Hypertension Part 2

Physical examination

The examination should include at least two standardized measurements of BP with the subject in the seated position. Initially, BP should also be measured in the opposite arm (to identify arterial narrowing, which can cause an inaccurately low reading in one arm) and in the standing position, especially in diabetic patients and older patients (to identify orthostatic declines). Height and weight should be determined, to permit calculation of body mass index, and waist circumference (a potential CV risk factor) should be recorded.

The physical examination is directed toward identifying target organ injury or features suggesting secondary hypertension [see Table 4]. Retinal examination should be performed, primarily to identify retinal changes of diabetes or severe hypertension (i.e., hemorrhages, exudates, papilledema). Arteriolar narrowing, focal constrictions, and arteriovenous nicking on retinal examination are more closely associated with atherosclerosis and are of limited value for predicting the severity of hypertension or assessing overall CV risk.43,45

Table 4 Features Suggesting Specific Causes of Secondary Hypertension

Condition	Features
Primary aldosteronism	Unprovoked hypokalemia
	Labile BP with episodic headache, sweats, tachycardia, pallor, abdominal pain, weight loss
Pheochromocytoma	Neurofibromas, cafe-au-lait spots
	Orofacial neuromas (multiple endocrine neoplasia type II)
	Retinal angiomas (von Hippel-Lindau syndrome)
	Abdominal or flank bruits
	Peripheral bruits/diminished pulses from atherosclerosis
	Elevated serum creatinine level, hypokalemia
	Flash pulmonary edema
Renovascular hypertension	Hypertension in a patient younger than 30 yr (fibromuscular dysplasia)
	Sudden onset or worsening of systolic-diastolic hypertension after age 50 yr (atheromatous disease)
	Accelerated-malignant hypertension
	Treatment-resistant hypertension
	Unexplained subacute decline in renal function
Cushing syndrome
	Truncal obesity, proximal muscle weakness and atrophy Stria, acne, thin skin, bruises, hyperpig-mentation
	Elevated plasma glucose, hypokalemia
Coarctation of the aorta
	Headaches
	Cold feet, claudication
	Delay of femoral pulse compared to radial pulse
	Weak or absent femoral pulses
	High BP in arms/low BP in legs
	Murmurs front/back chest
Polycystic renal disease	Abdominal/flank masses, family history of renal disease

Table 5 Drugs That Can Increase Blood Pressure or Interfere with Antihypertensive Drug Efficacy

Drug	Mechanism
Oral contraceptives	Sodium retention, increase level of angiotensinogen, facilitate action of catecholamines
Alcohol (moderate or heavy intake)	Activate sympathetic nervous system, increase cortisol secretion and intra-cellular calcium levels
Sympathomimetics and amphetamine-like substances (over-the-counter cold or allergy formulas, diet pills)	Increase peripheral vascular resistance
Nonsteroidal anti-inflammatory drugs	Sodium retention, renal vasoconstric-tion; interfere with efficacy of all anti-hypertensive drugs, especially diuretics, beta blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers
Corticosteroids	Iatrogenic Cushing disease
Tricyclic antidepressants	Inhibit action of centrally acting sympa-tholytics (clonidine, guanfacine)
Serotoninergics (antidepressants)	Systemic vasoconstriction (increase peripheral vascular resistance)
Cyclosporine	Renal and systemic vasoconstriction (sodium retention, increased peripheral vascular resistance)
Erythropoietin	Systemic vasoconstriction (increased peripheral vascular resistance)
Monoamine oxidase inhibitors + tyramine-containing foods (aged cheeses, red wine)	Prevents degradation of norepinephrine released by tyramine-containing foods; increase in BP with reserpine
Cocaine	Systemic vasoconstriction (increased peripheral vascular resistance)
Marijuana	Increases systolic blood pressure
Glycyrrhizinic acid (chewing tobacco, imported licorice, health food products)	Inhibits renal metabolism of cortisol to cortisone (increased mineralocorticoid activity causing sodium retention, loss of potassium)
Grapefruit products	Inhibit cytochrome P-450 metabolism of some drugs
Herbs
Bloodroot	CNS stimulant
Blue cohosh	Action of methylcytisine
Broad bean	Unknown
Scotch broom	Sympathomimetic
Cola nut	Sympathomimetic
Ephedra	Sympathomimetic, CNS stimulant
Foxglove	Cardiac inotrope
Gentian	Unknown
Ginseng	CNS stimulant, glucocorticoid effect
Goldenseal	Systemic vasoconstriction
Grindelia	CNS stimulant
Jimson weed	Anticholinergic effect
Juniper	Aquaretic
Kava	Unknown
Yohimbe	Central alpha blocker

