Systemic arterial hypertension is the condition of persistent, nonphysiologic elevation of systemic blood pressure (BP). It is typically defined as a resting systolic BP (SBP) 140 mm Hg or higher, or diastolic BP (DBP) 90 mm Hg or higher, or receiving therapy for the indication of BP-lowering. Hypertension afflicts a substantial proportion of the adult population worldwide, and a growing number of children. Numerous genetic, environmental, and behavioral factors influence the development of hypertension. In turn, hypertension has been identified as one of the major causal risk factors for cardiovascular disease (CVD), including heart disease, peripheral vascular disease and stroke, as well as renal disease. An understanding of the basic epidemiology of hypertension is essential for effective public health and clinical efforts to prevent, detect, treat, and control this common condition.
Epidemiology and Risk Factors
An epidemiologic association between a proposed risk factor and a disease is likely to be causal if it fulfills the following criteria: (1) exposure to the proposed risk factor precedes the onset of disease; (2) there is a strong association between exposure and incidence of disease; (3) the association is dose-dependent; (4) exposure is consistently predictive of disease in a variety of populations; (5) the association is independent of other risk factors; and (6) the association is biologically and pathogenetically plausible, and is supported by animal experiments and clinical investigation. In addition, more definitive support for a causal association between a proposed risk factor and disease may arise from clinical trials in which intervention to modify or abolish the risk factor (by behavioral or therapeutic means) is associated with a decreased incidence of the disease. As discussed later, hypertension fulfills all of these criteria, and represents an important target for intervention in reducing the population and individual burden of CVD and renal disease.
Prevalence and Secular Trends
Data from recent United States National Health and Nutrition Examination Surveys (NHANES) from 2011 to 2014 indicated that the prevalence of hypertension among adults 18 years of age and older in the U.S. was 29%, or nearly one in three adults, with 30% of men and 28.1% of women affected. In the context of the entire population, approximately 80 million U.S. adults are estimated to have hypertension. Despite significant advances in our understanding of the risk factors, pathogenesis, and sequelae of hypertension, and multiple trials over the past 5 decades indicating the benefits of antihypertensive therapy, hypertension remains a significant public health problem. Although there were steady and significant reductions over the last 4 decades in population levels of BP and prevalence of hypertension in the U.S., recent data indicate a plateau in these favorable trends. Between the late 1970s and the mid-1990s, the prevalence of hypertension in the U.S. declined from about 32% to 25%. However, more recent survey data indicate that there was an increase in prevalence between 1988 to 1994 and 1999 to 2002. The prevalence appears to have been stable from 1999 to 2014, however, at approximately 29%. The current pandemic of obesity and aging of the population are likely to increase rates of hypertension substantially over the next decades.
Huffman et al examined trends in SBP levels in the U.S. from 1991 to 2008. They observed that SBP levels declined in US adults during this time period. However, there were significant differences noted when stratified by age group in men and women. In the overall population, SBP declined significantly only in those older than 60 years of age, from an average of 139 to 133 mm Hg, whereas in younger and middle-aged individuals, SBP levels were essentially unchanged. Patterns were similar among untreated individuals, with untreated men over age 60 years experiencing an 11 mm Hg decline and women a 6 mm Hg decline in mean SBP from 1991 to 2008, and stable mean SBP in younger individuals. Among treated individuals, mean SBP levels declined from 1991 to 2008 in men and women of all age groups.
African Americans, and especially African-American women, have a prevalence of hypertension that is among the highest in the world. Currently, it is estimated that 41.2% of non-Hispanic African-American adults have hypertension (including 40.8% of men and 41.5% of women), compared with 28% of non-Hispanic whites, 24.9% of non-Hispanic Asians, and 25.9% of Hispanic Americans. Asian Americans and most other ethnic groups tend to have similar BP levels and hypertension prevalence as whites. Trends in the prevalence of hypertension have followed a similar pattern in all ethnicities from the 1990s to the present. Prevalence rates are similar between men and women, but they increase dramatically with age, from 7.3 to 32.2 to 64.9% among those aged 18 to 39, 40 to 59 and 60 years or older, respectively.
