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Hypertension: A Look at JNC 8

Author: Raymond Lengel

 

Hypertension: A Look at JNC 8 | Copyright © 2014 CEUFast.com


 

Purpose

This continuing education course will supply an overview and update of hypertension including its definition, complications, risk factors, evaluation, etiology and treatments options with a special focus on the eighth report of Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC).

 

Objectives
   
1. Discuss the incidence and prevalence of hypertension
   
2. Identify three body systems affected by long term hypertension
   
3. Differentiate between primary and secondary hypertension
   
4. Discuss the role of diet, exercise and other lifestyle choices in the management of hypertension
   
5. Discuss the role of five medication classes in the management of hypertension
   
6. List three changes made in treatment guidelines between JNC 7 and JNC 8

Hypertension is a critical risk factor for many cardiovascular diseases including coronary heart disease, congestive heart failure, stroke and peripheral vascular disease. In the United States, sixty-seven million Americans or 31% of adults have high blood pressure and only 47% of those with diagnosed hypertension have their hypertension under control. In addition, about 33 percent of Americans have prehypertension making about two in three American adults having blood pressure out of the ideal range (Center for Disease Control, 2014).

Hypertension is costly disease, both in money and effects. High blood pressure costs Americans 47.5 billion dollars annually. Seventy percent of adults who have their first heart attack or develop congestive heart failure have hypertension and 80 percent of those who have their first stroke have high blood pressure (Center for Disease Control, 2014).

In addition to its risk on many cardiovascular diseases, hypertension can negatively impact the outcome of other diseases. Those who have diabetes and hypertension are at higher risk of poor outcomes in regard to cardiovascular disease and kidney failure. High blood pressure accounts for 25% of all cases of kidney failure. In 2009 hypertension was the primary diagnosis for 139,910 patients with kidney failure (US Renal Data System, 2011).

 

What is Elevated Blood Pressure?

Defining high blood pressure is the first step in understanding the condition. The blood pressure reading is an average of two or more readings at two separate visits after an initial screening.

Blood pressure is reported as a systolic reading over a diastolic reading. Table one describes the classification of each blood pressure based on the reading. The patient is given the classification of the highest number obtained.

Table 1: Blood Pressure Classifications

Classification Reading expressed as mm Hg
Normal Below 120/80
Prehypertension 120-139/80-89
Stage 1 140-159/90-99
Stage 2 160/100 or higher

For example, if the average of two separate readings is 145/101 mm Hg, the patient is classified as having stage 2 hypertension because his diastolic reading is classified as stage 2; even though the systolic reading is classified as stage one.

Generally, the lower the blood pressure, the better. For every 20/10 mm Hg above 115/75 mm Hg the cardiovascular disease risk doubles (Chobanian, Bakris, Black, Cushman, Green, Izzo, Jones, Materson, Oparil, Wright & Roccella, 2003).

Those with diabetes mellitus (DM) and chronic renal insufficiency (CRI) are at higher risk for complications. Prior guidelines set blood pressure goals lower for those with DM or CRI, but the newest guidelines (JNC 8) recommend that those with DM and/or CRI should have a blood pressure goal of 140/90 mm Hg or lower.

Treatment guidelines suggest that those with prehypertension are at higher risk of progression to hypertension and management with lifestyles changes is important. Currently, it is not recommended to implement pharmacological interventions in those with prehypertension. Some individuals with diabetes and chronic renal insufficiency may be candidates for drug therapy when their blood pressure in the prehypertension category. Close monitoring of all patients with prehypertension should occur so if they progress to hypertension, they can be caught early.

Most individuals with hypertension have primary (essential) hypertension. Primary hypertension is high blood pressure that does not have an identifiable cause. This accounts for about 95% of the cases of hypertension. Those with secondary hypertension have high blood pressure caused by other conditions. Common causes of secondary hypertension include: hyperaldosteronism, renal artery stenosis, polycystic kidney disease, Cushing syndrome, brain tumors, pregnancy, sleep apnea and some medications.

Case Study One

A 54-year-old white woman presents to her primary care doctor's office with a chief complaint of bilateral knee pain that is minimally responsive to naproxen, which she has been taking regularly for the last six months. Her past medical history is positive for dyslipidemia, glucose intolerance and arthritis. Her physical exam is largely unremarkable except for a body weight of 228 pounds and a body mass index of 36.8 which classifies her as obese. She also has crepitus noted in both knees. Her blood pressure reading is 168/96 mm Hg with a heart rate of 88 beats per minute.

The doctor diagnosed her with bilateral knee arthritis, but she also has elevated blood pressure. She was diagnosed with stage 2 hypertension because here systolic reading was above 160 mm Hg.

Her physician encouraged her to lose weight and referred her to a registered dietitian to help her improve eating habits. He encouraged exercise and recommended a water aerobics class 3-5 times a week.

He drew some baseline labs which demonstrated that she had stage 3B renal insufficiency (creatinine 1.5 and a glomerular filtration rate of 36). She was also noted to have a fasting blood sugar of 178 mg/dl which was confirmed on a follow up lab draw and she was consequently given the diagnosis of diabetes. The patient was started on medications to manage her diabetes.

He started her on a low dose combination of hydrochlorothiazide and lisinopril and was asked to be seen back in the office in 4 weeks.

