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This continuing education course will offer an overview and update of hypertension including its definition, complications, risk factors, evaluation, etiology and treatments options with attention paid to recent updates in national and international guidelines.
Hypertension is a critical risk factor for many cardiovascular diseases including coronary heart disease, congestive heart failure, stroke and peripheral vascular disease. It was estimated in 2010 that across the world 1.4 billion people had hypertension.1 In the United States, sixty-seven million Americans or 32% of adults have high blood pressure and only 54% 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.2
Hypertension is a costly disease, both in money and effects. High blood pressure costs Americans 48.6 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.2
In addition to its risk of 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 regarding cardiovascular disease and kidney failure. High blood pressure accounts for 28.4% of all cases of kidney failure.3
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 blood pressure based on the reading. The patient is given the classification of the highest number obtained.
For example, if the average of two separate readings is 135/98 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.4
The American College of Cardiology and American Heart Association (ACC/AHA) updated their guidelines in 2017. These guidelines lowered the definition of hypertension to 130/80 mg Hg or higher. It is recommended to manage blood pressure above 130/80 mg Hg or higher in patients with known cardiovascular disease or those with a 10-year risk of atherosclerotic cardiovascular disease of 10% or more. Patients without known cardiovascular disease should be treated with medication when the average blood pressure is 140/90 mm Hg or higher. The guidelines acknowledge that intensive blood pressure control reduces morbidity and mortality associated with cardiovascular disease but may be associated with more adverse events.5
The European Society of Cardiology and European Society of Hypertension (ESC/ESH) recently published a guideline that differs from the American College of Cardiology and the American Heart Association. This new guideline defines hypertension as an office-based systolic blood pressure equal to or over 140 mm Hg or diastolic blood pressure equal to or over 90 mm Hg. Compared to the American College of Cardiology/American Heart Association which uses 130/80 as a cut-off.6
In addition, the 2017 ACC/AHA guidelines suggest diagnosing hypertension when there is a 24-hour mean blood pressure of 125/75 mm Hg or above, a daytime mean of 130/80 mm Hg or above or a nighttime mean of 110/65 mm Hg or above.7
| Classification | Reading expressed as mm Hg |
|---|---|
| Normal | Below 120/80 |
| Elevated Blood Pressure | 120-129/<80 |
| Stage 1 | 130-139/80-89 |
| Stage 2 | 140/90 or higher |
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 from the Joint National Committee (The Eighth Joint National Committee {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 elevated blood pressure (but not yet hypertension) 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 elevated blood pressure. Some high-risk individuals with diabetes and chronic renal insufficiency may be candidates for drug therapy when their blood pressure in the elevated blood pressure range. Close monitoring of all patients with elevated blood pressure 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.
A 58-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 regularly been taking 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 223 pounds and a body mass index of 36.5 – which classifies her as obese. She also has crepitus noted in both knees. Her blood pressure reading is 158/84 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 140 mm Hg.
Her physician encouraged her to lose weight and referred her to a registered dietitian to help improve her eating habits. He encouraged her to 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 40 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.
Understanding 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 result on blood pressure. Below is a listing of factors that affect systemic vascular resistance and cardiac output.
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 elevated diastolic blood pressure.8 Research suggests that for younger individuals (less than 50) diastolic blood pressure is a better predictor of death.9 In older individuals, elevated systolic blood pressure or greater pulse pressure (the difference between systolic and diastolic pressure) are predictors of risk.10
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 have controlled blood pressure.11
Less aggressive blood pressure goals are more appropriate in certain populations. This includes those with multiple side effects from medications, individuals older than 75 years old with multiple medical comorbidities, those with diastolic hypertension, individuals with postural hypotension and individuals taking 3 antihypertensive medications at the maximum dose.6,7
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 over time 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.8
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.