There have been substantial improvements in awareness, treatment, and control of hypertension over the last 2 decades, but the number of hypertensive individuals who are aware of their hypertension, receiving treatment, or treated and controlled remains well below optimal levels ( Table 1.1 ). Data from NHANES 2011 to 2012 indicate that 82.7% of hypertensive individuals were aware of their elevated BP, 75.6% of them were receiving antihypertensive therapy, but only 51.8% had a BP of less than 140/90 mm Hg, the level considered to be “controlled” or at goal. These data reflect a significant increase in treatment and control rates from approximately 60% and 30%, respectively, in 2000, to the current levels of treatment and control. Nonetheless, extrapolating these data to the current estimate of 80 million Americans with hypertension, there are still over 38 million hypertensive individuals who are unaware of their diagnosis, aware but untreated, or treated but uncontrolled ( Fig. 1.1 ).
| NHANES II 1976-1980 | NHANES III 1988-1991 | NHANES III 1991-1994 | NHANES 1999-2000 | NHANES 2007-2008 | NHANES 2011-2012 | |
|---|---|---|---|---|---|---|
| Prevalence | 31.8% | 25.0% | 24.5% | 28.7% | 29.6% | 29.1% |
| Awareness | 51% | 73% | 68% | 69% | 80.6% | 82.7% |
| Treatment | 31% | 55% | 54% | 60% | 73.7% | 75.6% |
| Control to <140/<90 mm Hg | 10% | 29% | 27% | 30% | 48.4% | 51.8% |
Rates of awareness, treatment, and control of BP tend to differ by age, sex, and race/ethnicity. After years of relative stagnation, trends in awareness, treatment, and control have shown remarkable progress in the last decade among all age, sex, and race groups. Overall, awareness of elevated BP increased significantly from 69.6% to 80.6% between 1999 and 2008, with women and non-Hispanic black adults being more likely to be aware, and Mexican Americans being the least likely to be aware of their hypertension. Currently, women are somewhat more likely than men to be aware of their hypertension, to receive treatment with antihypertensive drug therapy, and to be at goal BP ( Table 1.2 ). Individuals with hypertension aged 18 to 39 years are far less likely to be aware, treated, or controlled compared with middle-aged and older individuals. Compared with other race/ethnic groups, non-Hispanic Asians are significantly less likely to be aware of their hypertension or to have it treated, but control rates are similar across all race/ethnic groups (see Table 1.2 ).
| Awareness of Hypertension | Prevalence of Antihypertensive Treatment | Control to <140/<90 mm Hg | |
|---|---|---|---|
| Men | 80.2% | 70.9% | 49.3% |
| Women | 85.4% | 80.6% a | 55.2% a |
| Age 18-39 years | 61.8% | 44.5% | 34.4% |
| Age 40-59 years | 83.0% b | 73.7% b | 57.8% b |
| Age ≥60 years | 86.1% b | 82.2% b | 50.5% b |
| Non-Hispanic white | 82.7% | 76.7% | 53.9% |
| Non-Hispanic black | 85.7% | 77.4% | 49.5% |
| Non-Hispanic Asian | 72.8% c | 65.2% c | 46.0% |
| Hispanic-American | 82.2% | 73.5% | 46.5% |
a Significantly different compared with men
b Significantly different compared with ages 18-39 years
c Significantly different compared with all other race/ethnic groups
There is also substantial geographic variation in the epidemiology of hypertension in the U.S. Prevalence of hypertension is highest in the southeastern U.S., but so are awareness, treatment and control of hypertension. Areas of the southwestern U.S. in New Mexico, Colorado, and Texas have some of the lowest rates of awareness, treatment and control.
Global Burden of Hypertension
International data indicate that hypertension is even more prevalent in other countries, including developed countries. Hypertension is also the leading single cause of global burden of diseases. Fig. 1.2 reveals the estimated proportion of deaths attributable to high systolic blood pressure by country across the globe. There is substantial variation globally and regionally, with the lowest proportion of deaths attributable to high systolic blood pressure in Chad, at 3.8%, and the highest in Georgia, at 40.4%.
