Note from the National Guideline Clearinghouse (NGC) and the Institute for Clinical Systems Improvement (ICSI): For a description of what has changed since the previous version of this guidance, refer to Summary of Changes Report- October 2008.

The recommendations for the diagnosis and treatment of hypertension are presented in the form of an algorithm with 12 components, accompanied by detailed annotations. An algorithm is provided for Hypertension Diagnosis and Treatment. Clinical highlights and selected annotations (numbered to correspond with the algorithm) follow.

Class of evidence (A-D, M, R, X) ratings and key conclusion grades (I-III, Not Assignable) are defined at the end of the "Major Recommendations" field.

Clinical Highlights

• Confirmation of hypertension is based on the initial visit, plus two follow-up visits with at least two blood pressure measures at each visit. (Annotation #2)
• Standardized blood pressure measurement techniques (including out-of-office or home blood pressure measurements) should be employed when confirming an initially elevated blood pressure and for all subsequent measures during follow-up and treatment for hypertension. (Annotation #2, Appendix A - see original guideline document)
• A thiazide-type diuretic should be considered as initial therapy in most patients with uncomplicated hypertension. (Annotation #6)
• Physician reluctance to initiate and intensify treatment is a major obstacle to achieving treatment goals. (Annotation #8, 10)
• Systolic blood pressure level should be the major factor for the detection, evaluation, and treatment of hypertension, especially in adults 50 years and older. (Annotation #7)
• Fewer than 50% of patients with hypertension will be controlled with a single drug. (Annotation #8)

Hypertension Diagnosis and Treatment Algorithm Annotations

2. Confirm Elevated Blood Pressure

   Key Points:

   • All elevated blood pressure readings should be confirmed.
   • A standardized blood pressure measurement process is important for correctly identifying hypertensive patients.
   • Self-monitoring of blood pressure should be encouraged in most patients.

   If an elevated blood pressure reading has been obtained, the blood pressure level should be confirmed. Confirmation is based on the initial visit, plus two follow-up visits with at least two blood pressure readings at each visit. Explain the rationale; emphasize the reason for return and the need for confirmation of elevated blood pressure. Unconfirmed hypertension should be coded as indicated in the original guideline document. Confirmation and follow-up recommendations are noted in Tables 1 and 2 in the original guideline document.

   Standardized Office Blood Pressure Measurement

   Accurate, reproducible blood pressure measurement is important to allow comparisons between blood pressure values and to correctly classify blood pressure. Incorrectly labeling a hypertensive patient normotensive may increase risk for vascular events, since risk rises with increasing blood pressure. Labeling a patient with normal blood pressure as a hypertensive can affect insurability, employment, morbidity from medications, loss of time from work, and unnecessary lab and physician visits [D], [R].

   Standardized blood pressure technique should be employed when confirming an elevated reading and for all subsequent readings during follow-up and treatment for hypertension. See Appendix A, "Standards for Blood Pressure Measurement," in the original guideline document.

   Confirmed elevated blood pressure should be classified as to the appropriate hypertension stage.

   Out-of-Office Blood Pressure Measurement

   Out-of-office, self-measured blood pressure readings provide important information regarding the diagnosis and treatment of hypertension and should be a routine component of blood pressure monitoring in most patients [R]. Home blood pressure monitoring identifies patients with white-coat hypertension (i.e., patients with elevated office blood pressure who lack evidence of hypertensive target organ damage, and who have normal out-of-office blood pressure readings) and home readings are a stronger predictor of subsequent cardiovascular events than are office readings. Moreover, home blood pressure measurements can identify patients with "masked hypertension" (i.e., normal office and elevated home readings) [B]. Studies have shown that uncertainty about the "true blood pressure" is a common reason for lack of change in treatment during a clinic visit despite an elevated office blood pressure reading. Additional readings from self-monitoring will reduce this uncertainty. It is recommended that patients obtain 2 to 3 readings while rested in the seated position, both in the morning and at night for one week prior to a clinic visit [R]. Fully automated oscillometric devices using an appropriately sized upper arm cuff are preferred over aneroid devices or automated devices that measure blood pressure at the wrist or on the finger. Accuracy of the patient's automated device should be confirmed initially upon acquisition and periodically (e.g., annually) by the patient's health care professional [D]. The general home blood pressure goal with treatment is less than 135/85 mm Hg or less than 130/80 mm Hg in patients with diabetes, chronic kidney disease, coronary artery disease or heart failure.

   24-Hour Blood Pressure Measurement

   Ambulatory blood pressure monitoring provides information about blood pressure during daily activities and sleep. It is particularly helpful in the confirmation of white coat or office hypertension. This phenomenon may be present in 20% to 35% of patients diagnosed with hypertension [B]. In general, however, this diagnosis can be reliably established without ambulatory blood pressure monitoring in patients with elevated office readings who lack target organ damage, and who have accurately measured out-of-office blood pressure readings that are consistently less than 135/85 mm Hg. Other clinical situations in which ambulatory blood pressure monitoring may be helpful include the assessment of drug resistance, hypotensive symptoms, episodic hypertension, and suspected autonomic dysfunction. Ambulatory blood pressure monitoring predicts subsequent cardiovascular events more reliably than office blood pressure measurements.  Ambulatory blood pressure monitoring may be inaccurate with atrial fibrillation. Thresholds for ambulatory hypertension are 140/85 mm Hg for awake average, 120/70 mm Hg for asleep average and 130/80 for 24-hour average blood pressure [C].