With the help of the dietitian and the exercise program the patient lost 50 pounds over a one year period. Her knee pain significantly improved and now is managed with occasional acetaminophen. She was able to wean off the hydrochlorothiazide, but continued treatment with lisinopril and her blood pressure remained consistently at 118/72 mm Hg. After the weight loss and exercise program she was able to wean off all of her diabetes medications.

 

Pathophysiology

Having an understanding of the physiological mechanisms that affect blood pressure will help the nurse understand how blood pressure occurs and how it is treated. The pathophysiology of secondary hypertension is well understood but the pathophysiology of essential hypertension is not well understood. It is beyond the scope of this article to discuss the pathophysiology of the numerous causes of secondary hypertension.

Blood pressure is determined by the degree of systemic vascular resistance and the cardiac output. Anything that affects either of these two factors has a direct effect on blood pressure. Below is a listing of factors that affect systemic vascular resistance and cardiac output.

  Genetics multiple genes are involved in the pathophysiology of hypertension.
   
  The autonomic nervous system controls many factors (cardiac output, vascular resistance and retention of fluid) associated with blood pressure.
   
  The renin-angiotensin-aldosterone system is involved in regulating vascular resistance as well as fluid and salt levels. Many blood pressure medications target this system in the control of hypertension.
   
  The endothelium is the lining of the blood vessel and it is involved in the production of substances such as nitric oxide and endothelin which are involved with blood pressure.
   
  Other factors that may affect blood pressure include: circulating blood volume and blood viscosity.

 

Hypertension Management

A primary goal of hypertension management involves preventing target organ damage. Target organ damage manifests over time as blood pressure does damage to the body.

It is debated if the systolic or diastolic reading poses a greater risk. While both numbers need to be addressed, in those over the age of 50 a systolic reading more than 140 mm Hg is a larger cardiovascular risk than an elevated diastolic blood pressure (Madhur, 2014).

Individuals with established chronic disease are at greatest risk for end organ damage. Unfortunately, many with established chronic disease have poorly controlled blood pressure. Almost 75% of American adults with chronic diseases (coronary heart disease, diabetes, stroke and congestive heart failure) are also afflicted with hypertension. Most of these individuals are being treated, but are not at goal. Only about one-third to one-half of those with chronic disease has controlled blood pressure (Wong, Lopez, L'Italien, G., Chen, Kline & Franklin, 2007).

Prolonged hypertension can lead to direct damage to the heart. Enlargement of the left ventricle is a result of the left ventricle having to work hard overtime to overcome the resistance of the blood vessels in hypertension. Those who have an enlarged left ventricle are at increased risk for death. This occurs for multiple reasons. Those with enlargement of the left ventricle are more commonly affected with dysrhythmias and sudden death. Those with an enlarged left ventricle may also be affected with increased resistance in the coronary arteries. Managing hypertension reduces the risk of cardiovascular mortality (Madhur, 2014).

Hypertension also increases the risk of stroke. Elevated blood pressure places excess strain on the blood vessel wall, which can cause them to thicken and increases their risk for rupture. Elevated blood pressure increases the risk of embolism. Consequently, uncontrolled hypertension increases the risk of ischemic and hemorrhagic stroke.

Hypertension increases the risk of end-stage renal disease (ESRD). Overtime, higher blood pressure increases the risk of ESRD. In the United States, the two most common causes of ESRD are diabetes and hypertension. Those who are afflicted with both conditions are at increased risk for complications and the blood pressure (and blood sugar in diabetics) needs to be aggressively managed.

Hypertension may also be linked to memory loss and dementia. Individuals with hypertension and cognitive impairment have a higher risk of progression to dementia than those without hypertension (Oveisgharan & Hackhinski, 2010). Individuals with hypertension may see improvement in memory when hypertension is treated with diet and exercise. In a recent study, individuals who ate the DASH (Dietary Approaches to Stop Hypertension) diet and participated in a weight management program showed improvement in executive function-memory-learning and psychomotor speed (Smith, Blumenthal, Babyak, Craignhead, Welsh-Bohmer, Browndyke, Strauman & Sherwood, 2010).

 

Who is at risk?

Certain groups of people are at higher risk for hypertension than others. Adult African Americans have the highest rates of hypertension with 43.0 percent of men and 45.7 percent of women being afflicted. White adult males are afflicted at a rate of 33.9 percent and women at 31.3 percent. Mexican Americans are afflicted at a rate of 27.8 percent in men 28.9 percent in women (Center for Disease Control, 2014).

The risk of hypertension increases with age. The prevalence of men with hypertension between the ages of 20-34 is 11.1 percent and 6.8 percent for women while the prevalence of hypertension is 66.7 percent for men and 78.5 percent for women in those over the age of 74 (Center for Disease Control, 2014).

Other factors may help predict who is likely to suffer from hypertension. Common risk factors include: physical inactivity, obesity, diabetes, smoking, dyslipidemia, family history of heart disease, older age (women over 64 and men over 54), microalbuminuria and reduced glomerular filtration rate (GFR) (<60 mL/min).

Recent evidence suggests that there may be an association between blood pressure and vitamin D status. Scientists are unclear of the link between vitamin D and blood pressure and more research is needed before recommendations to use vitamin D to prevent or treat hypertension are made (Tamez, Kalim & Thadhani, 2013).

 

Work up

Hypertension is called the silent killer, because it typically does damage without causing symptoms. Primary hypertension typically presents without symptoms. Individuals with very severe hypertension may present with visual changes, headaches, nausea, vomiting or chest pain.

