Hypertension can be quantified on the basis of a large number of epidemiologic studies showing that the distribution of BP in the population is continuous, although the curve is skewed at the higher levels of BP. The unimodal distribution of BP implies that hypertension is unlikely to be the result of a single physiologic process or gene, and perhaps most importantly suggests that any BP level used to define hypertension is arbitrary.
Hypertension can be classified in different ways—helpful for its diagnosis and clinical management (Fig. 23–1). The two principal divisions are severity (the height of the BP) and underlying cause (primary or essential hypertension vs secondary hypertension). A third major component is age: the pathophysiology of hypertension in younger and older people is quite different.
Three-dimensional classification of hypertension according to severity (height of the blood pressure), etiology (primary vs secondary), and age. BP, blood pressure.
The original subdivision of hypertension according to its severity was benign and malignant. Although malignant hypertension carries a prognosis that is equivalent to that of other malignant diseases (if untreated), the term benign for less severe forms of hypertension is a misnomer and is no longer used. Malignant hypertension is now relatively uncommon in Western countries, but it does still occur and, when present, it requires urgent treatment, which can dramatically alter its natural history.
In hypertensive patients, either or both the systolic and diastolic BP are elevated, but elevations in systolic BP are most common. In particular, the most common circumstance is isolated systolic hypertension where the systolic BP is elevated, but the diastolic BP normal, occurring predominantly in older persons. Isolated diastolic hypertension can also occur and is the most common hypertensive subtype in younger persons. Hypertension can also be the result of the measurement method used; traditional methods of classification have all been based on office or clinic BP measurements, but with the wider use of out-of-office BP measurement, office measurements can be shown to significantly over- or underestimate the BP level during daily life. In most hypertensive patients, the BP is higher in the office than at other times, a phenomenon referred to as the white coat effect and that is usually defined as the difference between the office pressure and the average daytime pressure.
The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC) 7 classification for hypertension2 has continued the definition of hypertension as a BP at or above 140/90 mm Hg for adults aged 18 years or older. The classification is based on the average of two or more seated BPs, properly measured with well-maintained equipment, at each of two or more visits to the office or clinic. Hypertension has been divided into stages 1 and 2, as shown in Table 23–1. JNC 7 has defined normal BP as systolic BP less than 120 mm Hg and diastolic BP less than 80 mm Hg. What JNC-6 previously labeled as normal (120–129 mm Hg systolic BP or 80–84 mm Hg diastolic BP) and high normal (130–139 mm Hg systolic BP or 85–89 mm Hg diastolic BP) are now combined into a single group renamed as prehypertension, to increase awareness to these individuals with an intermediate level of risk that may progress to definite hypertension. The more recent American Heart Association/American College of Cardiology/Centers for Disease Control and Prevention Science Advisory3 “An Effective Approach to High Blood Pressure Control” has retained the JNC-7 cutoff points for stages 1 and 2 hypertension as well as the goal levels that were recommended for treatment, as has the recent clinical practice guidelines from the American Society of Hypertension and International Society of Hypertension.4
TABLE 23–1.JNC Classification of Blood Pressure Stages ||Download (.pdf) TABLE 23–1. JNC Classification of Blood Pressure Stages
|JNC VI || ||JNC 7 |
|Category ||SBP (mm Hg) || ||DBP (mm Hg) || ||Category ||SBP (mm Hg) || ||DBP (mm Hg) |
|Optimal ||< 120 ||and ||< 80 ||→ ||Normal ||< 120 ||and ||< 80 |
|Normal ||< 130 ||and ||< 85 || ||Prehypertension ||120–139 ||or ||80–89 |
|High-normal ||130–139 ||or ||85–89 || || || || || |
|Hypertension || || || || || || || || |
|Stage 1 ||140–159 ||or ||90–99 || ||Stage 1 ||140–159 ||or ||90–99 |
|Stage 2 ||160–179 ||or ||100–109 ||→ || || || || |
|Stage 3 ||≥ 180 ||or ||≥ 110 ||Stage 2 ||≥ 160 ||or ||≥ 100 |
