Chapter 41. Primary (Essential) Hypertension

• Primary hypertension in adults aged 18 years and older is defined as blood pressure of 140/90 mm Hg or more, based on an average of two or more properly measured seated blood pressure (BP) readings at each of two or more clinic visits.
• Normal BP is a systolic BP (SBP) <120 mm Hg and diastolic BP (DBP) <80 mm Hg.
• Prehypertension is defined as an SBP of 120–139 mm Hg or DBP of 80–89 mm Hg.
• Stage 1 hypertension is defined by an elevation in either SBP 140–159 mm Hg or diastolic BP of 90–99 mm Hg.
• Stage 2 hypertension is defined by an elevation in either SBP of ≥160 mm Hg or DBP of ≥100 mm Hg.
• The level of BP alone is inadequate for diagnosis and it should be interpreted in the context of the overall cardiovascular risk of the patient, which is most easily estimated by evaluating other concomitant disorders and target-organ damage (TOD).

Hypertension affects more than 29% adult Americans and is the most common reason for office visits to physicians in the United States. The prevalence of hypertension is expected to increase largely due to the epidemic of obesity and the aging population in the United States. Indeed, data from the Framingham health study suggest that people with a normal BP (<120/80 mm Hg) at 55 years of age have a 90% lifetime risk of developing hypertension. Additionally, it is now well established that a linear relationship exists between BP and risk of cardiovascular events, thus the more elevated the BP the greater the likelihood of myocardial infarction, congestive heart failure, kidney failure, or stroke.

Despite the increased prevalence of hypertension and its associated morbidity and mortality, current control rates are inadequate. Only 34% of people with hypertension have their BP controlled to a goal of BP < 140/90 mm Hg. Key factors for the inadequate BP control include failure of physicians to prescribe (1) lifestyle modifications, (2) adequate doses of antihypertensive medications, and (3) appropriate drug combinations and increased occurrence of pure systolic hypertension in the elderly, which is considerably more difficult to treat.

Risk Factors

The Joint National Committee (JNC) 7 recommends that specific public health interventions such as decreasing calories, saturated fat, and salt intake, especially in processed foods, and increasing physical activity be strongly encouraged at school and community levels. This strategy can achieve a downward shift in the distribution of a population's BP and thus potentially decrease the lifetime risk of morbidity and mortality from hypertension in an individual.

Measurement of Blood Pressure

Accurate measurement and interpretation of BP is crucial for the diagnosis and treatment of hypertension. The recommendations outlined below will help standardize the technique and improve the accuracy of BP readings:

• Patients should abstain from drinking caffeine or alcohol-containing beverages or using tobacco within 30 minutes prior to a BP measurement.
• The cuff size appropriate for the patient's arm circumference should be used (the cuff bladder should encircle at least 80% of the arm).
• The cuff bladder should be centered over the brachial artery, with its lower edge within 2.5 cm of the antecubital fossa.
• Listen over the brachial artery using the bell of the stethoscope with minimal pressure exerted on the skin. Inflate the cuff 20 mm Hg higher than the pressure at which the palpable pulse at the radial artery disappears. Use a properly calibrated syphgmomanometer.
• The deflation rate of the column of mercury should be 2–3 mm Hg/second.
• Multiple measurements should be made on different occasions in the sitting position with the back supported for 5 minutes and the arm at heart level.
• At least two readings should be taken on each visit separated by as much time as possible.
• Attempt to avoid “terminal digit preference” (more than 20% of measurements ending with a specific even digit).
• Measure BP in both arms initially, and in the arm with the higher BP thereafter if the difference is greater than 10/5 mm Hg.

Home Blood Pressure Measurements

Home BP measurements are indicated for (1) evaluating white-coat hypertension, (2) assessing TOD in response to antihypertensive drug therapy, and (3) improving patients' adherence to therapy. Home BP readings are typically lower (by an average of 12/7 mm Hg), and correlate better with a risk of future mortality, than office BP measurements. Persons with home BP readings of >135/85 mm Hg are generally considered to have hypertension.