Hypertension is typically diagnosed after screening. After an elevated blood pressure reading is noted on a screening, the average of two or more measurements on at least two separate visits over a few weeks is needed to diagnose hypertension.

When measuring blood pressure, make sure that the patient has been sitting quietly for 5 minutes prior to taking the blood pressure. Ideally, the blood pressure should be checked in each arm and one leg sitting, standing and lying down. It is important to utilize the correct size of blood pressure cuff. If a small cuff is used on a larger arm the reading will be falsely elevated and if a large cuff is used on a small arm the reading will be falsely low.

Part of the work up for hypertension should include home blood pressure monitoring. It will minimize limitations of office based blood pressure monitoring. Many individuals suffer from white coat hypertension, where there is an excessive rise of blood pressure in the doctor's office due to anxiety, and measuring blood pressure in the home setting on a day-to-day basis offers advantages in more accurate diagnosis of hypertension. The machine that is used must be validated. Measurements should be taken in morning and evening and those with cardiac dysrhythmia including atrial fibrillation should not use home monitoring as a reliable method to detect hypertension.

After hypertension is diagnosed, it needs to be evaluated. A critical aspect in the evaluation of hypertension is to rule out and/or determine the extent of target organ damage (TOD). TOD is damage to major organs that are fed by the circulatory system. It may include damage to the heart, brain, eyes and kidneys. It is typically only noted after years of untreated hypertension. Unfortunately, sometimes hypertension goes undiagnosed for years and at the initial diagnosis TOD is noted.

The physical exam can help diagnose TOD. Evaluating the eyes with a fundoscope can pick hypertensive retinopathy. The heart should be evaluated for any evidence of enlargement of the left ventricle. This can be indicated by a displaced apical impulse or the presence of an S4 heart sound. A neurological exam may help pick up any evidence of cerebrovascular atherosclerosis or damage. Findings that indicate neurological compromise include a carotid bruit or a focal neurological defect. No specific exam finding can help detect early kidney damage secondary to hypertension and to detect renal insufficiency the use of laboratory assessment should be done.

The next step in the work up of hypertension is to assess the other risk factors. This includes an assessment of lipid levels, tobacco use, physical activity levels, body weight, central adiposity, glucose tolerance and dietary habits.

The workup should also include ruling out secondary causes of hypertension. The physical exam may provide some clues to a secondary cause of hypertension. Below are a few points about the work-up that may indicate a secondary cause of hypertension.

  A bruit in the upper abdomen may point to renal artery stenosis.
   
  A reduced or absent femoral pulse or a reduced blood pressure in the leg (when compared to the upper extremity) may suggest a coarctation of the aorta.
   
  Pheochromocytoma may be suggested by labile blood pressure, sweating and palpitations.
   
  Obstructive sleep apnea should be considered in an obese patient who complains of feeling tired. In obstructive sleep apnea it is common for a bed partner to reports snoring and periods of apnea.
   
  Low energy, temperature intolerance, slow or fast heart rates and sweating may suggest thyroid dysfunction.
   
  Hyperaldosteronism may be present if there is weakness and lab tests show low potassium levels.
   
  Hyperparathyroidism may be present in an individual with kidney stones.
   
  Subclavian artery stenosis is indicated by a mismatch in blood pressure between the arms.

Other causes of secondary hypertension include: polycystic kidney disease, renovascular hypertension, urinary tract obstruction, Cushing syndrome, primary hyperaldosteronism, brain tumor, pregnancy induced hypertension and some medications such as alcohol, cocaine and decongestants.

 

Lab work

Laboratory evaluation is a critical aspect in the management of hypertension. Lab work is done for multiple reasons including: to rule out a secondary cause of hypertension, to evaluate other risk factors and to monitor medication therapy. Common blood tests include:

  Complete blood count
   
  Kidney function tests
   
  Electrolytes
   
  Uric acid level
   
  Thyroid panel to test of hyper or hypothyroidism
   
  Glucose level
   
  Lipid panel

More specialized tests may be indicated in certain situations. Testing for microalbuminuria in diabetics will further define the presence of diabetic nephropathy. Measuring aldosterone and plasma renin could help define primary hyperaldosteronism. Primary hyperaldosteronism may also present with low potassium levels and metabolic alkalosis. Urine catecholamines and fractionated metanephrines can help detect pheochromocytoma.

With the exceptions of electrocardiograms (EKGs), imaging studies are not typically done in routine cases of hypertension, but can be used to evaluate select patients for TOD or a secondary cause of hypertension. Echocardiogram can help detect left ventricle hypertrophy. Computed tomography angiography or magnetic resonance angiography can be used to identify renovascular stenosis. Captopril radionuclide scanning is done to evaluate for renovascular hypertension.

Individuals who have labile blood pressure are candidates for ambulatory blood pressure monitoring. This can also be useful for those with white coat hypertension.

 

Treatments

The first step in the treatment of hypertension is to implement lifestyle modifications. Exercise will help prevent and treat high blood pressure. Exercise has a direct effect on lowering blood pressure as well as an indirect effect on blood pressure management as it aids in weight loss. Aerobic exercise should be performed most days of the week for at least 30 minutes. Exercise may lower blood pressure 4-9 mm Hg (Chobanian, et. al, 2003).

If overweight or obese, weight loss is another important intervention to aid in blood pressure control. Those who are more than 10% over their ideal body weight may notice a reduction of 5-20 mm Hg if there is a loss of weight of 10 kg (Madhur, 2014).

