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Environmental Health Perspectives 

Vol. 78, pp. 3-7,1988 

Epidemiology of Hypertension as a 

Public Health Problem: An Overview as 

Background for Evaluation of Blood 

Lead-Blood Pressure Relationship 

by Herman A. Tyroler* 

An overview of the epidemiology of blood pressure is presented as background for the International 

Symposium of Blood Lead-Blood Pressure Relationships. The correlates of blood pressure 

distributions in populations are varied and numerous. They have to be considered as either potential 

confounders or modifiers of any blood pressure-blood lead relationship detected. The relation of 

blood pressure to cardiovascular morbidity and mortality emphasizes the importance of detecting and 

elucidating any possible causal association of blood lead with blood pressure at low levels. The task 

of this symposium is of public health importance, as relatively minor changes in the distribution and 

mean levels of blood pressure in populations are associated with major morbidity and mortality 

consequences. 

Introduction 

This symposium is addressed to a review of the evidence that there is a relationship between blood lead 

and blood pressure levels. We have organized presentations that permit discussion and evaluation of published investigations and work in progress relating to 

both human and animal studies. The human studies 

are further stratified as clinical, occupational epidemiologic, and general population epidemiologic studies. 

Most controversy in this field has been engendered by 

the general population studies, which have suggested a 

causal relationship between increases in blood lead 

levels within the range of values lower than those 

considered clinically significant and increases in 

blood pressure, also within the range below values 

considered clinically significant as hypertensive. The 

association has not been found in all studies and, 

when present, has been such that increase in blood 

pressure with increase in blood lead levels has been of 

small absolute magnitude and not constant across age, 

sex, and race subgroups. Despite the seemingly small 

elevations in blood pressure when viewed from the 

clinical perspective of each individual, the potential 

'Department of Epidemiology, School of Public Health, University of 

North Carolina. Chapel Hill, NC 27599. 

public health importance of a blood lead relationship is 

considerable due to the strong association of blood 

pressure with cardiovascular morbidity and mortality, the leading cause (s) of death in our society, and 

the large number of individuals exposed. Evaluation 

of the possible contribution of blood lead levels to these 

outcomes from observational epidemiologic studies 

requires assessment of whether there is evidence of an 

association of blood lead with blood pressure levels, its 

strength, dose-response nature, consistency across 

studies, freedom from measurement biases, and statistical independence from the effects of confounding 

influences. Finally, the biologic and pathophysiologic 

plausability of the epidemiologic observational association is to be assessed in light of the human and 

animal experimental studies. 

As background for the specific studies to be reviewed 

at the symposium, it was deemed appropriate to present 

an overview of some of the elements of the epidemiology of blood pressure relevant to the blood leadblood pressure issue. Selectivity was necessary in 

choosing from a vast literature, an epidemiologic literature whose summarizations themselves have been 

extensive (1-4). The guiding principle in choosing 

material was to illuminate methodologic and substantive issues that could misinform studies of blood 

pressure in relation to blood lead levels. Particular 
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H. A. TYROLER tt 

' « 

attention is called to the continuous distribution of 

blood pressure levels in populations; the large number 

and varied nature of correlates of blood pressure; the 

continuous nature of the cardiovascular morbidity 

and mortality risk functions associated with increasing blood pressure; and the resulting large potential 

population disease burden of increases in blood pressure, seemingly clinically insignificant for each 

individual. 

Distribution of Blood Pressure in 

Populations 

Blood pressure is difficult to measure reliably in 

population studies. There is marked intraindividual 

variability in response to the physical and social environmental circumstances of measurement and 

psychologic responses to the measuring situation. Although there are experiments suggesting an influence 

of lead on pressure responsivity, there are no large 

epidemiologic studies addressing this issue. 

Observer sources of measurement variation are 

considerable and require training, standardization, 

and quality control assessment to assure comparability 

among observers within a given study. Unfortunately, objective methods to assure measurement comparability across studies, or over time within study 

populations, have not been satisfactorily developed for 

large epidemiologic studies. Although follow-up 

studies over long periods of time demonstrate some 

tracking of individuals (i.e., maintenance of rank 

position based on blood pressure level), and one casual 

blood pressure level is predictive of morbidity and 

mortality, these associations are increased by assessments repeated and averaged over time. Thus, there are 

methodologic problems in evaluating population 

changes in blood pressure over time, problems of 

moment given changes in blood lead over time. 