Ambulatory Blood Pressure Monitoring

Ambulatory BP readings provide BP data during daily activities and sleep and correlate better than home or office readings with TOD, left ventricular hypertrophy (LVH), and cardiovascular event rates. They are indicated for the evaluation of white-coat hypertension in the absence of TOD, episodic hypertension, apparent drug-resistant hypertension, drug-induced hypotensive symptoms, and autonomic dysfunction. As in home BP readings patients are considered to have hypertension if their mean BP during the day is >135/85 mm Hg or >125/75 mm Hg during sleep. Recent outcome studies have demonstrated increased cardiovascular risk associated with abnormal ambulatory blood pressure monitoring (ABPM) profiles (eg, “nondipping” of BP at night).

White-Coat Hypertension

Approximately 25% of those with hypertension have BP readings that are considerably higher in the doctor's office or hospital than those measured at home, at work, or by ABPM. This occurs more commonly among the elderly. The clinical consequences of this diagnosis are higher risk for cardiovascular events and related mortality as compared to normotensive, non-white-coat hypertension patients, but with a lower risk than those with primary hypertension. Twenty-four hour ambulatory monitoring is needed along with a normal physical examination to confirm the diagnosis. It has been suggested that such stimuli raise BP only transiently and reversibly while others think that these patients will all eventually become sustained hypertensives. Currently, lifestyle modifications with frequent BP monitoring are recommended.

Laboratory Findings

Patients with essential hypertension should undergo a limited work-up because extensive laboratory testing may be unrewarding.

Cardiac Tests

LVH is an objective measure of both the severity and duration of hypertension. It should be routinely evaluated in all patients with an electrocardiogram although an echocardiogram appears to be a better predictor of future cardiovascular events. Other initial laboratory tests include a 9–12 hour fasting lipid profile that includes high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides, hematocrit, and routine blood chemistries including glucose.

Kidney Function Tests

Current recommendations for evaluation of kidney function include a serum blood urea nitrogen and creatinine, estimated glomerular filtration rate (GFR), electrolytes, and spot urinalysis to detect red blood cells, white blood cells, casts, or proteinuria. Optional tests include measurement of urine albumin excretion or albumin/creatinine ratio and microalbuminuria (protein excretion between 30 and 300 mg/day). Note: All patients with even trace positive protein on routine dipstick should have a spot urine albumin:creatinine checked.

Special Examinations

The initial clinic evaluation of a person with elevated BP readings should include the following objectives:

• Determine an accurate diagnosis of hypertension.
• Define the presence or absence of TOD related to hypertension (Table 41–1).
• Screen for other cardiovascular (CV) risk factors or comorbidity that often accompany hypertension (Table 41–1).
• Stratify the risk for cardiovascular disease.
• Assess the likelihood of secondary hypertension and initiate further diagnostic testing to confirm or exclude the diagnosis.
• Obtain data that may be helpful in the choice of therapy and prognosis.

The most important aspects of the history include the natural history of the hypertension, aggravating factors, the extent of TOD, and the presence of other risk factors. Clinical clues suggestive of the possible presence of secondary hypertension must be recognized. The main goals of the physical examination are to evaluate for features of target-organ damage and for evidence of secondary hypertension. Keys areas include verification of the BP in the contralateral arm, fundoscopy, body mass index, waist circumference, auscultation for carotid, abdominal, and femoral bruits, and detection of lower extremity edema.

Hypertension is associated with major cardiovascular risks such as premature cardiovascular disease, congestive heart failure, LVH, stroke, chronic kidney disease, and end-stage renal disease.

The primary goal of antihypertensive therapy is to reduce cardiovascular and renal morbidity and mortality using the least intrusive means possible. Indeed, in clinical trials adequate BP control has been associated with mean reductions of >50% in the incidence of congestive heart failure, >20% in myocardial infarction, and >35% in stroke. Thus, JNC 7 and other national guidelines recommend that all patients with hypertension should have their SBP lowered to below 140 mm Hg and DBP below 90 mm Hg. In patients with hypertension and diabetes or chronic kidney disease, the recommended BP goal is less than 130/80 mm Hg.