   For patients with prehypertension, early intervention with healthy lifestyle changes could reduce blood pressure, decrease the rate of the progression of blood pressure to hypertensive levels with age, or prevent hypertension entirely.

   Blood Pressure Screening Clarification

   Because all stages of hypertension are associated with increased vascular events, the previous classifications of mild and moderate hypertension were discarded in favor of stages that emphasize these risks. The current classification emphasizes systolic as well as diastolic standards, as systolic hypertension has been associated with increased fatal and nonfatal cardiovascular events, and treatment has been shown to reduce cardiovascular morbidity and mortality [A], [C], [R].

   A proposed follow-up schedule based on the initial blood pressure level as well as prior diagnosis and treatment of cardiovascular disease and risk factors – is noted in Table 2 of the original guideline document [R].

   Refer to the original guideline document for the International Classification of Diseases, Ninth Revision (ICD-9) code to be used for the initial encounter ("Elevated blood pressure reading without diagnosis of hypertension." Note: This category is to be used to record an episode of elevated blood pressure in a patient in whom no formal diagnosis of hypertension has been made, or as an incidental finding.)

   This guideline encourages increased use of this ICD-9 code because elevated blood pressure without hypertension is currently believed to be underreported.

3. Complete Initial Assessment: Evaluate, Accurately Stage, and Complete Risk Assessment

   Key Points:

   • It is important to assess and accurately stage newly confirmed hypertension.
   • A complete review of all medications (prescription and over-the-counter) and herbal supplements is very important.

   The goal of the clinical evaluation in newly confirmed hypertension is to determine whether the patient has primary or secondary hypertension, target organ disease, and other cardiovascular risk factors (risk assessment).

   • Accurately Stage

     This treatment guideline is designed to be used in new or previously diagnosed hypertensive patients in conjunction with the National Guideline Clearinghouse (NGC) summary of the Institute for Clinical Systems Improvement (ICSI) Preventive Services for Adults guideline. See Appendix A, "Standards for Blood Pressure Measurement," in the original guideline document.

     Hypertension Stages	Systolic		Diastolic
     Prehypertension	120-139	or	80-89
     Stage 1 hypertension	140-159	or	90-99
     Stage 2 hypertension	>160	or	>100

     Modified from the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003;42:1206-52. (Class R)

     When systolic and diastolic pressures fall into different categories, the higher category should be selected in classifying the individual's blood pressure status.

   • Risk Assessment

     The risk for cardiovascular disease in patients with hypertension is determined not only by the level of blood pressure but also by the presence or absence of target organ damage or other risk factors such as smoking, dyslipidemia and diabetes, as shown in Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7). These factors independently modify the risk for subsequent cardiovascular disease, and their presence or absence is determined during the routine evaluation of patients with hypertension (i.e., history, physical examination, laboratory tests).

   • Medical History

     The history should focus on modifiable lifestyle factors including weight change, dietary intake of sodium and cholesterol, level of exercise, psychosocial stressors, and patterns of alcohol and tobacco use.

     Determine all medications being used--including herbal supplements, over-the-counter, prescription, and illicit drugs--as many agents may temporarily elevate blood pressure and/or adversely affect blood pressure control [M], [R]. See Appendix C, "Recommended Education Messages" in the original guideline document.

     A family history of hypertension, cardiovascular disease, cerebrovascular disease, diabetes mellitus, and dyslipidemia should be documented.

     Assess for symptoms and signs of target organ disease and secondary hypertension via a directed history.

   • Physical Examination

     The initial physical examination should include the following:

     • Two or more blood pressure measurements separated by two minutes with the patient seated and after standing for at least two minutes in accordance with the recommended techniques as stated in Appendix A, "Standards for Blood Pressure Measurement" in the original guideline document
     • Verification in the contralateral arm (if values are different, the higher value should be used)
     • Measurement of height, weight, and waist circumference. Waist circumference provides incremental information regarding cardiovascular risk related to obesity [B], [C], [D]. See the NGC summary of the ICSI guideline Prevention and Management of Obesity (Mature Adolescents and Adults) for additional information and instructions on how to measure waist circumference.
     • Funduscopic examination for hypertensive retinopathy (i.e., arteriolar narrowing, focal arteriolar constrictions, arteriovenous crossing changes, hemorrhages and exudates, disc edema). While the reproducibility of office funduscopic findings is poor, there are clinical findings (in particular, retinal hemorrhages, papilledema) that instruct important clinical decisions.
     • Examination of the neck for carotid bruits, distended veins, or an enlarged thyroid gland
     • Examination of the heart for abnormalities in rate and rhythm, increased size, precordial heave, clicks, murmurs, and third and fourth heart sounds
     • Examination of the lungs for rales and evidence for bronchospasm
     • Examination of the abdomen for bruits, enlarged kidneys, masses, and abnormal aortic pulsation
     • Examination of the extremities for diminished or absent peripheral arterial pulsations, bruits, and edema
     • Neurological assessment
   • Initial Laboratory Studies

     Initial lab screen should include 12-lead electrocardiogram, urinalysis, fasting blood glucose, hematocrit, serum sodium, potassium, creatinine (estimated or measured glomerular filtration rate [GFR]), calcium, and lipid profile (total cholesterol, high density lipoprotein [HDL]-cholesterol, low density lipoprotein [LDL]-cholesterol and triglycerides). Additional laboratory and diagnostic studies may be required in individuals with suspected secondary hypertension and/or evidence of target-organ disease [R].

