Pathophysiology

Some conditions produce secondary hypertension as a consequence of other disease. The hypertension that results from these conditions is often treatable (see Table 17-3). The cause of primary hypertension (which accounts for approximately 95% of cases of hypertension) remains unknown. Although these are not completely understood, many factors have been linked to primary hypertension, including some that are genetically determined. Involved mechanisms include elevated peripheral resistance, alteration in the cell membrane related to elevated lipids, endothelial dysfunction, changes in sodium or calcium levels, and hyperinsulinemia. Sympathetic nervous system hyperactivity caused by insensitivity of the baroreflexes may contribute to hypertension accompanied by tachycardia and elevated cardiac output in younger patients.

Dysregulation of the renin-angiotensin system leads to hypertension, although this does not appear to be a major factor in the origin of hypertension. African Americans with hypertension and older adult patients tend to have lower plasma renin activity. Approximately 10% of hypertensive individuals have high levels, 60% have normal, and 30% have low renin levels.

Some patients have a decreased ability to excrete sodium, which leads to increased blood volume and increased BP. Sodium restriction may be necessary in these individuals. Abnormalities in sodium transport mechanisms lead to an increased level of intracellular sodium in blood cells. This may result in the increased vascular smooth muscle tone characteristic of hypertension.

Environmental, lifestyle, and dietary factors also play important, and modifiable, roles. Obesity leads to increased intravascular volume and increased cardiac output. Alcohol increases BP by increasing plasma catecholamines. Cigarette smoking raises BP by increasing plasma norepinephrine.

NSAIDs cause fluid retention, which can lead to hypertension. Excessive intake of sodium (salt) or low levels of potassium can contribute to hypertension by increasing blood volume. Physical inactivity is a recently recognized risk factor.

Hypertension is a powerful risk factor for cardiac disease. The higher the BP, the greater is the risk for ischemic heart disease, heart attack, heart failure, stroke, and kidney disease. In adults, each increase of 20 mm Hg in systolic blood pressure (SBP) or 10 mm Hg in diastolic blood pressure (DBP) doubles the patient’s risk of cardiovascular disease (CVD). This knowledge has led to an emphasis on the lower spectrum of BP, resulting in the classification of “prehypertension,” which is new to JNC 7.

A “metabolic syndrome” has recently been identified as a major cardiac risk factor. This constellation of symptoms is also referred to as syndrome X, the insulin resistance syndrome, or the obesity dyslipidemia syndrome. A patient who has abdominal obesity, hypertension, insulin resistance, and a lipid disorder has a greatly elevated risk of CVD. Instead of serving as separate risk factors, they work together to increase risk. Table 17-2 lists the major cardiovascular risk factors. The WHO diabetes group proposed a set of criteria for diagnosing the metabolic syndrome in 1998 and later updated these (Grundy et al, 2004). This definition is as follows:

TABLE 17-2

Major Cardiovascular Risk Factors for Hypertension

Metabolic syndrome

Hypertension

Dyslipidemia

Obesity (body mass index [BMI] ≥30)^∗

Diabetes mellitus

Cigarette smoking

Physical inactivity

Microalbuminuria or estimated glomerular filtration rate (GFR) <60 ml/min

Family history of premature cardiovascular disease (men younger than age 55 or women younger than 65 years)

^∗Body mass index is calculated as:

Weight(in kg)Height(in kg)

From Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure Education Program: The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, NIH publication No. 03-5233, Bethesda, MD, May 2003, National Institutes of Health, National Heart, Lung, and Blood Institute.

Hyperinsulinemia (defined as the upper quartile of a measure of insulin resistance in the nondiabetic population) OR a fasting plasma glucose (FPG) greater than or equal to 110 mg/dl (6.1 mmol/L) or a plasma glucose two hours after an oral glucose tolerance test greater than or equal to 200 mg/dl (11.1 mmol/L)

PLUS at least two of the following:

Disease Process

Fifty million Americans have hypertension, and the prevalence increases with age. Only about 34% of these people are adequately treated. Hypertension is a risk factor for CVD, stroke, CHF, renal failure, and peripheral vascular disease. CVD and stroke are the most common causes of death in the United States. Current levels of cardiovascular morbidity and mortality show that much greater effort is required to control hypertension (ALLHAT, 2002).

The pendulum continues to swing regarding which factor is the most important to control: systolic or diastolic BP. Systolic BP was first considered to be most important; subsequently, focus shifted to diastolic BP. Some researchers are exploring the significance of pulse pressure (i.e., difference between systolic and diastolic BP). However, ongoing research suggests that management scenarios must address both systolic and diastolic BP levels.

Assessment

The diagnosis of hypertension is based on the average of readings taken at an initial screening and two or more readings taken at each of two or more subsequent visits. The readings on these three separate occasions should not be influenced by any other known mechanism, such as recent exercise, anxiety, or an acute illness. Initial evaluation includes a thorough history, physical examination, and laboratory screening (Box 17-1).

Once the diagnosis of hypertension is made, further evaluation of three factors that are affecting the patient’s risk is necessary. Severity should be determined according to the classification in Table 17-4. Next, target organ damage (Table 17-5), which is the damage the hypertension has already caused, should be evaluated. Finally, assessment should be completed for compelling indications (Table 17-6), which include conditions managed in parallel with HTN. These three factors will affect management.

TABLE 17-5

Target Organ Damage Occurring with Hypertension

HEART

Left ventricular hypertrophy

Angina or prior myocardial infarction

Prior coronary revascularization

Heart failure

BRAIN

Stroke or transient ischemic attack

Chronic kidney disease

Peripheral arterial disease

Retinopathy

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