Although data from low-income and middle-income countries around the world had been sparse, in recent years the scope and trends in the global burden of hypertension have become clearer. Danaei and colleagues described the current levels and trends in SBP for adults 25 years and older in 199 countries using data from published and unpublished health examination surveys and epidemiologic studies including 5.4 million participants. In 2008, age-standardized mean SBP worldwide was 128.1 mm Hg in men and 124.4 mm Hg in women. The investigators estimated that between 1980 and 2008, global SBP decreased by 0.8 mm Hg per decade in men and 1.0 mm Hg per decade in women. There was significant regional variation in SBP trends over time. Female SBP decreased by 3.5 mm Hg or more per decade in Western Europe and Australasia. Male SBP fell most, by 2.8 mm Hg per decade in high-income North America. SBP rose in Oceania, East Africa, and South and Southeast Asia for both sexes, and in West Africa for women. Female SBP was highest in some East and West African countries, with means of 135 mm Hg or greater. Male SBP was highest in Baltic and East and West African countries, at 138 mm Hg or more. Men and women in Western Europe had the highest SBP in high-income regions. SBP is currently highest in low-income and middle-income countries overall, creating a substantial burden of disease in these countries.
Surveys of the prevalence of hypertension indicate a growing global burden. Using data from the 1990s, the prevalence of hypertension in adults aged 35 to 74 years in Canada has generally been similar to that of the U.S. (at approximately 28%), and concurrent data from six European countries revealed an overall prevalence of 44%. In Europe, clinical practice guidelines have typically recommended higher BP thresholds before initiation of drug therapy, causing even lower rates of treatment and control of BP. Of the European countries studied, Italy had the lowest prevalence (38%), whereas Germany had the highest (55%). The increase in BP and in prevalence of hypertension with age has been steeper in European countries compared with the U.S. and Canada. The correlation between hypertension prevalence and stroke mortality rates is very strong (r = 0.78), with a stroke mortality rate of 27.6 per 100,000 in North America and 41.2 per 100,000 in European countries. Furthermore, treatment rates in Europe have been substantially lower, in association with higher BP thresholds for treatment in clinical practice guidelines promulgated in Europe and Canada until recently. Among 35- to 64-year-old hypertensives, over half (53%) were treated in the U.S., compared with 36% in Canada and 25% to 32% in European countries. The associated differences in levels of BP control were dramatic, with 66% of U.S., 49% of Canadian, and 23% to 38% of European hypertensives controlled to BP levels of less than 160/95 mm Hg, and 29%, 17%, and 10% or lower, respectively, controlled to levels of less than 140/90 mm Hg.
Risk Factors for Hypertension
Hypertension is a complex phenotype with multiple genetic and environmental risk factors, as well as important gene-environment interactions. Age, with its concomitant changes in the vasculature, and demographic and socioeconomic variables are among the strongest risk factors for hypertension.
Age
The prevalence of hypertension increases sharply with advancing age: although only 8.6% of men and 6.2% of women ages 20 to 34 years are affected, 76.4% of men and 79.9% of women aged 75 years and over have hypertension ( Fig. 1.3 ). Thus, in older patients, hypertension is by far the most prevalent risk factor for CVD. About 81% of hypertensive individuals in the U.S. are aged 45 years and older, although this group comprises only 46% of the U.S. population. With the aging of the population, the overall prevalence of hypertension in the population is sure to increase.
Viewed from another perspective, hypertension already affects more individuals during their lifespan than any other trait or disease studied to date. The concept of the “lifetime risk” of a given disease provides a useful measure of the absolute burden and public health impact of a disease, as well as providing an average risk for an individual during his or her lifetime. Lifetime risk estimates account for the risk of developing disease during the remaining lifespan and the competing risk of death from other causes before developing the disease of interest. Data from the Framingham Heart Study (FHS), a longstanding study of CVD epidemiology, indicate that, for men and women free of hypertension at age 55, the remaining lifetime risks for development of hypertension through age 80 are 93% and 91%, respectively. In other words, more than 9 out of 10 older adults will develop hypertension before they die. Even those who reach age 65 free of hypertension still have a remaining lifetime risk of 90%.
In Western societies, SBP tends to rise monotonically and inexorably with advancing age. Conversely, DBP levels rise until about age 50 to 55 years, after which there is a plateau for several years and then a steady decline to the end of the usual lifespan. A variety of factors, particularly related to changes in arterial compliance and stiffness, contribute to the development of systolic hypertension and to decreasing DBP with age. Both of these phenomena contribute to a marked increase in pulse pressure (PP), defined as SBP minus DBP, after age 50 years. Thus, hypertension, and particularly systolic hypertension, is a nearly universal condition of aging, and few individuals escape its development. Only in societies where salt intake is low, physical activity levels are very high, and obesity is rare, are age-related increases in SBP avoided.