Appropriate lifestyle modifications are strongly recommended for all patients with either prehypertension or hypertension. Antihypertensive medications should be started if the BP is >140/90 mm Hg despite an adequate trial of nonpharmacologic treatment. The initiation of two drugs should be strongly considered in all patients with a baseline BP of more than 20/10 mm Hg above goal or stage 2 hypertension. This strategy will increase the likelihood of achieving goal BP within a reasonable time period but should be used cautiously in patients with diabetes and the elderly who are at a higher risk of developing orthostatic hypotension.

Life-Style Modification

JNC 7 recommends weight loss for overweight or obese patients with hypertension, limitation of dietary sodium intake to ≤100 mEq/L/day (ie, 2.4 g of sodium or 6 g of sodium chloride) as part of the Dietary Approaches to Stop Hypertension (DASH) eating plan, and moderate alcohol intake of no more than two drinks per day. Increased physical activity such as brisk walking for at least 30 minutes for about 5 days/week is also advised (Table 41–2). Additionally, smoking cessation is also recommended to improve cardiovascular health. The benefits of these interventions include lowering BP, enhancement of antihypertensive efficacy, and reduction of cardiovascular risks.

Pharmacologic Treatment

Recent clinical trials have convincingly shown that reduction of BP by most antihypertensive agents will reduce the cardiovascular and renal morbidity and mortality associated with hypertension. The JNC 7 recommends that low-dose thiazide-type diuretics (eg, 12.5–25 mg of chlorthalidone or hydrochlorothiazide) should be used as initial therapy for most patients with hypertension either alone in stage 1 hypertension or in combination with other agents such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs) or β-blockers in stage 2 hypertension. The thiazide-diuretic based regimen has been shown by recent clinical trials including Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) to prevent or reduce the cardiovascular complications of hypertension and is associated with a low rate of metabolic complications. Most patients will need two or more antihypertensive agents to achieve the recommended BP goal. If the low-dose thiazide monotherapy is inadequate to achieve the BP goal an ACE inhibitor or ARB should be added. This combination is synergistic and effective in lowering BP, especially among African-Americans and the elderly. Other antihypertensive agents can be added sequentially or substituted at monthly intervals until the BP goal is reached (Figure 41–1). After the BP goal has been achieved and remains stable, patients can be followed up at 3- to 6-month intervals.

Treatment of Specific Clinical Conditions

The general recommendations for initial therapy should be adapted for particular clinical conditions in which specific antihypertensive agents have been shown to be beneficial by outcome data from clinical trials, what JNC 7 refers to as compelling indications. These include the demonstration that renin–angiotensin–aldosterone blockers such as ACE inhibitors or ARBs improve outcome in high-risk settings such as patients with diabetes mellitus, congestive heart failure, myocardial infarction, stroke, chronic kidney disease, or albuminuria and that β-blockers improve survival in patients with systolic heart failure and prior myocardial infarction.

Diabetes and Hypertension

The combination of hypertension and diabetes significantly increases the risk of cardiovascular events and end-stage renal disease than either risk factor alone. Recent clinical outcome trials and guidelines have solidified the role of renal angiotensin aldosterone antagonists such as ACE inhibitors and ARBs in delaying the progression of diabetic nephropathy and reducing cardiovascular events and they are indicated as agents of first choice in all patients with diabetes. Additionally, based on the ALLHAT Trial, thiazide diuretics must be included as part of the drug therapy for most patients with diabetes. Combinations of two or more antihypertensive drugs are usually needed to achieve the recommended goal BP of less than 130/80 mm Hg. If the BP goal is not achieved other drugs such as CCBs and vasodilating β-blockers are added until goal BP is attained.