Dietary changes are highly effective measures to aid in blood pressure control. The DASH diet (Dietary Approaches to Stop Hypertension) is widely recognized as an important part in the management of hypertension. The diet entails a generous amount of fruits and vegetables and low fat dairy. This diet may lower blood pressure by 8-14 mm Hg (Svetkey, Moore, Simons-Morton, Appel, Bray & Sacks, 2001). Not only does the DASH diet lower blood pressure, but diets similar to it lowers the risk of cardiovascular disease, coronary heart disease, stroke and heart failure by 20, 21, 19 and 29 percent respectively (Salehi-Abargouei, Maghsoudi, Shirani & Azadbakht, 2013).

Minimizing sodium intake is another key to managing high blood pressure. Eating less than 2.4 grams of sodium (or 6 grams of sodium chloride) every day is the goal. Eating less than this amount of sodium will reduce the blood pressure 2-8 mm Hg (Chobanian, et. al, 2003).

Other minerals are also important to blood pressure control. Minerals linked to blood pressure include: potassium, calcium and magnesium. Eating a diet high in fruits, vegetables, whole grains, legumes and low fat dairy will help maintain an adequate potassium, calcium and magnesium level.

The DASH diet also recommends consuming low-fat dairy products. One study showed that children who eat 2 or more servings of dairy each day while in preschool had improved blood pressure readings throughout adolescence (Moore, Singer, Bradlee, Djousse, Proctor, Cupples, & Ellison, 2005). Other groups also benefit from dairy intake. In adults, there is an inverse association between low fat fluid dairy food (milk) and other low fat dairy food and elevated blood pressure (Ralston, Lee, Truby, Palermo & Walker, 2012).

A diet high in fat, especially saturated fat, is not good for cardiovascular health. Little research demonstrates that reducing fat in the diet has an effect on blood pressure. Omega-3 fatty acids are known to improve cardiovascular health. One mechanism that they do this is through improvement in blood pressure (Miller, Van Elswyk & Alexander, 2014).

Controlling toxic habits are another critical element in the management of hypertension. Consuming a maximum of one ounce of ethanol a day in men and one-half of an ounce of ethanol a day in women is recommended. One ounce is equal to 24 ounces of beer, 2 ounces of 100 proof hard liquor or 10 ounces of wine. Those who consume low levels of alcohol may moderately lower blood pressure (Ronksley, Brien, Turner, Mukama & Ghali, 2011).

While it theoretically makes sense to limit caffeine intake, research does not demonstrate a strong effect of caffeine intake on blood pressure. A review of the effect of coffee on blood pressure showed an unclear link between caffeine and hypertension. This review also failed to show a link between regular coffee consumption and an elevated risk of cardiovascular disease in hypertensive subjects (Mesas, Leon-Munoz, Rodriguez-Artalejo & Lopez-Garcia, 2011).

Tobacco use may increases blood pressure. It is well known that smoking transiently increased blood pressure, but smoking cession may not have a significant effect on blood pressure. None-the-less, smoking cessation has positive effects on cardiovascular health and should be encouraged.

While stress has the potential to increase blood pressure, relaxation techniques are not likely to reduce blood pressure unless accompanied by other lifestyle modification (Raspa, 2009).

 

Medications

Some individuals with hypertension need to implement more than lifestyle changes to achieve blood pressure goals. Many medications are available for the management of hypertension and the act of selecting an appropriate agent for a given individual is a combination of art and science. The next section will provide a discussion to help the nurse get an understanding of medications used in the management of hypertension.

General strategy

The decision to treat with medications depends on the overall risk and the degree of hypertension. The new JNC 8 guidelines, which were published in December of 2013, displace the prior report of JNC 7; utilize fewer antihypertensive agents; and have higher blood pressure goals when compared to JNC 7. Those over the age of 60, without chronic kidney disease or diabetes, should have a goal blood pressure of less than 150/90 mm Hg. Goal blood pressure for those between 18 and 59 years-old and those over 60 years-old with chronic kidney disease and/or diabetes should have a blood pressure goal of less than 140/90 mm Hg. Generally, when blood pressure is consistently above these goals, pharmacotherapy is recommended (James, Oparil, Carter, Cushman, Dennison-Himmelfarb, Handler, Lackland, LeFevre, MacKenzie, Ogedegbe, Smith, Svetkey, Taler, Townsend, Wright, Narva, & Ortiz, 2014).

Medications are typically not indicated until stage one hypertension. For most with prehypertension drug therapy is not indicated and implementing lifestyle modifications are critical because those with prehypertension are at high risk of developing hypertension.

First-line treatment of hypertension should include either a thiazide-type diuretic, calcium channel blocker (CCB), angiotensin converting enzyme inhibitor (ACE-I) or an angiotensin II receptor blocker (ARB) for the nonblack population. For the black population, the use of a thiazide type diuretic or a calcium channel blocker should be used as initial therapy (James, et. al, 2014).

For those with stage II hypertension a combination of two drugs is often needed to get blood pressure to goal. An agent that affects the renin-angiotensin system (ACE-I or ARB) combined with a thiazide diuretic or a calcium channel blocker may be considered. The combination of a thiazide type diuretic along with a calcium channel blocker may also be used.