Patients with atrial fibrillation and high blood pressure are at increased risk of ischemic stroke and that risk increases with longer durations of high blood pressure. In patients with atrial fibrillation, long-term strict blood pressure control significantly reduces the risk of ischemic stroke.12
Hypertension increases the risk of end-stage renal disease (ESRD). Over time, 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.13 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.14
Certain groups of people are at higher risk for hypertension than others. Adult African Americans have the highest rates of hypertension with 42.6 percent of men and 47.0 percent of women being afflicted. White adult males are afflicted at a rate of 33.4 percent and women at 30.7 percent. Mexican Americans are afflicted at a rate of 30.1 percent in men 28.8 percent in women.15
The risk of hypertension increases with age. The prevalence of men with hypertension between the ages of 20-34 is 9.1 percent and 6.7 percent for women while the prevalence of hypertension is 72.1 percent for men and 80.1 percent for women in those over the age of 74.15
Other factors may help predict who is likely to suffer from hypertension. Common risk factors include physical inactivity, obesity, diabetes, smoking, high alcohol consumption, dyslipidemia, black race, high sodium intake, family history of heart disease, older age (women over 64 and men over 54), microalbuminuria and reduced glomerular filtration rate (GFR) (<60 mL/min).
There has been much debate regarding the link 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.16
Stress increases the risk of hypertension. A recent study looked at the association between perceived psychological stress and hypertension among Asian Americans. Individuals with a high level of perceived stress were found to be 61% more likely to have hypertension when compared to those with low levels of perceived stress. In addition, social support was found to have beneficial effects on hypertension.17
Hypertension is called the silent killer because it typically does damage without causing symptoms. Individuals with very severe hypertension may present with visual changes, headaches, nausea, vomiting or chest pain.
Adults with normal blood pressure should have their blood pressure checked once a year. Patients with risk factors or any systolic blood pressure reading between 120 and 129 should have their blood pressure checked semiannually.
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. Individuals with a blood pressure of 180/120 mm Hg or greater can be diagnosed without confirmatory readings. In addition, individuals with blood pressures equal to or greater than 160/100 mm Hg with evidence of known target end organ damage can be diagnosed without further readings.
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 sitting, standing and lying down. It is important to utilize the correct size blood pressure cuff. Blood pressure readings between arms should be essentially the same and a discrepancy of more than 15 mm Hg indicates possible subclavian stenosis. 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.
When checking blood pressure make sure the patient’s legs are not crossed. Crossing the legs elevates blood pressure. In addition, when checking blood pressure make sure the patient has not had any recent caffeine or nicotine ingestion. Caffeine ingestion falsely elevates blood pressure above the hypertensive threshold in approximately 17% of patients with normal blood pressure.18
Part of the workup for hypertension should include home blood pressure monitoring. It will minimize the 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 at different times of the day. Those with cardiac dysrhythmia including atrial fibrillation should not use home monitoring as a reliable method to detect hypertension. When home blood pressure monitoring is used a minimum 12 measurements should be taken throughout the day over a period of one week.
Unattended automated office blood pressure monitoring is where no healthcare provider actually takes the blood pressure and multiple readings are taken. This is becoming a more popular way to check blood pressure and is more likely to reduce the effects of white coat hypertension.
Ambulatory blood pressure monitoring more accurately predicts target organ damage and cardiovascular events than traditional office-based blood pressure readings. This type of measurement typically occurs at 15-20 minute intervals during the day and 30-60 minute intervals at night. Ambulatory blood pressure monitoring can help the evaluation of suspected white coat hypertension, resistant hypertension, suspected episodic hypertension, evaluation of hypotension, autonomic dysfunction, and monitoring response to treatment.
Ambulatory blood pressure monitoring has many advantages. Blood pressure typically falls at night when people are sleeping. Nondipping blood pressure is when the blood pressure does not fall at least 10% during sleep. This is a strong predictor of adverse cardiovascular outcomes. Ambulatory blood pressure monitoring is a more accurate predictor of long-term cardiovascular outcomes when compared to outpatient blood pressure monitoring. Some experts suggest that ambulatory blood pressure monitoring should be the standard for evaluating blood pressure.18
After hypertension is diagnosed, it needs to be evaluated. A critical aspect of 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 workup 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 workup that may indicate a secondary cause of hypertension.
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.
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:
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.
Uric acid levels may be associated with hypertension. Uric acid is known to increase fat storage, lipogenesis, and increases salt sensitivity. Elevated levels of uric acid in the blood effects approximately 20% of adults and is thought to be related to insulin resistance, the typical western diet, and renal dysfunction. Controlling uric acid levels, particularly in patients with pre-hypertension or hypertension, may be helpful in managing high blood pressure. In addition, avoiding medications that increase uric acid levels is beneficial.19
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. An 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.