Congestive Heart Failure (CHF)

Hypertension is a major risk factor for the subsequent development of both systolic and diastolic heart failure. For many patients, LVH is an important intermediate step, resulting in “hypertensive heart disease” with impaired LV filling and increased ventricular stiffness. The BP goal for most patients with CHF is less than 140/90 mm Hg. Asymptomatic patients with “reduced LV function” [left ventricular ejection fraction (LVEF) <40%] improve both their BP and long-term prognosis with an ACEI and β-blocker while patients with symptomatic systolic heart failure will require additional agents such as ARBs, aldosterone antagonists, and loop diuretics. Treatment of hypertension in CHF patients with preserved LV function has not been as well studied. In general, β-blockers or non-dihydropyridine (DHP)-CCBs are recommended to increase diastolic filling time and decrease heart rate, but there are currently no randomized clinical trials with outcome data to demonstrate their long-term efficacy.

Coronary Artery Disease (CAD)

The coexistence of CAD and hypertension is an indication for therapy with multiple antihypertensive drugs to achieve a goal BP of less than 140/90 mm Hg. In patients with hypertension and stable angina, β-blockers are strongly recommended but long-acting CCBs are suitable and effective alternatives based on the results of recent outcome trials such as the International Verapamil/Trandolapril Study in which more than 22,000 patients with hypertension and coronary disease were randomized to either atenolol or verapamil. Patients with acute coronary syndromes or post-myocardial infarction should be initially treated with ACE inhibitors, β-blockers, and aldosterone antagonists. Additional recommendations include intensive treatment of dyslipidemia (to achieve or exceed an LDL-cholesterol target of <100 mg/dL) and antiplatelet therapy with aspirin or dypyridamole.

Left Ventricular Hypertrophy (LVH)

LVH is a well-recognized independent risk factor for cardiovascular events and premature death. It is common in the elderly and is often associated with diastolic dysfunction. Intensive BP management with agents that induce regression of LVH and reduce BP to a goal of less than 140/90 mm Hg is recommended. Recent clinical trials indicate that ARBs are very effective agents for the reduction of LVH but other interventions such as weight loss, exercise, and sodium restriction are also effective.

Stroke

In acute ischemic stroke, the optimal level of BP is controversial. Acute lowering of the BP may lead to a reduction in blood flow to “watershed” areas of the brain with worsening of the neurologic function. In this setting, control of BP to intermediate levels of 160/100 mm Hg is appropriate. In stable patients, ACE inhibitors and thiazide diuretics are recommended to lower BP to a goal of less than 140/90 mm Hg and reduce recurrence of stroke.

Chronic Kidney Disease (CKD)

A majority of patients with CKD have hypertension and the therapeutic goals are to slow the progression of renal disease and to prevent cardiovascular disease. Optimal BP control to a goal of less than 130/80 mm Hg is strongly recommended. ACE inhibitors and ARBs are recommended for initial therapy because they have been shown to retard the progression of both diabetic and nondiabetic renal disease. An increase of the serum creatinine level by as much as 35% over baseline after initiation of these drugs should not lead to discontinuation because of the long-term benefits of these agents. For increases of serum creatinine larger than 35%, an assessment for concomitant nonsteroidal anti-inflammatory drug (NSAID) use, volume depletion, and/or renovascular hypertension is appropriate. Most patients will require three or more BP drugs to achieve the goal BP and loop diuretics are usually added when the estimated GFR is less than 30 mL/minute/1.73 m2.

Albuminuria/Proteinuria

In all patients with hypertension, albuminuria or proteinuria is an established risk marker for progression of renal disease and has also emerged as an independent marker of cardiovascular risk. Recent pharmacologic interventions with agents that lower BP and reduce albuminuria have resulted in a significant delay and even an arrest in the progression of microalbuminuria to CKD. Moreover, a reduction in proteinuria of more than 50% from baseline following 6 months of treatment reduces the risk of end-stage renal disease by 72% at 5 years. Recent outcome clinical trial data and current guidelines recommend that patients with hypertension with albuminuria should be started on agents that block the renin–angiotensin–aldosterone system, such as ACE inhibitors or ARBs. It has also been shown that maximal dose combinations of ACE inhibitors and ARBs agents further reduce albuminuria by an additional 30–35% over either agent alone, which correlates with slower kidney disease progression independent of BP. Nondihydropyridine CCBs such as verapamil or diltiazem also reduce proteinuria in patients with hypertension with proteinuric kidney disease, and have additive effects when combined with ACE inhibitors.