Later line medications to manage hypertension include: beta-blockers (e.g., metoprolol), loop diuretics (e.g., furosemide), aldosterone antagonists (e.g., spironolactone), alpha blockers (e.g., doxazosin), alpha 1/beta-blockers (e.g., labetalol), central alpha 2 adrenergic agonists (e.g., clonidine), direct vasodilators (e.g., hydralazine), and peripherally acting adrenergic antagonists (e.g., reserpine).

This section will look at some specific agents that are used to treat high blood pressure. It will discuss in some detail common medications used and briefly touch on agents that are not commonly used.

Diuretics

Diuretics initially work by off-loading excess fluid, but over time a decrease in the peripheral vascular resistance is noted. Diuretics are available in multiple classes including thiazide, loop and potassium sparing.

Thiazide diuretics - hydrochlorothiazide (Esidrix, HydroDIURIL, Microzide), chlorthalidone and indapamide (Lozol) - are used as a first line medication to manage blood pressure in those with normal renal function. In those with renal insufficiency - loop diuretics, furosemide (Lasix), torsemide (Demadex), and bumetanide (Bumex) - are more effective. Loop diuretics are more potent and will off-load more fluid. Loop diuretics are more commonly associated with dehydration and electrolyte disturbances. Potassium sparing diuretics - triamterene (Dyzide) - are less likely to lead to low potassium levels, but are more expensive.

Thiazide diuretics are recommended as first line agents for uncomplicated hypertension (James, et. al, 2014). They are often considered as part of the initial combination for management of blood pressure 20/10 mm Hg over goal. In addition, thiazide diuretics are recommended for those with heart failure, high risk for cardiovascular disease, diabetes and for secondary stroke prevention.

Side effects of diuretics include: dehydration, orthostatic hypotension, electrolyte imbalance, an increase risk of a gout flare, photosensitivity, hyperglycemia and gastrointestinal upset. Because of these side effects there is an increase risk of falls especially in the older adult. The younger patient who is treated with thiazide diuretics may have an increased risk of diabetes.

Table 2: Selected Interactions with Diuretics

Drug Interaction
Digoxin Increased risk of digoxin toxicity
ACE-Is and ARBs Increased risk of hypotension
Non-steroidal anti-inflammatory drugs Reduced efficacy of the diuretic
High sodium diet Increased risk of hypokalemia

Diuretic therapy strongly influences the risk of developing heart failure. Those with risk factors for heart failure including hypertension benefit from early intervention of hypertension with diuretic therapy (Davis, Kostis & Simpson, 2008).

Angiotensin Converting Enzyme Inhibitors

Angiotensin-converting enzyme inhibitors (ACE-Is) reduce angiotensin II levels by blocking the conversion of angiotensin I to angiotensin II. They also increase bradykinin secretion and reduce aldosterone secretion. Angiotensin II leads to blood vessel constriction.

ACE-Is effect the renin-angiotensin system (RAS). Recent evidence suggests that RAS inhibition may help prevent end organ damage above and beyond their effect on blood pressure (Weir, 2007).

ACE-Is are popular drugs in the treatment of hypertension and are being used more commonly for uncomplicated hypertension. Compelling indications for ACE-Is include those with diabetes, congestive heart failure, renal insufficiency, after a heart attack, individuals at high risk for atherosclerotic heart disease and for secondary stroke prevention.

Common side effect with ACE-Is include: cough, hypotension, dizziness, rash, hyperkalemia and angioedema. Those with bilateral renovascular disease should not use ACE-Is as they may lead to hyperkalemia. They should also not be used in pregnancy as they may lead to birth defects.

Common drugs in this class include: captopril (Capoten), enalapril (Vasotec), lisinopril (Zestril) and ramipril (Altace).

Angiotensin II Receptor Blockers

Angiotensin II receptor blockers (ARBs) have a similar mechanism of action when compared to ACE-Is. These medications block angiotensin II at the receptors in the blood vessel and reduce the effect of angiotensin II; this inhibits vessel constriction and reduces blood pressure. Similar to the ACE-Is the use of ARBs may reduce the risk of end organ damage above their effect on blood pressure control.

Common drugs in this class include: candesartan (Atacand), lorsartan (Cozaar), eprosartan (Teveten), valsartan (Diovan) and olmesartan (Benicar).

These drugs carry similar benefits and side effects as ACE-Is. One advantage of ARBs over ACE-Is is that they have less propensity to cause cough and are commonly substituted in those who need an ACE-Is, but are intolerant of the cough as a side effect. Other side effects include: hyperkalemia, fatigue, hypotension, dizziness, headache and angioedema.

These medications can be used to treat uncomplicated hypertension, but compelling indications for ARBs include: diabetes, renal failure and heart failure particularly in those who are intolerant of ACE-Is.

The combination of ACE-Is and ARBs together are not recommended (James, et. al, 2014).

Calcium Channel Blockers

Calcium channel blockers (CCBs) lower blood pressure by decreasing the force of contraction of the heart, slowing the electrical conduction in the heart (thereby lowering heart rate) and causing vasodilatation. CCBs are classified as nondihydropyridines and dihydropyridines.

CCBs lower death rates and morbidity associated with high blood pressure. A recent study showed that amlodipine lowered the risk of total cardiovascular events and all-cause mortality compared with other anti-hypertensive agents. It was suggested that CCBs are beneficial for high-risk cardiac patients (Lee, Choi, Park, Ko, & Lee, 2014). CCBs are often used as add on therapy with diuretics, ACE-Is or ARBs. Compelling indications for CCBs include: high risk for cardiovascular disease and diabetes. They can also be used as first line therapy for isolated systolic hypertension (the dihydropyridine class) in the elderly and in black patients.