     Some of these tests are needed for determining presence of target organ disease and possible causes of hypertension. Others relate to cardiovascular risk factors or provide baseline values for judging biochemical effects of therapy.

     Additional tests may be ordered at the discretion of the provider based on clinical findings. These may include but are not limited to complete blood count, chest x-ray, uric acid, and urine microalbumin.

     See Appendix D, "Clinical Evaluation of Confirmed Hypertension" in the original guideline document.

     [B]

   JNC 7 Cardiovascular Risk Factors/Target Organ Damage

   Major Risk Factors Hypertension Age (older than 55 for men, 65 for women)* Diabetes mellitus** Elevated LDL cholesterol Low HDL cholesterol** Estimated glomerular filtration rate (GFR) less than 60 mL/min Microalbuminuria Family history of premature cardiovascular disease (men younger than 55 or women younger than 65) Obesity** (body mass index greater than or equal to 30 kg/m2, waist circumference greater than 40 inches for men and greater than 35 inches in women) Physical inactivity Tobacco usage, particularly cigarettes Target Organ Damage Heart Left ventricular hypertrophy Angina/prior myocardial infarction Prior coronary revascularization Heart failure Brain Stroke or transient ischemic attack Dementia Chronic kidney disease Peripheral arterial disease Retinopathy

   * Increased risk begins at approximately 55 and 65 for men and women, respectively. Adult Treatment Panel III used earlier age cutpoints to suggest the need for earlier action.

   ** Components of the metabolic syndrome. Reduced HDL and elevated triglycerides are components of the metabolic syndrome. Abdominal obesity is also a component of metabolic syndrome.

   A point scale approach for estimating 10-year coronary heart disease risk can also be used. See Appendix B, "Ten-Year Cardiovascular Disease Risk Calculator (Risk Assessment)" in the original guideline document.

4. Is Secondary Cause Suspected?

   The term "secondary hypertension" implies that a patient's blood pressure elevation is the result of an underlying discoverable disease process. Secondary causes account for only a small percentage of all documented cases of hypertension, but their detection is important as appropriate intervention may be curative and lead to reversal of hypertension.

   Evaluate for features suggestive of secondary hypertension. Suspect a diagnosis of secondary hypertension in patients with an abrupt onset of symptomatic hypertension, with Stage 2 hypertension, hypertensive crisis, sudden loss of blood pressure control after many years of stability on drug therapy, drug resistant hypertension, and in those individuals with no family history of hypertension. Differential diagnosis of secondary hypertension includes:

   • Chronic kidney disease/obstructive uropathy
   • Thyroid and parathyroid disease
   • Drugs (prescription, over-the-counter, herbal supplement, illicit drugs)
   • Excessive alcohol use
   • Obstructive sleep apnea
   • Primary aldosteronism
   • Renal artery stenosis
   • Pheochromocytoma
   • Cushing's syndrome
   • Aortic coarctation
   • Obesity

   See Appendix E, "Suspicion of Secondary Hypertension," in the original guideline document.

   Note recommendations for additional diagnostic procedures. Be sure advanced testing is correctly chosen and done properly to avert the need for repeat studies. This may require discussion with or referral to a specialist.

5. Order Additional Work-Up/Consider Referral

   Consider appropriate referral or additional work-up if secondary hypertension is identified, or suspected.

   If you suspect a diagnosis of secondary hypertension, it is recommended that you perform a phone consultation and/or refer the patient to a specialist early in order to confirm the most efficient and cost-effective approach to patient evaluation and management [R].

6. Lifestyle Modifications +/- Drug Therapy

   Key Points:

   • Lifestyle modifications should be the cornerstone of the initial therapy for hypertension.

   Clinical studies show that the blood pressure-lowering effects of lifestyle modifications can be equivalent to drug monotherapy [A]. Lifestyle modification is best initiated and sustained through an educational partnership between the patient and a multidisciplinary health care team. While team members may vary by clinical setting, behavior change strategies should include nutrition, exercise, and smoking cessation services. Lifestyle modifications should be reviewed and re-emphasized at least annually.

   Some patient education should occur and be documented at every visit. For recommended education messages, see Appendix C, "Recommended Education Messages," in the original guideline document.

   Table. Lifestyle Modifications to Prevent and Manage Hypertension*

   Modification	Recommendation	Approximate Systolic Blood Pressure Reduction (Range)**
   Weight reduction	Maintain normal body weight (body mass index 18.5 to 24.9 kg/m2)	5 to 20 mm Hg/10 kg
   Adopt Dietary Approaches to Stop Hypertension (DASH) eating plan	Consume a diet rich in fruits, vegetables, and low-fat dairy products with a reduced content of saturated and total fat.	8 to 14 mm Hg
   Dietary sodium reduction	Reduce dietary sodium intake to no more than 100 mmol per day (2.4 g sodium or 6 g sodium chloride).	2 to 8 mm Hg
   Physical activity	Engage in regular aerobic physical activity such as brisk walking (at least 30-45 minutes per day, most days of the week)	4 to 9 mm Hg
   Moderation of alcohol consumption	Limit consumption to no more than 2 drinks (e.g., 24 oz. beer, 10 oz. wine, or 3 oz. 80 proof whiskey) per day in most men and to no more than one drink per day in women and lighter-weight persons.	2 to 4 mm Hg

   *For overall cardiovascular risk reduction, stop smoking
   **The effects of implementing these modifications are dose- and time-dependent and could be greater for some individuals.