Weight
Increasing weight is one of the major determinants of increasing BP. In recent NHANES surveys, the prevalence of hypertension among obese individuals, with a body mass index (BMI) 30 kg/m 2 or higher, is 42.5%, compared with 27.8% for overweight individuals (25 to 29.9 kg/m 2 ), and 15.3% for individuals with BMI less than 25 kg/m 2 . Comparing NHANES 1988-1994 with NHANES 1999-2004, Cutler et al found an overall increase in the prevalence of hypertension by 13% in men and 24% in women. After adjustment for BMI, there was no statistically significant change in hypertension in men, indicating that the increase in BMI accounted for nearly all of the increase in hypertension in men. For women, after adjustment for BMI, there continued to be large relative increases in the prevalence of hypertension, indicating that some of the increases in hypertension in women were attributable to factors other than their increases in BMI in the recent NHANES period.
Data from Framingham also reveal marked increases in risk for development of hypertension with higher BMI. Compared with normal weight adult men and women, the multivariable-adjusted relative risks for development of hypertension in long-term follow up were 1.48 and 1.70 for overweight men and women, and 2.23 and 2.63 for obese men and women, respectively.
Numerous studies have also demonstrated the important role of weight gain in BP elevation and weight reduction in BP lowering. As discussed above, SBP and DBP tend to rise with age beginning at around age 25 years in most adults. However, recent data indicate that these “age-related” increases in SBP and DBP may be avoided in young adults who maintain stable BMI over long-term follow up. In the Coronary Artery Risk Development In young Adults (CARDIA) study, those who maintained a stable BMI at all six examinations over 15 years had no significant changes in either SBP or DBP, whereas those who had an increase in their BMI of 2 kg/m 2 or more had substantial increases in BP.
The influence of weight gain on BP, and the benefits of maintaining stable weight or losing weight extend down even to young children. One large birth cohort study of children examined BMI at ages 5 and 14 and the association with SBP and DBP at age 14. Children who were overweight at age 5 but had normal BMI at age 14 had similar mean systolic and diastolic BP to those who had a normal BMI at both time points. Conversely, children who were overweight at both ages, or who had a normal BMI at age 5 and were overweight at age 14, had higher systolic and diastolic BP at age 14 than those who had a normal BMI at both ages, even after adjustment for potential confounders.
Other Risk Factors
As discussed above, sex influences the prevalence of hypertension in an age-dependent fashion. Until about the sixth decade of life, men have a higher prevalence, after which women predominate increasingly ( Fig. 1.3 ). Overall, more women than men are affected by hypertension, in part because of their longer life expectancy.
Race/ethnicity has also been shown to be significantly associated with hypertension. Although non-Hispanic white persons make up about two-thirds of the U.S. adult hypertensive population, this is consistent with their representation in the overall population. African Americans are disproportionately affected, and have among the highest rates of hypertension in the world, with mean systolic BP levels approximately 5 mm Hg higher than whites, and prevalence rates at least 10% higher than whites. Other racial/ethnic groups in the U.S., including Hispanic Americans, have a prevalence of hypertension similar to whites. Education status also influences rates of hypertension, with lower education levels being strongly associated with hypertension. However, much of this inverse association of education with BP appears to be explained by differences in diet and in BMI between less educated and more educated individuals.
Among dietary influences on BP level, high dietary sodium intake has consistently been related to rates of hypertension in numerous populations and cohort studies. Conversely, higher potassium, calcium, and magnesium intakes appear to be associated with lower rates of hypertension in various populations. Patients with omnivorous diets have higher BP levels than those who are vegetarian, but the types of dietary fat do not appear to influence BP levels directly (with the possible exception of mild lowering by omega-3 fatty acids). The evidence linking heavy alcohol intake to hypertension is unequivocal. More than 50 epidemiologic studies have demonstrated an association between intake of 3 or more drinks per day and hypertension, although regular alcohol intake is associated with a lower risk of atherothrombotic CVD events.
Genetic Factors
Numerous studies have examined potential genetic susceptibilities for hypertension. Data consistently indicate that BP levels are heritable. Using data from the multigenerational FHS cohorts, Levy et al estimated that heritability for single-examination measures were 0.42 for SBP and 0.39 for DBP. Using data from multiple examinations, long-term systolic and diastolic BP phenotypes had high heritability estimates, at 0.57 and 0.56, respectively.