It is estimated that approximately 15% of BP–related deaths from coronary heart disease (CHD) occur in individuals with BP in the prehypertensive range.5 JNC 7 officially defined prehypertension (systolic BP of 120–139 mm Hg or diastolic BP of 80–89 mm Hg) based on data mainly from the Framingham Heart Study. It showed (1) that people who have BP in the prehypertensive range have a higher risk of heart disease and stroke than do people with BPs below this level, with 18% of those with BPs of 120–129/80–84 mm Hg and 37% of those with BPs of 130–139/85–89 mm Hg progressing to clinical hypertension within only a few years,6 and that (2) the lifetime risk of hypertension approaches 90%,7 warranting the importance of the concept of prehypertension to help motivate physicians and patients alike to promote lifestyle modifications to prevent or delay the transition to clinical hypertension. Data from the National Health and Nutrition Examination Survey (NHANES) 1999–2006 in persons without cardiovascular disease (CVD) or cancer shows a prevalence of prehypertension of 36.3%, higher in men than in women, and associated with adverse cardiometabolic risk factors.8 A recent meta-analysis of 17 prospective cohort studies comprising 591,664 participants showed that, compared with optimal blood pressure (< 120/80 mm Hg), those with prehypertension had a 43% higher risk of incident coronary heart disease (CHD; hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.26–1.63), a risk that was higher in Western subjects (relative risk [RR], 1.70; 95% CI, 1.49–1.94) than in Asian subjects (RR, 1.25; 95% CI, 1.12–1.38), with 24.1% of CHD attributable to prehypertension in Western subjects versus 8.4% in Asian subjects.9 A similar analysis by the same group, involving 19 prospective studies, showed prehypertension to be associated with a 66% greater risk of stroke; even those in the lower range of prehypertension (systolic BP 120–129 mm Hg or diastolic BP 80–84 mm Hg) had a significant 44% increased risk.10 Importantly, prehypertension has been recently shown to be associated with abnormalities of cardiac structure and function, specifically increased left ventricular remodeling and impaired diastolic function11; inflammatory factors including C-reactive protein, interleukin-6, and tumor necrosis factor-alpha12; as well as increased arterial stiffness in older persons.13
Isolated Systolic Hypertension
In many older adults, systolic BP tends to rise as diastolic BP falls. When the average systolic BP is at least 140 mm Hg and diastolic BP is less than 90 mm Hg, the patient is classified as isolated systolic hypertensive. The increased pulse pressure (systolic-diastolic) and systolic pressure predict risk and determine treatment.14 The transition of hypertensive subtypes has been described from data from the NHANES: isolated diastolic hypertension is most common in younger persons whereas isolated systolic hypertension is the most common subtype in those aged 60 years and over, accounting for more than 90% of hypertension in those aged 80 years and over (Fig. 23–2).15
Distribution of hypertensive subtypes in the untreated hypertensive population by age (National Health and Nutrition Examination Survey [NHANES III]). Numbers at top of bars represent the overall percentage distribution of untreated hypertension by age. DBP, diastolic blood pressure; IDH, isolated diastolic hypertension; ISH, isolated systolic hypertension; SBP, systolic blood pressure; SDH, systolic and diastolic hypertension Reproduced with permission from Franklin SS, Jacobs MJ, Wong ND, et al: Predominance of isolated systolic hypertension among middle-aged and elderly US hypertensives: analysis based on National Health and Nutrition Examination Survey (NHANES) III. Hypertension. 2001 Mar;37(3):869-874.
Isolated systolic hypertension can also occur in the young. High systolic pressure in younger persons may be the result of two changes: a high stroke volume and increased arterial stiffness. In contrast to essential hypertension, which raises both systolic and diastolic pressures, peripheral resistance is not increased.16 In long-term follow-up of 31 years, younger and middle-aged adults with isolated systolic hypertension had higher relative risk than those with high-normal BP.17
Isolated Diastolic Hypertension
More commonly seen in younger adults, a systolic BP of less than 140 mm Hg accompanied by a diastolic BP of 90 mm Hg or more defines isolated diastolic hypertension. This represents more than half of hypertension under the age of 40 years (see Fig. 23–2).15 Diastolic pressure is generally thought to be the best predictor of risk in patients aged younger than 50 years18; an analysis of data from the Framingham Heart Study also concluded that isolated diastolic hypertension may evolve into systolic and diastolic hypertension.19 The US NHANES survey also showed that obesity was associated with isolated diastolic hypertension in all age groups and both genders—but most frequently in young adults.20 Thus, any patients in whom isolated diastolic hypertension is diagnosed should be carefully followed.