   Taken from the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003;42:1206-52. (Class R)

   Weight Reduction and Maintenance

   Hypertension is closely correlated with excess body weight [R]. Approximately 50% of hypertensive patients are overweight [D]. In the Framingham study, 60% to 70% of hypertension could be attributed to being overweight or obese [B].

   Research studies have documented the positive effects of weight reduction as a strategy for blood pressure control [A]. In adults with hypertension, meta-analysis shows that weight loss through diet or use of orlistat is related to a modest reduction of blood pressure by up to 6 mm Hg systolic and 3 mm Hg diastolic; however, use of sibutramine increased blood pressure despite weight loss [M]. Whenever indicated, weight reduction should be recommended. Even an initial loss of as little as 10 pounds can have a positive effect on blood pressure. Weight loss can also improve the efficacy of antihypertensive medications and the cardiovascular risk profile.

   Initial weight loss and long-term weight control are both enhanced by a regular exercise program.

   Patient education and/or nutritional counseling should be provided.

   [A], [D], [R]

   Dietary Interventions

   Use of a Dietary Approaches to Stop Hypertension (DASH) eating plan has been shown in cohort studies to reduce incidence of congestive heart failure by 25% and incidence of stroke by 17% in women [B].

   A relationship between dietary sodium intake and blood pressure has been demonstrated in multiple clinical and epidemiological studies [R]. Modest sodium restriction may also reduce the amount of antihypertensive medications required [A]. However, individuals vary in response to a reduced sodium intake. Among hypertensives, African Americans, older patients, and patients with renal disease seem to be more sodium sensitive [A].

   Moderation of Alcohol Intake

   Alcohol consumption has complex effects on the cardiovascular system. Alcohol consumption raises both systolic and diastolic pressures, but its effects appear to be greater on systolic pressure. Significant elevations in blood pressure have been shown in individuals who consumed an average of at least three standard drinks per day compared with non-drinkers. Alcoholism may cause hypertension, and an alcoholic is less likely to respond to any hypertension treatment recommendations [R]. Some persons may develop transitory hypertension during the first days of detoxification. Alcohol is a concentrated calorie source that does not provide any nutrients, so reducing alcohol intake can hasten weight reduction and may decrease triglyceride levels. Although cohort studies suggest that modest alcohol consumption may reduce the rate of myocardial ischemic events, alcohol use of up to 2 ounces per day neither increases nor decreases total mortality or cardiovascular mortality in those with hypertension [B]. The recommendation is to not exceed a daily alcohol intake of 1 ounce of ethanol. One ounce (30 mL) of ethanol is equivalent to two drinks per day. It is recommended that men have no more than one ounce of ethanol per day (two drinks) and women have no more than 0.5 ounce of ethanol per day (one drink). One drink is 12 ounces of beer, 5 ounces of wine or 1.5 ounces of 80 proof liquor [D].

   Adequate Physical Activity

   Epidemiological studies suggest that regular aerobic physical activity may be beneficial for both prevention and treatment of hypertension, to enable weight loss, for functional health status, and to diminish all-cause mortality and risk of cardiovascular disease. Thirty to forty-five minutes of brisk walking or other activity most days of the week at target heart rate ([220-age] x 75% = target heart rate) is adequate, inexpensive, and effective [R]. However, regular physical activity of even lower intensity and duration has been shown to be associated with about a 20% decrease in mortality in cohort studies [B]. Other aerobic activities (biking, swimming, jogging, etc.) may be more enjoyable. Resistive isotonic activities, when done as the only form of exercise training, are not recommended to lower blood pressure in hypertensive patients [R].

   Potassium

   There is no direct evidence that potassium supplementation lowers blood pressure chronically [A], [M].

   Tobacco Avoidance

   Recent data using ambulatory blood pressure monitoring suggests that nicotine may indeed increase blood pressure and could account for some degree of blood pressure lability [C]. In addition, it is a major risk factor for atherosclerotic cardiovascular disease. At each visit, establish tobacco use status.

   Relaxation and Stress Management

   Although studies have not demonstrated a significant long-term effect of relaxation methods on blood pressure reduction, relaxation therapy may enhance an individual's quality of life and may have independent effects on lowering coronary heart disease risk [M], [R].