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.4
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.8
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 of 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.20 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.21
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.4
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 two or more servings of dairy each day while in preschool had improved blood pressure readings throughout adolescence.22 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 blood pressure.23
Controlling toxic habits is 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.24
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.25
Tobacco use may increase blood pressure. It is well known that smoking transiently increased blood pressure, but smoking cessation 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.
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.
Anti-hypertensive therapy reduces the relative risk of heart failure by 50%, the relative risk of stroke up to 40% and the relative risk of myocardial infarction up to 25%.26 Over a 4-5-year period, patients with systolic blood pressure between 140-159 mm Hg or diastolic blood pressure between 90 - 99 mm Hg, pharmacological therapy for elevated blood pressure prevents 0.7% of patients of having a coronary event and 1.3% of patients of having a cerebrovascular event.27 This translates into two patients out of 100 having a prevented adverse cardiovascular event over 4-5 years. The benefit may be greater over the long-term (more than 5 years). Benefits of antihypertensive therapy are less robust in patients without cardiovascular disease or those with a 10-year cardiovascular risk less than 10% and in those over the age of 75.7
According to the American College of Cardiology/American Heart Association, pharmacotherapy should be started in patients with ambulatory daytime blood pressure readings of 135/85 mm Hg or higher or an average office reading of 140/90 mm Hg or higher. Readings of 130/80 mm Hg or higher should have pharmacotherapy started in the face of clinical cardiovascular disease, type 2 diabetes, chronic kidney disease, individuals with a 10-year risk of over 10%, and those over the age of 65.7
The JNC 8 has slightly different recommendations when compared to the American College of Cardiology/American Heart Association. According to the JNC, 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. According to JNC 8, 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.28
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 non-black population. For the black population, the use of a thiazide-type diuretic or a calcium channel blocker should be used as initial therapy.29 For individuals with diabetic nephropathy or nondialysis diabetic chronic kidney disease complicated by proteinuria should be treated with an ACE-I or ARB. The use of beta-blockers is not recommended as initial monotherapy unless there is a specific indication such as heart failure with reduced ejection fraction or ischemic heart disease.
For those with blood pressure greater than 20/10 mm Hg, 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 calcium channel blocker is often recommended as a first line combination. The combination of a thiazide-type diuretic along with a calcium channel blocker may also be used.
Later line medications to manage hypertension include:
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 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.29 They are often considered as part of the initial combination for management of blood pressure 20/10 mm Hg over the goal. In addition, thiazide diuretics are recommended for those with heart failure, high risk for cardiovascular disease, diabetes and secondary stroke prevention.
Data from the ALLHAT trial was a strong contributor to the recommendation to use thiazide diuretics in the management of hypertension. Of note, the trial used chlorthalidone which is known to be much more potent and hydrochlorothiazide which is a commonly used thiazide diuretic. Therefore, it is difficult to normalize the results to all thiazide diuretics. One study showed that diuretics like chlorthalidone lowered the risk of cardiovascular events and heart failure by 12 and 21% respectively when compared to diuretics like hydrochlorothiazide.30
Based on the ALLHAT trial, there is no convincing evidence that low-dose hydrochlorothiazide alone diminishes cardiovascular events when compared to chlorthalidone. Even though chlorthalidone is more effective, it is associated with an increased risk of hypokalemia, glucose intolerance, and new onset diabetes mellitus when compared to hydrochlorothiazide.31
Another study showed that individuals treated with chlorthalidone compared to hydrochlorothiazide had significantly less risk of stroke, myocardial infarction, peripheral artery disease, coronary artery bypass surgery, heart failure, left ventricular hypertrophy, or angina.32 Chlorthalidone, when compared to hydrochlorothiazide, has been shown to be associated with an increased risk of hospitalization for electrolyte imbalance including hypokalemia and hyponatremia.33 Consuming a low-salt diet improves blood pressure control as well as reduces the risk of hypokalemia in individuals on chlorthalidone. Potassium loss typically occurs in the first 2 weeks of therapy and therefore a patient with normal serum potassium levels at 3 weeks is at very low risk to develop hypokalemia unless there is a change in the dose or another cause of potassium loss occurs.