In approximately 15% to 30% of people with stage 1 hypertension, BP is elevated only persistently in the presence of a health-care worker, particularly a physician. When measured elsewhere, including while at work, the BP is not elevated. When this phenomenon is detected in patients who are not taking medications, it is referred to as white coat hypertension or isolated office hypertension. The commonly used definition is a persistently elevated average office BP of 140/90 mm Hg or more and an average awake ambulatory reading of less than 135/85 mm Hg (Fig. 23–3).21 Although it can occur at any age, it is more common in women, older adults, nonsmokers, and those with recently diagnosed hypertension; a misdiagnosis of a person with white coat hypertension as being truly hypertensive can result in his or her being penalized for employment and consideration for insurance, as well as possibly being subjected to lifelong antihypertensive treatment.22 This assertion was recently confirmed by Ogedegbe et al in a study in which patients with white coat hypertension reported significantly higher levels of state anxiety compared with other hypertension diagnostic categories.23 Its magnitude can be reduced (but not eliminated) by the use of stationary oscillometric devices that automatically determine and analyze a series of BPs over 15 to 20 minutes with the patient in a quiet environment in the office or clinic. Although white coat hypertension has been generally thought to have a benign prognosis, a recent meta-analysis of 14 studies comprising 29,100 patients showed that cardiovascular mortality and morbidity in subjects with white coat hypertension is slightly higher than normotensive controls but well below the cardiovascular risks associated with sustained hypertension.24 All patients should be followed indefinitely with office and out-of-office measurements of BP. Treatment with antihypertensive drugs may lower the office BP but does not change the ambulatory measurement. This pattern of findings suggests that drug treatment of white coat hypertension is less beneficial than treatment of sustained hypertension.
Classification of white coat and masked hypertension according to clinic and ambulatory blood pressures.
The mirror image of white coat hypertension, masked hypertension is defined as a normal office BP (< 140/90 mm Hg) together with an elevated daytime BP (≥ 135/85 mm Hg) (see Fig. 23–3). It is present in approximately 10% to 40% of patients not receiving antihypertensive treatment. Also, persons with prehypertension are more likely to have masked hypertension and can even develop target organ damage before transitioning to established sustained hypertension. Twenty-four–hour ambulatory BP monitoring is the standard for diagnosing masked hypertension, but home BP monitoring can also be used. Importantly, reliance on in-office BP values to initiate treatment can result in up to a third of persons remaining at increased risk resulting from masked hypertension.25 Masked hypertension is associated both with target organ damage26 and an adverse prognosis,27 and has been detected both in subjects who have not been diagnosed or treated for hypertension and in patients on antihypertensive treatment.28 The Dallas Heart Study also recently showed a two-fold greater risk of future cardiovascular events in those with masked hypertension compared to those who were normotensive.29 Importantly, masked hypertension is more common in older persons, those with mental stress, smokers, and those with metabolic syndrome, diabetes, chronic kidney disease, obstructive sleep apnea. Thus, there is an underdiagnosis of clinical hypertension in such persons, emphasizing an even greater importance for the use of 24-hour ambulatory BP measures in these individuals.28 Furthermore, persons with masked hypertension frequently present with elevated nocturnal BP and a nondipping pattern that predicts worse cardiovascular outcomes; this again can only be diagnosed with 24-hour ambulatory BP monitoring.30
The term pseudohypertension is misleading; it suggests a false elevation of diastolic BP when in actuality it is low. This condition represents wide pulse pressure isolated systolic hypertension in the elderly. It frequently occurs with diabetes and diabetic kidney disease, and is associated with extensive calcification of many large arteries, including the brachial and elastic aorta. These conditions are obviously associated with severe CVD risk. Differential diagnosis must exclude benign white coat hypertension, which is a frequent finding in the elderly and is best diagnosed with ambulatory BP monitoring. Indeed, with the advent of 24-hour ambulatory BP measurement, description of cases of pseudohypertension have largely disappeared from the literature—except for false inclusion in textbooks.31
Orthostatic or Postural Hypotension