   Drug Therapy

   A thiazide-type diuretic should be considered as initial therapy in most patients with uncomplicated hypertension [R]. Because thiazide-type diuretics have been shown to be as good as or superior to other drug classes in preventing cardiovascular disease morbidity and mortality, they should be considered preferred initial therapy in most patients [R]. However, studies support the use of specific alternative drugs as initial therapy in the presence of specific co-existing diseases. Thiazide-type diuretics are especially useful for patients age 55 years or older with hypertension and additional risk factors for cardiovascular disease including the metabolic syndrome and for patients age 60 years or older with isolated systolic hypertension [A]. The risk of diabetes mellitus is higher with diuretic and beta-blockers than other first-line choices, and this may be a consideration for patients at higher risk for this disorder [M]. Studies have demonstrated the cost effectiveness in older patients of selecting drugs using evidence-based guidelines [M]. In patients for whom diuretics are contraindicated or poorly tolerated, use of an angiotensin-converting enzyme (ACE) inhibitor, angiotensin receptor blocker, beta-blocker, or calcium antagonist is appropriate.  Other considerations when selecting initial drug therapy include age, race, cost, drug interactions, side effects, and quality of life issues. See Appendix F, "Therapies," and Appendix G, "Cost of Antihypertensive Drugs" in the original guideline document. In general, diuretics and calcium channel blockers appear to be more effective as an initial treatment of hypertension in African Americans. The lowest recommended dose of the chosen drug should be used initially. If tolerated, the dose can be increased or additional medications added to achieve goal blood pressure.

   Other classes of drugs should be reserved for special situations or as additive therapy. See Appendix F, "Therapies" in the original guideline document. Co-existing medical conditions may also justify the use of one of these classes of drugs. An example is the use of an ACE inhibitor in a patient with heart failure or diabetic nephropathy. Please see the NGC summary of the ICSI guideline Diagnosis and Management of Type 2 Diabetes Mellitus in Adults for further information. ACE-inhibitors and angiotensin receptor blockers have been shown to be beneficial for patients with renal disease (both diabetic and non-diabetic) by reducing proteinuria and slowing the rate of decline in renal function [A], [M]. ACE inhibitors have also been shown to provide symptomatic relief and prolong life for patients with heart failure and are the initial drug of choice for this condition. ACE inhibitors and angiotensin-receptor blockers have similar blood-pressure-lowering effects, but angiotensin-receptor blockers are less often associated with the side effect of cough [M]. Initial monotherapy with one of these agents is appropriate in these patient populations. A diuretic should be added if blood pressure response is not satisfactory. Evidence from a recent large trial suggests that ACE inhibitors may be less effective in African Americans than thiazide-type diuretics in controlling blood pressure and in preventing stroke and cardiovascular disease [R].

   Based on meta-analyses of previous studies, beta-blockers may be less efficacious than other first-line alternatives in patients who are 60 years and older, especially for stroke prevention [M]. Thus, use of these drugs as initial therapy in older patients probably should be restricted to situations where there is another indication for their use (e.g., heart failure, previous myocardial infarction, angina.) They still should be considered alternative first-line agents in younger patients, where they appear to lessen cardiovascular morbidity as well as other recommended drugs. Beta-blockers reduce the risk of sudden death and recurrent myocardial infarction for patients with an initial myocardial infarction. ACE inhibitors also reduce the risk of subsequent myocardial infarction and progression to heart failure for patients who experience a large myocardial infarction associated with impairment of left ventricular function. They also may reduce risk for patients with (or at high risk for) cardiovascular disease [A].

   Long-acting dihydropyridine calcium antagonists have been shown to be effective for patients age 60 years or older with isolated systolic hypertension. Co-existing medical conditions may also justify the use of one of these classes of drugs. Evidence from a recent large study refutes concerns about increased risk of myocardial infarction, cancer or gastrointestinal bleeding from use of long-acting calcium antagonists. However, data does suggest that this class of drugs may be less effective in preventing heart failure [A). The work group suggests these drugs be limited to those conditions listed in Appendix F, "Therapies," in the original guideline document. Data supporting potential dangers of calcium antagonists are limited to short-acting preparations (especially nifedipine) that are not approved for the treatment of hypertension.

   A majority of patients will require more than one drug for blood pressure control. Combination therapies that include a diuretic are often effective, lessen the risk for side effects (by use of low doses of each component drug), and enhance adherence by simplification of the treatment program. For patients with chronic kidney disease three or more drugs may be needed to achieve goal [A], [B], [M].

7. Blood Pressure at Goal?

   Key Points:

   • Isolated systolic hypertension is an important modifiable cardiovascular risk factor.
   • Accurate home monitoring systems are an important tool for assessing blood pressure control.
   • Review drugs, over-the-counter medications, and herbal therapies that may interfere with blood pressure goal.

   Goal office blood pressures should be less than 140/90 mm Hg for adults with uncomplicated hypertension (in the absence of comorbidities). [Conclusion Grade II: See Conclusion Grading Worksheet A – Annotation #7 (Goal Blood Pressure for Patients with Cardiovascular Disease) in the original guideline document]. Goal blood pressures measured out of the office setting should be less than 135 mm Hg systolic and less than 85 mmHg diastolic. Goals differ in the office setting.

   Patients with comorbid conditions including diabetes or chronic kidney disease should have a goal office blood pressure of less than 130/80 mm Hg [M]. [Conclusion Grade II: See Conclusion Grading Worksheet A – Annotation #7 (Goal Blood Pressure for Patients with Cardiovascular Disease) in the original guideline document]. Progressive reduction of systolic blood pressure to as low as 110 mm Hg has been shown to be associated with lower risk of microvascular and macrovascular complications in diabetes [A], [B].