Side effects of diuretics include dehydration, orthostatic hypotension, electrolyte imbalance, increase risk of a gout flare, photosensitivity, hyperglycemia and gastrointestinal upset. Because of these side effects, there is an increased risk of falls, especially in the older adult. The younger patient who is treated with thiazide diuretics may have an increased risk of diabetes.
| 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 the early intervention of hypertension with diuretic therapy.34
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). RAS inhibition may help prevent end-organ damage above and beyond their effect on blood pressure.
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: asymptomatic left ventricular dysfunction, patients with heart failure, patients who had an ST-elevation myocardial infarction (MI), patients with non-ST elevation MI who had an anterior infarction, systolic dysfunction, chronic kidney disease with proteinuria, diabetic individuals at high risk for atherosclerotic heart disease and for secondary stroke prevention.4, 7, 35
Common side effect with ACE-Is includes 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 (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®), losartan (Cozaar®), eprosartan (Teveten®), valsartan (Diovan®) and olmesartan (Benicar®).
ACE-Is and ARBs are cardioprotective independent of blood pressure control in patients at risk for cardiovascular events. Angiotensin receptor blockers have similar compelling indications as ACE-Is. One trial suggested that patients with severe hypertension and EKG evidence of left ventricular hypertrophy may benefit more from ARBs when compared to ACE-Is.37
ARBs 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 generally recommended.29
Research shows that excessive dietary salt counteracts the renoprotective effects of the renin-angiotensin system blockade in patients afflicted with chronic kidney disease (CKD) and high blood pressure. It does this by activating the mineralocorticoid receptor. This research suggests that renin-angiotensin system blockade plus eplerenone may be effective for hypertension in CKD, particularly for those who have a high salt intake.36
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 non-dihydropyridines 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 antihypertensive agents. It was suggested that CCBs are beneficial for high-risk cardiac patients.37 CCBs are often used as add on therapy with diuretics, ACE-Is or ARBs. Compelling indications for CCBs include a high risk for cardiovascular disease and diabetes. They can also be used as first-line therapy for isolated systolic hypertension (the dihydropyridine class) especially 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 non-dihydropyridine CCBs are verapamil (Calan®, Isoptin®) and diltiazem (Cardizem®). The non-dihydropyridine class of medications caused 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 non-dihydropyridine class. They are more likely to lead to reflex tachycardia.
Beta-blockers (BBs) reduce blood pressure by reducing cardiac output as well as slightly reducing renin levels. JNC 8 has relegated them to a second line treatment for hypertension.29 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.38
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.
BB 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 of stroke more than other medications used for hypertension.39 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 - 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 a 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®). The enzyme renin is responsible for changing angiotensinogen to angiotensin I, which is then converted to angiotensin II. 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 antihypertensive agents.
Aliskiren is not recommended as a first line agent in the management of hypertension. A recent analysis suggested that aliskiren induced slightly greater blood pressure reductions when compared to other antihypertensive agents, but it did not lower total or cardiovascular mortality. In addition, the use of aliskiren with another renin-angiotensin-aldosterone system inhibitor should not be used in diabetics.40
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 the treatment of hypertension, they are also used to improve urine flow rates in men with prostatic hypertrophy. In the ALLHAT study, the doxazosin arm had to be stopped prematurely because of the significantly increased risk of heart failure.31
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 the 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®).
Hypertension is a disease that becomes more common as people 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 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.29
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, adding an agent based on 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 showed that generally treating hypertension lower the risks of falls. Of note, only one class of blood pressure medications, beta blockers, were associated with an increased risk of falls.41
A 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 the concern of adverse effects of therapy, few negative effects were noted.42
While JNC8 guidelines suggest more conservative treatment of blood pressure in older adults, other guidelines are more aggressive.
While antihypertensive medication classes are relatively equal in effectiveness, there is individual variability in effectiveness. It is generally agreed that blood pressure control is most important in reducing complications of hypertension and the choice of agent is a secondary consideration unless there is a compelling indication.
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.
| Drug | When to Consider |
|---|---|
| Thiazide Diuretics | Isolated systolic hypertension in the older adult, heart failure, high risk for cardiovascular disease, diabetes mellitus, osteoporosis 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 and heart failure |
| 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 |
Patients who suffer from osteoporosis and have hypertension may benefit from thiazide diuretics as they stimulate the distal tubular resorption of calcium which reduces urinary excretion of calcium. They ALLHAT trial showed that individuals treated with chlorthalidone had fewer hip and pelvic fractures when compared to patients treated with amlodipine or Lisinopril.43
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.