The result of all sources of variation of blood pressure 

measurements within and among individuals in 

populations is a continuous distribution, unimodal 

in nature, without any clear dividing points permitting level per se to distinguish the normotensive 

from the categorical (arbitrarily defined) hypertensive. In the epidemiologic domain the population is 

the unit of study, not the individual, and populations 

differ in the distribution of blood pressure. They differ 

both in the mean level and in the amount of variation 

around the mean. Generally, but not invariably, there 

is increasing variance and increasing skewness 

towards higher values with increasing mean levels of 

blood pressure. On comparison of two populations with 

different mean levels, the proportion of individuals 

with high levels gets progressively more dissimilar 

between the populations as one moves further out to 

higher values (arbitrarily categorized as hypertensive) in the tails of the distributions. Thus, seemingly 

small differences in mean values of blood pressure of 

populations can be accompanied by sizable differences 

in proportions of individuals, with, .elevated values or*, 

alternatively expressed, sizable differences in pro-1-

portions of hypertensives. 

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Correlates of Blood Pressure 

Levels in Populations 

The known correlates of blood pressure levels in 

populations are large in number, and thereby the 

potential for confounding of a blood pressure relationship with another attribute, such as blood lead 

levels, is commensurately large. In addition to the 

large number of correlates of blood pressure levels in 

populations, their operation at different levels of biosocial organization increases the complexity of assessing their possible confounding or effect modification 

of a blood lead-blood pressure relationship. A brief 

consideration of some of these correlates is organized 

by the following categories: demographic, familial, 

physical environment, social environment, and 

behavioral factors. 

Demographic Correlates 

The trends in blood pressure with age, among the 

most important factors in the etiology of hypertension, 

and the association of hypertension with sex are often 

considered invariable biological effects, minimally 

amenable to modification; however, age and sex may 

be surrogate indicators of social and physiochemical 

environmental processes. For example, although most 

populations show increases in mean blood pressure 

levels with age, some do not. The common characteristics of populations without evidence of increase in 

blood pressure with age have variously been identified 

as absence of industrialization, persistence of traditional social structures, and low sodium ingestion. 

Populations can be classified by the rate of change of 

blood pressure with age and the level of blood pressure. 

At one extreme are populations with low levels of blood 

pressure and no increase of mean pressure with age; at 

an opposite extreme are populations with high levels 

and marked increase in blood pressure with increasing age, e.g., rural southern U.S. blacks. 

Although linear increase in pressure with age is an 

appropriate approximation of most population observations for systolic blood pressure, the cross-sectional 

diastolic blood pressure data are more accurately represented by a curvilinear relationship to age, with 

mean diastolic pressure reaching a plateau in middle 

age and decreasing at older ages. The mean blood pressure of different aged individuals in cross-sectional 

surveys are single point-in-time values for different 

individuals at different achieved ages, and therefore 

represent the composite effects, if any, of aging per se, 

different experiences of different birth cohorts, and 

selective survival. Prospective studies in industrialized societies confirm the average rise in blood 

pressure (particularly systolic) with age observed in 
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EPIDEMIOLOGY OF HYPERTENSION 

cross-sectional surveys; however, not all individuals 

experience the rise, and, among those who do, there is 

considerable variation in the rate of rise. 

Mean blood pressure levels and the prevalence of 

hypertension vary with sex in a manner that differs 

with age epochs. Comparison in industrialized societies of studies of children younger than age 14 reveals 

no consistent sex differences; in adolescence, young 

adulthood, and through age 45 there is unanimity 

among reported studies of higher mean blood pressure 

levels in males and a male excess in the prevalence of 

hypertension; a cross-over then occurs in these crosssectional surveys at about age 45, after which mean 

blood pressure becomes higher in women than in 

men. 