   Recent American Heart Association/American College of Cardiology guidelines have called for goal office blood pressures less than 120/80 mm Hg for patients with a history of heart failure [A]. Patients with coronary artery disease should have a goal office blood pressure less than 130/80 mm Hg [Conclusion Grade II: See Conclusion Grading Worksheet A – Annotation #7 (Goal Blood Pressure for Patients with Cardiovascular Disease) in the original guideline document] [R]. These recommendations are based on expert opinion and limited clinical evidence. Pursuing these lower goals should be considered on an individual patient basis based on clinical judgment and patient preference.

   Systolic hypertension in patients age 60 and older is an important modifiable cardiovascular risk factor [R]. Drug therapy for patients in this age group with systolic blood pressures of 160 mm Hg or higher has been effective in reducing cardiovascular morbidity and mortality [A], [B], [M]). This is true even for patients above 80 years of age [A].

   For patients 60 years or older with isolated systolic hypertension who have markedly increased systolic blood pressure levels prior to treatment, it may not be possible to lower systolic blood pressure to less than 140 mm Hg. An interim goal of 160 mm Hg or what can be achieved by optimal doses of three antihypertensive drugs would be reasonable.

   The benefit of drug therapy in terms of reducing cardiovascular morbidity and mortality for patients age 60 and older with isolated systolic hypertension defined as a baseline systolic blood pressure of 140 mm Hg or greater has not yet been demonstrated by randomized clinical trials. The increased cardiovascular risks in this age group with blood pressures in the 140 to 159 mm Hg range, however, have been well demonstrated and have led most guidelines to recommend treatment of this group of patients [R], particularly if associated with other comorbidities or risk factors such as diabetes mellitus, kidney disease, coronary artery disease or heart failure.

   Concerns have been raised that excessive lowering of diastolic blood pressure increases the risk of coronary events in patients with established coronary artery disease or left ventricular hypertrophy by lowering diastolic perfusion pressure in the coronary circulation. This is known as the J-curve hypothesis. Recent studies have also raised concerns about a J-curve relationship between diastolic blood pressure level and risk for stroke in elderly patients treated for isolated systolic hypertension. No such J-shaped relationship has been observed between adverse event rates and systolic blood pressure level [M]. Although not resolved, caution should be applied in lowering diastolic blood pressure below 70 mm Hg in patients with coronary artery disease or left ventricular hypertrophy or below 55 mm Hg in all elderly patients with isolated systolic hypertension [A], [M]. In the latter situation, this may require compromise of the goal level of systolic blood pressure achieved [A], [B], [C], [R].

8. Change Treatment

   Once a hypertensive drug therapy is initiated, most patients should return for follow-up and medication adjustments at least at monthly intervals until blood pressure goal is reached.

   Fewer than 50% of patients with hypertension will be controlled with a single drug.

   If blood pressure goals are not met, the clinician has three options for subsequent therapy:

   • Increase the dose of the initial drug toward maximal levels.
   • Substitute an agent from another class.
   • Add a second drug from another class.

   Individualized drug selection is based on several principles:

   • If the initial response to one drug is adequate, continue the same drug.
   • If the response is partial on one agent, increase the dose or add a second drug of a different class.
   • If there is little response, substitute another single drug from a different class.
   • Consider low-dose diuretic use early or as a first addition.
   • Consider loop diuretic agents instead of thiazide or thiazide-like diuretics when creatinine is greater than 2.0 mg/dL or estimated glomerular filtration rate is less than 30 mL/min per 1.73 m².
   • Do not combine two drugs of the same class.
   • The use of combination agents can be effective.

   For many patients, two or more drugs in combination may be needed to reach hypertension goals. This is especially true for high-risk patients with treatment goals less than 130/80 mm Hg or with cardiovascular disease comorbidities. Systolic blood pressure control for adults with cardiovascular comorbidities is poor [D]. The combination of a diuretic appropriate for level of renal function with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker is often an effective two-drug program. A diuretic ACE inhibitor combination has been shown to reduce both the macrovascular and microvascular complications of type II diabetes [A].

   The combination of an ACE inhibitor with an angiotensin receptor blocker has little additional effect on blood pressure compared to either monotherapy and may be associated with increased risk of adverse effects including renal dysfunction and hyperkalemia [A]; however, this combination is more effective than either monotherapy alone in reducing proteinuria [M].

   The combination of a calcium channel antagonist with an ACE inhibitor is as effective or more effective than the traditional combination of a diuretic with a beta-blocker in lowering blood pressure and reducing cardiovascular events [A], [R]

9. Blood Pressure at Goal?

   Key Points:

   • Carefully review potential barriers to long-term adherence to therapy, including the possible secondary diagnosis of depression.
   • Systolic hypertension is an important modifiable cardiovascular risk factor.
   • Accurate home monitoring systems are an important tool for assessing blood pressure control.
   • Review drugs (prescription and over-the-counter) and herbal therapies that may interfere with blood pressure goal.