As a class CCBs should not be used in heart block or failure. Side effects vary by individual drug but common side effects include headache, edema, fatigue, dizziness, low blood pressure, constipation, GI upset and bradycardia.

The nondihydropyridine CCBs are verapamil (Calan, Isoptin) and diltiazem (Cardizem). The nondihydropyridine class of medications cause more bradycardia and reduced pumping action of the heart when compared to the dihydropyridine class. They should not be used in severe heart failure, 2nd or 3rd degree AV block or sick sinus syndrome. They should be used cautiously in those with impaired kidney or liver problems.

The dihydropyridine CCBs - amlodipine (Norvasc), felodipine (Plendil), nicardipine (Cardene), and nifedipine (Procardia) - cause more vasodilatation than the nondihydropyridine class. They are more likely to lead to a reflex tachycardia.

Other drugs

Beta blockers

Beta blockers (BBs) reduce blood pressure through reducing cardiac output as well as slightly reducing renin levels. JNC 8 has relegated them to a second line treatment for hypertension (James, et. al, 2014). Recent research has shown a trend that other agents calcium channel blockers, ACE-I, ARBs and thiazide diuretics have better outcomes when compared to BBs. Specifically, BBs have not shown any significant effect on mortality (Wiysonge, Bradley, Volmink, Mayosi, Mbewu & Opie, 2012).

Examples of BBs include atenolol (Tenormin), metoprolol (Lopressor, Toprol XL) and propranolol (Inderal, Inderal LA, InnoPran XL). As a class beta blockers have similar effects, but there are some differences between drugs.

Metoprolol and propranolol are more likely to lead to sedation and depression as they more readily cross into the blood-brain barrier. In general, beta blockers may cause bronchospasm and should be used cautiously in those with reactive airway disease, but nonselective agents such as nadolol (Corgard) and propranolol (Inderal) are more likely to cause bronchospasm.

As a class, side effects may include bradycardia, hypotension, fatigue, nausea, dizziness, depression, bronchospasm, heart failure and sleep disturbances.

Beta blockers are often used in those with atherosclerotic heart disease, prior myocardial infarction and compensated heart failure. Even though BBs may be helpful in those with diabetes, they need to be used with caution as they have the potential to mask the signs and symptoms of hypoglycemia.

BB may work less effectively in the older adult because older adults are often affected by vascular resistance as the cause of their high blood pressure and BB work primarily through lowering cardiac output. Vasodilatory beta blockers may be most effective in the older adult such as carvedilol and labetalol.

Some evidence suggests that the use of atenolol once a day increases the risk for stroke more than other medications used for hypertension (Warmack, Estes, Heldenbrand & Franks, 2009). The same study also indicates that there are more heart attacks and higher death rates with once a day atenolol (but not statistically significant) when compared to other agents used to treat hypertension.

Aldosterone antagonists

Aldosterone antagonists - spironolactone (Aldactone) and eplerenone (Inspra) - block aldosterone, induce smooth muscle relaxation and reduce sodium reabsorption. They are contraindicated in renal failure, anuria and hyperkalemia. They should be used cautiously in those with renal or liver impairment. Common side effects include hyperkalemia, nausea, headache, rash and gynecomastia. Eplerenone is pregnancy category B and is a selective aldosterone-receptor antagonist and therefore does not cause gynecomastia in men. This agent should not be used in those with type 2 diabetes and microalbuminuria or a creatinine clearance below 50 ml/min.

There are a variety of other medications that are used much less frequently in the treatment of hypertension. They are often used as treatment when other agents have failed or another medication is needed to gain control of high blood pressure. Robust data is not available showing their efficacy and high incidence of side effects are two common reasons that these medications are not used often. The next section will briefly touch on a few of them.

A newer medication recently added to the armamentarium to combat hypertension is the renin inhibitor - Aliskiren (Tekturna). It blocks renin and therefore reduces the amount of angiotensin. It is dosed 150 mg every day and the dose may be increased to 300 mg. It is available as a solo agent or combined with other anti-hypertensive agents.

Alpha 1- adrenergic blockers, such as doxazosin (Cardura) and prazosin (Minipres), lead to vasodilatation of the peripheral vessels as they selectively block the postsynaptic alpha 1-adrenergic receptor. In addition to treatment of hypertension, they are also used to improve urine flow rates in men with prostatic hypertrophy. Side effects include sleepiness, dizziness, headache and fatigue. They are associated with a high incidence of dizziness and orthostatic hypotension and are linked to falls and are therefore often dosed at bedtime. The risk of syncope is highest 90 minutes after the first dose.

Central alpha agonists, which reduce blood vessel constriction, such as clonidine (Catapres), guanfacine (Tenex) and methyldopa (Aldomet), have significant side effects including sedation, dry mouth and depression. Clonidine comes in a patch form (Catapres patch) and is changed one time a week. It can be beneficial in those with compliance issues because the oral form requires three times a day dosing.

Alpha/beta-adrenergic blocking agents decrease blood pressure by blocking both alpha and beta receptor sites. Agents in this class include labetalol (Normodyne, Trandate) and Carvedilol (Coreg).

