rates.  Aggressive antihypertensive therapy appears to be safe to reinitiate 1-2 weeks after the acute event, when the patient has been deemed clinically stable. Pregnancy  Methyldopa, Beta Blockers, and vasodialators are considered to be the safest medications.  ACEIs and ARBs should not be used due to the possibility of fetal defects.  Methydopa and labetalol are the most widely used medications to treat pregnant women.

Hypertensive Emergency  Hypertensive Urgency is defined as SBP > or =180 and/or DBP >or=120 without evidence of target organ dysfunction. These patients require immidiate intervention and may need to be hospitalized.  is defined as SBP >or= 180 and/or DBP >or=120 with evidence of target organ dysfunction, such as coronary ischemia, disordered cerebral function, cerebrovascular events, pulmonary edema, and renal failure. These patients require hospitalization and immediate treatment. References

Campbell, N. Hemmelgarn, B. (2012). New recommendations for the use of ambulatory blood pressure monitoring in the diagnosis of hypertension. Canadian Medical Association Journal, 184(6), 633-634.

Corrao, G., Nicotra, F., Parodi, A, Zambon, A. (2011). Cardiovascular protection by initial and subsequent combination of antihypertensive drugs in daily life practice. Hypertension, 58(4), 566-572.

Mukherjee, D. (2012). Atherogenic vascular stiffness and hypertension: Cause or effect? The Journal of the American Medical Association, 308(9), 919-920.

Park, C., Youn, H., Chae, S. (2012). Evaluation of the dose-relationship of Amlodipine and Losartan combination in patients with . American Journal Cardiovascular Drugs, 12(1), 35-47.

References

Sever, P., Messereli, F. (2011). Hypertension management 2011: Optimal medical therapy. European Heart Journal, 32(20), 2499-2506. http://www.heartfoundation.org.au/SiteCollectionDocuments/HypertensionGuidelines2008to2010 Update.pdf Retrieved December 11, 2012 http://www.icsi.org/hypertension_4/hypertension_diagnosis_and_treatment_4.html Retrieved December 11, 2012 http://www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.pdf Retrieved December 11, 2012

1. The percentage of adults in the United States with Hypertension is:

C )30%

2. Risk factors for Hypertension include all of the following except:

D) Cancer

3. Which of the following is a potential secondary drug-induced cause of hypertension?

C) Phenylpropanolamine

4. Which of the following patients is at very high risk for cardiovascular disease and should immediately receive a medication to lower blood pressure?

C) A 68-year-old man with heart failure and a baseline blood pressure of 150/88 mm Hg

5. Which of the following would be most appropriate for a patient with hypertension who has had a myocardial infarction?

C) Metoprolol 6. Which of the following is the most appropriate blood pressure goal for a 65- year-old African-American with hypertension and no other medical problems?

A) <140/90 mm Hg

7. In order to minimize the risk of hypokalemia from diuretics, the most appropriate strategy would include:

A) limiting the dose of hydrochlorothiazide to 12.5 to 25 mg 8. In a patient with heart failure, the best combination of medications would be:

C) Lisinopril and Coreg

9. Which of the following is an appropriate agent and starting dose for a patient with uncomplicated hypertension?

A) Atenolol 25 mg once daily 10. Which drug is most likely to cause vasodilation-type side effects (headache, flushing) because it blocks the movement of calcium across smooth muscle cells?

E) Verapamil

11. When patients with renal insufficiency develop severe cough from ACE inhibitors, what would be the best alternative to provide renal protection?

C) Losartan 12. Which of the following is true concerning clonidine?

A) It has been used for smoking cessation and narcotic withdrawal.

13. Which of the following is a contraindication to enalapril?

A) Bilateral renal artery stenosis 14. What potential side effects would you mention to a patient recently started on nifedipine?

D) Leg edema

15. A 39-year-old woman with hypertension is taking HCTZ, enalapril (Vasotec), and diltiazem (Cardizem). She desires to become pregnant. The most important step would be to

D) discontinue enalapril.

16. The agent of choice for a patient with diabetes is

E) enalapril. 17. Which one of the following nondrug measures is likely to be most effective to lower blood pressure chronically?

C) Lose 10-15 pounds