   If at this point acceptable response has not been achieved, several issues should be addressed or revisited. These include adherence to appropriate lifestyle modifications, consistent use of prescribed drugs, and tolerance of treatment modalities. Non-adherence rates to prescribed medications are estimated at 50% and are slightly higher for both elderly and adolescent patients [R]. Since there is not a simple test to accurately measure adherence, there are some practical methods that can be used for all patients: asking the patient about missed doses, watching treatment response, tracking missed appointments, tracking prescription refills, asking about issues of cost, and monitoring side effects. Although patients will generally overestimate their adherence, simply asking the question will help identify up to 50% of low-adherence patients. Standardized instruction in self-blood pressure measurement will allow assessment of "white coat" syndrome. Interfering substances which can adversely affect treatment include non-steroidal anti-inflammatory drugs, oral contraceptives, sympathomimetics, antidepressants, glucocorticoids, nasal decongestants, licorice-containing substances (e.g., chewing tobacco), cocaine, cyclosporine, and erythropoietin. Intermittent use of alcohol, particularly in alcoholics who are binge drinkers, may cause difficulties with widely fluctuating blood pressures.

   Non-specific symptoms such as fatigue, lightheadedness, or vaguely impaired cognition may be due to an acute decline in blood pressure level and may resolve within four to six weeks while continuing the drug. Other minor drug-related symptoms unrelated to blood pressure change may also resolve in time without discontinuing the drug. Non-office standardized blood pressure measurement is desirable to monitor blood pressure control.

   The factors that lead to non-adherence are multifactorial: misunderstanding of the treatment and the reason for it, adverse reactions (or fear of them), complex dosing regimens, financial constraints, or simple forgetfulness. Depression has also been identified as a risk factor in noncompliance with treatment for acute or chronic conditions [M]. Asking open-ended/non-judgmental questions about treatment regimens can lead to a good discussion between the provider and patient about why the patient may have difficulty adhering. There are a number of recommendations that in various combinations may lead to better patient adherence. These suggestions are based on available evidence from randomized clinical trials that evaluated the usefulness of adherence interventions. To increase adherence on a long-term basis, provide education about the medication and how it fits with the treatment plan, simplify the regimen (e.g., less frequent dosing, [M] combination medications, controlled release dosage forms), use patient adherence aids (e.g., pill boxes, alarms), offer support group sessions, send reminders for medication refills and appointments, cue medications to daily events (e.g., breakfast, bedtime), offer positive reinforcement (acknowledge the patient's efforts to adhere), monitor with regular physician follow-up, and actively involve family members and significant others [R]. When choosing antihypertensive drugs, preference should be given to long-acting drugs that can be dosed once daily to enhance long-term compliance [M], [R].

10. Resistant Hypertension?

    A patient has resistant hypertension when blood pressure goals are not met despite compliance with optimal doses of three antihypertensive drugs of different classes with one of the agents being a diuretic. Blood pressure remains uncontrolled most often because of elevated systolic blood pressure. Patient characteristics associated with resistant hypertension include older age, female gender, African American race, obesity and the presence of chronic kidney disease, diabetes, or left ventricular hypertrophy. Numerous reasons may exist for an inadequate or poor response [A], [D], [R].

    Consider causes of pseudo-resistant hypertension:

    • Improper blood pressure measurement (overinflation of the cuff inducing a pain response, using a cuff that is too small for the arm, or measurement of blood pressure before letting the patient rest quietly in the sitting position) can lead to inaccurately high readings.
    • Poor adherence to antihypertensive therapy. Lack of complete adherence to the drug program may be present in up to 40% of patients on multiple drug programs. Patients should be asked in a non-threatening way how successful they are in taking all of their medications in the doses prescribed. Questions should be directed to out-of-pocket costs, side effects, and dosing inconvenience. Family members may provide useful information regarding compliance. Review of pharmacy records for timely prescription renewals may be helpful.
    • Brachial arteries may be heavily calcified or arteriosclerotic and cannot be fully compressed (pseudo-hypertension), leading to inaccurately high cuff measurements.
    • Clinic or white-coat hypertension.

    Consider lifestyle factors:

    • Obesity
    • Excessive dietary sodium intake directly increases blood pressure and blunts the effectiveness of most antihypertensive drugs. Effects of salt are most pronounced in the elderly, African Americans, and in patients with chronic kidney disease.
    • Excessive alcohol intake

    Consider drug-related causes:

    • Several classes of drugs may directly increase blood pressure or interfere with the blood-pressure-lowering effect of antihypertensive therapies. These include non-steroidal anti-inflammatory agents, sympathomimetics (decongestants, diet pills, cocaine), stimulants (methylphenidate, dexmethylphenidate, dextroamphetamine, amphetamine, methamphetamine, modafinil), alcohol, oral contraceptives, cyclosporine, erythropoietin, corticosteroids, natural licorice and herbal compounds (ephedra, huang).

    Consider secondary causes:

    • Common causes include obesity, obstructive sleep apnea, chronic kidney disease, primary aldosteronism and renal artery stenosis. Uncommon causes include pheochromocytoma, Cushing's syndrome and aortic coarctation.