Prior to initiating two medications, it is important to evaluate the risk of orthostatic hypotension which is more common in patients with diabetes or older age. Assess these patient groups with orthostatic blood pressure readings. Orthostatic hypotension is considered when there is a 20 mm Hg fall in systolic blood pressure or a 10 mm Hg fall in diastolic blood pressure, with an increase in heart rate of 10 beats a minute or a feeling of dizziness upon standing.
To improve patient 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.
Agents that do not work well together include:
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.44 This was first noted in the ACCOMPLISH trial which showed that amlodipine plus an ACE inhibitor was associated with a 20% lower rate of cardiovascular events when compared with an ACE inhibitor and hydrochlorothiazide. This benefit was noted without any significant blood pressure difference. Of note, blood pressure was slightly higher in those taking amlodipine.45 This benefit was most pronounced in non-obese individuals.46
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.8 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. If an individual is on 4 antihypertensive medications, but blood pressure is controlled, they are classified as having controlled resistant hypertension.47
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.48
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. The use of certain substances can also contribute to resistant hypertension. These may include alcohol, cocaine, decongestants, nicotine, amphetamines and certain prescription drugs including oral contraception, antidepressants and nonsteroidal anti-inflammatory drugs.
Pseudo hypertension, a contributing factor to resistant hypertension, may occur in older patients with thick calcified arteries which lead to falsely elevated blood pressure. This often requires intra-arterial pressure to assess the actual blood pressure.
Excessive fluid may contribute to resistant hypertension. This may occur for many reasons including:
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 miles, 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 includes 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 serum creatinine of 1.4 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 (some guidelines recommend lower blood pressure readings).
The first step in the management of this patient’s blood pressure is to review lifestyle modifications. He was encouraged to:
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 the goal. Augmenting his blood pressure medications is likely necessary to manage his blood pressure and prevent long-term complications adequately. 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.
Hypertensive urgency is when there is very high blood pressure (such as a systolic reading over 180 mm Hg and/or a diastolic reading above 120 mm Hg) in a patient who is asymptomatic and without end-organ damage. In this situation, rapid reduction in blood pressure is not necessary. An important aspect of evaluation of a patient with ongoing hypertensive urgency is to assure that blood pressure is accurately measured, and there is no end-organ damage.
The management of severe asymptomatic hypertension is not optimally defined. It is reasonable to lower blood pressure over a period of hours to days. Lowering blood pressure too rapidly may reduce the body’s ability to autoregulate to maintain adequate tissue perfusion, therefore, increasing the risk of heart attack, acute kidney injury or stroke.
The blood pressure should likely be lowered to less than 160/100, but the mean arterial blood pressure should not be lowered more than 30% over the first 2-4 hours.49 Simply placing the patient in the quiet room may lower blood pressure. One study showed that 32% of individuals who rested 30 minutes in a quiet room had blood pressure lowered more than 20/10 mm Hg.50
The use of fast-acting medications, such as oral clonidine or oral captopril, will lower blood pressure over hours. It is not unreasonable to use longer-acting medications and follow-up in the primary care office over the next 1-2 days.
Complications associated with hypertensive urgency include retinal hemorrhage, papilledema, kidney injury, or hypertensive encephalopathy. Much more commonly significantly elevated blood pressure is asymptomatic. At times there may be a slight headache, but rarely.
In patients with severe asymptomatic hypertension rapidly lowering blood pressure has minimal benefit. A recent study of 60,000 people with severe asymptomatic hypertension evaluated in the emergency department compared immediate emergency department referral to sending the patient home for outpatient blood pressure management.51 This study demonstrated at 6-months, similar rates of blood pressure control and similar rates of cardiovascular events.
A hypertensive emergency is severe hypertension (>180/120 mm Hg) with evidence of end-organ damage. This is a potentially life-threatening situation that requires aggressive management, typically in the intensive care unit.
Other situations necessitate blood pressure needing to be lowered quickly. This includes individuals at high risk for imminent cardiovascular events from the high blood pressure. This includes those with aortic aneurysms or intracranial aneurysms. These individuals should have blood pressure lowered over hours. Multiple parental agents may be used in these emergency situations.
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.
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.