This condition is defined as a reduction of systolic or diastolic BP of at least 20 or 10 mm Hg, respectively, within 3 minutes of quiet standing.32 An alternative method is to detect a similar decline during head-up tilt at 60 degrees. This may be asymptomatic or accompanied by symptoms of light-headedness, faintness, dizziness, blurred vision, and cognitive impairment.33 If chronic, the fall of BP may be part of pure autonomic failure or a complication of diabetes. The major life-limiting failure is inability to control the level of BP, especially in those patients with orthostatic hypotension who concomitantly have supine hypertension. In these patients, there are great and swift changes in pressure so that the patients faint as a result of profound hypotension on standing and have very severe hypertension when supine. Often the heart rate is fixed as well. The supine hypertensive person is subject to serious consequences, such as left ventricular hypertrophy34 and stroke.35,36
Hypertensive Crises: Urgency, Emergency, and Malignant Hypertension
A hypertensive crisis can present as urgency or emergency that requires immediate medical treatment.37 A hypertensive urgency is defined as having two or more readings where the systolic BP is elevated at 180 mm Hg or higher or diastolic BP of 110 mm Hg or higher, without associated organ damage, and may or may not be accompanied by symptoms such as severe headache, nosebleeds, shortness of breath, or severe anxiety. This is distinguished from a hypertensive emergency where target organ damage has occurred (eg, chest pain, shortness of breath, back pain, numbness/weakness, change in vision, difficulty speaking) requiring the individual to seek immediate emergency medical assistance.38 Malignant hypertension is defined as the presence of elevated BP in association with bilateral retinal hemorrhages and/or exudates, with or without papilledema. Although there have been substantial improvements in the general management of hypertension, there is no good evidence of reduction in its prevalence.39 However, in the absence of retinopathy, a hypertensive emergency is based on the criteria of acute elevated BP accompanied by damage to one of many target organs. Its importance lies in the fact that if untreated, it has a 5-year survival rate of 1%.40 It is still relatively uncommon in developing countries,41 but its prevalence may be increasing with the global increase in hypertension prevalence.39 It can result from essential or secondary hypertension. Treatment of malignant hypertension has a dramatic effect on survival, and the first article demonstrating the benefits of antihypertensive drugs was based on patients with malignant hypertension.42
In more than 95% of cases of hypertension, no single and reversible cause can be detected, and the terms essential and primary hypertension have been used. The former term was introduced because it was thought that a higher-than-usual level of BP was needed to maintain perfusion of vital organs.
In approximately 5% of cases there is a definable cause of the hypertension.2 Table 23–2 shows a list adapted from JNC 7.2 From an epidemiologic point of view, the two most important conditions on the list are chronic kidney disease and sleep apnea. Although chronic kidney disease is certainly a major cause of hypertension, it is often difficult to decide whether the hypertension or the kidney disease came first, because a vicious cycle can develop where one condition exacerbates the other. In practice, however, this distinction is of little consequence, because most forms of chronic kidney disease are not reversible. The most common curable form of hypertension is renal artery stenosis, which has two principal causes: (1) fibromuscular disease in children and young adults and (2) atherosclerosis in middle-age and older patients.
TABLE 23–2.Conditions that Cause Secondary Forms of Hypertension ||Download (.pdf) TABLE 23–2. Conditions that Cause Secondary Forms of Hypertension
|Chronic kidney disease |
|Renal artery stenosis |
|Primary aldosteronism and other causes of mineralocorticoid excess |
|Sleep apnea |
|Cushing disease |
|Coarctation of the aorta |
|Drug-induced hypertension |
|Obstructive uropathy |
|Thyroid/parathyroid disease |
Sleep apnea is emerging as one of the major causes of hypertension that is of epidemiologic significance. Support for a causal association between sleep-disordered breathing and hypertension includes physiological mechanisms involving vascular dysfunction secondary to altered sympathovagal balance and insulin resistance. Also, respiratory disturbances accompanied by hypoxemia and sympathetic activation can trigger acute surges in BP.43 A population survey showed that 2% of women and 4% of men have sleep apnea, which was defined as having an apnea-hypopnea index (AHI) score of five or more and daytime sleepiness.44 The prevalence of an AHI of 5 or more increases with age, reaching a maximum prevalence in a population at approximately the age of 70 years.45 Both sleep apnea and hypertension are common, and unsurprisingly there are many individuals who have both conditions. Furthermore, both are closely linked to obesity (particularly central obesity, as seen in the metabolic syndrome), so there is a cluster of related syndromes: hypertension, sleep apnea, diabetes, and the metabolic syndrome. Thus, approximately 60% of sleep apnea patients are hypertensive46 and, conversely, approximately 25% of hypertensive patients have sleep apnea.47,48 One issue is the causal link between sleep apnea and hypertension. The largest study of this is the Sleep Heart Health Study, a prospective study of the relationship between sleep apnea and cardiovascular morbidity. In an initial cross-sectional study of 6132 subjects aged 40 years or older,49 a dose-response relationship existed between the AHI score and the prevalence of hypertension, although some of it was attributable to the effects of increased body mass index. A prospective follow-up of this cohort, restricted to the 2470 individuals without hypertension, showed effect sizes almost identical to that of the cross-sectional analyses: (1) an odds ratio of 2.19 in the age-, sex-, and ethnicity-adjusted models and (2) an odds ratio of 1.51 in a model that was further adjusted for body mass index. However, given the smaller sample in the prospective analysis, this did not quite reach statistical significance.50 The Wisconsin Sleep Cohort Study did find a consistent dose-response relationship, even after controlling for age, sex, body mass index, and antihypertensive medications.51