    A common cause of resistant hypertension is lack of control of extra-cellular volume due to inadequate diuretic therapy. Full doses of a diuretic appropriate for level of renal function should be used. In patients with chronic kidney disease who have an estimated glomerular filtration rate less than 30 mL/minute, loop diuretics are necessary for effective volume control. Furosemide is short acting and should be given twice daily. Longer acting loop diuretics can be used once daily (torsemide). The drug regimen should also include near maximal doses of two of the following additional classes of drugs:

    • Beta-adrenergic-blocker or other anti-adrenergic agent
    • Direct vasodilator
    • Calcium channel blocker
    • ACE inhibitor
    • Angiotensin receptor blocker

11. Hypertension Consultation

    Consider hypertension consultation if a patient's blood pressure is not controlled on two medications or if secondary hypertension is suspected. All patients with blood pressure that is not controlled on three medications should be referred for consultation.

12. Hypertension at Goal

    Key Points:

    • On follow-up visits, history and physical examination should be directed toward detection of hypertensive target organ damage.
    • In patients with office blood pressure at goal who demonstrate progressive target organ disease, home monitoring may be beneficial.

    Once blood pressure is at goal and stable, the patient should be seen usually at three- to six-month intervals by the provider to assess patient adherence, patient satisfaction, and any changes in target organ status. Patients' comorbidities such as heart failure, associated diseases such as diabetes, and need for laboratory tests influence the frequency of visits [R]. Lifestyle modifications should be reviewed, re-emphasized, and documented annually. Patients should monitor blood pressure more frequently by home monitoring or by other allied health professionals.

    Ongoing care can be facilitated by physicians or specially trained allied health care professionals who provide education, reinforcement, realistic short- and long-term goal setting, and adjustment of medications according to the individual clinical situation. Intervention strategies that seek to involve the patient in decision-making can improve long-term adherence to therapy and thus improve blood pressure control. Additionally, such an ongoing relationship might better identify those patients who are suitable candidates for a reduction or withdrawal from antihypertensive drug therapy following a prolonged interval of excellent blood pressure control [M].

    On follow-up visits, history and physical examination should be directed toward detection of hypertensive target organ damage.

    One may consider decreasing the dosage or number of antihypertensive drugs while maintaining lifestyle modification if:

    • Patient has uncomplicated hypertension that is well controlled.
    • Blood pressure has been maintained and documented for at least 1 year.

Definitions:

Classes of Research Reports:

1. Primary Reports of New Data Collection:

   Class A:

   • Randomized, controlled trial

   Class B:

   • Cohort study

   Class C:

   • Non-randomized trial with concurrent or historical controls
   • Case-control study
   • Study of sensitivity and specificity of a diagnostic test
   • Population-based descriptive study

   Class D:

   • Cross-sectional study
   • Case series
   • Case report

2. Reports that Synthesize or Reflect upon Collections of Primary Reports:

   Class M:

   • Meta-analysis
   • Systematic review
   • Decision analysis
   • Cost-effectiveness analysis

   Class R:

   • Consensus statement
   • Consensus report
   • Narrative review

   Class X:

   • Medical opinion

Conclusion Grades:

Grade I: The evidence consists of results from studies of strong design for answering the question addressed. The results are both clinically important and consistent with minor exceptions at most. The results are free of any significant doubts about generalizability, bias, and flaws in research design. Studies with negative results have sufficiently large samples to have adequate statistical power.

Grade II: The evidence consists of results from studies of strong design for answering the question addressed, but there is some uncertainty attached to the conclusion because of inconsistencies among the results from the studies or because of minor doubts about generalizability, bias, research design flaws, or adequacy of sample size. Alternatively, the evidence consists solely of results from weaker designs for the question addressed, but the results have been confirmed in separate studies and are consistent with minor exceptions at most.

Grade III: The evidence consists of results from studies of strong design for answering the question addressed, but there is substantial uncertainty attached to the conclusion because of inconsistencies among the results of different studies or because of serious doubts about generalizability, bias, research design flaws, or adequacy of sample size. Alternatively, the evidence consists solely of results from a limited number of studies of weak design for answering the question addressed.

Grade Not Assignable: There is no evidence available that directly supports or refutes the conclusion.

A detailed and annotated clinical algorithm is provided for the Diagnosis and Treatment of Hypertension.

ICSI, 8009 34th Avenue South, Suite 1200, Bloomington, MN 55425; telephone, (952) 814-7060; fax, (952) 858-9675; e-mail: icsi.info@icsi.org; Web site: www.icsi.org.

ICSI's conflict of interest policy and procedures are available for review on ICSI's website at www.icsi.org.

Electronic copies: Available from the Institute for Clinical Systems Improvement (ICSI) Web site.

Print copies: Available from ICSI, 8009 34th Avenue South, Suite 1200, Bloomington, MN 55425; telephone, (952) 814-7060; fax, (952) 858-9675; Web site: www.icsi.org; e-mail: icsi.info@icsi.org.

• Hypertension diagnosis and treatment. Executive summary. Bloomington (MN): Institute for Clinical Systems Improvement, 2008 Oct. 1 p. Electronic copies: Available from the Institute for Clinical Systems Improvement (ICSI) Web site.
• ICSI pocket guidelines. May 2007 edition. Bloomington (MN): Institute for Clinical Systems Improvement, 2007.

Print copies: Available from ICSI, 8009 34th Avenue South, Suite 1200, Bloomington, MN 55425; telephone, (952) 814-7060; fax, (952) 858-9675; Web site: www.icsi.org; e-mail: icsi.info@icsi.org.

Electronic copies: Available in Portable Document Format (PDF) from the Institute for Clinical Systems Improvement (ICSI) Web site.

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