Table 6 Laboratory Evaluation of Newly Diagnosed Hypertensive Patients

Purpose	Tests
Identify cardiovascular risk factors	Cholesterol (total, HDL), triglycerides, fasting blood glucose
Identify target-organ injury	Chest x-ray, ECG, urinalysis, serum creati-nine or BUN, uric acid
Screen for secondary hypertension	Serum creatinine, potassium, calcium; urinalysis
Calculate kidney function	Cockcroft and Gault equation: GFR = (140 – age in yr) x (weight in kg) x 0.85 (if patient is female)/72 x SCr Modification of Diet in Renal Disease (MDRD) equation: GFR = 170 x (SCr)-0.999 x (age in yr)-°.l76 x 0.762 (if patient is female) x 1.18 (if patient is black) x (BUN)-017 x (alb)0 3i8

alb—serum albumin concentration (g/dl)

BUN—blood urea nitrogen (mg/dl)

ECG—electrocardiogram GFR—glomerular filtration rate (ml/min)

HDL—high-density lipoprotein

Sq.—serum creatinine (mg/dl)

Laboratory tests

Laboratory studies are performed to support the general goals of the initial evaluation [see Table 6]. In addition, they provide baseline information for monitoring in patients who are subsequently treated with antihypertensive drugs that can influence laboratory values (i.e., diuretics, beta blockers, ACE inhibitors, and angiotensin receptor blockers [ARBs]). Additional studies are not advised unless the history, physical examination, or initial laboratory studies are inconsistent with essential hypertension or suggest a specific secondary etiology.

If the initial assessment suggests renal dysfunction, the patient should be evaluated for chronic kidney disease by measuring 24-hour urinary protein excretion and estimating glomeru-lar filtration rate (GFR). Equations are available to estimate GFR [see Table 6].46,47 The Modification of Diet in Renal Disease (MDRD) equation requires measurement of blood urea nitrogen and serum albumin concentrations in addition to serum creati-nine concentration. The estimate of GFR can also be calculated with an online tool (available at www.hdcn.com/calcf/gfr.htm).

Risk stratification

At any given level of BP, specific factors in an individual patient may result in deviations above or below the average CV risk observed in population studies. These factors are used to determine the BP threshold and timing of drug therapy and the BP goal for the individual patient. Individual specific factors that determine risk include the presence of other CV risk factors and the presence of injury to the target organs of hypertension or clinical CV disease.3 A simple and clinically useful scheme modified from the JNC VI report separates patients into three levels of risk [see Table 7].42 This scheme suggests aggressive treatment and lower BP goals for patients at the highest level of risk and more conservative treatment and BP goals for patients at the lowest level of risk. For example, in a patient with diabetes, drug therapy is indicated initially (along with lifestyle changes) when BP exceeds 130/80 mm Hg. In contrast, in a young patient who has no other CV risk factors or evidence of target organ injury or CV disease, a 6- to 12-month trial of lifestyle changes rather than drugs is indicated as initial therapy unless BP is of stage 2 (> 160 mm Hg systolic or > 100 mm Hg diastolic). In these low-risk cases, the goal BP is less than 140/90 mm Hg. Guidelines from Europe provide an even more detailed approach to risk stratification.43