Among the most consistent findings in the epidemiology of hypertension is an excess in its frequency and deleterious sequelae in adult black populations in the United States. Numerous studies have 

reported a shift in the distribution of blood pressure 

levels in blacks toward higher values for both sexes at 

all adult ages. The age at which blacks first manifest 

higher blood pressure than whites is not clear. Studies 

of teenagers have been approximately equally divided, 

with some showing and some not showing blackwhite differences in blood pressure distribution. 

Although it is not clear at what age the black-white 

difference is first manifest, there is uniformity among 

studies in finding higher blood pressure levels and an 

excess of end organ sequelae associated with hypertension from young adulthood on, in surveys of blacks 

sampled from national prevalence surveys and surveys of local communities. The higher blood lead levels 

in blacks invites the hypothesis that at least some of the 

shift toward higher blood pressure distributions in 

blacks is attributable to lead exposure. 

Genetic and Family Aggregation 

There is a large body of empirical data indicating 

similarity of blood pressure levels within families. 

Briefly summarized, first degree genetic relatives of all 

ages from infancy to old age, studied in diverse social 

and cultural settings, tend to resemble one another in 

levels of systolic and diastolic blood pressure. The 

similarity of blood pressure levels of relatives does not 

argue unequivocally for a genetic cause. In addition to 

sharing genes, relatives share common physical, 

social, and psychological environments, which can 

influence blood pressure. Aggregation of blood pressure 

levels among nongenetically related household members, including but not restricted to spouse pairs, has 

been reported in some studies. Greater similarity 

would be expected among age-contemporaneous sibling pairs than intergenerational parent-offspring 

pairs, based on both environmental and genetic hypotheses. The empirical findings are in conflict; about 

half of the reported studies show higher similarity in 

sibling pairs. The measure of similarity of blood 

pressure among genetic relatives is greater than that 

observed among spouses or other nongenetic related 

household members, in the instances where the latter 

do demonstrate significant similarity of blood 

pressure levels. As measured by the correlation coefficient, this is greater for monozygotic than for 

dizygotic twins, greater for first degree genetic relatives than spouse pairs, and greater among family 

members with natural than adopted children. These 

findings are consistent with genetic factors influencing blood pressure within populations. 

These studies neither clarify nor delineate the relative importance of genetic and familial environmental 

factors, nor the nature of the genetic mechanisms. The 

possibility that lead exerts a different blood pressureelevating effect among genetically different susceptibles 

has not been empirically tested. 

Social and Physical Environment 

The sensitivity of blood pressure regulatory mechanisms to acute psychological stimuli and strong 

emotional reactions is marked. Neurohumoral blood 

pressure and cardiovascular control is an integral 

component in normal hemodynamics and adaptation 

to sudden environmental challenges. Therefore, a wide 

variety of interpersonal experiences, external situations, emotions, and perceived and expected changes in 

life situations is associated with acute elevation of blood 

pressure. These psychophysiological responses are part 

of the normal repertoire of responses. Psychosocial 

theories of hypertension suggest that such factors are 

also involved in the etiology of sustained hypertension. Neurohumoral relations to a wide range of processes influencing blood pressure have been postulated, 

extending from the personality basis of altered blood 

pressure reactivity of the individual to the social origins of increased stressors, incorporating both 

acquired, learned modes of response and inborn 

constitutional predisposition. 

In most developed societies, social stratification, 

whether indexed by achieved education, occupational 

status, income level, or a combination of these measures, has been found to be inversely associated with 

blood pressure. This has been observed in the U.S. for 

both whites and blacks. For example, among the more 

than 150,000 individuals screened for the Hypertension Detection and Follow-Up Program, there was a 

stepwise increase in the prevalence of categorically 

defined hypertension with decreasing educational 

achievement for both whites and blacks. Much of the 

education-blood pressure association was explained by 

an increase in the prevalence of obesity with decreasing education. 

The association of blood lead levels with social status 

and the social environment, i.e., higher lead levels 

among the poor and among those residing in more 

highly exposed rural and urban places of residence, 

requires consideration of these circumstances in the 

study of processes relating blood lead to blood pressure. 