Peripheral vasodilators decrease blood pressure by relaxing blood vessels. Drugs in this class include hydralazine (Apresoline) and minoxidil (Rogaine, Loniten).

 

Old Age and Blood Pressure Treatment

Hypertension is a disease that becomes more common with old age. With the increasing numbers of older adults, it is important to understand how to treat blood pressure in the elderly. In years past, physicians have considered high blood pressure a consequence of aging. More recent data has suggested that treating blood pressure is a critical aspect of preventing cardiovascular and other complications regardless of the age.

A major recommendation of JNC 8 modifies the way blood pressure is controlled in older adults. According to JNC 7, goal blood pressure in those over 60 years-old was to treat to less than 140/90 mm Hg. According to JNC 8, individuals over 60 years-old should utilize medications to lower blood pressure to less than 150/90 mm Hg. If medications are well tolerated (no negative side effects), a lower blood pressure is reasonable (James, et. al, 2014).

Treatment in the older adult needs to not only treat blood pressure but reduce complications of hypertension including stroke and coronary heart disease. Thiazide diuretics and dihydropyridine CCB should be strongly considered as first line agents in this population. If a second drug is needed looking at the co-morbid conditions and picking an agent that targets a co-morbid condition or one of the risk factors should be considered. The use of once a day atenolol should be avoided.

Treatment guidelines for hypertension in older adults are cautious due to concerns about benefits versus risks. This problem is compounded by the fact little research is available on the management of hypertension in the older adult. Aggressive management of hypertension may increase the risk of hypotension, which will increase the risk of syncope and falls.

A recent study which used a thiazide diuretic and an ACE-I in the treatment of older adults (mean age of 83.6 years-old) with hypertension was conducted that resulted in a significant reduction in blood pressure and complications of hypertension. The actively treated group had lowered their blood pressure by 15/8.6 mm Hg. The study was cut short after 1.8 years because of a reduction in death rates by 21% in the group that was treated. The study also showed a 39% reduction in fatal stroke and a 64% reduction in heart failure. Despite concern of adverse affects of therapy, few negative effects were noted (Beckett, Peters, Fletcher, Staessen, Liu & Dumitrascu, 2008).

 

Compelling Indications

As part of the workup of hypertension, it is important to determine other co-morbidities in the individual with hypertension because they can influence which medications to use. Those with certain diseases will derive extra benefits from the addition of blood pressure medications in regard to the comorbid condition. For example, those with heart failure and systolic hypertension will see in improvement in not only their blood pressure but their heart failure with the addition of an ACE-I. Table three highlights some medications that should be considered when certain conditions are present.

Table 3: Conditions that Warrant Consideration for Certain Medications

Drug When to Consider
Thiazide Diuretics Isolated systolic hypertension in the older adult, heart failure, high risk for cardiovascular disease, diabetes mellitus and recurrent stroke prevention
Angiotensin Converting Enzyme Inhibitors Chronic renal disease, heart failure, diabetes mellitus, post-myocardial infarction and recurrent stroke prevention
Angiotensin Receptor Blockers Diabetes, chronic renal disease and heart failure
Beta Blockers After a heart attack, high risk for cardiovascular disease, heart failure and diabetes mellitus
Calcium Channel Blockers Isolated systolic hypertension in the older adult, high risk cardiovascular disease and diabetes; Dihydropyridine calcium channel blockers as additive therapy in chronic renal insufficiency
Aldosterone antagonist Heart failure and after a heart attack

 

Combination therapy

Those who suffer from blood pressure more than 20/10 mm Hg over goal should be considered for combination therapy. One major concern with combination therapy is the potential for a large drop in blood pressure and resultant hypotension, especially in those who have not been on medications before.

To improve compliance, some medications are combined into one pill. Some examples include: Diovan HCT combines valsartan and hydrochlorothiazide, Exforge combines amlodipine and valsartan; Lotrel combines amlodipine and benazepril; and Vaseretic combines enalapril and hydrochlorothiazide.

Certain medications work well together and others do not. Below is a list of medications that are frequently combined together.

  Diuretics with most other medications
   
  ACE-I or ARB and a calcium channel blocker
   
  Dihydropyridine calcium channel blocker and a beta blocker (but not a nondihydropyridine CCB)
   
  Thiazide diuretic and a potassium-sparing diuretic

Agents that do not work well together include:

  Beta blocker and alpha1-blocker
   
  Beta blocker with a nondihydropyridine CCB (verapamil/diltiazem) may lead to heart block or bradycardia
   
  ACE-I and an ARB

The combination of an ACE-I and a CCB may be the most effective combination. A recent study compared the combination of an ACE-I and diuretic versus an ACE-I plus a CCB. The ACE-I/CCB combination was more effective than ACE-I/diuretic in lowering cardiovascular events in high risk patients (Bakris, Briasoulis, Dahlof, Jamerson, Weber, Kelly, Hester, Hua, Zappe & Pitt, 2013).).

 

Resistant Hypertension

Individuals who are on three or more separate classes of medications to control blood pressure and are not at goal are considered to have resistant hypertension (Madhur, 2014). In order to be classified as resistant, each agent should be prescribed at the optimal dose and one of the drugs should be a diuretic.

Resistant hypertension is more common in older adults and in those with certain medical conditions such as diabetes, chronic kidney disease and obesity. Resistant hypertension is more commonly an uncontrolled systolic reading than a diastolic reading (Williams, Lindhom & Sever, 2008).