There is a fundamental difference between the genesis of hypertension in younger and older patients (Table 23–3). The most obvious difference is that in younger patients, whatever the underlying etiology of the hypertension (with a few exceptions noted below), both systolic and diastolic BPs are raised, whereas in people aged 60 years and older, the diastolic BP starts to fall (Fig. 23–4), but there is a marked increase of systolic BP. The underlying hemodynamics are also different: in younger patients, the characteristic changes are an increased peripheral resistance with a normal cardiac output, whereas in older patients, the reason for the selective increase of systolic BP is increased arterial stiffness.52 This has two consequences. First, when the left ventricle pumps into a stiffened aorta, systolic BP will be higher because the stiffer vessel will be less able to accommodate the stroke volume. Second, the velocity of the arterial pulse wave traveling out to the peripheral vessels will be increased. Just like a wave resulting from a stone dropped in a pool, the wave is reflected when it reaches the periphery, so that the pressure waves in the circulation will be a combination of the outgoing and reflected waves. In younger people, where the pulse wave velocity is low, the reflected wave arrives relatively late and coincides with the diastolic downslope of the incident wave, so that it has no effect on the systolic or diastolic pressure. But in older individuals, it returns earlier and forms a second or late systolic peak, which augments the height of the systolic pressure. Another difference concerns the physiologic measurements. In younger patients, the increased peripheral resistance is a result of active vasoconstriction that is mediated hormonally, particularly by the sympathetic nervous system and the renin-angiotensin system. In older patients with systolic hypertension, hormonal mediation is less important and the changes are mostly mechanical (eg, loss of elastin fibers in the media of the arterial wall).52 The affected vessels (principally the aorta and central elastic vessels) dilate and stiffen. The effects of increased aortic stiffness may be bidirectional; that is, hypertension will itself increase arterial stiffness, so there may be a vicious cycle.53
TABLE 23–3.Differences Between Hypertension in Younger and Older Patients ||Download (.pdf) TABLE 23–3. Differences Between Hypertension in Younger and Older Patients
|Factor ||Younger (< 60 y) ||Older (≥ 60 y) |
|Blood pressure increase ||Systolic and diastolic ||Systolic |
|Major cause ||Hormonal ||Mechanical |
|Hemodynamic change ||Increased peripheral resistance ||Increased arterial stiffness |
|Sleep apnea ||Yes ||No |
|Treatment threshold ||140/90 mm Hg ||Higher than in younger subjects |
Pathways in the development of hypertension according to age. CO, cardiac output; IDH, isolated diastolic hypertension; ISH, isolated systolic hypertension; SDH, systolic and diastolic hypertension. Data from Sorof JM: Systolic hypertension in children: benign or beware? Pediatr Nephrol. 2001 Jun;16(6):517-525.
Treatment thresholds are also different. In younger patients, it is clearly established that starting drug treatment when the pressure exceeds 140/90 mm Hg is beneficial. This may also be true in older patients, but the clinical trials that have investigated the benefits of treatment have almost all used an initial systolic BP of 160 mm Hg or greater as an entry criterion and have not lowered the pressure to below 140 or 150 mm Hg.54 Thus, the benefits of treatment in older patients with systolic pressures below 160 mm Hg remain unproven. Of interest, however, the recently reported Systolic Blood Pressure Intervention Trial (SPRINT) of 9361 persons with diabetes with a mean age of 68 years did show treatment to a target of less than 120 mm Hg systolic BP compared to less than 140 mm Hg (achieved 121.4 vs 136.2 mm Hg) did result in a 25% reduced risk of the composite cardiovascular end point, with a trend toward greater benefit of treatment in those 75 years of age or older. Interpreting the SPRINT study results should be in the context of its use of an automated device for measuring BP that eliminated the white coat effect to obtain a more accurate estimate of cardiovascular risk.55
There is some evidence that in the very old (aged 85 years or older), mortality may be higher in patients with the lowest BPs56 and that lowering the diastolic pressure with treatment may actually increase mortality.57 The benefit or harm of treating very old patients is currently being evaluated.58