Numerous elements in the food, water, air, and soil 
P.5 

H. A. TYROLER 

of the ambient physical environment and in the 

workplace are related to blood pressure. Among the elements most studied and quantitatively most important are sodium, potassium, calcium, and magnesium. Complex interactions among these elements 

with blood pressure and their possible role(s) in any 

lead-blood pressure association require systematic 

investigations. 

Behavior and Obesity 

A sizable correlation between blood pressure and 

indices of body weight in relation to height in 

children and adults has repeatedly been demonstrated 

in both cross-sectional and longitudinal populationbased studies. The relationships are continuous across 

the range of blood pressure levels. 

In addition to measurements of the association 

between blood pressure and overweight as continuous 

traits, quantitative estimates have been derived from 

the relation between baseline weight, weight gain, and 

the incidence of hypertension, classified categorically. 

Individual behavior is a strong determinant of 

blood pressure levels in populations. The balance of 

dietary caloric intake and caloric expenditure by 

physical activity is reflected in weight and obesity, 

major correlates of blood pressure, and its distribution 

in communities. Obesity per se is probably related to 

blood pressure; not just the amount, but the bodily 

regional distribution of fat appears to be associated 

with elevated blood pressure. Accumulation in the 

abdominal area contrasted with the extremity areas 

seems to have stronger association not just with blood 

pressure, but also with other cardiovascular risk 

factors. Dietary fat intake, the ratio of saturated to 

unsaturated fat, and the possibility that the fat content 

of marine animals influence blood pressure levels are 

under intensive investigation at present. Relationships have been observed in population-based studies 

between the amount of alcohol consumed and average 

blood pressure levels. Smoking represents an area of 

considerable controversy in that several studies have 

found an inverse association between smoking and 

blood pressure, but most investigators attribute that to 

the lower weight of smokers. The increment in weight 

on cessation of smoking is associated with an increase 

in blood pressure. 

The possibility of confounding of the blood leadblood pressure association by the behavioral, dietary, 

alcohol consumption, and smoking attributes discussed requires detailed attention and analysis. 

Consequences of Blood Pressure 

Levels in Populations 

Given the overview presentation of the distribution 

and antecedents, we can now turn our attention to 

some of the consequences of blood pressure levels in 

populations. Numerous studies have documented the 

relation of blood pressure to morbidity and mortality; 

one is a recent study based on the screening of more, 

than 300,000 men for the Multiple Risk Factor Intervention Trial and the subsequent 6-year follow-up for 

coronary heart disease mortality. Blood pressures were 

stratified into age-specific quintiles, and there generally was a monotonic increase in coronary mortality 

with increasing levels of blood pressure in each age 

group. There was, however, a suggestion of a J-shaped 

curve in the oldest age stratum, with the lowest 

quintile group of blood pressures having slightly 

higher mortality. Although this risk function shape 

has been observed in the Framingham study and 

other studies, this is a controversial area; in general, 

the relationship found is of a monotonically increasing nature. Comparing the within-age group risk of 

mortality of those in the highest quintile to those in 

the lowest quintile shows a consistent decrease in the 

relative risk with increasing age. In contrast, attributable risk, i.e., the arithmetic difference in the rates 

between those in the highest and lowest quintile, shows 

a stepwise, consistent increase with increasing age. 

Elevated blood pressure is a risk factor not only for 

coronary disease, but also for more specifically pressure-related conditions such as congestive heart failure and strokes. The relative risk for the pressurerelated phenomena, particularly for stroke, is markedly higher than for coronary disease: somewhat more 

than 2 for coronary and 10 for stroke. 

An estimation of the population impact is assessed by 

considering the continuous distribution of blood 

pressure levels in populations, the risk function of 

stepwise increases in disease frequency with increasing levels of blood pressure, and the excess risk associated with elevated levels above arbitrarily chosen cut 

points. Most of the excess disease in populations is associated with what clinically would be considered relatively mild to moderate elevations of blood pressure. 

Although the relative risk increases markedly with 

progression to higher levels of blood pressure, the 

prevalence in the population of individuals with mild 

to moderate hypertension is proportionately greater. 