Many things cause resistant hypertension. A common cause of resistant hypertension is inadequate treatment (not giving the right combination of drugs or giving an inadequate dose). A patient not taking the medications as prescribed is another common cause of resistant hypertension. An undiagnosed secondary cause of hypertension should be considered when resistant hypertension is present. White coat hypertension should also be considered.

Pseudo hypertension may occur in older patients with thick calcified arteries which lead to a falsely elevated blood pressure. This often requires intra-arterial pressure to assess the actual blood pressure. The use of certain substances can also contribute to resistant hypertension. These may include alcohol, cocaine, nicotine, amphetamines and certain prescription drugs including oral contraception, antidepressants and nonsteroidal anti-inflammatory drugs.

Excessive fluid may contribute to resistant hypertension. This may occur for many reasons including:

  Eating a diet high in salt
   
  Renal insufficiency
   
  Sodium retention
   
  Inadequate dose of a diuretic

 

Case Study 2

A 64 year-old black male is being evaluated for resistant hypertension. He was diagnosed with hypertension two and a half years ago. His past medical history includes diabetes, mild renal insufficiency, depression and a history of a transient ischemic attack. He had a stent placed in his left anterior descending artery four years ago.

He reports feeling well and specifically denies chest pain, shortness of breath, dizziness, vision changes, fatigue, weakness, urinary changes or abdominal pain. He takes all of his medicines and denies any significant side effects.

He denies the use of alcohol and quit smoking 10 years ago. He is a widower and has one son who lives in another state. He walks approximately 2 mile, 2-3 times a week and eats a diet that contains a reasonable amount of fruits and vegetables, but does not cook and eats a lot of processed and frozen food.

Physical exam reveals a blood pressure of 150/96 mm Hg and a heart rate of 68 beats per minute. He is 6' 1" and weighs 219 pounds for a body mass index of 28.9 which classifies him as overweight.

A current list of medications include: lisinopril 20 mg once a day, amlodipine 10 mg once a day, metoprolol 50 mg twice a day, aspirin 81 mg every day and simvastatin 40 mg once a day.

A recent laboratory analysis showed a serum creatinine of 1.6 mg/dl, blood urea nitrogen of 24 mg/dl, serum potassium 4.2 mEq/L and a serum sodium of 136 mEq/L. Blood sugar was 134 mg/dl and his cholesterol is within normal limits. There is no protein in the urine.

Treatment plan

A main treatment goal is to prevent any complications of hypertension. This patient is at high risk for stroke due to his history of TIAs. He is also at high risk for renal failure because of his renal insufficiency and his diabetes. Due to his diagnosis of diabetes his blood pressure goal is to get the pressure at least below 140/90 mm Hg.

The first step in the management of this patient's blood pressure is to review lifestyle modifications. He was encouraged to:
 
  Increase exercise to at least 30 minutes 4 to 5 times a week.
   
  Continue to eat fresh fruits and vegetables and to reduce the amount of processed and frozen food due to its high sodium content.
   
  Lose weight which will aid in blood pressure control.

 Medical Management

The patient is currently on three medications to manage his hypertension and his blood pressure is still not controlled. The lifestyle interventions will help, but will not likely get the patient to goal. Augmenting his blood pressure medications is likely necessary to adequately manage his blood pressure and prevent long-term complications. The one major medication class that has not been added to his regime is a diuretic. The physician adds hydrochlorothiazide 25 mg once a day. A follow up appointment is scheduled in two weeks for a blood pressure check and laboratory assessment.

At the follow up appointment his blood pressure was noted to be 128/84 mm Hg and his laboratory evaluation is stable. He reports that he has cut down on processed and frozen food, lost 4 pounds and is exercising 5 days a week.

He is asked to follow up in one month for a recheck on his blood pressure and laboratory work. At this follow up appointment his blood pressure is 124/80 mm Hg and labs are stable. He is maintaining the lifestyle interventions discussed above.

Resistant hypertension is a vexing problem. This individual does not technically suffer from resistant hypertension, because he does not meet the strict guidelines. While his blood pressure was not controlled on three medications, there was no diuretic in his regime and the doses of metoprolol and lisinopril were not maximized.

If blood pressure could not be managed on the above regime the dose of lisinopril or metoprolol could be increased or the addition of spironolactone 25 mg daily could be considered.

 

How to Prevent Hypertension

A healthy lifestyle will aid in the prevention of hypertension. To prevent hypertension maintaining a healthy body weight, engaging in regular aerobic exercise and eating a generous amount of fruits and vegetables will help. Assure that the diet contains adequate amounts of potassium, calcium and magnesium. This is accomplished by a balanced diet including recommended amounts of fruits and vegetables. Reducing sodium intake through reducing processed, frozen or canned foods - will assist in the prevention of hypertension. Eliminating or limiting alcohol intake will likely reduce the risk of hypertension. Avoiding illicit drug use particularly amphetamines, anabolic steroids and cocaine will help prevent high blood pressure.

 

Conclusion

Hypertension is a major problem that is a risk factor for many diseases and is partly responsible for much morbidity and mortality. It is a disease that typically causes no symptoms and therefore regular screening of blood pressure is critical in its diagnosis. Many treatment options are available including lifestyle changes and medications. Determining which medication to use in the treatment of hypertension is often challenging and requires some trial and error. Continued follow up is critical to assure adequate control of the blood pressure and to monitor for any complications of hypertension.

 

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