The availability of high-throughput technology has recently allowed for genome-wide association studies to be performed in large pooled cohorts to assess for linkage between identified areas of the genome and BP levels. A large consortium of studies tested 2.5 million genotyped and imputed single-nucleotide polymorphisms (SNPs) across the genome for association with systolic and diastolic BP levels in 34,433 subjects of European ancestry and followed up findings with direct genotyping in 71,225 participants of European ancestry and 12,889 of Indian Asian ancestry. They also performed in silico comparison in another large consortium ( n = 29,136). This group identified associations between systolic or diastolic BP and common variants in eight genomic regions near a number of potential genes of interest: CYP17A1 ( p = 7×10 −24 ), CYP1A2 ( p = 1×10 −23 ), FGF5 ( p = 1×10 −21 ), SH2B3 ( p = 3×10 −18 ), MTHFR ( p = 2×10 −13 ), c10orf107 ( p = 1×10 −9 ), ZNF652 ( p = 5×10 −9 ) and PLCD3 ( p = 1×10 −8 ) genes. All variants associated with continuous BP were associated with the phenotype of dichotomous hypertension as well. The authors concluded that these associations between common variants and BP and hypertension could offer mechanistic insights into the regulation of BP and may point to novel targets for interventions to prevent cardiovascular disease.
Updates to these genome-wide association studies continue to appear with the addition of more cohorts and refined genotyping methods. To date, more than 60 loci (many in novel or unexpected genes) have now been associated with blood pressure phenotypes or the diagnosis of hypertension, with similarities noted in diverse race/ethnic groups. Similarly, rare inherited genetic syndromes are associated with hypertension, including Liddle syndrome and 11β-hydroxylase and 17α-hydroxylase deficiencies. However, because hypertension is a complex phenotype, and BP levels are determined by the complex interactions of multiple neurologic, renal, endocrinologic, cardiac and vascular processes, as well as environmental and behavioral factors, there have not been any single-gene polymorphisms discovered that explain more than a small fraction of hypertension alone or jointly in the population at large. The study of rare and low-frequency genetic polymorphisms, gene-gene interactions, gene-environment interactions and epigenetics is likely to lead to novel insights on blood pressure regulation, and may provide potential future targets for prevention or treatment of hypertension.
Classification of Blood Pressure
Formal classification of BP stages by consensus panels began to take shape in the early 1970s with the first National Conference on High Blood Pressure Education. The first report of the Joint National Committee (JNC) was published in 1977 and has been followed by six subsequent reports in 1980, 1984, 1988, 1993, 1997, and 2003. The seventh report (JNC 7, published in 2003) was the clinical standard for the prevention, detection, evaluation and treatment of hypertension in the U.S. until recently. Current U.S. and international guidelines still use the same classification system. JNC 7 recognized several important concepts that have evolved in our understanding of hypertension over the past decades. First, systolic hypertension confers at least as much, and usually greater, risk for adverse events as diastolic hypertension, which was not fully appreciated in the first four JNC reports. Thus, the JNC report recommends that for middle-aged and older hypertensives (who represent the vast majority of hypertensives in the population), SBP should be the primary target for staging of BP and initiation of therapy. Second, hypertension rarely occurs in isolation, and is usually present in the context of one or more other CVD risk factors. Therefore, in recommending treatment for hypertension, the JNC 7 report recommended some consideration of global risk for CVD.
It has long been recognized that BP confers risk for CVD beginning at levels well within the clinically “normal” range, with risk increasing in a continuous, graded fashion to the highest levels, as discussed in detail later. Thus, although clinical practice guidelines impose certain thresholds for considering individuals to be hypertensive, and for initiation of therapy, this conception is an artificial construct designed to assist clinicians and patients with treatment decisions.
The current scheme for classifying BP stages is shown in Table 1.3 . Although BP lower than 120/80 had previously been termed “optimal,” it is now termed “normal.” A category of “prehypertension” is defined, including individuals with untreated SBP 120 to 139 or DBP of 80 to 89 mm Hg. The prior classification of Stage 3 hypertension was dropped because of its relatively uncommon occurrence, and all individuals with SBP 160 mm Hg or higher or DBP 100 mm Hg or higher are now classified as having Stage 2 hypertension.
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