The net effect is that most of the excess morbidity and 

mortality is associated with clinically relatively 

minor increases in the mid-portion of the range of 

distribution of blood pressure. This is an important 

consideration for this symposium. The proportion of 

all the disease in a given population associated with 

elevated blood pressure is the product of the attributable 

risk and the prevalence of elevated pressure at any 

chosen level and is called the population attributable 

risk. In the instance of mortality, if one divides the 

population attributable risk by all cause mortality, the 

quotient is the population attributable fraction; 

namely, the proportion of all mortality in the community associated with elevated pressures. As studied 

in one community-based study, Evans County, a very 

high proportion of all cause mortality (ranging from 

approximately 18% for white females to > 40% for black 

females) was associated with elevated blood pressure. 
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EPIDEMIOLOGY OF HYPERTENSION 

Temporal and Spatial Variation in 

Hypertension-Related Mortality 

Major temporal trends have been manifest for hypertension-related causes of death in the United States. 

After an earlier period of rise, coronary heart disease 

mortality rates have consistently shown an approximately 2% decline per year since mid-1960. There has 

been more than a 40% decline in coronary mortality in 

the last 20 years, reflected in all cardiovascular disease 

and in all-cause mortality rate declines. The decline 

started earlier and has been even greater for stroke 

mortality. In fact, stroke mortality started declining 

long before effective antihypertensive therapy was 

developed, so the determinants of declining stroke 

mortality clearly include factors other than medical 

treatment. However, since about 1972-73, coincidental 

with the initiation of a National High Blood Pressure 

Education Program in the U.S., there has been an 

acceleration of the decline in stroke mortality. 

Many of the studies reviewed at this symposium 

have been performed during a period of sharply decreasing cardiovascular mortality. There also is 

marked geographic variation in the United States in 

stroke mortality. Most of the high rate areas are in the 

eastern portion of the United States; particularly, the 

southeastern portion, and most of the low rate areas are 

in the western portion. The geographic pattern, although decreasing, has persisted over the past 20 to 25 

years, despite the marked decline in the level of mortality. Therefore, it is important to consider the possibility that there is geographic variation in blood 

pressure distributions and to account for this possibility in analyses of associations of blood pressure 

with blood lead using data derived from national 

samples. 

Conclusions 

In summary, then, this paper has presented an 

overview of the correlates, antecedents, and determinants, which are extremely varied in kind and 

numerous in amount, of blood pressure distributions 

in populations. These factors have to be considered as 

either potential confounders or modifiers of any blood 

pressure-blood lead relationship detected. The relation 

of blood pressure to cardiovascular morbidity and 

mortality emphasizes the importance of detecting and 

elucidating any possible causal association of blood 

lead with blood pressure at low levels. The task of this 

symposium is of public health importance, as relatively minor changes in the distribution and mean 

levels of blood pressure in populations are associated 

with major morbidity and mortality consequences. 

REFERENCES 

1. Stamler, J., Stamler, R, and Pullman, T. N., Eds. The Epidemiology 

of Hypertension. Grune and Stratton, New York, 1967. 

2. Paul, 0., Ed. Epidemiology and Control of Hypertension. 

Intercontinental Medical Book Corporation, New York, 1975. 

3. Bulpitt, C. J., Ed. Epidemiology of Hypertension. In: Handbook of 

Hypertension, Vol. 6 (W. H. Bukenhager and J. L. Reid, Eds.), 

Elsevier, Amsterdam, 1985. 

4. Tyroler, H. A. Hypertension. In: Public Health and Preventive 

Medicine (John M. Last, Ed.), Appleton-Century-Crofts, East 

Nonvalk, CT, 1986. 
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"!%&: 

sssavaSYMPOSIUM ON LEAD-BLOOD PRESSURE 

RELATIONSHIPS 

April 27-29,1987 

Chapel Hill, North Carolina 

Sponsored by: University of North Carolina at Chapel Hill 

International Lead Zinc Research Organization, Inc. 

U.S. Environmental Protection Agency 

American Heart Association 

Editor: W. Victery 
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