Table 7 Risk Stratification and Treatment in Hypertensive Patients^8,42,43

Blood Pressure Stage (mm Hg)	Risk Group A (no risk factors, no TOD/CCD*)	Risk Group B (a 1 risk factor, not including diabetes; no TOD/CCD)	Risk Group C (TOD/CCD and/or diabetes ± other risk factors)
Prehypertension 120-139/80-89)	Lifestyle modification	Lifestyle modification	Lifestyle modification, drug therapy*
Stage 1 (140-159/90-99)	Lifestyle modification (up to 12 mo)	Lifestyle modification (up to 6 mo)’	Lifestyle modification, drug therapy
Stage 2 (a 160/a 100)	Lifestyle modification, drug therapy	Lifestyle modification, drug therapy	Lifestyle modification, drug therapy

*Risk factors are cigarette smoking, dyslipidemia, diabetes, age > 55 yr in men and > 65 yr in women, male sex, postmenopausal status in women, family history of premature cardiovascular disease (women < 65 yr, men < 55 yr), nephropathy (microalbuminuria or glomerular filtration rate < 60 ml/min), obesity (body mass index > 30 kg/m2; waist circumference > 102 cm in men and > 88 cm in women), C-reactive protein level > 1 mg/dl, physical inactivity. TOD/CCD includes left ventricular hypertrophy, angina, prior myocardial infarction, heart failure, previous coronary revascularization procedure, stroke, transient ischemic attack, nephropathy, peripheral arterial disease, retinopathy.

+For patients with multiple risk factors, consider drugs initially in addition to lifestyle modifications.

-Use drugs if BP > 130 mm Hg systolic or > 80 mm Hg diastolic and patient has heart failure, chronic kidney disease, or diabetes. TOD/CCD—target-organ disease/clinical cardiovascular disease

Prevention of Hypertension

In many cases, the assessment will show BP in the prehyper-tensive range (i.e., 120 to 139/80 to 89 mm Hg); in the United States, 22% of adults, or approximately 45 million persons, fit this category. Preventive care is indicated in these patients.

Multiple studies support the effectiveness of environmental manipulation in preventing or delaying the onset of hyperten-sion.48-51 Prevention of hypertension is important, given that treatment of established hypertension is only partly effective in reducing the associated morbidity and mortality.52 Furthermore, the relationship between BP level and CV morbidity and mortality is continuous and extends into nonhypertensive levels; approximately one third of the coronary artery disease deaths attributable to BP occur in persons whose BP is in the prehypertensive range. Prevention strategies that lower BP in prehypertensive patients extend the benefits of BP reduction to this large group.

The risk of developing hypertension is increased in African Americans and in all persons with prehypertension or a family history of hypertension. Reversible patient characteristics associated with an increased risk of developing hypertension include being overweight or obese; having a sedentary lifestyle; ingesting a high-sodium, low-potassium diet; using excessive amounts of alcohol; and manifesting the so-called metabolic syndrome. The metabolic syndrome is defined as three or more of the following conditions: abdominal obesity (waist circumference > 40 inches in men or > 35 inches in women), glucose intolerance (fasting blood glucose > 110 mg/dl), BP of 130/85 mm Hg or higher, elevated triglycerides (> 150 mg/dl) or low high-density lipoprotein (HDL) cholesterol (< 40 mg/dl in men or < 50 mg/dl in women).53 Clinical trials support the efficacy of six interventions in such people for the primary prevention of hypertension [see Table 8].48,49,51 Combining interventions is beneficial.54,55 For patients with the metabolic syndrome, in addition to intensive lifestyle modifications, drug therapy is recommended for management of each of its components when appropriate.

Treatment

The overall goal of treatment in hypertensive patients is to reduce the risk of CV morbidity and mortality by lowering BP and treating other modifiable risk factors. In general, the goal is to lower BP to below 140/90 mm Hg. In patients with heart failure, diabetes, or renal disease, the goal is to lower BP to below 130/80 mm Hg. In older patients with ISH, the goal is to lower systolic BP to below 140 mm Hg.

These goals are achieved through lifestyle modification and, in most cases, drug therapy. In addition, comorbid conditions such as dyslipidemia or diabetes should be addressed.53 Low-dose aspirin should be considered once BP is controlled.56 Self-measurement of BP should be encouraged.